Sensitive periods in epigenetics: bringing us closer to complex behavioral phenotypes.

Science.gov (United States)

Nagy, Corina; Turecki, Gustavo

2012-08-01

Genetic studies have attempted to elucidate causal mechanisms for the development of complex disease, but genome-wide associations have been largely unsuccessful in establishing these links. As an alternative link between genes and disease, recent efforts have focused on mechanisms that alter the function of genes without altering the underlying DNA sequence. Known as epigenetic mechanisms, these include DNA methylation, chromatin conformational changes through histone modifications, ncRNAs and, most recently, 5-hydroxymethylcytosine. Although DNA methylation is involved in normal development, aging and gene regulation, altered methylation patterns have been associated with disease. It is generally believed that early life constitutes a period during which there is increased sensitivity to the regulatory effects of epigenetic mechanisms. The purpose of this review is to outline the contribution of epigenetic mechanisms to genomic function, particularly in the development of complex behavioral phenotypes, focusing on the sensitive periods.

Elementary-school age as a sensitive period in relation to development of the creative thinking: theoretical aspects

OpenAIRE

Chapiuk, Iu. S.

2016-01-01

Analysis of scientific position about the concept of "sensitivity" is conducted, the features of primary school age as a sensitive period for the development of creative thinking of children are found out in the article. The difference between concepts  "sensitive age"  and "sensitive period" is showed and key attributes of creative thinking in younger scholars are stressed.Key words: creative thinking, development, personality, sensitivity, primary school age.У статті здійснено аналіз науков...

Contact and respiratory sensitizers can be identified by cytokine profiles following inhalation exposure

NARCIS (Netherlands)

Jong, W.H. de; Arts, J.H.E.; Klerk, A. de; Schijf, M.A.; Ezendam, J.; Kuper, C.F.; Loveren, H. van

2009-01-01

There are currently no validated animal models that can identify low molecular weight (LMW) respiratory sensitizers. The Local Lymph Node Assay (LLNA) is a validated animal model developed to detect contact sensitizers using skin exposure, but all LMW respiratory sensitizers tested so far were also

Behavioral metabolomics analysis identifies novel neurochemical signatures in methamphetamine sensitization

Science.gov (United States)

Adkins, Daniel E.; McClay, Joseph L.; Vunck, Sarah A.; Batman, Angela M.; Vann, Robert E.; Clark, Shaunna L.; Souza, Renan P.; Crowley, James J.; Sullivan, Patrick F.; van den Oord, Edwin J.C.G.; Beardsley, Patrick M.

2014-01-01

Behavioral sensitization has been widely studied in animal models and is theorized to reflect neural modifications associated with human psychostimulant addiction. While the mesolimbic dopaminergic pathway is known to play a role, the neurochemical mechanisms underlying behavioral sensitization remain incompletely understood. In the present study, we conducted the first metabolomics analysis to globally characterize neurochemical differences associated with behavioral sensitization. Methamphetamine-induced sensitization measures were generated by statistically modeling longitudinal activity data for eight inbred strains of mice. Subsequent to behavioral testing, nontargeted liquid and gas chromatography-mass spectrometry profiling was performed on 48 brain samples, yielding 301 metabolite levels per sample after quality control. Association testing between metabolite levels and three primary dimensions of behavioral sensitization (total distance, stereotypy and margin time) showed four robust, significant associations at a stringent metabolome-wide significance threshold (false discovery rate < 0.05). Results implicated homocarnosine, a dipeptide of GABA and histidine, in total distance sensitization, GABA metabolite 4-guanidinobutanoate and pantothenate in stereotypy sensitization, and myo-inositol in margin time sensitization. Secondary analyses indicated that these associations were independent of concurrent methamphetamine levels and, with the exception of the myo-inositol association, suggest a mechanism whereby strain-based genetic variation produces specific baseline neurochemical differences that substantially influence the magnitude of MA-induced sensitization. These findings demonstrate the utility of mouse metabolomics for identifying novel biomarkers, and developing more comprehensive neurochemical models, of psychostimulant sensitization. PMID:24034544

Sensitive Periods of Emotion Regulation: Influences of Parental Care on Frontoamygdala Circuitry and Plasticity

Science.gov (United States)

Gee, Dylan G.

2016-01-01

Early caregiving experiences play a central role in shaping emotional development, stress physiology, and refinement of limbic circuitry. Converging evidence across species delineates a sensitive period of heightened neuroplasticity when frontoamygdala circuitry is especially amenable to caregiver inputs early in life. During this period, parental…

Sensitivity Enhancement in Low Cutoff Wavelength Long-Period Fiber Gratings by Cladding Diameter Reduction

Directory of Open Access Journals (Sweden)

Ignacio Del Villar

2017-09-01

Full Text Available The diameter of long-period fiber gratings (LPFGs fabricated in optical fibers with a low cutoff wavelength was be reduced by hydrofluoric acid etching, enhancing the sensitivity to refractive index by more than a factor of 3, to 2611 nm/refractive index unit in the range from 1.333 to 1.4278. The grating period selected for the LPFGs allowed access to the dispersion turning point at wavelengths close to the visible range of the optical spectrum, where optical equipment is less expensive. As an example of an application, a pH sensor based on the deposition of a polymeric coating was analyzed in two situations: with an LPFG without diameter reduction and with an LPFG with diameter reduction. Again, a sensitivity increase of a factor of near 3 was obtained, demonstrating the ability of this method to enhance the sensitivity of thin-film-coated LPFG chemical sensors.

Sensitivity Enhancement in Low Cutoff Wavelength Long-Period Fiber Gratings by Cladding Diameter Reduction.

Science.gov (United States)

Del Villar, Ignacio; Partridge, Matthew; Rodriguez, Wenceslao Eduardo; Fuentes, Omar; Socorro, Abian Bentor; Diaz, Silvia; Corres, Jesus Maria; James, Stephen Wayne; Tatam, Ralph Peter

2017-09-13

The diameter of long-period fiber gratings (LPFGs) fabricated in optical fibers with a low cutoff wavelength was be reduced by hydrofluoric acid etching, enhancing the sensitivity to refractive index by more than a factor of 3, to 2611 nm/refractive index unit in the range from 1.333 to 1.4278. The grating period selected for the LPFGs allowed access to the dispersion turning point at wavelengths close to the visible range of the optical spectrum, where optical equipment is less expensive. As an example of an application, a pH sensor based on the deposition of a polymeric coating was analyzed in two situations: with an LPFG without diameter reduction and with an LPFG with diameter reduction. Again, a sensitivity increase of a factor of near 3 was obtained, demonstrating the ability of this method to enhance the sensitivity of thin-film-coated LPFG chemical sensors.

Identifying airway sensitizers: cytokine mRNA profiles induced by various anhydrides

International Nuclear Information System (INIS)

Plitnick, L.M.; Loveless, S.E.; Ladics, G.S.; Holsapple, M.P.; Smialowicz, R.J.; Woolhiser, M.R.; Anderson, P.K.; Smith, C.; Selgrade, M.J.K.

2003-01-01

Exposure to low molecular weight (LMW) chemicals in the workplace has been linked to a variety of respiratory effects. Within the LMW chemicals, one of the major classes involved in these effects are the acid anhydrides. The immunological basis of respiratory hypersensitivity involves CD4+ cells. By virtue of their induction of cytokines typical of CD4+ T-helper type 2 (Th2) cells--interleukin (IL)-4, 10, and 13--respiratory sensitizers may be identified and differentiated from contact sensitizers which induce Th1 cytokines (IL-2 and IFN-γ). Our previous work suggested that the ribonuclease protection assay (RPA) was useful in identifying the respiratory sensitizer, trimellitic anhydride (TMA), based on quantitative differences in Th2 cytokine mRNA as compared to the contact sensitizer dinitrochlorobenzene (DNCB). Therefore, the purpose of the studies described in this report was to expand the chemicals tested in the RPA. To this end, four acid anhydrides with known respiratory sensitization potential, TMA, maleic anhydride (MA), phthalic anhydride (PA) and hexahydrophthalic anhydride (HHPA), were tested. Although previously determined to induce immunologically equivalent responses in a local lymph node assay (LLNA), the initial dose chosen (2.5%) failed to induce Th2 cytokine mRNA expression. To determine if the lack of cytokine expression was related to dose, LLNAs were conducted at higher doses for each of the anhydrides. The highest doses evaluated (four- to six-fold higher than those used in the initial RPA) gave equivalent proliferative responses for the various anhydrides and were used for subsequent RPA testing. At these higher doses, significant increases in Th2 versus Th1 cytokine mRNA were observed for all anhydrides tested. These results suggest that the RPA has the potential to serve as a screen for the detection of LMW airway sensitizing chemicals. However, the basis for selecting immunologically equivalent doses may require some modification

CHARACTERIZATION OF THE PERIOD OF SENSITIVITY OF FETAL MALE SEXUAL DEVELOPMENT TO VINCLOZOLIN

Science.gov (United States)

Characterization of the period of sensitivity of fetal male sexual development to vinclozolin.Wolf CJ, LeBlanc GA, Ostby JS, Gray LE Jr.Endocrinology Branch, MD 72, Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U....

The Psychological Essence of the Child Prodigy Phenomenon: Sensitive Periods and Cognitive Experience.

Science.gov (United States)

Shavinina, Larisa V.

1999-01-01

Examination of the child prodigy phenomenon suggests it is a result of extremely accelerated mental development during sensitive periods that leads to the rapid growth of a child's cognitive resources and their construction into specific exceptional achievements. (Author/DB)

Estrogenic exposure affects metamorphosis and alters sex ratios in the northern leopard frog (Rana pipiens): identifying critically vulnerable periods of development.

Science.gov (United States)

Hogan, Natacha S; Duarte, Paula; Wade, Michael G; Lean, David R S; Trudeau, Vance L

2008-05-01

During the transformation from larval tadpole to juvenile frog, there are critical periods of metamorphic development and sex differentiation that may be particularly sensitive to endocrine disruption. The aim of the present study was to identify sensitive developmental periods for estrogenic endocrine disruption in the northern leopard frog (Rana pipiens) using short, targeted exposures to the synthetic estrogen, ethinylestradiol (EE2). Post-hatch tadpoles (Gosner stage 27) were exposed over five distinct periods of metamorphosis: early (stage 27-30), mid (stage 30-36), early and mid (stage 27-36), late (stage 36-42), and the entire metamorphic period (chronic; stage 27-42). For each period, animals were sampled immediately following the EE2 exposure and at metamorphic climax (stage 42). The effects of EE2 on metamorphic development and sex differentiation were assessed through measures of length, weight, developmental stage, days to metamorphosis, sex ratios and incidence of gonadal intersex. Our results show that tadpoles exposed to EE2 during mid-metamorphosis were developmentally delayed immediately following exposure and took 2 weeks longer to reach metamorphic climax. In the unexposed groups, there was low proportion (0.15) of intersex tadpoles at stage 30 and gonads appeared to be morphologically distinct (male and female) in all individuals by stage 36. Tadpoles exposed early in development displayed a strong female-biased sex ratio compared to the controls. Moreover, these effects were also seen at metamorphic climax, approximately 2-3 months after the exposure period, demonstrating that transient early life-stage exposure to estrogen can induce effects on the reproductive organs that persist into the beginning of adult life-stages.

The nature and nurture of high IQ: an extended sensitive period for intellectual development.

Science.gov (United States)

Brant, Angela M; Munakata, Yuko; Boomsma, Dorret I; Defries, John C; Haworth, Claire M A; Keller, Matthew C; Martin, Nicholas G; McGue, Matthew; Petrill, Stephen A; Plomin, Robert; Wadsworth, Sally J; Wright, Margaret J; Hewitt, John K

2013-08-01

IQ predicts many measures of life success, as well as trajectories of brain development. Prolonged cortical thickening observed in individuals with high IQ might reflect an extended period of synaptogenesis and high environmental sensitivity or plasticity. We tested this hypothesis by examining the timing of changes in the magnitude of genetic and environmental influences on IQ as a function of IQ score. We found that individuals with high IQ show high environmental influence on IQ into adolescence (resembling younger children), whereas individuals with low IQ show high heritability of IQ in adolescence (resembling adults), a pattern consistent with an extended sensitive period for intellectual development in more-intelligent individuals. The pattern held across a cross-sectional sample of almost 11,000 twin pairs and a longitudinal sample of twins, biological siblings, and adoptive siblings.

3-D periodic mesoporous nickel oxide for nonenzymatic uric acid sensors with improved sensitivity

International Nuclear Information System (INIS)

Huang, Wei; Cao, Yang; Chen, Yong; Zhou, Yang; Huang, Qingyou

2015-01-01

Graphical abstract: The enzyme-less amperometric sensor based on 3-D periodic mesoporous NiO nanomaterials used in the detection of uric acid with detection limit of 0.005 μM (S/N = 3) over wide linear detection ranges up to 0.374 mM and with a high sensitivity of 756.26 μA mM"−"1 cm"−"2. - Highlights: • Microwave-assisted method was used to fabricate the 3-D periodic mesoporous NiO particles. • The mesoporous nickel oxide was applied to nonenzymatic uric acid biosensor. • The detection limit is 0.005 μM over wide linear detection ranges up to 0.374 mM. • The sensitivity is 756.26 μA mM"−"1 cm"−"2. - Abstract: 3-D periodic mesoporous nickel oxide (NiO) particles with crystalline walls have been synthesized through the microwave-assisted hard template route toward the KIT-6 silica. It was investigated as a nonenzymatic amperometric sensor for the detection of uric acid. 3-D periodic nickel oxide matrix has been obtained by the hard template route from the KIT-6 silica template. The crystalline nickel oxide belonged to the Ia3d space group, and its structure was characterized by X-ray diffraction (XRD), N_2 adsorption–desorption, and transmission electron microscopy (TEM). The analysis results showed that the microwave-assisted mesoporous NiO materials were more appropriate to be electrochemical sensors than the traditional mesoporous NiO. Cyclic voltammetry (CV) revealed that 3-D periodic NiO exhibited a direct electrocatalytic activity for the oxidation of uric acid in sodium hydroxide solution. The enzyme-less amperometric sensor used in the detection of uric acid with detection limit of 0.005 μM (S/N = 3) over wide linear detection ranges up to 0.374 mM and with a high sensitivity of 756.26 μA mM"−"1 cm"−"2, and a possible mechanism was also given in the paper.

3-D periodic mesoporous nickel oxide for nonenzymatic uric acid sensors with improved sensitivity

Energy Technology Data Exchange (ETDEWEB)

Huang, Wei; Cao, Yang, E-mail: caowang507@163.com; Chen, Yong; Zhou, Yang; Huang, Qingyou

2015-12-30

Graphical abstract: The enzyme-less amperometric sensor based on 3-D periodic mesoporous NiO nanomaterials used in the detection of uric acid with detection limit of 0.005 μM (S/N = 3) over wide linear detection ranges up to 0.374 mM and with a high sensitivity of 756.26 μA mM{sup −1} cm{sup −2}. - Highlights: • Microwave-assisted method was used to fabricate the 3-D periodic mesoporous NiO particles. • The mesoporous nickel oxide was applied to nonenzymatic uric acid biosensor. • The detection limit is 0.005 μM over wide linear detection ranges up to 0.374 mM. • The sensitivity is 756.26 μA mM{sup −1} cm{sup −2}. - Abstract: 3-D periodic mesoporous nickel oxide (NiO) particles with crystalline walls have been synthesized through the microwave-assisted hard template route toward the KIT-6 silica. It was investigated as a nonenzymatic amperometric sensor for the detection of uric acid. 3-D periodic nickel oxide matrix has been obtained by the hard template route from the KIT-6 silica template. The crystalline nickel oxide belonged to the Ia3d space group, and its structure was characterized by X-ray diffraction (XRD), N{sub 2} adsorption–desorption, and transmission electron microscopy (TEM). The analysis results showed that the microwave-assisted mesoporous NiO materials were more appropriate to be electrochemical sensors than the traditional mesoporous NiO. Cyclic voltammetry (CV) revealed that 3-D periodic NiO exhibited a direct electrocatalytic activity for the oxidation of uric acid in sodium hydroxide solution. The enzyme-less amperometric sensor used in the detection of uric acid with detection limit of 0.005 μM (S/N = 3) over wide linear detection ranges up to 0.374 mM and with a high sensitivity of 756.26 μA mM{sup −1} cm{sup −2}, and a possible mechanism was also given in the paper.

Radioecological sensitivity

International Nuclear Information System (INIS)

Howard, Brenda J.; Strand, Per; Assimakopoulos, Panayotis

2003-01-01

After the release of radionuclide into the environment it is important to be able to readily identify major routes of radiation exposure, the most highly exposed individuals or populations and the geographical areas of most concern. Radioecological sensitivity can be broadly defined as the extent to which an ecosystem contributes to an enhanced radiation exposure to Man and biota. Radioecological sensitivity analysis integrates current knowledge on pathways, spatially attributes the underlying processes determining transfer and thereby identifies the most radioecologically sensitive areas leading to high radiation exposure. This identifies where high exposure may occur and why. A framework for the estimation of radioecological sensitivity with respect to humans is proposed and the various indicators by which it can be considered have been identified. These are (1) aggregated transfer coefficients (Tag), (2) action (and critical) loads, (3) fluxes and (4) individual exposure of humans. The importance of spatial and temporal consideration of all these outputs is emphasized. Information on the extent of radionuclide transfer and exposure to humans at different spatial scales is needed to reflect the spatial differences which can occur. Single values for large areas, such as countries, can often mask large variation within the country. Similarly, the relative importance of different pathways can change with time and therefore assessments of radiological sensitivity are needed over different time periods after contamination. Radioecological sensitivity analysis can be used in radiation protection, nuclear safety and emergency preparedness when there is a need to identify areas that have the potential of being of particular concern from a risk perspective. Prior identification of radioecologically sensitive areas and exposed individuals improve the focus of emergency preparedness and planning, and contribute to environmental impact assessment for future facilities. The

Identifying ozone-sensitive communities of (semi-)natural vegetation suitable for mapping exceedance of critical levels

International Nuclear Information System (INIS)

Mills, G.; Hayes, F.; Jones, M.L.M.; Cinderby, S.

2007-01-01

Using published data on the responses of individual species to ozone, 54 EUNIS (European Nature Information System) level 4 communities with six or more ozone-sensitive species (%OS) and c. 20% or more species tested for ozone sensitivity, were identified as potentially ozone-sensitive. The largest number of these communities (23) was associated with Grasslands, with Heathland, scrub and tundra, and Mires, bogs and fens having the next highest representation at 11 and 8 level 4 communities each respectively. Within the grasslands classification, E4 (Alpine and sub-alpine grasslands), E5 (Woodland fringes and clearings) and E1 (Dry grasslands) were the most sensitive with 68.1, 51.6 and 48.6%OS respectively. It is feasible to map the land-cover for these and other communities at level 2, but it may not be currently possible to map the land-cover for all communities identified to be ozone-sensitive at levels 3 and 4. - Grassland communities such as alpine and sub-alpine grasslands have the highest potential sensitivity ozone, based on the responses of their component species

Increasing sensitivity of arc-induced long-period gratings—pushing the fabrication technique toward its limits

International Nuclear Information System (INIS)

Smietana, M; Bock, W J; Mikulic, P; Chen, J

2011-01-01

This paper presents an investigation of the sensing properties of long-period gratings (LPGs) written with the electric-arc technique in commonly used standard germanium-doped Corning SMF28 and boron co-doped Fibercore PS1250/1500 fibers. In order to increase the sensitivity of the LPGs, we studied and established for each fiber the writing parameters allowing for the coupling of the highest possible order of cladding modes at a resonance wavelength around λ = 1550 nm. The sensitivity of the LPGs to refractive index, to temperature and to hydrostatic pressure was investigated. The experimental results were supported by extensive numerical simulations. Thanks to the well-established and precisely controlled arc-writing process, we were able to reduce the minimum period of the gratings down to 345 and 221 µm, respectively, for LPGs based on the SMF28 and PS1250/1500 fibers. To the best of our knowledge, these are the shortest periods ever achieved for these fibers using the arc-manufacturing technique. The pressure sensitivities of 13 and 220 pm bar −1 are the highest ever measured for LPGs written in the SMF28 and PS1250/1500 fibers, respectively. Moreover, a reduction in the diameters of the SMF28 fiber induced by the arc was found, which significantly affected the distribution of resonances generated by the coupled cladding modes

The Sensitivity of Income Polarization - Time, length of accounting periods, equivalence scales, and income definitions

DEFF Research Database (Denmark)

Azhar, Hussain

This study looks at polarization and its components’ sensitivity to assumptions about equivalence scales, income definition, ethical income distribution parameters, and the income accounting period. A representative sample of Danish individual incomes from 1984 to 2002 is utilised. Results show...... that polarization has increased over time, regardless of the applied measure, when the last part of the period is compared to the first part of the period. Primary causes being increased inequality (alienation) and faster income growth among high incomes relative to those in the middle of the distribution....... Increasing the accounting period confirms the reduction in inequality found for shorter periods, but polarization is virtually unchanged, because income group identification increases. Applying different equivalence scales does not change polarization ranking for different years, but identification ranks...

Analyzing and Identifying Teens' Stressful Periods and Stressor Events From a Microblog.

Science.gov (United States)

Li, Qi; Xue, Yuanyuan; Zhao, Liang; Jia, Jia; Feng, Ling

2017-09-01

Increased health problems among adolescents caused by psychological stress have aroused worldwide attention. Long-standing stress without targeted assistance and guidance negatively impacts the healthy growth of adolescents, threatening the future development of our society. So far, research focused on detecting adolescent psychological stress revealed from each individual post on microblogs. However, beyond stressful moments, identifying teens' stressful periods and stressor events that trigger each stressful period is more desirable to understand the stress from appearance to essence. In this paper, we define the problem of identifying teens' stressful periods and stressor events from the open social media microblog. Starting from a case study of adolescents' posting behaviors during stressful school events, we build a Poisson-based probability model for the correlation between stressor events and stressful posting behaviors through a series of posts on Tencent Weibo (referred to as the microblog throughout the paper). With the model, we discover teens' maximal stressful periods and further extract details of possible stressor events that cause the stressful periods. We generalize and present the extracted stressor events in a hierarchy based on common stress dimensions and event types. Taking 122 scheduled stressful study-related events in a high school as the ground truth, we test the approach on 124 students' posts from January 1, 2012 to February 1, 2015 and obtain some promising experimental results: (stressful periods: recall 0.761, precision 0.737, and F 1 -measure 0.734) and (top-3 stressor events: recall 0.763, precision 0.756, and F 1 -measure 0.759). The most prominent stressor events extracted are in the self-cognition domain, followed by the school life domain. This conforms to the adolescent psychological investigation result that problems in school life usually accompanied with teens' inner cognition problems. Compared with the state-of-the-art top

Information sensitivity functions to assess parameter information gain and identifiability of dynamical systems.

Science.gov (United States)

Pant, Sanjay

2018-05-01

A new class of functions, called the 'information sensitivity functions' (ISFs), which quantify the information gain about the parameters through the measurements/observables of a dynamical system are presented. These functions can be easily computed through classical sensitivity functions alone and are based on Bayesian and information-theoretic approaches. While marginal information gain is quantified by decrease in differential entropy, correlations between arbitrary sets of parameters are assessed through mutual information. For individual parameters, these information gains are also presented as marginal posterior variances, and, to assess the effect of correlations, as conditional variances when other parameters are given. The easy to interpret ISFs can be used to (a) identify time intervals or regions in dynamical system behaviour where information about the parameters is concentrated; (b) assess the effect of measurement noise on the information gain for the parameters; (c) assess whether sufficient information in an experimental protocol (input, measurements and their frequency) is available to identify the parameters; (d) assess correlation in the posterior distribution of the parameters to identify the sets of parameters that are likely to be indistinguishable; and (e) assess identifiability problems for particular sets of parameters. © 2018 The Authors.

PERIODS OF VERTEBRAL COLUMN SENSITIVITY TO BORIC ACID TREATMENT IN CD-1 MICE IN UTERO

Science.gov (United States)

Periods of vertebral column sensitivity to boric acid treatment in CD-1 mice in utero.Cherrington JW, Chernoff N.Department of Toxicology, North Carolina State University, Raleigh, NC 27695, USA. jana_cherrington@hotmail.comBoric acid (BA) has many uses as...

Identifying School Psychologists' Intercultural Sensitivity

Science.gov (United States)

Puyana, Olivia E.; Edwards, Oliver W.

2016-01-01

School psychologists are encouraged to analyze their intercultural sensitivity because they may be subject to personal attitudes and beliefs that pejoratively influence their work with students and clients who are culturally and linguistically diverse (CLD). However, gaps remain in the literature regarding whether school psychologists are prepared…

Novel HTS strategy identifies TRAIL-sensitizing compounds acting specifically through the caspase-8 apoptotic axis.

Directory of Open Access Journals (Sweden)

Darren Finlay

Full Text Available Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL is potentially a very important therapeutic as it shows selectivity for inducing apoptosis in cancer cells whilst normal cells are refractory. TRAIL binding to its cognate receptors, Death Receptors-4 and -5, leads to recruitment of caspase-8 and classical activation of downstream effector caspases, leading to apoptosis. As with many drugs however, TRAIL's usefulness is limited by resistance, either innate or acquired. We describe here the development of a novel 384-well high-throughput screening (HTS strategy for identifying potential TRAIL-sensitizing agents that act solely in a caspase-8 dependent manner. By utilizing a TRAIL resistant cell line lacking caspase-8 (NB7 compared to the same cells reconstituted with the wild-type protein, or with a catalytically inactive point mutant of caspase-8, we are able to identify compounds that act specifically through the caspase-8 axis, rather than through general toxicity. In addition, false positive hits can easily be "weeded out" in this assay due to their activity in cells lacking caspase-8-inducible activity. Screening of the library of pharmacologically active compounds (LOPAC was performed as both proof-of-concept and to discover potential unknown TRAIL sensitizers whose mechanism is caspase-8 mediated. We identified known TRAIL sensitizers from the library and identified new compounds that appear to sensitize specifically through caspase-8. In sum, we demonstrate proof-of-concept and discovery of novel compounds with a screening strategy optimized for the detection of caspase-8 pathway-specific TRAIL sensitizers. This screen was performed in the 384-well format, but could easily be further miniaturized, allows easy identification of artifactual false positives, and is highly scalable to accommodate diverse libraries.

Parameter sensitivity and identifiability for a biogeochemical model of hypoxia in the northern Gulf of Mexico

Science.gov (United States)

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 ...

Citation searches are more sensitive than keyword searches to identify studies using specific measurement instruments.

Science.gov (United States)

Linder, Suzanne K; Kamath, Geetanjali R; Pratt, Gregory F; Saraykar, Smita S; Volk, Robert J

2015-04-01

To compare the effectiveness of two search methods in identifying studies that used the Control Preferences Scale (CPS), a health care decision-making instrument commonly used in clinical settings. We searched the literature using two methods: (1) keyword searching using variations of "Control Preferences Scale" and (2) cited reference searching using two seminal CPS publications. We searched three bibliographic databases [PubMed, Scopus, and Web of Science (WOS)] and one full-text database (Google Scholar). We report precision and sensitivity as measures of effectiveness. Keyword searches in bibliographic databases yielded high average precision (90%) but low average sensitivity (16%). PubMed was the most precise, followed closely by Scopus and WOS. The Google Scholar keyword search had low precision (54%) but provided the highest sensitivity (70%). Cited reference searches in all databases yielded moderate sensitivity (45-54%), but precision ranged from 35% to 75% with Scopus being the most precise. Cited reference searches were more sensitive than keyword searches, making it a more comprehensive strategy to identify all studies that use a particular instrument. Keyword searches provide a quick way of finding some but not all relevant articles. Goals, time, and resources should dictate the combination of which methods and databases are used. Copyright © 2015 Elsevier Inc. All rights reserved.

Using linked hospitalisation data to detect nursing sensitive outcomes: a retrospective cohort study.

Science.gov (United States)

Schreuders, Louise Winton; Bremner, Alexandra P; Geelhoed, Elizabeth; Finn, Judith

2014-03-01

Nursing sensitive outcomes are adverse patient health outcomes that have been shown to be associated with nursing care. Researchers have developed specific algorithms to identify nursing sensitive outcomes using administrative data sources, although contention still surrounds the ability to adjust for pre-existing conditions. Existing nursing sensitive outcome detection methods could be improved by using look-back periods that incorporate relevant health information from patient's previous hospitalisations. Retrospective cohort study at three tertiary metropolitan hospitals in Perth, Western Australia. The objective of this research was to explore the effect of using linked hospitalisation data on estimated incidence rates of eleven adverse nursing sensitive outcomes by retrospectively extending the timeframe during which relevant patient disease information may be identified. The research also explored whether patient demographics and/or the characteristics of their hospitalisations were associated with nursing sensitive outcomes. During the 5 year study period there were 356,948 hospitalisation episodes involving 189,240 patients for a total of 2,493,654 inpatient days at the three tertiary metropolitan hospitals. There was a reduction in estimated rates for all nursing sensitive outcomes when a look-back period was applied to identify relevant health information from earlier hospitalisations within the preceding 2 years. Survival analysis demonstrates that the majority of relevant patient disease information is identified within approximately 2 years of the baseline nursing sensitive outcomes hospitalisation. Compared to patients without, patients with nursing sensitive outcomes were significantly more likely to be older (70 versus 58 years), female, have Charleson comorbidities, be direct transfers from another hospital, have a longer inpatient stay and spend time in intensive care units (p≤0.001). The results of this research suggest that nursing sensitive

A genome scale RNAi screen identifies GLI1 as a novel gene regulating vorinostat sensitivity.

Science.gov (United States)

Falkenberg, K J; Newbold, A; Gould, C M; Luu, J; Trapani, J A; Matthews, G M; Simpson, K J; Johnstone, R W

2016-07-01

Vorinostat is an FDA-approved histone deacetylase inhibitor (HDACi) that has proven clinical success in some patients; however, it remains unclear why certain patients remain unresponsive to this agent and other HDACis. Constitutive STAT (signal transducer and activator of transcription) activation, overexpression of prosurvival Bcl-2 proteins and loss of HR23B have been identified as potential biomarkers of HDACi resistance; however, none have yet been used to aid the clinical utility of HDACi. Herein, we aimed to further elucidate vorinostat-resistance mechanisms through a functional genomics screen to identify novel genes that when knocked down by RNA interference (RNAi) sensitized cells to vorinostat-induced apoptosis. A synthetic lethal functional screen using a whole-genome protein-coding RNAi library was used to identify genes that when knocked down cooperated with vorinostat to induce tumor cell apoptosis in otherwise resistant cells. Through iterative screening, we identified 10 vorinostat-resistance candidate genes that sensitized specifically to vorinostat. One of these vorinostat-resistance genes was GLI1, an oncogene not previously known to regulate the activity of HDACi. Treatment of vorinostat-resistant cells with the GLI1 small-molecule inhibitor, GANT61, phenocopied the effect of GLI1 knockdown. The mechanism by which GLI1 loss of function sensitized tumor cells to vorinostat-induced apoptosis is at least in part through interactions with vorinostat to alter gene expression in a manner that favored apoptosis. Upon GLI1 knockdown and vorinostat treatment, BCL2L1 expression was repressed and overexpression of BCL2L1 inhibited GLI1-knockdown-mediated vorinostat sensitization. Taken together, we present the identification and characterization of GLI1 as a new HDACi resistance gene, providing a strong rationale for development of GLI1 inhibitors for clinical use in combination with HDACi therapy.

Sensitivity of Hurst parameter estimation to periodic signals in time series and filtering approaches

Science.gov (United States)

Marković, D.; Koch, M.

2005-09-01

The influence of the periodic signals in time series on the Hurst parameter estimate is investigated with temporal, spectral and time-scale methods. The Hurst parameter estimates of the simulated periodic time series with a white noise background show a high sensitivity on the signal to noise ratio and for some methods, also on the data length used. The analysis is then carried on to the investigation of extreme monthly river flows of the Elbe River (Dresden) and of the Rhine River (Kaub). Effects of removing the periodic components employing different filtering approaches are discussed and it is shown that such procedures are a prerequisite for an unbiased estimation of H. In summary, our results imply that the first step in a time series long-correlation study should be the separation of the deterministic components from the stochastic ones. Otherwise wrong conclusions concerning possible memory effects may be drawn.

A Sensitivity Analysis Approach to Identify Key Environmental Performance Factors

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Xi Yu

2014-01-01

Full Text Available Life cycle assessment (LCA is widely used in design phase to reduce the product’s environmental impacts through the whole product life cycle (PLC during the last two decades. The traditional LCA is restricted to assessing the environmental impacts of a product and the results cannot reflect the effects of changes within the life cycle. In order to improve the quality of ecodesign, it is a growing need to develop an approach which can reflect the changes between the design parameters and product’s environmental impacts. A sensitivity analysis approach based on LCA and ecodesign is proposed in this paper. The key environmental performance factors which have significant influence on the products’ environmental impacts can be identified by analyzing the relationship between environmental impacts and the design parameters. Users without much environmental knowledge can use this approach to determine which design parameter should be first considered when (redesigning a product. A printed circuit board (PCB case study is conducted; eight design parameters are chosen to be analyzed by our approach. The result shows that the carbon dioxide emission during the PCB manufacture is highly sensitive to the area of PCB panel.

Identifying group-sensitive physical activities: a differential item functioning analysis of NHANES data.

Science.gov (United States)

Gao, Yong; Zhu, Weimo

2011-05-01

The purpose of this study was to identify subgroup-sensitive physical activities (PA) using differential item functioning (DIF) analysis. A sub-unweighted sample of 1857 (men=923 and women=934) from the 2003-2004 National Health and Nutrition Examination Survey PA questionnaire data was used for the analyses. Using the Mantel-Haenszel, the simultaneous item bias test, and the ANOVA DIF methods, 33 specific leisure-time moderate and/or vigorous PA (MVPA) items were analyzed for DIF across race/ethnicity, gender, education, income, and age groups. Many leisure-time MVPA items were identified as large DIF items. When participating in the same amount of leisure-time MVPA, non-Hispanic blacks were more likely to participate in basketball and dance activities than non-Hispanic whites (NHW); NHW were more likely to participated in golf and hiking than non-Hispanic blacks; Hispanics were more likely to participate in dancing, hiking, and soccer than NHW, whereas NHW were more likely to engage in bicycling, golf, swimming, and walking than Hispanics; women were more likely to participate in aerobics, dancing, stretching, and walking than men, whereas men were more likely to engage in basketball, fishing, golf, running, soccer, weightlifting, and hunting than women; educated persons were more likely to participate in jogging and treadmill exercise than less educated persons; persons with higher incomes were more likely to engage in golf than those with lower incomes; and adults (20-59 yr) were more likely to participate in basketball, dancing, jogging, running, and weightlifting than older adults (60+ yr), whereas older adults were more likely to participate in walking and golf than younger adults. DIF methods are able to identify subgroup-sensitive PA and thus provide useful information to help design group-sensitive, targeted interventions for disadvantaged PA subgroups. © 2011 by the American College of Sports Medicine

Spectrum and Sensitivity of Bacterial Keratitis Isolates in Auckland

OpenAIRE

Marasini, S.; Swift, S.; Dean, S. J.; Ormonde, S. E.; Craig, J. P.

2016-01-01

Background. The bacteria isolated from severe cases of keratitis and their antibiotic sensitivity are recognised to vary geographically and over time. Objectives. To identify the most commonly isolated bacteria in keratitis cases admitted over a 24-month period to a public hospital in Auckland, New Zealand, and to investigate in vitro sensitivity to antibiotics. Methods. Hospital admissions for culture-proven bacterial keratitis between January 2013 and December 2014 were identified. Laborato...

Can we identify mothers at-risk for postpartum anxiety in the immediate postpartum period using the State-Trait Anxiety Inventory?

Science.gov (United States)

Dennis, Cindy-Lee; Coghlan, Michelle; Vigod, Simone

2013-09-25

This study assessed the stability of maternal anxiety and concordance between State-Trait Anxiety Inventory (STAI) scores in the immediate postpartum period to 8 weeks postpartum. A population-based sample of 522 mothers completed the STAI at 1, 4, and 8 weeks postpartum. Sensitivity, specificity, and predictive power of the 1-week STAI in relation to identifying mothers with elevated STAI scores at 4 and 8 weeks was determined. Predictive power of the STAI was further assessed using odds ratios and receiver operator characteristic (ROC) curves. At 1 week postpartum, 22.6% of mothers scored >40 on the STAI, decreasing to 17.2% at 4 weeks and 14.8% at 8 weeks. Using the cut-off score of >40, the 1-week STAI accurately classified 84.0% mothers at 4 weeks and 83.6% at 8 weeks with or without anxiety symptomatology. The 1-week STAI was significantly correlated to the 4-week (r=0.68, p40 were 15.2 times more likely at 4 weeks (95% CI=8.9-26.1) and 14.0 times more likely at 8 weeks (95% CI=7.9-24.8) to exhibit postpartum anxiety symptomatology. Psychiatric interviews were not completed in collaboration with the STAI and specific types of anxiety disorders were not identified. A cut-off score of >40 on the STAI administered early in the postpartum period is recommended in a 2-phase identification program in order to not miss mothers with postpartum anxiety. © 2013 Elsevier B.V. All rights reserved.

The relationship between the age of onset of musical training and rhythm synchronization performance: validation of sensitive period effects.

Science.gov (United States)

Bailey, Jennifer A; Penhune, Virginia B

2013-01-01

A sensitive period associated with musical training has been proposed, suggesting the influence of musical training on the brain and behavior is strongest during the early years of childhood. Experiments from our laboratory have directly tested the sensitive period hypothesis for musical training by comparing musicians who began their training prior to age seven with those who began their training after age seven, while matching the two groups in terms of musical experience (Watanabe et al., 2007; Bailey and Penhune, 2010, 2012). Using this matching paradigm, the early-trained groups have demonstrated enhanced sensorimotor synchronization skills and associated differences in brain structure (Bailey et al., 2013; Steele et al., 2013). The current study takes a different approach to investigating the sensitive period hypothesis for musical training by examining a single large group of unmatched musicians (N = 77) and exploring the relationship between age of onset of musical training as a continuous variable and performance on the Rhythm Synchronization Task (RST), a previously used auditory-motor RST. Interestingly, age of onset was correlated with task performance for those who began training earlier, however, no such relationship was observed among those who began training in their later childhood years. In addition, years of formal training showed a similar pattern. However, individual working memory scores were predictive of task performance, regardless of age of onset of musical training. Overall, these results support the sensitive period hypothesis for musical training and suggest a non-linear relationship between age of onset of musical training and auditory-motor rhythm synchronization abilities, such that a relationship exists early in childhood but then plateaus later on in development, similar to maturational growth trajectories of brain regions implicated in playing music.

The relationship between the age of onset of musical training and rhythm synchronization performance: Validation of sensitive period effects

Directory of Open Access Journals (Sweden)

Jennifer Anne Bailey

2013-11-01

Full Text Available A sensitive period associated with musical training has been proposed, suggesting the influence of musical training on the brain and behaviour is strongest during the early childhood years. Experiments from our laboratory have directly tested the sensitive period hypothesis for musical training by comparing musicians who began their training before age seven with those who began their training after age seven, while matching the two groups in terms of musical experience (Bailey & Penhune, 2010; 2012; Watanabe, Savion-Lemieux, & Penhune, 2007. Using this matching paradigm, the early-trained groups have demonstrated enhanced sensorimotor synchronization skills and associated differences in brain structure (Bailey, Zatorre, & Penhune, under review; Steele, Bailey, Zatorre, & Penhune, 2013. The current study takes a different approach to investigating the sensitive period hypothesis for musical training by examining a single large group of unmatched musicians (N=77 and exploring the relationship between age of onset of musical training as a continuous variable and performance on the Rhythm Synchronization Task (RST, a previously used auditory-motor rhythm synchronization task. Interestingly, age of onset was correlated with task performance for those who began training earlier; however, no such relationship was observed among those who began training in their later childhood years. In addition, years of formal training showed a similar pattern. However, individual working memory scores were predictive of task performance, regardless of age of onset of musical training. Overall, these results support the sensitive period hypothesis for musical training and suggest a non-linear relationship between age of onset of musical training and auditory-motor rhythm synchronization abilities, such that a relationship exists early in childhood but then plateaus later on in development, similar to maturational growth trajectories of brain regions implicated in

Using citizen science data to identify the sensitivity of species to human land use.

Science.gov (United States)

Todd, Brian D; Rose, Jonathan P; Price, Steven J; Dorcas, Michael E

2016-12-01

Conservation practitioners must contend with an increasing array of threats that affect biodiversity. Citizen scientists can provide timely and expansive information for addressing these threats across large scales, but their data may contain sampling biases. We used randomization procedures to account for possible sampling biases in opportunistically reported citizen science data to identify species' sensitivities to human land use. We analyzed 21,044 records of 143 native reptile and amphibian species reported to the Carolina Herp Atlas from North Carolina and South Carolina between 1 January 1990 and 12 July 2014. Sensitive species significantly associated with natural landscapes were 3.4 times more likely to be legally protected or treated as of conservation concern by state resource agencies than less sensitive species significantly associated with human-dominated landscapes. Many of the species significantly associated with natural landscapes occurred primarily in habitats that had been nearly eradicated or otherwise altered in the Carolinas, including isolated wetlands, longleaf pine savannas, and Appalachian forests. Rare species with few reports were more likely to be associated with natural landscapes and 3.2 times more likely to be legally protected or treated as of conservation concern than species with at least 20 reported occurrences. Our results suggest that opportunistically reported citizen science data can be used to identify sensitive species and that species currently restricted primarily to natural landscapes are likely at greatest risk of decline from future losses of natural habitat. Our approach demonstrates the usefulness of citizen science data in prioritizing conservation and in helping practitioners address species declines and extinctions at large extents. © 2016 Society for Conservation Biology.

Identifying intimate partner violence (IPV) during the postpartum period in a Greek sample.

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Vivilaki, Victoria G; Dafermos, Vassilis; Daglas, Maria; Antoniou, Evagelia; Tsopelas, Nicholas D; Theodorakis, Pavlos N; Brown, Judith B; Lionis, Christos

2010-12-01

Research has highlighted the wide impact of intimate partner violence (IPV) and the public health role of community health professionals in detection of victimized women. The purpose of this study was to identify postpartum emotional and physical abuse and to validate the Greek version of the Women Abuse Screening Tool (WAST) along with its sensitivity and specificity. Five hundred seventy-nine mothers within 12 weeks postpartum were recruited from the perinatal care registers of the Maternity Departments of two public hospitals in Athens, Greece. Participants were randomly selected by clinic or shift. The WAST and the Partner Violence Screen (PVS) surveys were administered in random order to the mothers from September 2007 to January 2008. The WAST was compared with the PVS as a criterion standard. Agreement between the screening instruments was examined. The psychometric measurements that were performed included: two independent sample t tests, reliability coefficients, explanatory factor analysis using a Varimax rotation, and Principal Components Method. Confirmatory analysis-also called structural equation modeling-of principal components was conducted by Linear Structural Relations. A receiver operating characteristic (ROC) analysis was carried out to evaluate the global functioning of the scale. Two hundred four (35.6%) of the mothers screened were identified as experiencing IPV. Scores on the WAST correlated well with those on the PVS; the internal consistency of the WAST Greek version-tested using Cronbach's alpha coefficient-was found to be 0.926 and that of Guttman's split-half coefficient was 0.924. Our findings confirm the multidimensionality of the WAST, demonstrating a two-factor structure. The area under ROC curve (AUC) was found to be 0.824, and the logistic estimate for the threshold score of 0/1 fitted the model sensitivity at 99.7% and model specificity at 64.4%. Our data confirm the validity of the Greek version of the WAST in identifying IPV

Identifying Time Periods of Minimal Thermal Gradient for Temperature-Driven Structural Health Monitoring

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John Reilly

2018-03-01

Full Text Available Temperature changes play a large role in the day to day structural behavior of structures, but a smaller direct role in most contemporary Structural Health Monitoring (SHM analyses. Temperature-Driven SHM will consider temperature as the principal driving force in SHM, relating a measurable input temperature to measurable output generalized strain (strain, curvature, etc. and generalized displacement (deflection, rotation, etc. to create three-dimensional signatures descriptive of the structural behavior. Identifying time periods of minimal thermal gradient provides the foundation for the formulation of the temperature–deformation–displacement model. Thermal gradients in a structure can cause curvature in multiple directions, as well as non-linear strain and stress distributions within the cross-sections, which significantly complicates data analysis and interpretation, distorts the signatures, and may lead to unreliable conclusions regarding structural behavior and condition. These adverse effects can be minimized if the signatures are evaluated at times when thermal gradients in the structure are minimal. This paper proposes two classes of methods based on the following two metrics: (i the range of raw temperatures on the structure, and (ii the distribution of the local thermal gradients, for identifying time periods of minimal thermal gradient on a structure with the ability to vary the tolerance of acceptable thermal gradients. The methods are tested and validated with data collected from the Streicker Bridge on campus at Princeton University.

Identifying Time Periods of Minimal Thermal Gradient for Temperature-Driven Structural Health Monitoring.

Science.gov (United States)

Reilly, John; Glisic, Branko

2018-03-01

Temperature changes play a large role in the day to day structural behavior of structures, but a smaller direct role in most contemporary Structural Health Monitoring (SHM) analyses. Temperature-Driven SHM will consider temperature as the principal driving force in SHM, relating a measurable input temperature to measurable output generalized strain (strain, curvature, etc.) and generalized displacement (deflection, rotation, etc.) to create three-dimensional signatures descriptive of the structural behavior. Identifying time periods of minimal thermal gradient provides the foundation for the formulation of the temperature-deformation-displacement model. Thermal gradients in a structure can cause curvature in multiple directions, as well as non-linear strain and stress distributions within the cross-sections, which significantly complicates data analysis and interpretation, distorts the signatures, and may lead to unreliable conclusions regarding structural behavior and condition. These adverse effects can be minimized if the signatures are evaluated at times when thermal gradients in the structure are minimal. This paper proposes two classes of methods based on the following two metrics: (i) the range of raw temperatures on the structure, and (ii) the distribution of the local thermal gradients, for identifying time periods of minimal thermal gradient on a structure with the ability to vary the tolerance of acceptable thermal gradients. The methods are tested and validated with data collected from the Streicker Bridge on campus at Princeton University.

Identifying environmentally sensitive areas under the Oil Pollution Act

International Nuclear Information System (INIS)

Lively-Diebold, B.; Pease, A.L.; Watson, S.N.; Wasel, P.A.

1993-01-01

Section 4202(a)(6) of the Oil Pollution Act (OPA) requires the President to issue regulations that require owners or operators of tank vessels, offshore facilities, and certain onshore facilities that could impact environmentally sensitive areas, drinking water intakes, and other economically sensitive areas to prepare and submit plans for responding to a worst case discharge of oil and to a substantial threat of such a discharge. The authority to implement the response plan regulations has been delegated to various agencies, including the US Environmental Protection Agency and the US Department of Transportation. In addition, Area Committees designated under the OPA are responsible for assuring preplanning of response efforts, including procedures for protecting environmentally sensitive areas, and protection, rescue and rehabilitation of fisheries and wildlife. Area Contingency Plans for each of the designated areas will describe the areas of special economic and environmental importance that might be damaged by discharges. This paper will discuss and compare the identification of environmentally sensitive areas and vulnerability analyses required as elements of response plans for agencies implementing regulations under the OPA authority. This paper will also describe the progress of the Area Committees with respect to contingency planning development for protection of environmentally sensitive areas

3-D periodic mesoporous nickel oxide for nonenzymatic uric acid sensors with improved sensitivity

Science.gov (United States)

Huang, Wei; Cao, Yang; Chen, Yong; Zhou, Yang; Huang, Qingyou

2015-12-01

3-D periodic mesoporous nickel oxide (NiO) particles with crystalline walls have been synthesized through the microwave-assisted hard template route toward the KIT-6 silica. It was investigated as a nonenzymatic amperometric sensor for the detection of uric acid. 3-D periodic nickel oxide matrix has been obtained by the hard template route from the KIT-6 silica template. The crystalline nickel oxide belonged to the Ia3d space group, and its structure was characterized by X-ray diffraction (XRD), N2 adsorption-desorption, and transmission electron microscopy (TEM). The analysis results showed that the microwave-assisted mesoporous NiO materials were more appropriate to be electrochemical sensors than the traditional mesoporous NiO. Cyclic voltammetry (CV) revealed that 3-D periodic NiO exhibited a direct electrocatalytic activity for the oxidation of uric acid in sodium hydroxide solution. The enzyme-less amperometric sensor used in the detection of uric acid with detection limit of 0.005 μM (S/N = 3) over wide linear detection ranges up to 0.374 mM and with a high sensitivity of 756.26 μA mM-1 cm-2, and a possible mechanism was also given in the paper.

A novel diagnostic protocol to identify patients suitable for discharge after a single high-sensitivity troponin

Science.gov (United States)

Carlton, Edward W; Cullen, Louise; Than, Martin; Gamble, James; Khattab, Ahmed; Greaves, Kim

2015-01-01

Objective To establish whether a novel accelerated diagnostic protocol (ADP) for suspected acute coronary syndrome (ACS) could successfully identify low-risk patients suitable for discharge after a single high-sensitivity troponin T (hs-cTnT) taken at presentation to the emergency department. We also compared the diagnostic accuracy of this ADP with strategies using initial undetectable hs-cTnT. Methods This prospective observational study evaluated the ability of the Triage Rule-out Using high-Sensitivity Troponin (TRUST) ADP to identify low-risk patients with suspected ACS. The ADP incorporated a single presentation hs-cTnT of <14 ng/L, a non-ischaemic ECG and a modified Goldman risk score. Diagnostic performance of the ADP was compared with the detection limit cut-offs of hs-cTnT (<5 ng/L and <3 ng/L). The primary end point was fatal/non-fatal acute myocardial infarction (AMI) within 30 days. Results 960 participants were recruited, mean age 58.0 years, 80 (8.3%) had an AMI. The TRUST ADP classified 382 (39.8%) as low-risk with a sensitivity for identifying AMI of 98.8% (95% CI 92.5% to 99.9%). hs-cTnT detection limits (<5 ng/L and <3 ng/L) had a sensitivity of 100% (94.3 to 100) and 100% (94.4 to 100), respectively. The TRUST ADP identified more patients suitable for early discharge at 39.8% vs 29.3% (<5 ng/L) and 7.9% (<3 ng/L) (p<0.001) with a lower false-positive rate for AMI detection; specificity 43.3% (95% CI 42.7% to 43.4%) vs 32.0% (95% CI 31.5% to 32.0%) and 8.6% (95% CI 8.1% to 8.6%), respectively. Conclusions The TRUST ADP, which incorporates structured risk-assessment and a single presentation hs-cTnT blood draw, has potential to allow early discharge in 40% of patients with suspected ACS and has greater clinical utility than undetectable hs-cTnT strategies. Trial registration number ISRCTN No. 21109279. PMID:25691511

Current knowledge of environmental exposure in children during the sensitive developmental periods

Directory of Open Access Journals (Sweden)

Norma Helena Perlroth

2017-01-01

Full Text Available Objective: This study aims to identify the scientific evidence on the risks and effects of exposure to environmental contaminants in children during sensitive developmental periods. Data source: The search was performed in the Bireme database, using the terms: children's health, environmental exposure, health vulnerability, toxicity pathways and developmental disabilities in the LILACS, MEDLINE and SciELO systems. Data synthesis: Children differ from adults in their unique physiological and behavioral characteristics and the potential exposure to risks caused by several threats in the environment. Exposure to toxic agents is analyzed through toxicokinetic processes in the several systems and organs during the sensitive phases of child development. The caused effects are reflected in the increased prevalence of congenital malformations, diarrhea, asthma, cancer, endocrine and neurological disorders, among others, with negative impacts throughout adult life. Conclusion: To identify the causes and understand the mechanisms involved in the genesis of these diseases is a challenge for science, as there is still a lack of knowledge on children's susceptibility to many environmental contaminants. Prevention policies and more research on child environmental health, improving the recording and surveillance of environmental risks to children's health, should be an ongoing priority in the public health field. Resumo: Objetivo: O presente estudo busca identificar as evidências científicas sobre os riscos e efeitos da exposição de contaminantes ambientais no organismo infantil durante os períodos sensíveis de seu desenvolvimento. Fonte de dados: As pesquisas foram realizadas pelo banco de dados da Bireme, com os termos children's health, environmental exposure, health vulnerability, toxicity pathways and developmental disabilities nos sistemas LILACS, MEDLINE e SciELO. Síntese de dados: A criança difere do adulto por suas características singulares

Parvalbumin, a cross-reactive fish allergen, contains IgE-binding epitopes sensitive to periodate treatment and Ca2+ depletion.

Science.gov (United States)

Bugajska-Schretter, A; Elfman, L; Fuchs, T; Kapiotis, S; Rumpold, H; Valenta, R; Spitzauer, S

1998-01-01

Type I allergy to fish is a severe health problem in countries in which a large percentage of the population derive income from fishing. The aim of the study was to characterize cross-reactive IgE-binding components in six different fish species (cod, tuna, salmon, perch, carp, and eel). The effect of reducing extraction conditions, periodate treatment, and depletion of Ca2+ on binding of IgE to the allergens was investigated. Extracts were prepared under nonreducing and reducing conditions. IgE-binding components were characterized by IgE immunoblotting, and cross-reactive epitopes were studied by IgE-immunoblot inhibition experiments. To reveal calcium-sensitive or carbohydrate-containing epitopes, nitrocellulose-blotted extracts were exposed to ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and periodate. Sera from all patients allergic to fish (n = 30) displayed IgE reactivity to parvalbumin, a 12 kd protein present in fish extracts from six different species. Reducing extraction conditions had no effect on IgE binding to parvalbumins, whereas periodate treatment and depletion of protein-bound calcium led to a substantial reduction of IgE binding. Parvalbumins from six different species contained cross-reactive IgE epitopes. Parvalbumin represents a cross-reactive fish allergen. It contains IgE epitopes that are sensitive to periodate treatment and Ca2+-depletion.

Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

Science.gov (United States)

Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2015-01-01

Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using random forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers were 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the ScoreCard database of possible skin or sense organ toxicants as primary candidates for experimental validation. PMID:25560674

Psychometric properties of the postpartum depression screening scale beyond the postpartum period.

Science.gov (United States)

Vogeli, Jo M; Hooker, Stephanie A; Everhart, Kevin D; Kaplan, Peter S

2018-04-01

Accurate postpartum depression screening measures are needed to identify mothers with depressive symptoms both in the postpartum period and beyond. Because it had not been tested beyond the immediate postpartum period, the reliability and validity of the Postpartum Depression Screening Scale (PDSS) and its sensitivity, specificity, and predictive value for diagnoses of major depressive disorder (MDD) were assessed in a diverse community sample of 238 mothers of 4- to 15-month-old infants. Mothers (N = 238; M age = 30.2, SD = 5.3) attended a lab session and completed the PDSS, the Beck Depression Inventory-II (BDI-II), and a structured clinical interview (SCID) to diagnose MDD. The reliability, validity, specificity, sensitivity, and predictive value of the PDSS to identify maternal depression were assessed. Confirmatory factor analysis supported the construct validity of five but not seven content subscales. The PDSS total and subscale scores demonstrated acceptable to high reliability (α = 0.68-0.95). Discriminant function analysis showed the scale correctly provided diagnostic classification at a rate higher than chance alone. Sensitivity and specificity for major depressive disorder (MDD) diagnosis were good and comparable to those of the BDI-II. Even in mothers who were somewhat more diverse and had older infants than those in the original normative study, the PDSS appears to be a psychometrically sound screener for identifying depressed mothers in the 15 months after childbirth. © 2018 Wiley Periodicals, Inc.

Detection of high-sensitivity troponin in outpatients with stable pulmonary hypertension identifies a subgroup at higher risk of adverse outcomes.

Science.gov (United States)

Roy, Andrew K; McCullagh, Brian N; Segurado, Ricardo; McGorrian, Catherine; Keane, Elizabeth; Keaney, John; Fitzgibbon, Maria N; Mahon, Niall G; Murray, Patrick T; Gaine, Sean P

2014-01-01

The detection of elevations in cardiorenal biomarkers, such as troponins, B-type natriuretic peptides (BNPs), and neutrophil gelatinase-associated lipocalins, are associated with poor outcomes in patients hospitalized with acute heart failure. Less is known about the association of these markers with adverse events in chronic right ventricular dysfunction due to pulmonary hypertension, or whether their measurement may improve risk assessment in the outpatient setting. We performed a cohort study of 108 patients attending the National Pulmonary Hypertension Unit in Dublin, Ireland, from 2007 to 2009. Cox proportional hazards analysis and receiver operating characteristic curves were used to determine predictors of mortality and hospitalization. Death or hospitalization occurred in 50 patients (46.3%) during the median study period of 4.1 years. Independent predictors of mortality were: 1) decreasing 6-minute walk test (6MWT; hazard ratio [HR] 12.8; P < .001); 2) BNP (HR 6.68; P < .001); and 3) highly sensitive troponin (hsTnT; HR 5.48; P < .001). Adjusted hazard analyses remained significant when hsTnT was added to a model with BNP and 6MWT (HR 9.26, 95% CI 3.61-23.79), as did the predictive ability of the model for death and rehospitalization (area under the receiver operating characteristic curve 0.81, 95% CI 0.73-0.90). Detection of troponin using a highly sensitive assay identifies a pulmonary hypertension subgroup with a poorer prognosis. hsTnT may also be used in a risk prediction model to identify patients at higher risk who may require escalation of targeted pulmonary vasodilator therapies and closer clinical surveillance. Copyright © 2014 Elsevier Inc. All rights reserved.

Critical features of acute stress-induced cross-sensitization identified through the hypothalamic-pituitary-adrenal axis output.

Science.gov (United States)

Belda, Xavier; Nadal, Roser; Armario, Antonio

2016-08-11

Stress-induced sensitization represents a process whereby prior exposure to severe stressors leaves animals or humans in a hyper-responsive state to further stressors. Indeed, this phenomenon is assumed to be the basis of certain stress-associated pathologies, including post-traumatic stress disorder and psychosis. One biological system particularly prone to sensitization is the hypothalamic-pituitary-adrenal (HPA) axis, the prototypic stress system. It is well established that under certain conditions, prior exposure of animals to acute and chronic (triggering) stressors enhances HPA responses to novel (heterotypic) stressors on subsequent days (e.g. raised plasma ACTH and corticosterone levels). However, such changes remain somewhat controversial and thus, the present study aimed to identify the critical characteristics of the triggering and challenging stressors that affect acute stress-induced HPA cross-sensitization in adult rats. We found that HPA cross-sensitization is markedly influenced by the intensity of the triggering stressor, whereas the length of exposure mainly affects its persistence. Importantly, HPA sensitization is more evident with mild than strong challenging stressors, and it may remain unnoticed if exposure to the challenging stressor is prolonged beyond 15 min. We speculate that heterotypic HPA sensitization might have developed to optimize biologically adaptive responses to further brief stressors.

Stretchable Spin Valve with Stable Magnetic Field Sensitivity by Ribbon-Patterned Periodic Wrinkles.

Science.gov (United States)

Li, Huihui; Zhan, Qingfeng; Liu, Yiwei; Liu, Luping; Yang, Huali; Zuo, Zhenghu; Shang, Tian; Wang, Baomin; Li, Run-Wei

2016-04-26

A strain-relief structure by combining the strain-engineered periodic wrinkles and the parallel ribbons was employed to fabricate flexible dual spin valves onto PDMS substrates in a direct sputtering method. The strain-relief structure can accommodate the biaxial strain accompanying with stretching operation (the uniaxial applied tensile strain and the induced transverse compressive strain due to the Poisson effect), thus significantly reducing the influence of the residual strain on the giant magnetoresistance (GMR) performance. The fabricated GMR dual spin-valve sensor exhibits the nearly unchanged MR ratio of 9.9%, magnetic field sensitivity up to 0.69%/Oe, and zero-field resistance in a wide range of stretching strain, making it promising for applications on a conformal shape or a movement part.

Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

Energy Technology Data Exchange (ETDEWEB)

Alves, Vinicius M. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Muratov, Eugene [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Laboratory of Theoretical Chemistry, A.V. Bogatsky Physical-Chemical Institute NAS of Ukraine, Odessa 65080 (Ukraine); Fourches, Denis [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Strickland, Judy; Kleinstreuer, Nicole [ILS/Contractor Supporting the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Andrade, Carolina H. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Tropsha, Alexander, E-mail: alex_tropsha@unc.edu [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States)

2015-04-15

Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. - Highlights: • It was compiled the largest publicly-available skin sensitization dataset. • Predictive QSAR models were developed for skin sensitization. • Developed models have higher prediction accuracy than OECD QSAR Toolbox. • Putative

Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds

International Nuclear Information System (INIS)

Alves, Vinicius M.; Muratov, Eugene; Fourches, Denis; Strickland, Judy; Kleinstreuer, Nicole; Andrade, Carolina H.; Tropsha, Alexander

2015-01-01

Repetitive exposure to a chemical agent can induce an immune reaction in inherently susceptible individuals that leads to skin sensitization. Although many chemicals have been reported as skin sensitizers, there have been very few rigorously validated QSAR models with defined applicability domains (AD) that were developed using a large group of chemically diverse compounds. In this study, we have aimed to compile, curate, and integrate the largest publicly available dataset related to chemically-induced skin sensitization, use this data to generate rigorously validated and QSAR models for skin sensitization, and employ these models as a virtual screening tool for identifying putative sensitizers among environmental chemicals. We followed best practices for model building and validation implemented with our predictive QSAR workflow using Random Forest modeling technique in combination with SiRMS and Dragon descriptors. The Correct Classification Rate (CCR) for QSAR models discriminating sensitizers from non-sensitizers was 71–88% when evaluated on several external validation sets, within a broad AD, with positive (for sensitizers) and negative (for non-sensitizers) predicted rates of 85% and 79% respectively. When compared to the skin sensitization module included in the OECD QSAR Toolbox as well as to the skin sensitization model in publicly available VEGA software, our models showed a significantly higher prediction accuracy for the same sets of external compounds as evaluated by Positive Predicted Rate, Negative Predicted Rate, and CCR. These models were applied to identify putative chemical hazards in the Scorecard database of possible skin or sense organ toxicants as primary candidates for experimental validation. - Highlights: • It was compiled the largest publicly-available skin sensitization dataset. • Predictive QSAR models were developed for skin sensitization. • Developed models have higher prediction accuracy than OECD QSAR Toolbox. • Putative

A Sensitive Period for Language in the Visual Cortex: Distinct Patterns of Plasticity in Congenitally versus Late Blind Adults

Science.gov (United States)

Bedny, Marina; Pascual-Leone, Alvaro; Dravida, Swethasri; Saxe, Rebecca

2012-01-01

Recent evidence suggests that blindness enables visual circuits to contribute to language processing. We examined whether this dramatic functional plasticity has a sensitive period. BOLD fMRI signal was measured in congenitally blind, late blind (blindness onset 9-years-old or later) and sighted participants while they performed a sentence…

High-resolution linkage analyses to identify genes that influence Varroa sensitive hygiene behavior in honey bees.

Science.gov (United States)

Tsuruda, Jennifer M; Harris, Jeffrey W; Bourgeois, Lanie; Danka, Robert G; Hunt, Greg J

2012-01-01

Varroa mites (V. destructor) are a major threat to honey bees (Apis melilfera) and beekeeping worldwide and likely lead to colony decline if colonies are not treated. Most treatments involve chemical control of the mites; however, Varroa has evolved resistance to many of these miticides, leaving beekeepers with a limited number of alternatives. A non-chemical control method is highly desirable for numerous reasons including lack of chemical residues and decreased likelihood of resistance. Varroa sensitive hygiene behavior is one of two behaviors identified that are most important for controlling the growth of Varroa populations in bee hives. To identify genes influencing this trait, a study was conducted to map quantitative trait loci (QTL). Individual workers of a backcross family were observed and evaluated for their VSH behavior in a mite-infested observation hive. Bees that uncapped or removed pupae were identified. The genotypes for 1,340 informative single nucleotide polymorphisms were used to construct a high-resolution genetic map and interval mapping was used to analyze the association of the genotypes with the performance of Varroa sensitive hygiene. We identified one major QTL on chromosome 9 (LOD score = 3.21) and a suggestive QTL on chromosome 1 (LOD = 1.95). The QTL confidence interval on chromosome 9 contains the gene 'no receptor potential A' and a dopamine receptor. 'No receptor potential A' is involved in vision and olfaction in Drosophila, and dopamine signaling has been previously shown to be required for aversive olfactory learning in honey bees, which is probably necessary for identifying mites within brood cells. Further studies on these candidate genes may allow for breeding bees with this trait using marker-assisted selection.

Identification of a mitochondrial target of thiazolidinedione insulin sensitizers (mTOT--relationship to newly identified mitochondrial pyruvate carrier proteins.

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Jerry R Colca

Full Text Available Thiazolidinedione (TZD insulin sensitizers have the potential to effectively treat a number of human diseases, however the currently available agents have dose-limiting side effects that are mediated via activation of the transcription factor PPARγ. We have recently shown PPARγ-independent actions of TZD insulin sensitizers, but the molecular target of these molecules remained to be identified. Here we use a photo-catalyzable drug analog probe and mass spectrometry-based proteomics to identify a previously uncharacterized mitochondrial complex that specifically recognizes TZDs. These studies identify two well-conserved proteins previously known as brain protein 44 (BRP44 and BRP44 Like (BRP44L, which recently have been renamed Mpc2 and Mpc1 to signify their function as a mitochondrial pyruvate carrier complex. Knockdown of Mpc1 or Mpc2 in Drosophila melanogaster or pre-incubation with UK5099, an inhibitor of pyruvate transport, blocks the crosslinking of mitochondrial membranes by the TZD probe. Knockdown of these proteins in Drosophila also led to increased hemolymph glucose and blocked drug action. In isolated brown adipose tissue (BAT cells, MSDC-0602, a PPARγ-sparing TZD, altered the incorporation of (13C-labeled carbon from glucose into acetyl CoA. These results identify Mpc1 and Mpc2 as components of the mitochondrial target of TZDs (mTOT and suggest that understanding the modulation of this complex, which appears to regulate pyruvate entry into the mitochondria, may provide a viable target for insulin sensitizing pharmacology.

Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

International Nuclear Information System (INIS)

Taylor, David J; Parsons, Christine E; Han, Haiyong; Jayaraman, Arul; Rege, Kaushal

2011-01-01

Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward malignant cells over normal pancreatic epithelial cells

Parallel screening of FDA-approved antineoplastic drugs for identifying sensitizers of TRAIL-induced apoptosis in cancer cells

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Taylor David J

2011-11-01

Full Text Available Abstract Background Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL and agonistic antibodies to death receptor 4 and 5 are promising candidates for cancer therapy due to their ability to induce apoptosis selectively in a variety of human cancer cells, while demonstrating little cytotoxicity in normal cells. Although TRAIL and agonistic antibodies to DR4 and DR5 are considered safe and promising candidates in cancer therapy, many malignant cells are resistant to DR-mediated, TRAIL-induced apoptosis. In the current work, we screened a small library of fifty-five FDA and foreign-approved anti-neoplastic drugs in order to identify candidates that sensitized resistant prostate and pancreatic cancer cells to TRAIL-induced apoptosis. Methods FDA-approved drugs were screened for their ability to sensitize TRAIL resistant prostate cancer cells to TRAIL using an MTT assay for cell viability. Analysis of variance was used to identify drugs that exhibited synergy with TRAIL. Drugs demonstrating the highest synergy were selected as leads and tested in different prostate and pancreatic cancer cell lines, and one immortalized human pancreatic epithelial cell line. Sequential and simultaneous dosing modalities were investigated and the annexin V/propidium iodide assay, in concert with fluorescence microscopy, was employed to visualize cells undergoing apoptosis. Results Fourteen drugs were identified as having synergy with TRAIL, including those whose TRAIL sensitization activities were previously unknown in either prostate or pancreatic cancer cells or both. Five leads were tested in additional cancer cell lines of which, doxorubicin, mitoxantrone, and mithramycin demonstrated synergy in all lines. In particular, mitoxantrone and mithramycin demonstrated significant synergy with TRAIL and led to reduction of cancer cell viability at concentrations lower than 1 μM. At these low concentrations, mitoxantrone demonstrated selectivity toward

Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.

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Agné Kulyté

Full Text Available Although the mechanisms linking obesity to insulin resistance (IR and type 2 diabetes (T2D are not entirely understood, it is likely that alterations of adipose tissue function are involved. The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin resistant (OIR or sensitive (OIS adipocytes. Insulin sensitivity was first determined by measuring lipogenesis in isolated adipocytes from abdominal subcutaneous white adipose tissue (WAT in a large observational study. Lipogenesis was measured under conditions where glucose transport was the rate limiting step and reflects in vivo insulin sensitivity. We then performed microarray-based transcriptome profiling on subcutaneous WAT specimen from a subgroup of 9 lean, 21 OIS and 18 obese OIR women. We could identify 432 genes that were differentially expressed between the OIR and OIS group (FDR ≤5%. These genes are enriched in pathways related to glucose and amino acid metabolism, cellular respiration, and insulin signaling, and include genes such as SLC2A4, AKT2, as well as genes coding for enzymes in the mitochondria respiratory chain. Two IR-associated genes, KLF15 encoding a transcription factor and SLC25A10 encoding a dicarboxylate carrier, were selected for functional evaluation in adipocytes differentiated in vitro. Knockdown of KLF15 and SLC25A10 using siRNA inhibited insulin-stimulated lipogenesis in adipocytes. Transcriptome profiling of siRNA-treated cells suggested that KLF15 might control insulin sensitivity by influencing expression of PPARG, PXMP2, AQP7, LPL and genes in the mitochondrial respiratory chain. Knockdown of SLC25A10 had only modest impact on the transcriptome, suggesting that it might directly influence insulin sensitivity in adipocytes independently of transcription due to its important role in fatty acid synthesis. In summary, this study identifies novel genes associated with insulin sensitivity in

High-resolution linkage analyses to identify genes that influence Varroa sensitive hygiene behavior in honey bees.

Directory of Open Access Journals (Sweden)

Jennifer M Tsuruda

Full Text Available Varroa mites (V. destructor are a major threat to honey bees (Apis melilfera and beekeeping worldwide and likely lead to colony decline if colonies are not treated. Most treatments involve chemical control of the mites; however, Varroa has evolved resistance to many of these miticides, leaving beekeepers with a limited number of alternatives. A non-chemical control method is highly desirable for numerous reasons including lack of chemical residues and decreased likelihood of resistance. Varroa sensitive hygiene behavior is one of two behaviors identified that are most important for controlling the growth of Varroa populations in bee hives. To identify genes influencing this trait, a study was conducted to map quantitative trait loci (QTL. Individual workers of a backcross family were observed and evaluated for their VSH behavior in a mite-infested observation hive. Bees that uncapped or removed pupae were identified. The genotypes for 1,340 informative single nucleotide polymorphisms were used to construct a high-resolution genetic map and interval mapping was used to analyze the association of the genotypes with the performance of Varroa sensitive hygiene. We identified one major QTL on chromosome 9 (LOD score = 3.21 and a suggestive QTL on chromosome 1 (LOD = 1.95. The QTL confidence interval on chromosome 9 contains the gene 'no receptor potential A' and a dopamine receptor. 'No receptor potential A' is involved in vision and olfaction in Drosophila, and dopamine signaling has been previously shown to be required for aversive olfactory learning in honey bees, which is probably necessary for identifying mites within brood cells. Further studies on these candidate genes may allow for breeding bees with this trait using marker-assisted selection.

Attachment and parental divorce: a test of the diffusion and sensitive period hypotheses.

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Fraley, R Chris; Heffernan, Marie E

2013-09-01

One of the assumptions of attachment theory is that disruptions in parental relationships are prospectively related to insecure attachment patterns in adulthood. The majority of research that has evaluated this hypothesis, however, has been based on retrospective reports of the quality of relationships with parents-research that is subject to retrospective biases. In the present research, the authors examined the impact of parental divorce-an event that can be assessed relatively objectively-on attachment patterns in adulthood across two samples. The data indicate that parental divorce has selective rather than diffuse implications for insecure attachment. Namely, parental divorce was more strongly related to insecure relationships with parents in adulthood than insecure relationships with romantic partners or friends. In addition, parental insecurity was most pronounced when parental divorce took place in early childhood. This finding is consistent with hypotheses about sensitive periods in attachment development.

Spectrum and Sensitivity of Bacterial Keratitis Isolates in Auckland

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S. Marasini

2016-01-01

Full Text Available Background. The bacteria isolated from severe cases of keratitis and their antibiotic sensitivity are recognised to vary geographically and over time. Objectives. To identify the most commonly isolated bacteria in keratitis cases admitted over a 24-month period to a public hospital in Auckland, New Zealand, and to investigate in vitro sensitivity to antibiotics. Methods. Hospital admissions for culture-proven bacterial keratitis between January 2013 and December 2014 were identified. Laboratory records of 89 culture positive cases were retrospectively reviewed and antibiotic sensitivity patterns compared with previous studies from other NZ centres. Results. From 126 positive cultures, 35 species were identified. Staphylococcus was identified to be the most common isolate (38.2%, followed by Pseudomonas (21.3%. Over the last decade, infection due to Pseudomonas species, in the same setting, has increased (p≤0.05. Aminoglycosides, cefazolin, ceftazidime, erythromycin, tetracycline, and doxycycline were 100% effective against tested isolates in vitro. Amoxicillin (41.6%, cefuroxime (33.3%, and chloramphenicol (94.7% showed reduced efficacy against Gram-negative bacteria, whereas penicillin (51% and ciprofloxacin (98.8% showed reduced efficacy against Gram-positive bacteria. Conclusions. Despite a shift in the spectrum of bacterial keratitis isolates, antibiotic sensitivity patterns have generally remained stable and show comparability to results within the last decade from NZ centres.

Spectrum and Sensitivity of Bacterial Keratitis Isolates in Auckland.

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Marasini, S; Swift, S; Dean, S J; Ormonde, S E; Craig, J P

2016-01-01

Background. The bacteria isolated from severe cases of keratitis and their antibiotic sensitivity are recognised to vary geographically and over time. Objectives. To identify the most commonly isolated bacteria in keratitis cases admitted over a 24-month period to a public hospital in Auckland, New Zealand, and to investigate in vitro sensitivity to antibiotics. Methods. Hospital admissions for culture-proven bacterial keratitis between January 2013 and December 2014 were identified. Laboratory records of 89 culture positive cases were retrospectively reviewed and antibiotic sensitivity patterns compared with previous studies from other NZ centres. Results. From 126 positive cultures, 35 species were identified. Staphylococcus was identified to be the most common isolate (38.2%), followed by Pseudomonas (21.3%). Over the last decade, infection due to Pseudomonas species, in the same setting, has increased (p ≤ 0.05). Aminoglycosides, cefazolin, ceftazidime, erythromycin, tetracycline, and doxycycline were 100% effective against tested isolates in vitro. Amoxicillin (41.6%), cefuroxime (33.3%), and chloramphenicol (94.7%) showed reduced efficacy against Gram-negative bacteria, whereas penicillin (51%) and ciprofloxacin (98.8%) showed reduced efficacy against Gram-positive bacteria. Conclusions. Despite a shift in the spectrum of bacterial keratitis isolates, antibiotic sensitivity patterns have generally remained stable and show comparability to results within the last decade from NZ centres.

Spectrum and Sensitivity of Bacterial Keratitis Isolates in Auckland

Science.gov (United States)

Swift, S.; Dean, S. J.; Ormonde, S. E.

2016-01-01

Background. The bacteria isolated from severe cases of keratitis and their antibiotic sensitivity are recognised to vary geographically and over time. Objectives. To identify the most commonly isolated bacteria in keratitis cases admitted over a 24-month period to a public hospital in Auckland, New Zealand, and to investigate in vitro sensitivity to antibiotics. Methods. Hospital admissions for culture-proven bacterial keratitis between January 2013 and December 2014 were identified. Laboratory records of 89 culture positive cases were retrospectively reviewed and antibiotic sensitivity patterns compared with previous studies from other NZ centres. Results. From 126 positive cultures, 35 species were identified. Staphylococcus was identified to be the most common isolate (38.2%), followed by Pseudomonas (21.3%). Over the last decade, infection due to Pseudomonas species, in the same setting, has increased (p ≤ 0.05). Aminoglycosides, cefazolin, ceftazidime, erythromycin, tetracycline, and doxycycline were 100% effective against tested isolates in vitro. Amoxicillin (41.6%), cefuroxime (33.3%), and chloramphenicol (94.7%) showed reduced efficacy against Gram-negative bacteria, whereas penicillin (51%) and ciprofloxacin (98.8%) showed reduced efficacy against Gram-positive bacteria. Conclusions. Despite a shift in the spectrum of bacterial keratitis isolates, antibiotic sensitivity patterns have generally remained stable and show comparability to results within the last decade from NZ centres. PMID:27213052

Sensitized mutagenesis screen in Factor V Leiden mice identifies thrombosis suppressor loci.

Science.gov (United States)

Westrick, Randal J; Tomberg, Kärt; Siebert, Amy E; Zhu, Guojing; Winn, Mary E; Dobies, Sarah L; Manning, Sara L; Brake, Marisa A; Cleuren, Audrey C; Hobbs, Linzi M; Mishack, Lena M; Johnston, Alexander J; Kotnik, Emilee; Siemieniak, David R; Xu, Jishu; Li, Jun Z; Saunders, Thomas L; Ginsburg, David

2017-09-05

Factor V Leiden ( F5 L ) is a common genetic risk factor for venous thromboembolism in humans. We conducted a sensitized N -ethyl- N -nitrosourea (ENU) mutagenesis screen for dominant thrombosuppressor genes based on perinatal lethal thrombosis in mice homozygous for F5 L ( F5 L/L ) and haploinsufficient for tissue factor pathway inhibitor ( Tfpi +/- ). F8 deficiency enhanced the survival of F5 L/L Tfpi +/- mice, demonstrating that F5 L/L Tfpi +/- lethality is genetically suppressible. ENU-mutagenized F5 L/L males and F5 L/+ Tfpi +/- females were crossed to generate 6,729 progeny, with 98 F5 L/L Tfpi +/- offspring surviving until weaning. Sixteen lines, referred to as "modifier of Factor 5 Leiden ( MF5L1-16 )," exhibited transmission of a putative thrombosuppressor to subsequent generations. Linkage analysis in MF5L6 identified a chromosome 3 locus containing the tissue factor gene ( F3 ). Although no ENU-induced F3 mutation was identified, haploinsufficiency for F3 ( F3 +/- ) suppressed F5 L/L Tfpi +/- lethality. Whole-exome sequencing in MF5L12 identified an Actr2 gene point mutation (p.R258G) as the sole candidate. Inheritance of this variant is associated with suppression of F5 L/L Tfpi +/- lethality ( P = 1.7 × 10 -6 ), suggesting that Actr2 p.R258G is thrombosuppressive. CRISPR/Cas9 experiments to generate an independent Actr2 knockin/knockout demonstrated that Actr2 haploinsufficiency is lethal, supporting a hypomorphic or gain-of-function mechanism of action for Actr2 p.R258G Our findings identify F8 and the Tfpi/F3 axis as key regulators in determining thrombosis balance in the setting of F5 L and also suggest a role for Actr2 in this process.

In vivo conditions to identify Prkci phosphorylation targets using the analog-sensitive kinase method in zebrafish.

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Elena Cibrián Uhalte

Full Text Available Protein kinase C iota is required for various cell biological processes including epithelial tissue polarity and organ morphogenesis. To gain mechanistic insight into different roles of this kinase, it is essential to identify specific substrate proteins in their cellular context. The analog-sensitive kinase method provides a powerful tool for the identification of kinase substrates under in vivo conditions. However, it has remained a major challenge to establish screens based on this method in multicellular model organisms. Here, we report the methodology for in vivo conditions using the analog-sensitive kinase method in a genetically-tractable vertebrate model organism, the zebrafish. With this approach, kinase substrates can uniquely be labeled in the developing zebrafish embryo using bulky ATPγS analogs which results in the thiophosphorylation of substrates. The labeling of kinase substrates with a thiophosphoester epitope differs from phosphoesters that are generated by all other kinases and allows for an enrichment of thiophosphopeptides by immunoaffinity purification. This study provides the foundation for using the analog-sensitive kinase method in the context of complex vertebrate development, physiology, or disease.

A method to identify aperiodic disturbances in the ionosphere

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Wang, J.-S.; Chen, Z.; Huang, C.-M.

2014-05-01

In this paper, variations in the ionospheric F2 layer's critical frequency are decomposed into their periodic and aperiodic components. The latter include disturbances caused both by geophysical impacts on the ionosphere and random noise. The spectral whitening method (SWM), a signal-processing technique used in statistical estimation and/or detection, was used to identify aperiodic components in the ionosphere. The whitening algorithm adopted herein is used to divide the Fourier transform of the observed data series by a real envelope function. As a result, periodic components are suppressed and aperiodic components emerge as the dominant contributors. Application to a synthetic data set based on significant simulated periodic features of ionospheric observations containing artificial (and, hence, controllable) disturbances was used to validate the SWM for identification of aperiodic components. Although the random noise was somewhat enhanced by post-processing, the artificial disturbances could still be clearly identified. The SWM was then applied to real ionospheric observations. It was found to be more sensitive than the often-used monthly median method to identify geomagnetic effects. In addition, disturbances detected by the SWM were characterized by a Gaussian-type probability density function over all timescales, which further simplifies statistical analysis and suggests that the disturbances thus identified can be compared regardless of timescale.

Geriatric-specific triage criteria are more sensitive than standard adult criteria in identifying need for trauma center care in injured older adults.

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Ichwan, Brian; Darbha, Subrahmanyam; Shah, Manish N; Thompson, Laura; Evans, David C; Boulger, Creagh T; Caterino, Jeffrey M

2015-01-01

We evaluate the sensitivity of Ohio's 2009 emergency medical services (EMS) geriatric trauma triage criteria compared with the previous adult triage criteria in identifying need for trauma center care among older adults. We studied a retrospective cohort of injured patients aged 16 years or older in the 2006 to 2011 Ohio Trauma Registry. Patients aged 70 years or older were considered geriatric. We identified whether each patient met the geriatric and the adult triage criteria. The outcome measure was need for trauma center care, defined by surrogate markers: Injury Severity Score greater than 15, operating room in fewer than 48 hours, any ICU stay, and inhospital mortality. We calculated sensitivity and specificity of both triage criteria for both age groups. We included 101,577 patients; 33,379 (33%) were geriatric. Overall, 57% of patients met adult criteria and 68% met geriatric criteria. Using Injury Severity Score, for older adults geriatric criteria were more sensitive for need for trauma center care (93%; 95% confidence interval [CI] 92% to 93%) than adult criteria (61%; 95% CI 60% to 62%). Geriatric criteria decreased specificity in older adults from 61% (95% CI 61% to 62%) to 49% (95% CI 48% to 49%). Geriatric criteria in older adults (93% sensitivity, 49% specificity) performed similarly to the adult criteria in younger adults (sensitivity 87% and specificity 44%). Similar patterns were observed for other outcomes. Standard adult EMS triage guidelines provide poor sensitivity in older adults. Ohio's geriatric trauma triage guidelines significantly improve sensitivity in identifying Injury Severity Score and other surrogate markers of the need for trauma center care, with modest decreases in specificity for older adults. Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

Neurobiology of mammalian olfactory learning that occurs during sensitive periods

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Hideto KABA

2010-12-01

Full Text Available This review examines the organizational principles underlying olfactory learning in three specialized contexts that occur during sensitive periods of enhanced neural plasticity and emphasizes some of their common features. All three forms of olfactory learning are associated with neural changes in the olfactory bulb (OB at the first stage of sensory processing. These changes require the association of the olfactory and somatosensory signals in the OB. They all depend on somatosensory stimulation-induced release of noradrenaline that induces structural and functional changes at mitral-granule cell reciprocal synapses in the OB, resulting in increases in inhibitory transmission. In the accessory olfactory bulb, this represents the enhanced self-inhibition of mitral cells, which selectively disrupts the transmission of the mating male’s pregnancy-blocking signal at this level. In contrast, an extensive network of secondary dendrites of mitral cells in the main olfactory bulb probably results in a sharpening of the odor-induced pattern of activity, due to increases in lateral inhibition, leading to offspring recognition in sheep and neonatal learning in rats and rabbits. These findings show that inhibitory interneurons play a critical role in olfactory learning. Further work on how these neurons shape olfactory circuit function could provide important clues to understand memory functions of interneurons in other systems. Moreover, recent research has suggested that three forms of olfactory learning are controlled by synergistic, redundant, and distributed neural mechanisms. This has general implications regarding the mechanisms that may contribute to the robustness of memories [Current Zoology 56 (6: 819–833, 2010].

Periodical rocking long period gratings in PANDA fibers for high temperature and refractive index sensing

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Jin, Wa; Bi, Wei-hong; Fu, Xing-hu; Fu, Guang-wei

2017-09-01

We report periodical rocking long period gratings (PR-LPGs) in PANDA fibers fabricated with CO2 laser. The PR-LPGs achieve very high coupling efficiency of 19 dB with 12 periods and a 3.5° twist angle in just one scanning cycle, which is much more effective than the conventional CO2 laser fabrication technique. This type of LPGs exhibits polarization-selective resonance dips which demonstrate different sensitivities to environmental parameters. The high temperature and external refractive index sensitivities are measured simultaneously, so it can be used as a wavelength-selective polarization filter and sensor.

Parameter Estimation, Sensitivity Analysis and Optimal Control of a Periodic Epidemic Model with Application to HRSV in Florida

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Silvério Rosa

2018-02-01

Full Text Available A state wide Human Respiratory Syncytial Virus (HRSV surveillance system was implemented in Florida in 1999 to support clinical decision-making for prophylaxis of premature infants. The research presented in this paper addresses the problem of fitting real data collected by the Florida HRSV surveillance system by using a periodic SEIRS mathematical model. A sensitivity and cost-effectiveness analysis of the model is done and an optimal control problem is formulated and solved with treatment as the control variable.

Sensitivity Analysis and Bounding of Causal Effects with Alternative Identifying Assumptions

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Jo, Booil; Vinokur, Amiram D.

2011-01-01

When identification of causal effects relies on untestable assumptions regarding nonidentified parameters, sensitivity of causal effect estimates is often questioned. For proper interpretation of causal effect estimates in this situation, deriving bounds on causal parameters or exploring the sensitivity of estimates to scientifically plausible…

Identifying populations sensitive to environmental chemicals by simulating toxicokinetic variability.

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Ring, Caroline L; Pearce, Robert G; Setzer, R Woodrow; Wetmore, Barbara A; Wambaugh, John F

2017-09-01

The thousands of chemicals present in the environment (USGAO, 2013) must be triaged to identify priority chemicals for human health risk research. Most chemicals have little of the toxicokinetic (TK) data that are necessary for relating exposures to tissue concentrations that are believed to be toxic. Ongoing efforts have collected limited, in vitro TK data for a few hundred chemicals. These data have been combined with biomonitoring data to estimate an approximate margin between potential hazard and exposure. The most "at risk" 95th percentile of adults have been identified from simulated populations that are generated either using standard "average" adult human parameters or very specific cohorts such as Northern Europeans. To better reflect the modern U.S. population, we developed a population simulation using physiologies based on distributions of demographic and anthropometric quantities from the most recent U.S. Centers for Disease Control and Prevention National Health and Nutrition Examination Survey (NHANES) data. This allowed incorporation of inter-individual variability, including variability across relevant demographic subgroups. Variability was analyzed with a Monte Carlo approach that accounted for the correlation structure in physiological parameters. To identify portions of the U.S. population that are more at risk for specific chemicals, physiologic variability was incorporated within an open-source high-throughput (HT) TK modeling framework. We prioritized 50 chemicals based on estimates of both potential hazard and exposure. Potential hazard was estimated from in vitro HT screening assays (i.e., the Tox21 and ToxCast programs). Bioactive in vitro concentrations were extrapolated to doses that produce equivalent concentrations in body tissues using a reverse dosimetry approach in which generic TK models are parameterized with: 1) chemical-specific parameters derived from in vitro measurements and predicted from chemical structure; and 2) with

AN EXTENDED AND MORE SENSITIVE SEARCH FOR PERIODICITIES IN ROSSI X-RAY TIMING EXPLORER/ALL-SKY MONITOR X-RAY LIGHT CURVES

International Nuclear Information System (INIS)

Levine, Alan M.; Bradt, Hale V.; Chakrabarty, Deepto; Corbet, Robin H. D.; Harris, Robert J.

2011-01-01

We present the results of a systematic search in ∼14 years of Rossi X-ray Timing Explorer All-Sky Monitor (ASM) data for evidence of periodicities. Two variations of the commonly used Fourier analysis search method have been employed to significantly improve upon the sensitivity achieved by Wen et al. in 2006, who also searched for periodicities in ASM data. In addition, the present search is comprehensive in terms of sources studied and frequency range covered, and has yielded the detection of the signatures of the orbital periods of eight low-mass X-ray binary systems and of ten high-mass X-ray binaries not listed in the tables of Wen et al. Orbital periods, epochs, signal amplitudes, modulation fractions, and folded light curves are given for each of these systems. Seven of the orbital periods are the most precise reported to date. In the course of this work, the 18.545 day orbital period of IGR J18483-0311 was co-discovered, and the first detections in X-rays were made of the ∼3.9 day orbital period of LMC X-1 and the ∼3.79 hr orbital period of 4U 1636-536. The results inform future searches for orbital and other periodicities in X-ray binaries.

Sensitive Periods, Vasotocin-Family Peptides, and the Evolution and Development of Social Behavior

Directory of Open Access Journals (Sweden)

Nicole M. Baran

2017-08-01

Full Text Available Nonapeptides, by modulating the activity of neural circuits in specific social contexts, provide an important mechanism underlying the evolution of diverse behavioral phenotypes across vertebrate taxa. Vasotocin-family nonapeptides, in particular, have been found to be involved in behavioral plasticity and diversity in social behavior, including seasonal variation, sexual dimorphism, and species differences. Although nonapeptides have been the focus of a great deal of research over the last several decades, the vast majority of this work has focused on adults. However, behavioral diversity may also be explained by the ways in which these peptides shape neural circuits and influence social processes during development. In this review, I synthesize comparative work on vasotocin-family peptides during development and classic work on early forms of social learning in developmental psychobiology. I also summarize recent work demonstrating that early life manipulations of the nonapeptide system alter attachment, affiliation, and vocal learning in zebra finches. I thus hypothesize that vasotocin-family peptides are involved in the evolution of social behaviors through their influence on learning during sensitive periods in social development.

Understanding the Day Cent model: Calibration, sensitivity, and identifiability through inverse modeling

Science.gov (United States)

Necpálová, Magdalena; Anex, Robert P.; Fienen, Michael N.; Del Grosso, Stephen J.; Castellano, Michael J.; Sawyer, John E.; Iqbal, Javed; Pantoja, Jose L.; Barker, Daniel W.

2015-01-01

The ability of biogeochemical ecosystem models to represent agro-ecosystems depends on their correct integration with field observations. We report simultaneous calibration of 67 DayCent model parameters using multiple observation types through inverse modeling using the PEST parameter estimation software. Parameter estimation reduced the total sum of weighted squared residuals by 56% and improved model fit to crop productivity, soil carbon, volumetric soil water content, soil temperature, N2O, and soil3NO− compared to the default simulation. Inverse modeling substantially reduced predictive model error relative to the default model for all model predictions, except for soil 3NO− and 4NH+. Post-processing analyses provided insights into parameter–observation relationships based on parameter correlations, sensitivity and identifiability. Inverse modeling tools are shown to be a powerful way to systematize and accelerate the process of biogeochemical model interrogation, improving our understanding of model function and the underlying ecosystem biogeochemical processes that they represent.

A New Perspective for Identifying Potential Cardiac Sensitizers

National Research Council Canada - National Science Library

Smith, E

1999-01-01

.... The dog and the swine were used as surrogates for the human. Physiologic and electrocardiographic measurements were taken during the control period and after each dose of ouabain, a digitalis glycoside known to provoke ventricular arrhythmia...

Excess seawater nutrients, enlarged algal symbiont densities and bleaching sensitive reef locations: 1. Identifying thresholds of concern for the Great Barrier Reef, Australia.

Science.gov (United States)

Wooldridge, Scott A

2016-05-23

Here, I contribute new insight into why excess seawater nutrients are an increasingly identified feature at reef locations that have low resistance to thermal stress. Specifically, I link this unfavourable synergism to the development of enlarged (suboptimal) zooxanthellae densities that paradoxically limit the capacity of the host coral to build tissue energy reserves needed to combat periods of stress. I explain how both theoretical predictions and field observations support the existence of species-specific 'optimal' zooxanthellae densities ~1.0-3.0×10 6 cellscm- 2 . For the central Great Barrier Reef (GBR), excess seawater nutrients that permit enlarged zooxanthellae densities beyond this optimum range are linked with seawater chlorophyll a>0.45μg·L -1 ; a eutrophication threshold previously shown to correlate with a significant loss in species for hard corals and phototrophic octocorals on the central GBR, and herein shown to correlate with enhanced bleaching sensitivity during the 1998 and 2002 mass bleaching events. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using synchrotron radiation angiography with a highly sensitive detector to identify impaired peripheral perfusion in rat pulmonary emphysema

Energy Technology Data Exchange (ETDEWEB)

Ito, Hiromichi [University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Matsushita, Shonosuke, E-mail: shomatsu@md.tsukuba.ac.jp [University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan); Tsukuba University of Technology, Tsukuba, Ibaraki 305-8521 (Japan); Hyodo, Kazuyuki [High Energy Accelerator Research Organization, KEK, Tsukuba, Ibaraki 305-0801 (Japan); Sato, Yukio; Sakakibara, Yuzuru [University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan)

2013-03-01

Synchrotron radiation angiography with a HARP detector made it possible to evaluate impaired pulmonary microcirculation in pulmonary emphysema by means of high sensitivity. Owing to limitations in spatial resolution and sensitivity, it is difficult for conventional angiography to detect minute changes of perfusion in diffuse lung diseases, including pulmonary emphysema (PE). However, a high-gain avalanche rushing amorphous photoconductor (HARP) detector can give high sensitivity to synchrotron radiation (SR) angiography. SR angiography with a HARP detector provides high spatial resolution and sensitivity in addition to time resolution owing to its angiographic nature. The purpose of this study was to investigate whether this SR angiography with a HARP detector could evaluate altered microcirculation in PE. Two groups of rats were used: group PE and group C (control). Transvenous SR angiography with a HARP detector was performed and histopathological findings were compared. Peak density of contrast material in peripheral lung was lower in group PE than group C (p < 0.01). The slope of the linear regression line in scattering diagrams was also lower in group PE than C (p < 0.05). The correlation between the slope and extent of PE in histopathology showed significant negative correlation (p < 0.05, r = 0.61). SR angiography with a HARP detector made it possible to identify impaired microcirculation in PE by means of its high spatial resolution and sensitivity.

Using synchrotron radiation angiography with a highly sensitive detector to identify impaired peripheral perfusion in rat pulmonary emphysema

International Nuclear Information System (INIS)

Ito, Hiromichi; Matsushita, Shonosuke; Hyodo, Kazuyuki; Sato, Yukio; Sakakibara, Yuzuru

2013-01-01

Synchrotron radiation angiography with a HARP detector made it possible to evaluate impaired pulmonary microcirculation in pulmonary emphysema by means of high sensitivity. Owing to limitations in spatial resolution and sensitivity, it is difficult for conventional angiography to detect minute changes of perfusion in diffuse lung diseases, including pulmonary emphysema (PE). However, a high-gain avalanche rushing amorphous photoconductor (HARP) detector can give high sensitivity to synchrotron radiation (SR) angiography. SR angiography with a HARP detector provides high spatial resolution and sensitivity in addition to time resolution owing to its angiographic nature. The purpose of this study was to investigate whether this SR angiography with a HARP detector could evaluate altered microcirculation in PE. Two groups of rats were used: group PE and group C (control). Transvenous SR angiography with a HARP detector was performed and histopathological findings were compared. Peak density of contrast material in peripheral lung was lower in group PE than group C (p < 0.01). The slope of the linear regression line in scattering diagrams was also lower in group PE than C (p < 0.05). The correlation between the slope and extent of PE in histopathology showed significant negative correlation (p < 0.05, r = 0.61). SR angiography with a HARP detector made it possible to identify impaired microcirculation in PE by means of its high spatial resolution and sensitivity

Strategy to Identify and Test Putative Light-Sensitive Non-Opsin G-Protein-Coupled Receptors: A Case Study.

Science.gov (United States)

Faggionato, Davide; Serb, Jeanne M

2017-08-01

The rise of high-throughput RNA sequencing (RNA-seq) and de novo transcriptome assembly has had a transformative impact on how we identify and study genes in the phototransduction cascade of non-model organisms. But the advantage provided by the nearly automated annotation of RNA-seq transcriptomes may at the same time hinder the possibility for gene discovery and the discovery of new gene functions. For example, standard functional annotation based on domain homology to known protein families can only confirm group membership, not identify the emergence of new biochemical function. In this study, we show the importance of developing a strategy that circumvents the limitations of semiautomated annotation and apply this workflow to photosensitivity as a means to discover non-opsin photoreceptors. We hypothesize that non-opsin G-protein-coupled receptor (GPCR) proteins may have chromophore-binding lysines in locations that differ from opsin. Here, we provide the first case study describing non-opsin light-sensitive GPCRs based on tissue-specific RNA-seq data of the common bay scallop Argopecten irradians (Lamarck, 1819). Using a combination of sequence analysis and three-dimensional protein modeling, we identified two candidate proteins. We tested their photochemical properties and provide evidence showing that these two proteins incorporate 11-cis and/or all-trans retinal and react to light photochemically. Based on this case study, we demonstrate that there is potential for the discovery of new light-sensitive GPCRs, and we have developed a workflow that starts from RNA-seq assemblies to the discovery of new non-opsin, GPCR-based photopigments.

Southern hemisphere searches for short period pulsars

International Nuclear Information System (INIS)

Manchester, R.N.

1984-01-01

Two searches of the southern sky for short period pulsars are briefly described. The first, made using the 64-m telescope at Parkes, is sensitive to pulsars with periods greater than about 10 ms and the second, made using the Molonglo radio telescope, has sensitivity down to periods of about 1.5 ms. Four pulsars were found in the Parkes survey and none in the Molonglo survey, although analysis of the latter is as yet incomplete. 10 references, 1 figure, 2 tables

Proteomics approach reveals mechanism underlying susceptibility of loquat fruit to sunburn during color changing period.

Science.gov (United States)

Jiang, Ji-Mou; Lin, Yong-Xiang; Chen, Yi-Yong; Deng, Chao-Jun; Gong, Hui-Wen; Xu, Qi-Zhi; Zheng, Shao-Quan; Chen, Wei

2015-06-01

The objective of this work was to investigate why loquat fruit peels are more sensitive to high temperature and strong sunlight, making them highly susceptible to sunburn, during the color changing period (CCP). Two dimensional gel electrophoresis (2-DE) of the fruit peel proteins was performed over three developmental periods, namely green fruit period (GFP), color changing period and yellow ripening period (YRP). Fifty-five protein spots with at least 2-fold differences in abundance were successfully identified by MALDI-TOF-TOF/MS. The identified proteins were divided into categories related to heat-shock response, stress response and defense, energy metabolism, photosynthesis and protein biosynthesis. The results showed that expression of proteins related to anaerobic respiration and photorespiration were increased while the proteins related to ROS scavenging, polyamine biosynthesis, defense pathogens and photosynthesis were decreased during CCP under heat stress. Our findings provide new insights into the molecular mechanism of loquat fruit susceptible to sunburn during CCP. Copyright © 2014 Elsevier Ltd. All rights reserved.

A simple algorithm for identifying periods of snow accumulation on a radiometer

Science.gov (United States)

Lapo, Karl E.; Hinkelman, Laura M.; Landry, Christopher C.; Massmann, Adam K.; Lundquist, Jessica D.

2015-09-01

Downwelling solar, Qsi, and longwave, Qli, irradiances at the earth's surface are the primary energy inputs for many hydrologic processes, and uncertainties in measurements of these two terms confound evaluations of estimated irradiances and negatively impact hydrologic modeling. Observations of Qsi and Qli in cold environments are subject to conditions that create additional uncertainties not encountered in other climates, specifically the accumulation of snow on uplooking radiometers. To address this issue, we present an automated method for estimating these periods of snow accumulation. Our method is based on forest interception of snow and uses common meteorological observations. In this algorithm, snow accumulation must exceed a threshold to obscure the sensor and is only removed through scouring by wind or melting. The algorithm is evaluated at two sites representing different mountain climates: (1) Snoqualmie Pass, Washington (maritime) and (2) the Senator Beck Basin Study Area, Colorado (continental). The algorithm agrees well with time-lapse camera observations at the Washington site and with multiple measurements at the Colorado site, with 70-80% of observed snow accumulation events correctly identified. We suggest using the method for quality controlling irradiance observations in snow-dominated climates where regular, daily maintenance is not possible.

A cell-based in vitro alternative to identify skin sensitizers by gene expression

International Nuclear Information System (INIS)

Hooyberghs, Jef; Schoeters, Elke; Lambrechts, Nathalie; Nelissen, Inge; Witters, Hilda; Schoeters, Greet; Heuvel, Rosette van den

2008-01-01

The ethical and economic burden associated with animal testing for assessment of skin sensitization has triggered intensive research effort towards development and validation of alternative methods. In addition, new legislation on the registration and use of cosmetics and chemicals promote the use of suitable alternatives for hazard assessment. Our previous studies demonstrated that human CD34 + progenitor-derived dendritic cells from cord blood express specific gene profiles upon exposure to low molecular weight sensitizing chemicals. This paper presents a classification model based on this cell type which is successful in discriminating sensitizing chemicals from non-sensitizing chemicals based on transcriptome analysis of 13 genes. Expression profiles of a set of 10 sensitizers and 11 non-sensitizers were analyzed by RT-PCR using 9 different exposure conditions and a total of 73 donor samples. Based on these data a predictive dichotomous classifier for skin sensitizers has been constructed, which is referred to as . In a first step the dimensionality of the input data was reduced by selectively rejecting a number of exposure conditions and genes. Next, the generalization of a linear classifier was evaluated by a cross-validation which resulted in a prediction performance with a concordance of 89%, a specificity of 97% and a sensitivity of 82%. These results show that the present model may be a useful human in vitro alternative for further use in a test strategy towards the reduction of animal use for skin sensitization

Chemical biology drug sensitivity screen identifies sunitinib as synergistic agent with disulfiram in prostate cancer cells.

Directory of Open Access Journals (Sweden)

Kirsi Ketola

Full Text Available Current treatment options for castration- and treatment-resistant prostate cancer are limited and novel approaches are desperately needed. Our recent results from a systematic chemical biology sensitivity screen covering most known drugs and drug-like molecules indicated that aldehyde dehydrogenase inhibitor disulfiram is one of the most potent cancer-specific inhibitors of prostate cancer cell growth, including TMPRSS2-ERG fusion positive cancers. However, the results revealed that disulfiram alone does not block tumor growth in vivo nor induce apoptosis in vitro, indicating that combinatorial approaches may be required to enhance the anti-neoplastic effects.In this study, we utilized a chemical biology drug sensitivity screen to explore disulfiram mechanistic details and to identify compounds potentiating the effect of disulfiram in TMPRSS2-ERG fusion positive prostate cancer cells. In total, 3357 compounds including current chemotherapeutic agents as well as drug-like small molecular compounds were screened alone and in combination with disulfiram. Interestingly, the results indicated that androgenic and antioxidative compounds antagonized disulfiram effect whereas inhibitors of receptor tyrosine kinase, proteasome, topoisomerase II, glucosylceramide synthase or cell cycle were among compounds sensitizing prostate cancer cells to disulfiram. The combination of disulfiram and an antiangiogenic agent sunitinib was studied in more detail, since both are already in clinical use in humans. Disulfiram-sunitinib combination induced apoptosis and reduced androgen receptor protein expression more than either of the compounds alone. Moreover, combinatorial exposure reduced metastatic characteristics such as cell migration and 3D cell invasion as well as induced epithelial differentiation shown as elevated E-cadherin expression.Taken together, our results propose novel combinatorial approaches to inhibit prostate cancer cell growth. Disulfiram

Sensitivity of hepatitis C virus core antigen and antibody combination assays in a global panel of window period samples

Science.gov (United States)

Laperche, Syria; Nubling, C. Micha; Stramer, Susan L.; Brojer, Ewa; Grabarczyk, Piotr; Yoshizawa, Hiroshi; Kalibatas, Vytenis; El Elkyabi, Magdy; Moftah, Faten; Girault, Annie; van Drimmelen, Harry; Busch, Michael P.; Lelie, Nico

2016-01-01

BACKGROUND Hepatitis C virus (HCV) antigen and antibody combination assays have been launched as a cost-effective alternative to nucleic acid testing (NAT) for reducing the antibody-negative window period (WP). Later, a HCV antigen chemiluminescence immunoassay (CLIA) became available. STUDY DESIGN AND METHODS A panel composed of 337 HCV NAT–yield samples that were characterized for viral load (VL) and genotype was used to compare the sensitivity of two combination enzyme-linked immunosorbent assays (Monolisa, Bio-Rad; and Murex, formerly Abbott) and a HCV antigen CLIA (Abbott). Analytic sensitivity was compared with HCV RNA detection using Ultrio (Grifols) by testing serial dilutions of 10 genotype (gt)1 to gt4 samples. RESULTS HCV antigen CLIA detected 92.4% of samples, whereas Monolisa and Murex detected 38.3 and 47.5%, respectively. In the HCV RNA VL range of 105 to 107 IU/mL, Monolisa and Murex detected 38% to 56% of gt1, 85% to 78% of gt2, and 21% to 37% of gt3. The overall geometric mean 50% limit of detection (range) of Ultrio on gt1 to gt4 dilution series was 3.5 (1.2–7.7) copies/mL, compared to 3.3 × 106 (4.4 × 105-2.7 × 107), 3.4 × 106 (2.2 × 105–4.2 × 107), and 2728 (415–7243) copies/mL for Monolisa, Murex, and HCV antigen CLIA, respectively. CONCLUSION Analytical sensitivity of NAT was on average 1 million- and 780-fold higher than combination assays and HCV antigen CLIA, respectively. Relative sensitivities of combination assays differed for genotypes with Murex being more sensitive for gt1 and gt3 and Monolisa more sensitive for gt2. Although being less sensitive than NAT, combination assays could be considered in resource-limited settings since they detect 38% to 47% of seronegative WP donations. PMID:26013970

THP-1 monocytes but not macrophages as a potential alternative for CD34+ dendritic cells to identify chemical skin sensitizers

International Nuclear Information System (INIS)

Lambrechts, Nathalie; Verstraelen, Sandra; Lodewyckx, Hanne; Felicio, Ana; Hooyberghs, Jef; Witters, Hilda; Tendeloo, Viggo van; Cauwenberge, Paul van; Nelissen, Inge; Heuvel, Rosette van den; Schoeters, Greet

2009-01-01

Early detection of the sensitizing potential of chemicals is an emerging issue for chemical, pharmaceutical and cosmetic industries. In our institute, an in vitro classification model for prediction of chemical-induced skin sensitization based on gene expression signatures in human CD34 + progenitor-derived dendritic cells (DC) has been developed. This primary cell model is able to closely mimic the induction phase of sensitization by Langerhans cells in the skin, but it has drawbacks, such as the availability of cord blood. The aim of this study was to investigate whether human in vitro cultured THP-1 monocytes or macrophages display a similar expression profile for 13 predictive gene markers previously identified in DC and whether they also possess a discriminating capacity towards skin sensitizers and non-sensitizers based on these marker genes. To this end, the cell models were exposed to 5 skin sensitizers (ammonium hexachloroplatinate IV, 1-chloro-2,4-dinitrobenzene, eugenol, para-phenylenediamine, and tetramethylthiuram disulfide) and 5 non-sensitizers (L-glutamic acid, methyl salicylate, sodium dodecyl sulfate, tributyltin chloride, and zinc sulfate) for 6, 10, and 24 h, and mRNA expression of the 13 genes was analyzed using real-time RT-PCR. The transcriptional response of 7 out of 13 genes in THP-1 monocytes was significantly correlated with DC, whereas only 2 out of 13 genes in THP-1 macrophages. After a cross-validation of a discriminant analysis of the gene expression profiles in the THP-1 monocytes, this cell model demonstrated to also have a capacity to distinguish skin sensitizers from non-sensitizers. However, the DC model was superior to the monocyte model for discrimination of (non-)sensitizing chemicals.

Sensitivity analysis of infectious disease models: methods, advances and their application

Science.gov (United States)

Wu, Jianyong; Dhingra, Radhika; Gambhir, Manoj; Remais, Justin V.

2013-01-01

Sensitivity analysis (SA) can aid in identifying influential model parameters and optimizing model structure, yet infectious disease modelling has yet to adopt advanced SA techniques that are capable of providing considerable insights over traditional methods. We investigate five global SA methods—scatter plots, the Morris and Sobol’ methods, Latin hypercube sampling-partial rank correlation coefficient and the sensitivity heat map method—and detail their relative merits and pitfalls when applied to a microparasite (cholera) and macroparasite (schistosomaisis) transmission model. The methods investigated yielded similar results with respect to identifying influential parameters, but offered specific insights that vary by method. The classical methods differed in their ability to provide information on the quantitative relationship between parameters and model output, particularly over time. The heat map approach provides information about the group sensitivity of all model state variables, and the parameter sensitivity spectrum obtained using this method reveals the sensitivity of all state variables to each parameter over the course of the simulation period, especially valuable for expressing the dynamic sensitivity of a microparasite epidemic model to its parameters. A summary comparison is presented to aid infectious disease modellers in selecting appropriate methods, with the goal of improving model performance and design. PMID:23864497

Prevalence of bacterial agents isolated from clinical cases of bovine mastitis in the dry period and the determination of their antibiotic sensitivity in Tabriz, Iran

Directory of Open Access Journals (Sweden)

Samad Mosaferi

2015-09-01

Full Text Available Objective: To determine the prevalence of mastitis-causing bacteria in the dry period and its antibiotic sensitivity. Methods: In this study, 852 dry cows were examined. A total of 30 cows with clinical mastitis symptoms were detected and their milk samples were collected. In order to purify the bacteria, brain heart infusion and blood agar media were applied and single colonies were used for Gram staining, oxidase and catalase testing, cultivating in O-F medium to determine the genus and species of bacteria. Then, antimicrobial susceptibility was tested by the agar disk diffusion method. Results: The prevalence of isolated bacteria was 2.46%, in which coagulase positive Staphylococcus, coagulase negative Staphylococcus, Streptococcus dysgalactiae, Streptococcus faecalis, Escherichia coli, Pseudomonas, Bacillus and yeast were (9/99%, (6/66%, (13/32%, (3/33%, (6/66%, (13/32%, (9/99% and (6/66%, respectively. After tests of antibiotic susceptibility, the most and the least sensitivity were reported to enrofloxacin and ampicillin respectively. Conclusions: This study indicated that Streptococcus dysgalactiae is the most commonly isolated bacteria with the greatest sensitivity to enrofloxacin and tetracycline which can be used to treat mastitis in the dry period in Tabriz.

Periodic feedback stabilization for linear periodic evolution equations

CERN Document Server

Wang, Gengsheng

2016-01-01

This book introduces a number of recent advances regarding periodic feedback stabilization for linear and time periodic evolution equations. First, it presents selected connections between linear quadratic optimal control theory and feedback stabilization theory for linear periodic evolution equations. Secondly, it identifies several criteria for the periodic feedback stabilization from the perspective of geometry, algebra and analyses respectively. Next, it describes several ways to design periodic feedback laws. Lastly, the book introduces readers to key methods for designing the control machines. Given its coverage and scope, it offers a helpful guide for graduate students and researchers in the areas of control theory and applied mathematics.

Forecast demand and supply of energy in the short period. Its forecast and sensitivity analysis until the 2004 fiscal year

International Nuclear Information System (INIS)

Yamashita, Yukari; Suehiro, Shigeru; Yanagisawa, Akira; Imaeda, Toshiya; Komiyama, Ryouichi

2004-01-01

The object of this report is forecast demand and supply of energy in the 2003 and 2004 fiscal year, which correspond to a business recovery period. A macroeconomics model and an energy supply model are calculated by changing actual GNP, crude oil rate and the rerunning period of nuclear power plants. The calculation results are compared with the reference case. In the first chapter, forecast Japanese economy until the 2004 fiscal year is explained. In the second chapter, the results of energy demand and supply in the first chapter are investigated by the home supply and consumption of primary energy (the reference case) and each energy resources. The sensitivity analytical results of actual GNP, consumer price index, home supply of the primary energy, energy expenditure, sales account of electric power, city gas and fuel by five cases such as reference, increase and decrease of oil cost and increase and decrease of economic growth are investigated. The effects of fast rerunning period of nuclear power plant and atmosphere temperature on these above demands of energies are indicated in the third chapter. (S.Y.)

Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

International Nuclear Information System (INIS)

Huang, Shang-Lang; Chao, Chuck C.-K.

2015-01-01

A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug

Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

Energy Technology Data Exchange (ETDEWEB)

Huang, Shang-Lang [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Chao, Chuck C.-K., E-mail: cckchao@mail.cgu.edu.tw [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan (China)

2015-06-16

A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug.

Childhood Maltreatment, Depression and Suicidal Ideation: Critical Importance of Parental and Peer Emotional Abuse During Developmental Sensitive Periods in Males and Females

Directory of Open Access Journals (Sweden)

Alaptagin eKhan

2015-03-01

Full Text Available BACKGROUND: The Adverse Childhood Experience (ACE study found that risk for depression increased as a function of number of types of childhood maltreatment, and interpret this as a result of cumulative stress. An alternative hypothesis is that risk depends on type and timing of maltreatment. This will also present as a linear increase, since exposure to more types of abuse increases likelihood of experiencing a critical type of abuse at a critical age.METHODS: 560 (223M/337F young adults (18-25 years were recruited from the community without regard to diagnosis and balanced to have equal exposure to 0-4 plus types of maltreatment. The Maltreatment and Abuse Chronology of Exposure scale assessed severity of exposure to 10 types of maltreatment across each year of childhood. Major depression (MDD and current symptoms were evaluated by SCID, interview and self-report. Predictive analytics assessed importance of exposure at each age and evaluated whether exposure at one or two ages was a more important predictor than number, severity or duration of maltreatment across childhood.RESULTS: The most important predictors of lifetime history of MDD was non-verbal emotional abuse (NVEA in males and peer emotional abuse (EA in females at 14 years of age, and these were more important predictors across models than number of types of maltreatment (Males: t9=16.39, p<10-7; Females t9=5.78, p<10-4. Suicidal ideation was predicted, in part, by NVEA and peer EA at age 14, but most importantly by parental verbal abuse at age 5 in males and sexual abuse at age 18 in females. CONCLUSIONS: This study provides evidence for sensitive exposure periods when maltreatment maximally impacts risk for depression, and provides an alternative interpretation of the ACE study results. These findings fit with emerging neuroimaging evidence for regional sensitivity periods. The presence of sensitive exposure periods has important implications for prevention, preemption and

Sensitivity analysis of the noble gas transport and fate model: CASCADR9

International Nuclear Information System (INIS)

Lindstrom, F.T.; Cawlfield, D.E.; Barker, L.E.

1994-03-01

CASCADR9 is a desert alluvial soil site-specific noble gas transport and fate model. Input parameters for CASCADR9 are: man-made source term, background concentration of radionuclides, radon half-life, soil porosity, period of barometric pressure wave, amplitude of barometric pressure wave, and effective eddy diffusivity. Using average flux, total flow, and radon concentration at the 40 day mark as output parameters, a sensitivity analysis for CASCADR9 is carried out, under a variety of scenarios. For each scenario, the parameter to which output parameters are most sensitive are identified

Sensitivity of UK butterflies to local climatic extremes: which life stages are most at risk?

Science.gov (United States)

McDermott Long, Osgur; Warren, Rachel; Price, Jeff; Brereton, Tom M; Botham, Marc S; Franco, Aldina M A

2017-01-01

There is growing recognition as to the importance of extreme climatic events (ECEs) in determining changes in species populations. In fact, it is often the extent of climate variability that determines a population's ability to persist at a given site. This study examined the impact of ECEs on the resident UK butterfly species (n = 41) over a 37-year period. The study investigated the sensitivity of butterflies to four extremes (drought, extreme precipitation, extreme heat and extreme cold), identified at the site level, across each species' life stages. Variations in the vulnerability of butterflies at the site level were also compared based on three life-history traits (voltinism, habitat requirement and range). This is the first study to examine the effects of ECEs at the site level across all life stages of a butterfly, identifying sensitive life stages and unravelling the role life-history traits play in species sensitivity to ECEs. Butterfly population changes were found to be primarily driven by temperature extremes. Extreme heat was detrimental during overwintering periods and beneficial during adult periods and extreme cold had opposite impacts on both of these life stages. Previously undocumented detrimental effects were identified for extreme precipitation during the pupal life stage for univoltine species. Generalists were found to have significantly more negative associations with ECEs than specialists. With future projections of warmer, wetter winters and more severe weather events, UK butterflies could come under severe pressure given the findings of this study. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Salt-Sensitive Hypertension and Cardiac Hypertrophy in Transgenic Mice Expressing a Corin Variant Identified in African Americans

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Wang, Wei; Cui, Yujie; Shen, Jianzhong; Jiang, Jingjing; Chen, Shenghan; Peng, Jianhao; Wu, Qingyu

2012-01-01

African Americans represent a high risk population for salt-sensitive hypertension and heart disease but the underlying mechanism remains unclear. Corin is a cardiac protease that regulates blood pressure by activating natriuretic peptides. A corin gene variant (T555I/Q568P) was identified in African Americans with hypertension and cardiac hypertrophy. In this study, we test the hypothesis that the corin variant contributes to the hypertensive and cardiac hypertrophic phenotype in vivo. Transgenic mice were generated to express wild-type or T555I/Q568P variant corin in the heart under the control of α-myosin heavy chain promoter. The mice were crossed into a corin knockout background to create KO/TgWT and KO/TgV mice that expressed WT or variant corin, respectively, in the heart. Functional studies showed that KO/TgV mice had significantly higher levels of pro-atrial natriuretic peptide in the heart compared with that in control KO/TgWT mice, indicating that the corin variant was defective in processing natriuretic peptides in vivo. By radiotelemetry, corin KO/TgV mice were found to have hypertension that was sensitive to dietary salt loading. The mice also developed cardiac hypertrophy at 12–14 months of age when fed a normal salt diet or at a younger age when fed a high salt diet. The phenotype of salt-sensitive hypertension and cardiac hypertrophy in KO/TgV mice closely resembles the pathological findings in African Americans who carry the corin variant. The results indicate that corin defects may represent an important mechanism in salt-sensitive hypertension and cardiac hypertrophy in African Americans. PMID:22987923

[Temperature sensitivity of wheat plant respiration and soil respiration influenced by increased UV-B radiation from elongation to flowering periods].

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Chen, Shu-Tao; Hu, Zheng-Hua; Li, Han-Mao; Ji, Yu-Hong; Yang, Yan-Ping

2009-05-15

Field experiment was carried out in the spring of 2008 in order to investigate the effects of increased UV-B radiation on the temperature sensitivity of wheat plant respiration and soil respiration from elongation to flowering periods. Static chamber-gas chromatography method was used to measure ecosystem respiration and soil respiration under 20% UV-B radiation increase and control. Environmental factors such as temperature and moisture were also measured. Results indicated that supplemental UV-B radiation inhibited the ecosystem respiration and soil respiration from wheat elongation to flowering periods, and the inhibition effect was more obvious for soil respiration than for ecosystem respiration. Ecosystem respiration rates, on daily average, were 9%, 9%, 3%, 16% and 30% higher for control than for UV-B treatment forthe five measurement days, while soil respiration rates were 99%, 93%, 106%, 38% and 10% higher for control than for UV-B treatment. The Q10s (temperature sensitivity coefficients) for plant respiration under control and UV-B treatments were 1.79 and 1.59, respectively, while the Q10s for soil respiration were 1.38 and 1.76, respectively. The Q10s for ecosystem respiration were 1.65 and 1.63 under CK and UV-B treatments, respectively. Supplemental UV-B radiation caused a lower Q10 for plant respiration and a higher Q10 for soil respiration, although no significant effect of supplemental UV-B radiation on the Q10 for ecosystem respiration was found.

Microbial Contaminants of Cord Blood Units Identified by 16S rRNA Sequencing and by API Test System, and Antibiotic Sensitivity Profiling.

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Luís França

Full Text Available Over a period of ten months a total of 5618 cord blood units (CBU were screened for microbial contamination under routine conditions. The antibiotic resistance profile for all isolates was also examined using ATB strips. The detection rate for culture positive units was 7.5%, corresponding to 422 samples.16S rRNA sequence analysis and identification with API test system were used to identify the culturable aerobic, microaerophilic and anaerobic bacteria from CBUs. From these samples we recovered 485 isolates (84 operational taxonomic units, OTUs assigned to the classes Bacteroidia, Actinobacteria, Clostridia, Bacilli, Betaproteobacteria and primarily to the Gammaproteobacteria. Sixty-nine OTUs, corresponding to 447 isolates, showed 16S rRNA sequence similarities above 99.0% with known cultured bacteria. However, 14 OTUs had 16S rRNA sequence similarities between 95 and 99% in support of genus level identification and one OTU with 16S rRNA sequence similarity of 90.3% supporting a family level identification only. The phenotypic identification formed 29 OTUs that could be identified to the species level and 9 OTUs that could be identified to the genus level by API test system. We failed to obtain identification for 14 OTUs, while 32 OTUs comprised organisms producing mixed identifications. Forty-two OTUs covered species not included in the API system databases. The API test system Rapid ID 32 Strep and Rapid ID 32 E showed the highest proportion of identifications to the species level, the lowest ratio of unidentified results and the highest agreement to the results of 16S rRNA assignments. Isolates affiliated to the Bacilli and Bacteroidia showed the highest antibiotic multi-resistance indices and microorganisms of the Clostridia displayed the most antibiotic sensitive phenotypes.

Microbial Contaminants of Cord Blood Units Identified by 16S rRNA Sequencing and by API Test System, and Antibiotic Sensitivity Profiling.

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França, Luís; Simões, Catarina; Taborda, Marco; Diogo, Catarina; da Costa, Milton S

2015-01-01

Over a period of ten months a total of 5618 cord blood units (CBU) were screened for microbial contamination under routine conditions. The antibiotic resistance profile for all isolates was also examined using ATB strips. The detection rate for culture positive units was 7.5%, corresponding to 422 samples.16S rRNA sequence analysis and identification with API test system were used to identify the culturable aerobic, microaerophilic and anaerobic bacteria from CBUs. From these samples we recovered 485 isolates (84 operational taxonomic units, OTUs) assigned to the classes Bacteroidia, Actinobacteria, Clostridia, Bacilli, Betaproteobacteria and primarily to the Gammaproteobacteria. Sixty-nine OTUs, corresponding to 447 isolates, showed 16S rRNA sequence similarities above 99.0% with known cultured bacteria. However, 14 OTUs had 16S rRNA sequence similarities between 95 and 99% in support of genus level identification and one OTU with 16S rRNA sequence similarity of 90.3% supporting a family level identification only. The phenotypic identification formed 29 OTUs that could be identified to the species level and 9 OTUs that could be identified to the genus level by API test system. We failed to obtain identification for 14 OTUs, while 32 OTUs comprised organisms producing mixed identifications. Forty-two OTUs covered species not included in the API system databases. The API test system Rapid ID 32 Strep and Rapid ID 32 E showed the highest proportion of identifications to the species level, the lowest ratio of unidentified results and the highest agreement to the results of 16S rRNA assignments. Isolates affiliated to the Bacilli and Bacteroidia showed the highest antibiotic multi-resistance indices and microorganisms of the Clostridia displayed the most antibiotic sensitive phenotypes.

Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta

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Barbara Gasse

2017-06-01

Full Text Available Amelogenesis imperfecta (AI designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene (MMP20 produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues, pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI.

Evolutionary Analysis Predicts Sensitive Positions of MMP20 and Validates Newly- and Previously-Identified MMP20 Mutations Causing Amelogenesis Imperfecta.

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Gasse, Barbara; Prasad, Megana; Delgado, Sidney; Huckert, Mathilde; Kawczynski, Marzena; Garret-Bernardin, Annelyse; Lopez-Cazaux, Serena; Bailleul-Forestier, Isabelle; Manière, Marie-Cécile; Stoetzel, Corinne; Bloch-Zupan, Agnès; Sire, Jean-Yves

2017-01-01

Amelogenesis imperfecta (AI) designates a group of genetic diseases characterized by a large range of enamel disorders causing important social and health problems. These defects can result from mutations in enamel matrix proteins or protease encoding genes. A range of mutations in the enamel cleavage enzyme matrix metalloproteinase-20 gene ( MMP20 ) produce enamel defects of varying severity. To address how various alterations produce a range of AI phenotypes, we performed a targeted analysis to find MMP20 mutations in French patients diagnosed with non-syndromic AI. Genomic DNA was isolated from saliva and MMP20 exons and exon-intron boundaries sequenced. We identified several homozygous or heterozygous mutations, putatively involved in the AI phenotypes. To validate missense mutations and predict sensitive positions in the MMP20 sequence, we evolutionarily compared 75 sequences extracted from the public databases using the Datamonkey webserver. These sequences were representative of mammalian lineages, covering more than 150 million years of evolution. This analysis allowed us to find 324 sensitive positions (out of the 483 MMP20 residues), pinpoint functionally important domains, and build an evolutionary chart of important conserved MMP20 regions. This is an efficient tool to identify new- and previously-identified mutations. We thus identified six functional MMP20 mutations in unrelated families, finding two novel mutated sites. The genotypes and phenotypes of these six mutations are described and compared. To date, 13 MMP20 mutations causing AI have been reported, making these genotypes and associated hypomature enamel phenotypes the most frequent in AI.

Identifying crucial parameter correlations maintaining bursting activity.

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Anca Doloc-Mihu

2014-06-01

Full Text Available Recent experimental and computational studies suggest that linearly correlated sets of parameters (intrinsic and synaptic properties of neurons allow central pattern-generating networks to produce and maintain their rhythmic activity regardless of changing internal and external conditions. To determine the role of correlated conductances in the robust maintenance of functional bursting activity, we used our existing database of half-center oscillator (HCO model instances of the leech heartbeat CPG. From the database, we identified functional activity groups of burster (isolated neuron and half-center oscillator model instances and realistic subgroups of each that showed burst characteristics (principally period and spike frequency similar to the animal. To find linear correlations among the conductance parameters maintaining functional leech bursting activity, we applied Principal Component Analysis (PCA to each of these four groups. PCA identified a set of three maximal conductances (leak current, [Formula: see text]Leak; a persistent K current, [Formula: see text]K2; and of a persistent Na+ current, [Formula: see text]P that correlate linearly for the two groups of burster instances but not for the HCO groups. Visualizations of HCO instances in a reduced space suggested that there might be non-linear relationships between these parameters for these instances. Experimental studies have shown that period is a key attribute influenced by modulatory inputs and temperature variations in heart interneurons. Thus, we explored the sensitivity of period to changes in maximal conductances of [Formula: see text]Leak, [Formula: see text]K2, and [Formula: see text]P, and we found that for our realistic bursters the effect of these parameters on period could not be assessed because when varied individually bursting activity was not maintained.

Lengthened Cutaneous Silent Period in Fibromyalgia Suggesting Central Sensitization as a Pathogenesis.

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Seol-Hee Baek

Full Text Available The pathogenesis of fibromyalgia (FM has not been clearly elucidated, but central sensitization, which plays an important role in the development of neuropathic pain, is considered to be the main mechanism. The cutaneous silent period (CSP, which is a spinal reflex mediated by A-delta cutaneous afferents, is useful for the evaluation of sensorimotor integration at the spinal and supraspinal levels. To understand the pathophysiology of FM, we compared CSP patterns between patients with FM and normal healthy subjects. Twenty-four patients with FM diagnosed in accordance with the 1990 American College of Rheumatology classification system and 24 age- and sex-matched healthy volunteers were recruited. The CSP was measured from the abductor pollicis brevis muscle. Demographic data, number of tender points, and visual analog scale and FM impact questionnaire scores were collected. The measured CSP and clinical parameters of the patient and control groups were compared. In addition, possible correlations between the CSP parameters and the other clinical characteristics were analyzed. Mean CSP latencies did not differ between patients (55.50 ± 10.97 ms and healthy controls (60.23 ± 11.87 ms; p = 0.158, although the mean CSP duration was significantly longer in patients (73.75 ± 15.67 ms than in controls (63.50 ± 14.05 ms; p = 0.021. CSP variables did not correlate with any clinical variables. The significantly longer CSP duration in FM patients suggests central dysregulation at the spinal and supraspinal levels, rather than peripheral small fiber dysfunction.

Sensitive Interviewing in Qualitative Research.

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Dempsey, Laura; Dowling, Maura; Larkin, Philip; Murphy, Kathy

2016-12-01

In this paper we focus on important considerations when planning and conducting qualitative interviews on sensitive topics. Drawing on experiences of conducting interviews with dementia caregivers, a framework of essential elements in qualitative interviewing was developed to emphasize study participants' needs while also providing guidance for researchers. Starting with a definition of sensitive research, the framework includes preparing for interviews, interacting with gatekeepers of vulnerable groups, planning for interview timing, and location, building relationships and conducting therapeutic interactions, protecting ethically vulnerable participants, and planning for disengagement. This framework has the potential to improve the effectiveness of sensitive interviewing with vulnerable groups. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

High sensitive reflection type long period fiber grating biosensor for real time detection of thyroglobulin, a differentiated thyroid cancer biomarker: the Smart Health project

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Quero, G.; Severino, R.; Vaiano, P.; Consales, M.; Ruvo, M.; Sandomenico, A.; Borriello, A.; Giordano, M.; Zuppolini, S.; Diodato, L.; Cutolo, A.; Cusano, A.

2015-09-01

We report the development of a reflection-type long period fiber grating (LPG) biosensor able to perform the real time detection of thyroid cancer markers in the needle washout of fine-needle aspiration biopsy. A standard LPG is first transformed in a practical probe working in reflection mode, then it is coated by an atactic-polystyrene overlay in order to increase its surrounding refractive index sensitivity and to provide, at the same time, the desired interfacial properties for a stable bioreceptor immobilization. The results provide a clear demonstration of the effectiveness and sensitivity of the developed biosensing platform, allowing the in vitro detection of human Thyroglobulin at sub-nanomolar concentrations.

Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization

DEFF Research Database (Denmark)

Bønnelykke, Klaus; Matheson, Melanie C; Pers, Tune Hannes

2013-01-01

Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease. We performed the first large-scale genome-wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up th...

Identifying Watershed Regions Sensitive to Soil Erosion and Contributing to Lake Eutrophication—A Case Study in the Taihu Lake Basin (China)

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Lin, Chen; Ma, Ronghua; He, Bin

2015-01-01

Taihu Lake in China is suffering from severe eutrophication partly due to non-point pollution from the watershed. There is an increasing need to identify the regions within the watershed that most contribute to lake water degradation. The selection of appropriate temporal scales and lake indicators is important to identify sensitive watershed regions. This study selected three eutrophic lake areas, including Meiliang Bay (ML), Zhushan Bay (ZS), and the Western Coastal region (WC), as well as multiple buffer zones next to the lake boundary as the study sites. Soil erosion intensity was designated as a watershed indicator, and the lake algae area was designated as a lake quality indicator. The sensitive watershed region was identified based on the relationship between these two indicators among different lake divisions for a temporal sequence from 2000 to 2012. The results show that the relationship between soil erosion modulus and lake quality varied among different lake areas. Soil erosion from the two bay areas was more closely correlated with water quality than soil erosion from the WC region. This was most apparent at distances of 5 km to 10 km from the lake, where the r2 was as high as 0.764. Results indicate that soil erosion could be used as an indicator for identifying key watershed protection areas. Different lake areas need to be considered separately due to differences in geographical features, land use, and the corresponding effects on lake water quality. PMID:26712772

Identifying Watershed Regions Sensitive to Soil Erosion and Contributing to Lake Eutrophication--A Case Study in the Taihu Lake Basin (China).

Science.gov (United States)

Lin, Chen; Ma, Ronghua; He, Bin

2015-12-24

Taihu Lake in China is suffering from severe eutrophication partly due to non-point pollution from the watershed. There is an increasing need to identify the regions within the watershed that most contribute to lake water degradation. The selection of appropriate temporal scales and lake indicators is important to identify sensitive watershed regions. This study selected three eutrophic lake areas, including Meiliang Bay (ML), Zhushan Bay (ZS), and the Western Coastal region (WC), as well as multiple buffer zones next to the lake boundary as the study sites. Soil erosion intensity was designated as a watershed indicator, and the lake algae area was designated as a lake quality indicator. The sensitive watershed region was identified based on the relationship between these two indicators among different lake divisions for a temporal sequence from 2000 to 2012. The results show that the relationship between soil erosion modulus and lake quality varied among different lake areas. Soil erosion from the two bay areas was more closely correlated with water quality than soil erosion from the WC region. This was most apparent at distances of 5 km to 10 km from the lake, where the r² was as high as 0.764. Results indicate that soil erosion could be used as an indicator for identifying key watershed protection areas. Different lake areas need to be considered separately due to differences in geographical features, land use, and the corresponding effects on lake water quality.

Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities

DEFF Research Database (Denmark)

Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B.

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any...... associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents...... including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong...

Effect of prolonged exposure to low antigen concentration for sensitization

International Nuclear Information System (INIS)

Och, Francois M.M. van; Vandebriel, Rob J.; Jong, Wim H. de; Loveren, Henk van

2003-01-01

The local lymph node assay (LLNA) is an assay in mice to identify potential allergens. Compounds that do not induce a stimulation index (SI)≥3 are not considered sensitizers. Of the chemicals that do, the SI of 3 is used as a benchmark, and indicates the sensitizing potency of a chemical. Compared to the exposure duration of the LLNA (3 days), real life exposure often lasts for months or years. We therefore investigated whether prolonged exposure to sensitizers at concentrations that do not induce a SI≥3 in the LLNA, were able to surpass this threshold. Mice were treated for 2 months at 7-day intervals with a range of concentrations of the known allergens ethyl-p-aminobenzoate (benzocaine, BENZ), 2,4-dinitrochlorobenzene (DNCB), and tetramethyl thiuram disulfide (TMTD). Both proliferative activity and cytokine production were established at day 60. Neither BENZ nor TMTD showed a significant increase in the proliferation rate compared to vehicle controls. Only DNCB at concentrations originally above the EC 3 a significant increase in proliferation was seen after prolonged exposure. No significant effect on IFN-γ and IL-4 production was observed for all three compounds compared. These findings indicate that for classification of sensitizers the shorter exposure period employed in the standard LLNA is sufficient, and longer periods of exposure have no bearing on this classification

Identifying sensitive areas on intercultural contacts: An exploratory study

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Ignacio Ramos-Vidal

2011-06-01

Full Text Available This paper analyzes the negative influence that cultural friction areas can promote on intercultural contacts. First, we expose the critical incident method like cross-cultural training model (Arthur, 2001. Then we show the negative effects that sensitive cultural zones can exert on the formation of prejudices and stereotypes about culturally diverse groups, analyzing 77 critical incidents collected in two different formative contexts. The main cultural shock areas detected are a intercultural communication barriers, b gender roles, and c the cultural expressions statement. Strategies to improve the method validity are proposed.

The Newborn Screening Paradox: Sensitivity vs. Overdiagnosis in VLCAD Deficiency.

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Diekman, Eugene; de Sain-van der Velden, Monique; Waterham, Hans; Kluijtmans, Leo; Schielen, Peter; van Veen, Evert Ben; Ferdinandusse, Sacha; Wijburg, Frits; Visser, Gepke

2016-01-01

To improve the efficacy of newborn screening (NBS) for very long chain acyl-CoA dehydrogenase deficiency (VLCADD). Data on all dried blood spots collected by the Dutch NBS from October 2007 to 2010 (742.728) were included. Based solely on the C14:1 levels (cutoff ≥0.8 μmol/L), six newborns with VLCADD had been identified through NBS during this period. The ratio of C14:1 over C2 was calculated. DNA of all blood spots with a C14:1/C2 ratio of ≥0.020 was isolated and sequenced. Children homozygous or compound heterozygous for mutations in the ACADVL gene were traced back and invited for detailed clinical, biochemical, and genetic evaluation. Retrospective analysis based on the C14:1/C2 ratio with a cutoff of ≥0.020 identified an additional five children with known ACADVL mutations and low enzymatic activity. All were still asymptomatic at the time of diagnosis (age 2-5 years). Increasing the cutoff to ≥0.023 resulted in a sensitivity of 93% and a positive predictive value of 37%. The sensitivity of the previously used screening approach (C14:1 ≥0.8) was 50%. This study shows that the ratio C14:1/C2 is a more sensitive marker than C14:1 for identifying VLCADD patients in NBS. However, as these patients were all asymptomatic at the time of diagnosis, this suggests that a more sensitive screening approach may also identify individuals who may never develop clinical disease. Long-term follow-up studies are needed to establish the risk of these VLCADD-deficient individuals for developing clinical signs and symptoms.

A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity.

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Heijink, Anne Margriet; Blomen, Vincent A; Bisteau, Xavier; Degener, Fabian; Matsushita, Felipe Yu; Kaldis, Philipp; Foijer, Floris; van Vugt, Marcel A T M

2015-12-08

The Wee1 cell cycle checkpoint kinase prevents premature mitotic entry by inhibiting cyclin-dependent kinases. Chemical inhibitors of Wee1 are currently being tested clinically as targeted anticancer drugs. Wee1 inhibition is thought to be preferentially cytotoxic in p53-defective cancer cells. However, TP53 mutant cancers do not respond consistently to Wee1 inhibitor treatment, indicating the existence of genetic determinants of Wee1 inhibitor sensitivity other than TP53 status. To optimally facilitate patient selection for Wee1 inhibition and uncover potential resistance mechanisms, identification of these currently unknown genes is necessary. The aim of this study was therefore to identify gene mutations that determine Wee1 inhibitor sensitivity. We performed a genome-wide unbiased functional genetic screen in TP53 mutant near-haploid KBM-7 cells using gene-trap insertional mutagenesis. Insertion site mapping of cells that survived long-term Wee1 inhibition revealed enrichment of G1/S regulatory genes, including SKP2, CUL1, and CDK2. Stable depletion of SKP2, CUL1, or CDK2 or chemical Cdk2 inhibition rescued the γ-H2AX induction and abrogation of G2 phase as induced by Wee1 inhibition in breast and ovarian cancer cell lines. Remarkably, live cell imaging showed that depletion of SKP2, CUL1, or CDK2 did not rescue the Wee1 inhibition-induced karyokinesis and cytokinesis defects. These data indicate that the activity of the DNA replication machinery, beyond TP53 mutation status, determines Wee1 inhibitor sensitivity, and could serve as a selection criterion for Wee1-inhibitor eligible patients. Conversely, loss of the identified S-phase genes could serve as a mechanism of acquired resistance, which goes along with development of severe genomic instability.

Exploring fMRI Data for Periodic Signal Components

DEFF Research Database (Denmark)

Hansen, Lars Kai; Nielsen, Finn Årup; Larsen, Jan

2002-01-01

We use a Bayesian framework to detect periodic components in fMRI data. The resulting detector is sensitive to periodic components with a flexible number of harmonics and with arbitrary amplitude and phases of the harmonics. It is possible to detect the correct number of harmonics in periodic sig...

Sobol' sensitivity analysis for stressor impacts on honeybee ...

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We employ Monte Carlo simulation and nonlinear sensitivity analysis techniques to describe the dynamics of a bee exposure model, VarroaPop. Daily simulations are performed of hive population trajectories, taking into account queen strength, foraging success, mite impacts, weather, colony resources, population structure, and other important variables. This allows us to test the effects of defined pesticide exposure scenarios versus controlled simulations that lack pesticide exposure. The daily resolution of the model also allows us to conditionally identify sensitivity metrics. We use the variancebased global decomposition sensitivity analysis method, Sobol’, to assess firstand secondorder parameter sensitivities within VarroaPop, allowing us to determine how variance in the output is attributed to each of the input variables across different exposure scenarios. Simulations with VarroaPop indicate queen strength, forager life span and pesticide toxicity parameters are consistent, critical inputs for colony dynamics. Further analysis also reveals that the relative importance of these parameters fluctuates throughout the simulation period according to the status of other inputs. Our preliminary results show that model variability is conditional and can be attributed to different parameters depending on different timescales. By using sensitivity analysis to assess model output and variability, calibrations of simulation models can be better informed to yield more

Microarray analysis identifies keratin loci as sensitive biomarkers for thyroid hormone disruption in the salamander Ambystoma mexicanum.

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Page, Robert B; Monaghan, James R; Samuels, Amy K; Smith, Jeramiah J; Beachy, Christopher K; Voss, S Randal

2007-02-01

Ambystomatid salamanders offer several advantages for endocrine disruption research, including genomic and bioinformatics resources, an accessible laboratory model (Ambystoma mexicanum), and natural lineages that are broadly distributed among North American habitats. We used microarray analysis to measure the relative abundance of transcripts isolated from A. mexicanum epidermis (skin) after exogenous application of thyroid hormone (TH). Only one gene had a >2-fold change in transcript abundance after 2 days of TH treatment. However, hundreds of genes showed significantly different transcript levels at days 12 and 28 in comparison to day 0. A list of 123 TH-responsive genes was identified using statistical, BLAST, and fold level criteria. Cluster analysis identified two groups of genes with similar transcription patterns: up-regulated versus down-regulated. Most notably, several keratins exhibited dramatic (1000 fold) increases or decreases in transcript abundance. Keratin gene expression changes coincided with morphological remodeling of epithelial tissues. This suggests that keratin loci can be developed as sensitive biomarkers to assay temporal disruptions of larval-to-adult gene expression programs. Our study has identified the first collection of loci that are regulated during TH-induced metamorphosis in a salamander, thus setting the stage for future investigations of TH disruption in the Mexican axolotl and other salamanders of the genus Ambystoma.

A genome-wide siRNA screen to identify modulators of insulin sensitivity and gluconeogenesis.

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Ruojing Yang

Full Text Available BACKGROUND: Hepatic insulin resistance impairs insulin's ability to suppress hepatic glucose production (HGP and contributes to the development of type 2 diabetes (T2D. Although the interests to discover novel genes that modulate insulin sensitivity and HGP are high, it remains challenging to have a human cell based system to identify novel genes. METHODOLOGY/PRINCIPAL FINDINGS: To identify genes that modulate hepatic insulin signaling and HGP, we generated a human cell line stably expressing beta-lactamase under the control of the human glucose-6-phosphatase (G6PC promoter (AH-G6PC cells. Both beta-lactamase activity and endogenous G6PC mRNA were increased in AH-G6PC cells by a combination of dexamethasone and pCPT-cAMP, and reduced by insulin. A 4-gene High-Throughput-Genomics assay was developed to concomitantly measure G6PC and pyruvate-dehydrogenase-kinase-4 (PDK4 mRNA levels. Using this assay, we screened an siRNA library containing pooled siRNA targeting 6650 druggable genes and identified 614 hits that lowered G6PC expression without increasing PDK4 mRNA levels. Pathway analysis indicated that siRNA-mediated knockdown (KD of genes known to positively or negatively affect insulin signaling increased or decreased G6PC mRNA expression, respectively, thus validating our screening platform. A subset of 270 primary screen hits was selected and 149 hits were confirmed by target gene KD by pooled siRNA and 7 single siRNA for each gene to reduce G6PC expression in 4-gene HTG assay. Subsequently, pooled siRNA KD of 113 genes decreased PEPCK and/or PGC1alpha mRNA expression thereby demonstrating their role in regulating key gluconeogenic genes in addition to G6PC. Last, KD of 61 of the above 113 genes potentiated insulin-stimulated Akt phosphorylation, suggesting that they suppress gluconeogenic gene by enhancing insulin signaling. CONCLUSIONS/SIGNIFICANCE: These results support the proposition that the proteins encoded by the genes identified in

Sensitivity of Billing Claims for Cardiovascular Disease Events among Kidney Transplant Recipients

Science.gov (United States)

Lentine, Krista L.; Schnitzler, Mark A.; Abbott, Kevin C.; Bramesfeld, Kosha; Buchanan, Paula M.; Brennan, Daniel C.

2009-01-01

Background and objectives: Billing claims are increasingly examined beyond administrative functions as outcomes measures in observational research. Few studies have described the performance of billing claims as surrogate measures of clinical events among kidney transplant recipients. Design, setting, participants, & measurements: We investigated the sensitivity of Medicare billing claims for clinically verified cardiovascular diagnoses (five categories) and procedures (four categories) in a novel database linking Medicare claims to electronic medical records of one transplant program. Cardiovascular events identified in medical records for 571 Medicare-insured transplant recipients in 1991 through 2002 served as reference measures. Results: Within a claims-ascertainment period spanning ±30 d of clinically recorded dates, aggregate sensitivity of single claims was higher for case definitions incorporating Medicare Parts A and B for diagnoses and procedures (90.9%) compared with either Part A (82.3%) or Part B (84.6%) alone. Perfect capture of the four procedures was possible within ±30 d or with short claims window expansion, but sensitivity for the diagnoses trended lower with all study algorithms (91.2% with window up to ±90 d). Requirement for additional confirmatory diagnosis claims did not appreciably reduce sensitivity. Sensitivity patterns were similar in the early compared with late periods of the study. Conclusions: Combined use of Medicare Parts A and B billing claims composes a sensitive measure of cardiovascular events after kidney transplant. Further research is needed to define algorithms that maximize specificity as well as sensitivity of claims from Medicare and other insurers as research measures in this population. PMID:19541817

Vibrating wire apparatus for periodic magnetic structure measurement

International Nuclear Information System (INIS)

Temnykh, A.B.

2003-01-01

Devices with periodic magnetic structures such as wigglers and undulators are often key elements in synchrotron radiation sources. In applications where the coherence of the emitted radiation is important, magnetic field errors distorting the periodicity of the field can significantly reduce the performance of the devices. Thus, the measurement, localization, and correction of the field errors can be a critical issue. This article presents a new method for magnetic field measurements in periodic magnetic structures. The method uses a vibrating taut wire passing through the magnetic structure, and it involves measurements of the amplitudes and phases of the standing waves excited on the wire by the Lorentz force between an AC current in the wire and the surrounding magnetic field. For certain arrangements of the wire, vibrations in the wire will be excited by only non-periodic magnetic field component, i.e., by the error field. By measuring the phase and amplitude of these waves, one can reconstruct the error field distribution and then correct it. The method was tested on a permanent magnet wiggler with 19.8 cm period and a peak field of ∼7000G. It demonstrated ∼0.6G RMS sensitivity, δB rms /B rms ∼1.2x10 -4 and spatial resolution sufficient to identify poles generating the field error. Good agreement was found between field error measurements obtained with the vibrating wire method and with traditional Hall probe field mapping

Genetic and pharmacological screens converge in identifying FLIP, BCL2 and IAP proteins as key regulators of sensitivity to the TRAIL-inducing anti-cancer agent ONC201/TIC10

OpenAIRE

Allen, Joshua E.; Prabhu, Varun V.; Talekar, Mala; van den Heuvel, AP; Lim, Bora; Dicker, David T.; Fritz, Jennifer L.; Beck, Adam; El-Deiry, Wafik S.

2015-01-01

ONC201/TIC10 is a small molecule inducer of the TRAIL gene under current investigation as a novel anticancer agent. In this study, we identify critical molecular determinants of ONC201 sensitivity offering potential utility as pharmacodynamic or predictive response markers. By screening a library of kinase siRNAs in combination with a subcytotoxic dose of ONC201, we identified several kinases that ablated tumor cell sensitivity, including the MAPK pathway inducer KSR1. Unexpectedly, KSR1 sile...

Windows of sensitivity to toxic chemicals in the motor effects development.

Science.gov (United States)

Ingber, Susan Z; Pohl, Hana R

2016-02-01

Many chemicals currently used are known to elicit nervous system effects. In addition, approximately 2000 new chemicals introduced annually have not yet undergone neurotoxicity testing. This review concentrated on motor development effects associated with exposure to environmental neurotoxicants to help identify critical windows of exposure and begin to assess data needs based on a subset of chemicals thoroughly reviewed by the Agency for Toxic Substances and Disease Registry (ATSDR) in Toxicological Profiles and Addenda. Multiple windows of sensitivity were identified that differed based on the maturity level of the neurological system at the time of exposure, as well as dose and exposure duration. Similar but distinct windows were found for both motor activity (GD 8-17 [rats], GD 12-14 and PND 3-10 [mice]) and motor function performance (insufficient data for rats, GD 12-17 [mice]). Identifying specific windows of sensitivity in animal studies was hampered by study designs oriented towards detection of neurotoxicity that occurred at any time throughout the developmental process. In conclusion, while this investigation identified some critical exposure windows for motor development effects, it demonstrates a need for more acute duration exposure studies based on neurodevelopmental windows, particularly during the exposure periods identified in this review. Published by Elsevier Inc.

The Role of Cash Holdings in Reducing Investment-Cash Flow Sensitivity: Evidence from a Financial Crisis Period in an Emerging Market

OpenAIRE

Ozgur Arslan; Chrisostomos Florackis; Aydin Ozkan

2006-01-01

This paper investigates the relationship between financing constraints and investment-cash flow sensitivities by focusing on cash holdings of firms as the basic classification scheme to separate firms into financially constrained and unconstrained categories. The idea is that high cash reserves increase the ability of firms to undertake profitable investment opportunities. Our classification scheme is based on an optimal cash model, which helps us identify the firms that deviate significantly...

Long-term changes in the sensitivity of quadrupole mass spectrometers

International Nuclear Information System (INIS)

Blanchard, W.R.; McCarthy, P.J.; Dylla, H.F.; LaMarche, P.H.; Simpkins, J.E.

1986-02-01

We routinely use quadrupole mass spectrometers (QMS) to monitor vacuum conditions, gas purity, and plasma-wall interactions in the Tokamak Fusion Test Reactor (TFTR) at Princeton. Two QMS systems have been operating on TFTR continuously for a two-year period. Both QMS systems are absolutely calibrated at weekly intervals using a six-part standard gas mixture. The calibration procedure is based on the use of transfer standards (ion gauge and capacitance manometer) that are calibrated against a primary standard (spinning rotor gauge) on an external vacuum system. We have identified variations in the efficiency of the QMS ionizer and drifts in the sensitivity of the electron multiplier ion detector to be the major reasons for the observed changes in overall OMS sensitivity. Weekly variations in sensitivity greater than 100% have been observed following system bakeout at 150 0 C and with the use of rhenium filaments which were initially in the QMS ionizer. Operation of the QMS systems with tungsten filaments and at constant temperature has yielded more stable operation with weekly sensitivity changes generally being less than 10%. 7 refs., 7 figs

Maternal sensitivity: a concept analysis.

Science.gov (United States)

Shin, Hyunjeong; Park, Young-Joo; Ryu, Hosihn; Seomun, Gyeong-Ae

2008-11-01

The aim of this paper is to report a concept analysis of maternal sensitivity. Maternal sensitivity is a broad concept encompassing a variety of interrelated affective and behavioural caregiving attributes. It is used interchangeably with the terms maternal responsiveness or maternal competency, with no consistency of use. There is a need to clarify the concept of maternal sensitivity for research and practice. A search was performed on the CINAHL and Ovid MEDLINE databases using 'maternal sensitivity', 'maternal responsiveness' and 'sensitive mothering' as key words. The searches yielded 54 records for the years 1981-2007. Rodgers' method of evolutionary concept analysis was used to analyse the material. Four critical attributes of maternal sensitivity were identified: (a) dynamic process involving maternal abilities; (b) reciprocal give-and-take with the infant; (c) contingency on the infant's behaviour and (d) quality of maternal behaviours. Maternal identity and infant's needs and cues are antecedents for these attributes. The consequences are infant's comfort, mother-infant attachment and infant development. In addition, three positive affecting factors (social support, maternal-foetal attachment and high self-esteem) and three negative affecting factors (maternal depression, maternal stress and maternal anxiety) were identified. A clear understanding of the concept of maternal sensitivity could be useful for developing ways to enhance maternal sensitivity and to maximize the developmental potential of infants. Knowledge of the attributes of maternal sensitivity identified in this concept analysis may be helpful for constructing measuring items or dimensions.

Mapping seabird sensitivity to offshore wind farms.

Science.gov (United States)

Bradbury, Gareth; Trinder, Mark; Furness, Bob; Banks, Alex N; Caldow, Richard W G; Hume, Duncan

2014-01-01

We present a Geographic Information System (GIS) tool, SeaMaST (Seabird Mapping and Sensitivity Tool), to provide evidence on the use of sea areas by seabirds and inshore waterbirds in English territorial waters, mapping their relative sensitivity to offshore wind farms. SeaMaST is a freely available evidence source for use by all connected to the offshore wind industry and will assist statutory agencies in assessing potential risks to seabird populations from planned developments. Data were compiled from offshore boat and aerial observer surveys spanning the period 1979-2012. The data were analysed using distance analysis and Density Surface Modelling to produce predicted bird densities across a grid covering English territorial waters at a resolution of 3 km×3 km. Coefficients of Variation were estimated for each grid cell density, as an indication of confidence in predictions. Offshore wind farm sensitivity scores were compiled for seabird species using English territorial waters. The comparative risks to each species of collision with turbines and displacement from operational turbines were reviewed and scored separately, and the scores were multiplied by the bird density estimates to produce relative sensitivity maps. The sensitivity maps reflected well the amassed distributions of the most sensitive species. SeaMaST is an important new tool for assessing potential impacts on seabird populations from offshore development at a time when multiple large areas of development are proposed which overlap with many seabird species' ranges. It will inform marine spatial planning as well as identifying priority areas of sea usage by marine birds. Example SeaMaST outputs are presented.

Kinesthetic sensitivity and related measures of hand sensitivity in children with nonproficient handwriting.

Science.gov (United States)

Brink, Anne O'Leary; Jacobs, Anne Burleigh

2011-01-01

This study compared measures of hand sensitivity and handwriting quality in children aged 10 to 12 years identified by their teachers as having nonproficient or proficient handwriting. We hypothesized that children with nonproficient handwriting have decreased kinesthetic sensitivity of the hands and digits. Sixteen subjects without documented motor or cognitive concerns were tested for kinesthetic sensitivity, discriminate tactile awareness, diadochokinesia, stereognosis, and graphesthesia. Eight children were considered to have nonproficient handwriting; 8 had proficient handwriting. Nonparametric Mann-Whitney U tests were used to identify differences between groups on sensory tests. The 2 groups showed a statistically significant difference in handwriting legibility (P = .018). No significant difference was found on tests of kinesthetic sensitivity or other measures of sensation. Children presenting with handwriting difficulty as the only complaint have similar sensitivity in hands and digits as those with proficient handwriting. Failure to detect differences may result from a small sample size.

Endogenous Money, Non-neutrality and Interest-sensitivity in the Theory of Long Period Unemployment

OpenAIRE

Peter Docherty

2006-01-01

This paper investigates the role played by endogenous money in models with interest-sensitive expenditures. In particular, it examines the impact of endogenous money on a baseline neoclassical model arguing against the frequently asserted claim that traditional neoclassical macroeconomics is compatible with endogenous money. It demonstrates firstly that endogenous money is a sufficient condition to render unstable a neoclassical model characterised by interest-sensitive expenditures, full emp...

Optical treatment of amblyopia in astigmatic children: the sensitive period for successful treatment.

Science.gov (United States)

Harvey, Erin M; Dobson, Velma; Clifford-Donaldson, Candice E; Miller, Joseph M

2007-12-01

To compare the effectiveness of eyeglass treatment of astigmatism-related amblyopia in children younger than 8 years (range, 4.75-7.99 years) versus children 8 years of age and older (range, 8.00-13.53 years) over short (6-week) and long (1-year) treatment intervals. Prospective, interventional, comparative case-control study. Four hundred forty-six nonastigmatic (right and left eye, or =1.00 D) Native American (Tohono O'odham) children in kindergarten or grades 1 through 6. Eyeglass correction of refractive error, prescribed for full-time wear, in astigmatic children. Amount of change in mean right-eye best-corrected letter visual acuity for treated astigmatic children versus untreated, age-matched nonastigmatic children after short (6-week) and long (1-year) treatment intervals. Astigmatic children had significantly reduced mean best-corrected visual acuity at baseline compared to nonastigmatic children. Astigmats showed significantly greater improvement in mean best-corrected visual acuity (0.08 logarithm of the minimum angle of resolution [logMAR] unit; approximately 1 line), than the nonastigmatic children (0.01 logMAR unit) over the 6-week treatment interval. No additional treatment effect was observed between 6 weeks and 1 year. Treatment effectiveness was not dependent on age group ( or =8 years) and was not influenced by previous eyeglass treatment. Despite significant improvement, mean best-corrected visual acuity in astigmatic children remained significantly poorer than in nonastigmatic children after 1 year of eyeglass treatment, even when analyses were limited to results from highly compliant children. Sustained eyeglass correction results in significant improvement in best-corrected visual acuity in astigmatic children, including those previously believed to be beyond the sensitive period for successful treatment.

Sensitivity analysis of the STICS-MACRO model to identify cropping practices reducing pesticides losses.

Science.gov (United States)

Lammoglia, Sabine-Karen; Makowski, David; Moeys, Julien; Justes, Eric; Barriuso, Enrique; Mamy, Laure

2017-02-15

STICS-MACRO is a process-based model simulating the fate of pesticides in the soil-plant system as a function of agricultural practices and pedoclimatic conditions. The objective of this work was to evaluate the influence of crop management practices on water and pesticide flows in contrasted environmental conditions. We used the Morris screening sensitivity analysis method to identify the most influential cropping practices. Crop residues management and tillage practices were shown to have strong effects on water percolation and pesticide leaching. In particular, the amount of organic residues added to soil was found to be the most influential input. The presence of a mulch could increase soil water content so water percolation and pesticide leaching. Conventional tillage was also found to decrease pesticide leaching, compared to no-till, which is consistent with many field observations. The effects of the soil, crop and climate conditions tested in this work were less important than those of cropping practices. STICS-MACRO allows an ex ante evaluation of cropping systems and agricultural practices, and of the related pesticides environmental impacts. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimal Decisions in a Single-Period Supply Chain with Price-Sensitive Random Demand under a Buy-Back Contract

Directory of Open Access Journals (Sweden)

Feng Wang

2014-01-01

Full Text Available This paper studies a single-period supply chain with a buy-back contract under a Stackelberg game model, in which the supplier (leader decides on the wholesale price, and the retailer (follower responds to determine the retail price and the order quantity. We analytically investigate the decentralized retailer’s optimal decision. Our results demonstrate that the retailer has a unique optimal simultaneous decision on the retail price and the order quantity, under a mild restriction on the demand distribution. Moreover, as it can be shown that the decentralized supply chain facing price-sensitive random demand cannot be coordinated with buy-back contract, we propose a scheme for the system to achieve Pareto-improvement. Theoretical analysis suggests that there exists a unique Pareto-equilibrium for the supply chain. In particular, when the Pareto-equilibrium is reached, the supply chain is coordinated. Numerical experiments confirm our results.

Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities.

Science.gov (United States)

Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B; Papamarkou, Theodore; Huber, Kilian V M; Mutz, Cornelia; Toretsky, Jeffrey A; Bennett, Keiryn L; Olsen, Jesper V; Brunak, Søren; Kovar, Heinrich; Superti-Furga, Giulio

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong synergistic propensity in Ewing sarcoma, revealing its targets in critical Ewing sarcoma signaling routes. Using a multilevel experimental approach including quantitative phosphoproteomics, we analyzed the molecular rationale behind the disease-specific synergistic effect of simultaneous application of PKC412 and IGF1R inhibitors. The mechanism of the drug synergy between these inhibitors is different from the sum of the mechanisms of the single agents. The combination effectively inhibited pathway crosstalk and averted feedback loop repression, in EWS-FLI1-dependent manner. Mol Cancer Ther; 16(1); 88-101. ©2016 AACR. ©2016 American Association for Cancer Research.

Critical periods after stroke study: translating animal stroke recovery experiments into a clinical trial

Science.gov (United States)

Dromerick, Alexander W.; Edwardson, Matthew A.; Edwards, Dorothy F.; Giannetti, Margot L.; Barth, Jessica; Brady, Kathaleen P.; Chan, Evan; Tan, Ming T.; Tamboli, Irfan; Chia, Ruth; Orquiza, Michael; Padilla, Robert M.; Cheema, Amrita K.; Mapstone, Mark E.; Fiandaca, Massimo S.; Federoff, Howard J.; Newport, Elissa L.

2015-01-01

Introduction: Seven hundred ninety-five thousand Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS) is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 h of upper extremity therapy either immediately upon rehab admission, 2–3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test (ARAT) at 1 year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial. PMID

Critical Periods after Stroke Study: Translating animal stroke recovery experiments into a clinical trial

Directory of Open Access Journals (Sweden)

Alexander W Dromerick

2015-04-01

Full Text Available Introduction: 795,000 Americans will have a stroke this year, and half will have a chronic hemiparesis. Substantial animal literature suggests that the mammalian brain has much potential to recover from acute injury using mechanisms of neuroplasticity, and that these mechanisms can be accessed using training paradigms and neurotransmitter manipulation. However, most of these findings have not been tested or confirmed in the rehabilitation setting, in large part because of the challenges in translating a conceptually straightforward laboratory experiment into a meaningful and rigorous clinical trial in humans. Through presentation of methods for a Phase II trial, we discuss these issues and describe our approach. Methods: In rodents there is compelling evidence for timing effects in rehabilitation; motor training delivered at certain times after stroke may be more effective than the same training delivered earlier or later, suggesting that there is a critical or sensitive period for strongest rehabilitation training effects. If analogous critical/sensitive periods can be identified after human stroke, then existing clinical resources can be better utilized to promote recovery. The Critical Periods after Stroke Study (CPASS is a phase II randomized, controlled trial designed to explore whether such a sensitive period exists. We will randomize 64 persons to receive an additional 20 hours of upper extremity therapy either immediately upon rehab admission, 2-3 months after stroke onset, 6 months after onset, or to an observation-only control group. The primary outcome measure will be the Action Research Arm Test at one year. Blood will be drawn at up to 3 time points for later biomarker studies. Conclusion: CPASS is an example of the translation of rodent motor recovery experiments into the clinical setting; data obtained from this single site randomized controlled trial will be used to finalize the design of a Phase III trial.

Thickly Syndetical Sensitivity of Topological Dynamical System

Directory of Open Access Journals (Sweden)

Heng Liu

2014-01-01

Full Text Available Consider the surjective continuous map f:X→X, where X is a compact metric space. In this paper we give several stronger versions of sensitivity, such as thick sensitivity, syndetic sensitivity, thickly syndetic sensitivity, and strong sensitivity. We establish the following. (1 If (X,f is minimal and sensitive, then (X,f is syndetically sensitive. (2 Weak mixing implies thick sensitivity. (3 If (X,f is minimal and weakly mixing, then it is thickly syndetically sensitive. (4 If (X,f is a nonminimal M-system, then it is thickly syndetically sensitive. Devaney chaos implies thickly periodic sensitivity. (5 We give a syndetically sensitive system which is not thickly sensitive. (6 We give thickly syndetically sensitive examples but not cofinitely sensitive ones.

Incorporating deep learning with convolutional neural networks and position specific scoring matrices for identifying electron transport proteins.

Science.gov (United States)

Le, Nguyen-Quoc-Khanh; Ho, Quang-Thai; Ou, Yu-Yen

2017-09-05

In several years, deep learning is a modern machine learning technique using in a variety of fields with state-of-the-art performance. Therefore, utilization of deep learning to enhance performance is also an important solution for current bioinformatics field. In this study, we try to use deep learning via convolutional neural networks and position specific scoring matrices to identify electron transport proteins, which is an important molecular function in transmembrane proteins. Our deep learning method can approach a precise model for identifying of electron transport proteins with achieved sensitivity of 80.3%, specificity of 94.4%, and accuracy of 92.3%, with MCC of 0.71 for independent dataset. The proposed technique can serve as a powerful tool for identifying electron transport proteins and can help biologists understand the function of the electron transport proteins. Moreover, this study provides a basis for further research that can enrich a field of applying deep learning in bioinformatics. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Sensitivity of Ocean Reflectance Inversion Models for Identifying and Discriminating Between Phytoplankton Functional Groups

Science.gov (United States)

Werdell, P. Jeremy; Ooesler, Collin S.

2012-01-01

The daily, synoptic images provided by satellite ocean color instruments provide viable data streams for observing changes in the biogeochemistrY of marine ecosystems. Ocean reflectance inversion models (ORMs) provide a common mechanism for inverting the "color" of the water observed a satellite into marine inherent optical properties (lOPs) through a combination of empiricism and radiative transfer theory. lOPs, namely the spectral absorption and scattering characteristics of ocean water and its dissolved and particulate constituents, describe the contents of the upper ocean, information critical for furthering scientific understanding of biogeochemical oceanic processes. Many recent studies inferred marine particle sizes and discriminated between phytoplankton functional groups using remotely-sensed lOPs. While all demonstrated the viability of their approaches, few described the vertical distributions of the water column constituents under consideration and, thus, failed to report the biophysical conditions under which their model performed (e.g., the depth and thickness of the phytoplankton bloom(s)). We developed an ORM to remotely identifY Noctiluca miliaris and other phytoplankton functional types using satellite ocean color data records collected in the northern Arabian Sea. Here, we present results from analyses designed to evaluate the applicability and sensitivity of the ORM to varied biophysical conditions. Specifically, we: (1) synthesized a series of vertical profiles of spectral inherent optical properties that represent a wide variety of bio-optical conditions for the northern Arabian Sea under aN Miliaris bloom; (2) generated spectral remote-sensing reflectances from these profiles using Hydrolight; and, (3) applied the ORM to the synthesized reflectances to estimate the relative concentrations of diatoms and N Miliaris for each example. By comparing the estimates from the inversion model to those from synthesized vertical profiles, we were able to

Mapping seabird sensitivity to offshore wind farms.

Directory of Open Access Journals (Sweden)

Gareth Bradbury

Full Text Available We present a Geographic Information System (GIS tool, SeaMaST (Seabird Mapping and Sensitivity Tool, to provide evidence on the use of sea areas by seabirds and inshore waterbirds in English territorial waters, mapping their relative sensitivity to offshore wind farms. SeaMaST is a freely available evidence source for use by all connected to the offshore wind industry and will assist statutory agencies in assessing potential risks to seabird populations from planned developments. Data were compiled from offshore boat and aerial observer surveys spanning the period 1979-2012. The data were analysed using distance analysis and Density Surface Modelling to produce predicted bird densities across a grid covering English territorial waters at a resolution of 3 km×3 km. Coefficients of Variation were estimated for each grid cell density, as an indication of confidence in predictions. Offshore wind farm sensitivity scores were compiled for seabird species using English territorial waters. The comparative risks to each species of collision with turbines and displacement from operational turbines were reviewed and scored separately, and the scores were multiplied by the bird density estimates to produce relative sensitivity maps. The sensitivity maps reflected well the amassed distributions of the most sensitive species. SeaMaST is an important new tool for assessing potential impacts on seabird populations from offshore development at a time when multiple large areas of development are proposed which overlap with many seabird species' ranges. It will inform marine spatial planning as well as identifying priority areas of sea usage by marine birds. Example SeaMaST outputs are presented.

Combinatorial Drug Screening Identifies Ewing Sarcoma-specific Sensitivities

DEFF Research Database (Denmark)

Radic-Sarikas, Branka; Tsafou, Kalliopi P; Emdal, Kristina B.

2017-01-01

Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any...... including approved drugs. We were able to retrieve highly synergistic drug combinations specific for Ewing sarcoma and identified signaling processes important for Ewing sarcoma cell proliferation determined by EWS-FLI1 We generated a molecular target profile of PKC412, a multikinase inhibitor with strong...

Low sensitivity of qSOFA, SIRS criteria and sepsis definition to identify infected patients at risk of complication in the prehospital setting and at the emergency department triage.

Science.gov (United States)

Tusgul, Selin; Carron, Pierre-Nicolas; Yersin, Bertrand; Calandra, Thierry; Dami, Fabrice

2017-11-03

Sepsis is defined as life-threatening organ dysfunction caused by a host response to infection. The quick SOFA (qSOFA) score has been recently proposed as a new bedside clinical score to identify patients with suspected infection at risk of complication (intensive care unit (ICU) admission, in-hospital mortality). The aim of this study was to measure the sensitivity of the qSOFA score, SIRS criteria and sepsis definitions to identify the most serious sepsis cases in the prehospital setting and at the emergency department (ED) triage. We performed a retrospective study of all patients transported by emergency medical services (EMS) to the Lausanne University Hospital (CHUV) over twelve months. All patients with a suspected or proven infection after the ED workup were included. We retrospectively analysed the sensitivity of the qSOFA score (≥2 criteria), SIRS criteria (≥2 clinical criteria) and sepsis definition (SIRS criteria + one sign of organ dysfunction or hypoperfusion) in the pre-hospital setting and at the ED triage as predictors of ICU admission, ICU stay of ≥3 days and early (i.e. 48 h) mortality. No direct comparison between the three tools was attempted. Among 11,411 patients transported to the University hospital, 886 (7.8%) were included. In the pre-hospital setting, the sensitivity of qSOFA reached 36.3% for ICU admission, 17.4% for ICU stay of three days or more and 68.0% for 48 h mortality. The sensitivity of SIRS criteria reached 68.8% for ICU admission, 74.6% for ICU stay of three days or more and 64.0% for 48 h mortality. The sensitivity of sepsis definition did not reach 60% for any outcome. At ED triage, the sensitivity of qSOFA reached 31.2% for ICU admission, 30.5% for ICU stay of ≥3 days and 60.0% for mortality at 48 h. The sensitivity of SIRS criteria reached 58.8% for ICU admission, 57.6% for ICU stay of ≥3 days 80.0% for mortality at 48 h. The sensitivity of sepsis definition reached 60.0% for 48 h mortality. Incidence

Systemic analysis of different colorectal cancer cell lines and TCGA datasets identified IGF-1R/EGFR-PPAR-CASPASE axis as important indicator for radiotherapy sensitivity.

Science.gov (United States)

Chen, Lin; Zhu, Zhe; Gao, Wei; Jiang, Qixin; Yu, Jiangming; Fu, Chuangang

2017-09-05

Insulin-like growth factor 1 receptor (IGF-1R) is proved to contribute the development of many types of cancers. But, little is known about its roles in radio-resistance of colorectal cancer (CRC). Here, we demonstrated that low IGF-1R expression value was associated with the better radiotherapy sensitivity of CRC. Besides, through Quantitative Real-time PCR (qRT-PCR), the elevated expression value of epidermal growth factor receptor (EGFR) was observed in CRC cell lines (HT29, RKO) with high radio-sensitivity compared with those with low sensitivity (SW480, LOVO). The irradiation induced apoptosis rates of wild type and EGFR agonist (EGF) or IGF-1R inhibitor (NVP-ADW742) treated HT29 and SW480 cells were quantified by flow cytometry. As a result, the apoptosis rate of EGF and NVP-ADW742 treated HT29 cells was significantly higher than that of those wild type ones, which indicated that high EGFR and low IGF-1R expression level in CRC was associated with the high sensitivity to radiotherapy. We next conducted systemic bioinformatics analysis of genome-wide expression profiles of CRC samples from the Cancer Genome Atlas (TCGA). Differential expression analysis between IGF-1R and EGFR abnormal CRC samples, i.e. CRC samples with higher IGF-1R and lower EGFR expression levels based on their median expression values, and the rest of CRC samples identified potential genes contribute to radiotherapy sensitivity. Functional enrichment of analysis of those differential expression genes (DEGs) in the Database for Annotation, Visualization and Integrated Discovery (DAVID) indicated PPAR signaling pathway as an important pathway for the radio-resistance of CRC. Our study identified the potential biomarkers for the rational selection of radiotherapy for CRC patients. Copyright © 2017 Elsevier B.V. All rights reserved.

The sensitivity of income polarization

DEFF Research Database (Denmark)

Hussain, Azhar

2009-01-01

This study looks at polarization and its components' sensitivity to assumptions about equivalence scales, income definition, ethical income distribution parameters, and the income accounting period. A representative sample of Danish individual incomes from 1984 to 2002 is utilised. Results show....... Increasing the accounting period confirms the reduction in inequality found for shorter periods, but polarization is virtually unchanged, because income group identification increases. Applying different equivalence scales does not change polarization ranking for different years, but identification ranks...

Parametric Sensitivity Analysis of Oscillatory Delay Systems with an Application to Gene Regulation.

Science.gov (United States)

Ingalls, Brian; Mincheva, Maya; Roussel, Marc R

2017-07-01

A parametric sensitivity analysis for periodic solutions of delay-differential equations is developed. Because phase shifts cause the sensitivity coefficients of a periodic orbit to diverge, we focus on sensitivities of the extrema, from which amplitude sensitivities are computed, and of the period. Delay-differential equations are often used to model gene expression networks. In these models, the parametric sensitivities of a particular genotype define the local geometry of the evolutionary landscape. Thus, sensitivities can be used to investigate directions of gradual evolutionary change. An oscillatory protein synthesis model whose properties are modulated by RNA interference is used as an example. This model consists of a set of coupled delay-differential equations involving three delays. Sensitivity analyses are carried out at several operating points. Comments on the evolutionary implications of the results are offered.

Consumer price sensitivity in Dutch health insurance

NARCIS (Netherlands)

M. van Dijk (Machiel); M. Pomp (Marc); R.C.H.M. Douven (Rudy); T. Laske-Aldershof (Trea); F.T. Schut (Erik); W. de Boer (Willem); A. Boo (Anne)

2008-01-01

textabstractAim: To estimate the price sensitivity of consumer choice of health insurance firm. Method: Using paneldata of the flows of insured betweenpairs of Dutch sickness funds during the period 1993-2002, we estimate the sensitivity of these flows to differences in insurance premium. Results:

Determination of a lower bound on Earth's climate sensitivity

Directory of Open Access Journals (Sweden)

STEPHEN E. Schwartz

2013-09-01

Full Text Available Transient and equilibrium sensitivity of Earth's climate has been calculated using global temperature, forcing and heating rate data for the period 1970–2010. We have assumed increased long-wave radiative forcing in the period due to the increase of the long-lived greenhouse gases. By assuming the change in aerosol forcing in the period to be zero, we calculate what we consider to be lower bounds to these sensitivities, as the magnitude of the negative aerosol forcing is unlikely to have diminished in this period. The radiation imbalance necessary to calculate equilibrium sensitivity is estimated from the rate of ocean heat accumulation as 0.37±0.03 W m−2 (all uncertainty estimates are 1−σ. With these data, we obtain best estimates for transient climate sensitivity 0.39±0.07 K (W m−2−1 and equilibrium climate sensitivity 0.54±0.14 K (W m−2−1, equivalent to 1.5±0.3 and 2.0±0.5 K (3.7 W m−2−1, respectively. The latter quantity is equal to the lower bound of the ‘likely’ range for this quantity given by the 2007 IPCC Assessment Report. The uncertainty attached to the lower-bound equilibrium sensitivity permits us to state, within the assumptions of this analysis, that the equilibrium sensitivity is greater than 0.31 K (W m−2−1, equivalent to 1.16 K (3.7 W m−2−1, at the 95% confidence level.

Isolation of temperature-sensitive mutants of 16 S rRNA in Escherichia coli

DEFF Research Database (Denmark)

Triman, K; Becker, E; Dammel, C

1989-01-01

Temperature-sensitive mutants have been isolated following hydroxylamine mutagenesis of a plasmid containing Escherichia coli rRNA genes carrying selectable markers for spectinomycin resistance (U1192 in 16 S rRNA) and erythromycin resistance (G2058 in 23 S rRNA). These antibiotic resistance....... The mutations were localized by in vitro restriction fragment replacement followed by in vivo marker rescue and were identified by DNA sequence analysis. We report here seven single-base alterations in 16 S rRNA (A146, U153, A350, A359, A538, A1292 and U1293), five of which produce temperature......-sensitive spectinomycin resistance and two that produce unconditional loss of resistance. In each case, loss of ribosomal function can be accounted for by disruption of base-pairing in the secondary structure of 16 S rRNA. For the temperature-sensitive mutants, there is a lag period of about two generations between...

A Sensitive in Vitro High-Throughput Screen To Identify Pan-filoviral Replication Inhibitors Targeting the VP35–NP Interface

Energy Technology Data Exchange (ETDEWEB)

Liu, Gai; Nash, Peter J.; Johnson, Britney; Pietzsch, Colette; Ilagan, Ma. Xenia G.; Bukreyev, Alexander; Basler, Christopher F.; Bowlin, Terry L.; Moir, Donald T.; Leung, Daisy W.; Amarasinghe, Gaya K. (WU-MED); (GSU); (Texas-MED); (Microbiotix)

2017-01-24

The 2014 Ebola outbreak in West Africa, the largest outbreak on record, highlighted the need for novel approaches to therapeutics targeting Ebola virus (EBOV). Within the EBOV replication complex, the interaction between polymerase cofactor, viral protein 35 (VP35), and nucleoprotein (NP) is critical for viral RNA synthesis. We recently identified a peptide at the N-terminus of VP35 (termed NPBP) that is sufficient for interaction with NP and suppresses EBOV replication, suggesting that the NPBP binding pocket can serve as a potential drug target. Here we describe the development and validation of a sensitive high-throughput screen (HTS) using a fluorescence polarization assay. Initial hits from this HTS include the FDA-approved compound tolcapone, whose potency against EBOV infection was validated in a nonfluorescent secondary assay. High conservation of the NP–VP35 interface among filoviruses suggests that this assay has the capacity to identify pan-filoviral inhibitors for development as antivirals.

Uncertainty and sensitivity analyses of ballast life-cycle cost and payback period

OpenAIRE

Mcmahon, James E.

2000-01-01

The paper introduces an innovative methology for evaluating the relative significance of energy-efficient technologies applied to fluorescent lamp ballasts. The method involves replacing the point estimates of life cycle cost of the ballasts with uncertainty distributions reflecting the whole spectrum of possible costs, and the assessed probability associated with each value. The results of uncertainty and sensitivity analyses will help analysts reduce effort in data collection and carry on a...

Rainfall Variability and Landuse Conversion Impacts to Sensitivity of Citarum River Flow

Directory of Open Access Journals (Sweden)

Dyah Marganingrum

2013-07-01

Full Text Available The objective of this study is to determine the sensitivity of Citarum river flow to climate change and land conversion. It will provide the flow information that required in the water resources sustainability. Saguling reservoir is one of the strategic reservoirs, which 75% water is coming from the inflow of Upper Citarum measured at Nanjung station. Climate variability was identified as rainfall variability. Sensitivity was calculated as the elasticity value of discharge using three-variate model of statistical approach. The landuse conversion was calculated used GIS at 1994 and 2004. The results showed that elasticity at the Nanjung station and Saguling station decreased from 1.59 and 1.02 to 0.68 and 0.62 respectively. The decreasing occurred in the before the dam was built period (1950-1980 to the after reservoirs operated period (1986-2008. This value indicates that: 1 Citarum river flow is more sensitive to rainfall variability that recorded at Nanjung station than Saguling station, 2 rainfall character is more difficult to predict. The landuse analysis shows that forest area decrease to ± 27% and built up area increased to ± 26%. Those implied a minimum rainfall reduction to± 8% and minimum flow to ± 46%. Those were caused by land conversion and describing that the vegetation have function to maintain the base flow for sustainable water resource infrastructure.

Sensitivity of Claims-Based Algorithms to Ascertain Smoking Status More Than Doubled with Meaningful Use.

Science.gov (United States)

Huo, Jinhai; Yang, Ming; Tina Shih, Ya-Chen

2018-03-01

The "meaningful use of certified electronic health record" policy requires eligible professionals to record smoking status for more than 50% of all individuals aged 13 years or older in 2011 to 2012. To explore whether the coding to document smoking behavior has increased over time and to assess the accuracy of smoking-related diagnosis and procedure codes in identifying previous and current smokers. We conducted an observational study with 5,423,880 enrollees from the year 2009 to 2014 in the Truven Health Analytics database. Temporal trends of smoking coding, sensitivity, specificity, positive predictive value, and negative predictive value were measured. The rate of coding of smoking behavior improved significantly by the end of the study period. The proportion of patients in the claims data recorded as current smokers increased 2.3-fold and the proportion of patients recorded as previous smokers increased 4-fold during the 6-year period. The sensitivity of each International Classification of Diseases, Ninth Revision, Clinical Modification code was generally less than 10%. The diagnosis code of tobacco use disorder (305.1X) was the most sensitive code (9.3%) for identifying smokers. The specificities of these codes and the Current Procedural Terminology codes were all more than 98%. A large improvement in the coding of current and previous smoking behavior has occurred since the inception of the meaningful use policy. Nevertheless, the use of diagnosis and procedure codes to identify smoking behavior in administrative data is still unreliable. This suggests that quality improvements toward medical coding on smoking behavior are needed to enhance the capability of claims data for smoking-related outcomes research. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

A 2-wk reduction of ambulatory activity attenuates peripheral insulin sensitivity

DEFF Research Database (Denmark)

Krogh-Madsen, Rikke; Thyfault, John P; Broholm, Christa

2010-01-01

decreased after step reduction, with a post hoc analysis revealing the most pronounced effect after 4 h of insulin infusion. In addition, the 2-wk period induced a 7% decline in VO2 max (ml/min; cardiovascular fitness). Lean mass of legs, but not arms and trunk, decreased concurrently. Taken together, one...... possible biological cause for the public health problem of Type 2 diabetes has been identified. Reduced ambulatory activity for 2 wk in healthy, nonexercising young men significantly reduced peripheral insulin sensitivity, cardiovascular fitness, and lean leg mass........ A reduced number of daily steps induced a significant reduction of 17% in the glucose infusion rate (GIR) during the clamp. This reduction was due to a decline in peripheral insulin sensitivity with no effect on hepatic endogenous glucose production. The insulin-stimulated ratio of pAktthr308/total Akt...

A two-week reduction of ambulatory activity attenuates peripheral insulin sensitivity

DEFF Research Database (Denmark)

Krogh-Madsen, Rikke; Thyfault, John P; Broholm, Christa

2009-01-01

after step reduction, with a post hoc analysis revealing the most pronounced effect after 4 h of insulin infusion. In addition, the two-week period induced a 7% decline in VO2max (ml/min; cardiovascular fitness). Lean mass of legs, but not arms and truck, decreased concurrently. Taken together, one...... possible biological cause for the public health problem of type 2 diabetes has been identified. Reduced ambulatory activity for two weeks in healthy, non-exercising young men significantly reduced peripheral insulin sensitivity, cardiovascular fitness, and lean leg mass. Key words: Inactivity, Insulin...... number of daily steps induced a significant reduction of 17% in the glucose infusion rate (GIR) during the clamp. This reduction was due to a decline in peripheral insulin sensitivity with no effect on hepatic endogenous glucose production. The insulin-stimulated ratio of pAkt(thr308)/total Akt decreased...

Super periodic potential

Science.gov (United States)

Hasan, Mohammd; Mandal, Bhabani Prasad

2018-04-01

In this paper we introduce the concept of super periodic potential (SPP) of arbitrary order n, n ∈I+, in one dimension. General theory of wave propagation through SPP of order n is presented and the reflection and transmission coefficients are derived in their closed analytical form by transfer matrix formulation. We present scattering features of super periodic rectangular potential and super periodic delta potential as special cases of SPP. It is found that the symmetric self-similarity is the special case of super periodicity. Thus by identifying a symmetric fractal potential as special cases of SPP, one can obtain the tunnelling amplitude for a particle from such fractal potential. By using the formalism of SPP we obtain the close form expression of tunnelling amplitude of a particle for general Cantor and Smith-Volterra-Cantor potentials.

An improved test for periodicity

International Nuclear Information System (INIS)

Davies, S.R.

1990-01-01

I discuss two widely used methods of testing for periodicity, phase dispersion minimization and epoch-folding. Using an analysis of variance approach, I demonstrate the close relationship between these two methods. I also show that the significance test sometimes used in phase dispersion minimization is statistically inaccurate, and that the test used in epoch-folding is an approximation valid only for large sample sizes. I propose a new test statistic, applicable to either epoch-folding or PDM, which is statistically sound for all sample sizes, and which is also more sensitive to periodicity than the test statistics previously used with these two methods. (author)

Sediments and herbivory as sensitive indicators of coral reef degradation

Directory of Open Access Journals (Sweden)

Christopher H. R. Goatley

2016-03-01

Full Text Available Around the world, the decreasing health of coral reef ecosystems has highlighted the need to better understand the processes of reef degradation. The development of more sensitive tools, which complement traditional methods of monitoring coral reefs, may reveal earlier signs of degradation and provide an opportunity for pre-emptive responses. We identify new, sensitive metrics of ecosystem processes and benthic composition that allow us to quantify subtle, yet destabilizing, changes in the ecosystem state of an inshore coral reef on the Great Barrier Reef. Following severe climatic disturbances over the period 2011-2012, the herbivorous reef fish community of the reef did not change in terms of biomass or functional groups present. However, fish-based ecosystem processes showed marked changes, with grazing by herbivorous fishes declining by over 90%. On the benthos, algal turf lengths in the epilithic algal matrix increased more than 50% while benthic sediment loads increased 37-fold. The profound changes in processes, despite no visible change in ecosystem state, i.e., no shift to macroalgal dominance, suggest that although the reef has not undergone a visible regime-shift, the ecosystem is highly unstable, and may sit on an ecological knife-edge. Sensitive, process-based metrics of ecosystem state, such as grazing or browsing rates thus appear to be effective in detecting subtle signs of degradation and may be critical in identifying ecosystems at risk for the future.

Evaluation of an inpatient fall risk screening tool to identify the most critical fall risk factors in inpatients.

Science.gov (United States)

Hou, Wen-Hsuan; Kang, Chun-Mei; Ho, Mu-Hsing; Kuo, Jessie Ming-Chuan; Chen, Hsiao-Lien; Chang, Wen-Yin

2017-03-01

To evaluate the accuracy of the inpatient fall risk screening tool and to identify the most critical fall risk factors in inpatients. Variations exist in several screening tools applied in acute care hospitals for examining risk factors for falls and identifying high-risk inpatients. Secondary data analysis. A subset of inpatient data for the period from June 2011-June 2014 was extracted from the nursing information system and adverse event reporting system of an 818-bed teaching medical centre in Taipei. Data were analysed using descriptive statistics, receiver operating characteristic curve analysis and logistic regression analysis. During the study period, 205 fallers and 37,232 nonfallers were identified. The results revealed that the inpatient fall risk screening tool (cut-off point of ≥3) had a low sensitivity level (60%), satisfactory specificity (87%), a positive predictive value of 2·0% and a negative predictive value of 99%. The receiver operating characteristic curve analysis revealed an area under the curve of 0·805 (sensitivity, 71·8%; specificity, 78%). To increase the sensitivity values, the Youden index suggests at least 1·5 points to be the most suitable cut-off point for the inpatient fall risk screening tool. Multivariate logistic regression analysis revealed a considerably increased fall risk in patients with impaired balance and impaired elimination. The fall risk factor was also significantly associated with days of hospital stay and with admission to surgical wards. The findings can raise awareness about the two most critical risk factors for falls among future clinical nurses and other healthcare professionals and thus facilitate the development of fall prevention interventions. This study highlights the needs for redefining the cut-off points of the inpatient fall risk screening tool to effectively identify inpatients at a high risk of falls. Furthermore, inpatients with impaired balance and impaired elimination should be closely

Periods found in heat measurements obtained by calorimetry

International Nuclear Information System (INIS)

Jordan, K.C.

1984-01-01

During a span of 640 days, a periodicity of 1.5158 +- 0.0008 days was discovered in successive heater equilibria on Calorimeter No. 127. Measurements were taken at 12-h intervals, with occasional changes of exactly 3 or 6 h in the schedule of measurements. This schedule eliminated all other possible periods except a period of 0.150156 days. Periods of 1.519125 and 1.511283 days were discovered in data on the excess length of day as obtained by the US Naval Observatory over a period of 24 y. These two periods could equally well represent periods of 0.150189 and 0.150112 days, since measurements were obtained only once every 24 h. It is suggested that periods observed in sensitive calorimeters and in length of day data may be related. 1 reference, 6 figures, 5 tables

The period-luminosity relation for Cepheids

International Nuclear Information System (INIS)

Brodie, J.P.

1980-01-01

Numerical simulations of the empirical determination of the period-luminosity-colour relation for classical Cepheids are presented. In this study the quantitative effects of random errors, reddening, sample size and the presence of both colour and period cut-offs (imposed by the finite extent of the instability strip) on the observational redetermination of the original relation are evaluated. Both random errors in the photometry and correlated errors in the reddening corrections are shown to have systematic effects. Especially sensitive to these errors is the colour coefficient in the period-luminosity-colour relation, where the ratio of the error to the width of the instability strip is the determining factor. With present observations only broad confidence limits can be placed on present knowledge of the intrinsic period-luminosity-colour relation and/or its variations from galaxy to galaxy. (author)

Age-related sensitive periods influence visual language discrimination in adults.

Science.gov (United States)

Weikum, Whitney M; Vouloumanos, Athena; Navarra, Jordi; Soto-Faraco, Salvador; Sebastián-Gallés, Núria; Werker, Janet F

2013-01-01

Adults as well as infants have the capacity to discriminate languages based on visual speech alone. Here, we investigated whether adults' ability to discriminate languages based on visual speech cues is influenced by the age of language acquisition. Adult participants who had all learned English (as a first or second language) but did not speak French were shown faces of bilingual (French/English) speakers silently reciting sentences in either language. Using only visual speech information, adults who had learned English from birth or as a second language before the age of 6 could discriminate between French and English significantly better than chance. However, adults who had learned English as a second language after age 6 failed to discriminate these two languages, suggesting that early childhood exposure is crucial for using relevant visual speech information to separate languages visually. These findings raise the possibility that lowered sensitivity to non-native visual speech cues may contribute to the difficulties encountered when learning a new language in adulthood.

Relationship between RDX properties and sensitivity

Energy Technology Data Exchange (ETDEWEB)

Doherty, Ruth M. [Research, Development, Test and Evaluation Directorate, Naval Surface Warfare Center Indian Head Division, Indian Head, MD 20640-5102 (United States); Watt, Duncan S. [Novare, Level 6 80 Petrie Terrace, Brisbane 4000 (Australia)

2008-02-15

An interlaboratory comparison of seven lots of commercially available RDX was conducted to determine what properties of the nitramine particles can be used to assess whether the RDX has relatively high or relatively low sensitivity. The materials chosen for the study were selected to give a range of HMX content, manufacturing process and reported shock sensitivity. The results of two different shock sensitivity tests conducted on a PBX made with the RDX lots in the study showed that there are measurable differences in the shock sensitivity of the PBXs, but the impact sensitivity for all of the lots is essentially the same. Impact sensitivity is not a good predictor of shock sensitivity for these types of RDX. Although most RDX that exhibits RS has low HMX content, that characteristic alone is not sufficient to guarantee low sensitivity. A range of additional analytical chemistry tests were conducted on the material; two of these (HPLC and DSC) are discussed within. (Abstract Copyright [2008], Wiley Periodicals, Inc.)

Repeated touch and needle-prick stimulation in the neonatal period increases the baseline mechanical sensitivity and postinjury hypersensitivity of adult spinal sensory neurons.

Science.gov (United States)

van den Hoogen, Nynke J; Patijn, Jacob; Tibboel, Dick; Joosten, Bert A; Fitzgerald, Maria; Kwok, Charlie H T

2018-03-08

Noxious stimulation at critical stages of development has long-term consequences on somatosensory processing in later life, but it is not known whether this developmental plasticity is restricted to nociceptive pathways. Here, we investigate the effect of repeated neonatal noxious or innocuous hind paw stimulation on adult spinal dorsal horn cutaneous mechanical sensitivity. Neonatal Sprague-Dawley rats of both sexes received 4 unilateral left hind paw needle pricks (NPs, n = 13) or 4 tactile (cotton swab touch) stimuli, per day (TC, n = 11) for the first 7 days of life. Control pups were left undisturbed (n = 17). When adult (6-8 weeks), lumbar wide-dynamic-range neuron activity in laminae III-V was recorded using in vivo extracellular single-unit electrophysiology. Spike activity evoked by cutaneous dynamic tactile (brush), pinch and punctate (von Frey hair) stimulation, and plantar receptive field areas were recorded, at baseline and 2 and 5 days after left plantar hind paw incision. Baseline brush receptive fields, von Frey hair, and pinch sensitivity were significantly enhanced in adult NP and TC animals compared with undisturbed controls, although effects were greatest in NP rats. After incision, injury sensitivity of adult wide-dynamic-range neurons to both noxious and dynamic tactile hypersensitivity was significantly greater in NP animals compared with TC and undisturbed controls. We conclude that both repeated touch and needle-prick stimulation in the neonatal period can alter adult spinal sensory neuron sensitivity to both innocuous and noxious mechanical stimulation. Thus, spinal sensory circuits underlying touch and pain processing are shaped by a range of early-life somatosensory experiences.This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Sensitivity of the Arctic Ocean gas hydrate to climate changes in the period of 1948-2015

Science.gov (United States)

Malakhova, Valentina V.; Golubeva, Elena N.; Iakshina, Dina F.

2017-11-01

The objective of the present study is to analyze the interactions between a methane hydrates stability zone and the ocean temperature variations and to define the hydrate sensitivity to the contemporary warming in the Arctic Ocean. To obtain the spatial-temporary variability of the ocean bottom temperature we employ the ICMMG regional Arctic-North Atlantic ocean model that has been developed in the Institute of Computational Mathematics and Mathematical Geophysics. With the ice-ocean model the Arctic bottom water temperatures were analyzed. The resulting warming ocean bottom water is spatially inhomogeneous, with a strong impact by the Atlantic inflow on shallow regions of 200-500 m depth. Results of the mathematical modeling of the dynamics of methane hydrate stability zone in the Arctic Ocean sediment are reported. We find that the reduction of the methane hydrate stability zone occurs in the Arctic Ocean between 250 and 400 m water depths within the upper 100 m of sediment in the area influenced by the Atlantic inflow. We have identified the areas of the Arctic Ocean where an increase in methane release is probable to occur at the present time.

Validation of search filters for identifying pediatric studies in PubMed.

Science.gov (United States)

Leclercq, Edith; Leeflang, Mariska M G; van Dalen, Elvira C; Kremer, Leontien C M

2013-03-01

To identify and validate PubMed search filters for retrieving studies including children and to develop a new pediatric search filter for PubMed. We developed 2 different datasets of studies to evaluate the performance of the identified pediatric search filters, expressed in terms of sensitivity, precision, specificity, accuracy, and number needed to read (NNR). An optimal search filter will have a high sensitivity and high precision with a low NNR. In addition to the PubMed Limits: All Child: 0-18 years filter (in May 2012 renamed to PubMed Filter Child: 0-18 years), 6 search filters for identifying studies including children were identified: 3 developed by Kastner et al, 1 developed by BestBets, one by the Child Health Field, and 1 by the Cochrane Childhood Cancer Group. Three search filters (Cochrane Childhood Cancer Group, Child Health Field, and BestBets) had the highest sensitivity (99.3%, 99.5%, and 99.3%, respectively) but a lower precision (64.5%, 68.4%, and 66.6% respectively) compared with the other search filters. Two Kastner search filters had a high precision (93.0% and 93.7%, respectively) but a low sensitivity (58.5% and 44.8%, respectively). They failed to identify many pediatric studies in our datasets. The search terms responsible for false-positive results in the reference dataset were determined. With these data, we developed a new search filter for identifying studies with children in PubMed with an optimal sensitivity (99.5%) and precision (69.0%). Search filters to identify studies including children either have a low sensitivity or a low precision with a high NNR. A new pediatric search filter with a high sensitivity and a low NNR has been developed. Copyright © 2013 Mosby, Inc. All rights reserved.

Three dimensional periodic foundations for base seismic isolation

International Nuclear Information System (INIS)

Yan, Y; Mo, Y L; Cheng, Z; Shi, Z; Menq, F; Tang, Y

2015-01-01

Based on the concept of phononic crystals, periodic foundations made of periodic materials are investigated in this paper. The periodic foundations can provide low frequency band gaps, which cover the main frequency ranges of seismic waves. Therefore, the periodic foundations are able to protect the upper structures during earthquake events. In this paper, the basic theory of three dimensional periodic foundations is studied and the finite element method was used to conduct the sensitivity study. A simplified three-dimensional periodic foundation with a superstructure was tested in the field and the feasibility of three dimensional periodic foundations was proved. The test results showed that the response of the upper structure with the three dimensional periodic foundation was reduced under excitation waves with the main frequency falling in the attenuation zones. The finite element analysis results are consistent with the experimental data, indicating that three dimensional periodic foundations are a feasible way of reducing seismic vibrations. (paper)

Maternal stress and infant mortality: The importance of the preconception period

Science.gov (United States)

Class, Quetzal A.; Khashan, Ali S.; Lichtenstein, Paul; Långström, Niklas; D’Onofrio, Brian M.

2013-01-01

Although preconception and prenatal maternal stress are associated with adverse birth and childhood outcomes, the relation to infant mortality remains uncertain. We used logistic regression to study infant mortality risk following maternal stress within a population-based sample of offspring born in Sweden from 1973 to 2008 (N= 3,055,361). Preconception (6-0 months before conception) and prenatal (conception to birth) stress was defined as death of a first-degree relative of the mother. A total of 20,651 offspring were exposed to preconception stress, 26,731 to prenatal stress, and 8,398 cases of infant mortality were identified. Preconception stress increased the risk of infant mortality independent of measured covariates (adjusted OR=1.53; 95% CI=1.25–1.88) and the association was timing-specific and robust across low-risk groups. Prenatal stress did not increase risk of infant mortality (adjusted OR=1.05; 95% CI=0.84–1.30). The period immediately before conception may be a sensitive developmental period influencing risk for infant mortality. PMID:23653129

Gene expression analysis identifies global gene dosage sensitivity in cancer

DEFF Research Database (Denmark)

Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata

2015-01-01

Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gen...

Occupation, exposure to chemicals, sensitizing agents, and risk of multiple myeloma in Sweden.

Science.gov (United States)

Lope, Virginia; Pérez-Gómez, Beatriz; Aragonés, Nuria; López-Abente, Gonzalo; Gustavsson, Per; Plato, Nils; Zock, Jan-Paul; Pollán, Marina

2008-11-01

This study sought to identify occupations with high incidence of multiple myeloma and to investigate possible excess risk associated with occupational exposure to chemicals and sensitizing agents in Sweden. A historical cohort of 2,992,166 workers was followed up (1971--1989) through record linkage with the National Cancer and Death Registries. For each job category, age and period standardized incidence ratios and age and period adjusted relative risks of multiple myeloma were calculated using Poisson models. Exposure to chemicals and to sensitizing agents was also assessed using two job-exposure matrices. Men and women were analyzed separately. During follow-up, 3,127 and 1,282 myelomas were diagnosed in men and women, respectively. In men, excess risk was detected among working proprietors, agricultural, horticultural and forestry enterprisers, bakers and pastry cooks, dental technicians, stone cutters/carvers, and prison/reformatory officials. In women, this excess was observed among attendants in psychiatric care, metal workers, bakers and pastry cooks, and paper/paperboard product workers. Workers, particularly bakers and pastry cooks, exposed to high molecular weight sensitizing agents registered an excess risk of over 40% across the sexes. Occasional, although intense, exposure to pesticides was also associated with risk of myeloma in our cohort. Our study supports a possible etiologic role for farming and use of pesticides in myeloma risk. The high incidence found in both female and male bakers and pastry cooks has not been described previously. Further research is required to assess the influence of high molecular weight sensitizing agents on risk of multiple myeloma.

A pilot trial of cognitive behavioural therapy for interpersonal sensitivity in individuals with persecutory delusions.

Science.gov (United States)

Bell, Victoria; Freeman, Daniel

2014-12-01

Advances in understanding delusions may be used to improve clinical interventions. Interpersonal sensitivity - feeling vulnerable in the presence of others due to the expectation of criticism or rejection - has been identified as a potential causal factor in the occurrence of persecutory delusions. The purpose of this study was to examine the potential impact on persecutory delusions of a (newly devised) cognitive behavioural intervention targeting interpersonal sensitivity (CBT-IPS). CBT-IPS was tested in an uncontrolled pilot study with eleven patients with persistent persecutory delusions in the context of a psychotic disorder. Patients had two baseline assessments over a fortnight period to establish the stability of the delusions, which was followed by six sessions of CBT-IPS, a post-therapy assessment, and a further follow-up assessment one month later. Interpersonal sensitivity and the persecutory delusions were stable during the baseline period. At the post-therapy assessment there were significant reductions of large effect size for both interpersonal sensitivity and the persecutory delusions. These gains were maintained at follow-up. The main limitation is that in this initial test there was no control group. The intervention may not have caused the reduction in delusions. Further, bias may have been introduced by the outcome data being collected by the therapist. The findings from this evaluation are consistent with the hypothesised causal role for interpersonal sensitivity in the occurrence of persecutory delusions. CBT-IPS shows promise as a therapeutic intervention but requires a rigorous test of its efficacy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Changes in the pattern of sensitization to common contact allergens in denmark between 1985-86 and 1997-98, with a special view to the effect of preventive strategies

DEFF Research Database (Denmark)

Johansen, J d; Menné, T; Christophersen, J

2000-01-01

sensitization during that period, and particular areas of concern are identified. Members of the Danish Contact Dermatitis Group collected patch-test results from consecutive eczema patients as well as information about exposures and demographic variables over a 6-month period in 1985-86. The investigation......The objective of the present study is to describe any changes in the prevalence of sensitization to common contact allergens in patch-tested patients over a 12-year period. Attention is given to possible effects of preventive strategies introduced in Denmark regarding nickel and chromate...... was repeated in 1997-98 in the same clinics, at the same time of year, using identical methods and patch-test substances, including nickel sulphate 5%, potassium dichromate 0.5% and fragrance mix 8%. Nickel was the most common contact allergen in both study periods, followed by the fragrance mix. In children 0...

An ancestral haplotype of the human PERIOD2 gene associates with reduced sensitivity to light-induced melatonin suppression.

Directory of Open Access Journals (Sweden)

Tokiho Akiyama

Full Text Available Humans show various responses to the environmental stimulus in individual levels as "physiological variations." However, it has been unclear if these are caused by genetic variations. In this study, we examined the association between the physiological variation of response to light-stimulus and genetic polymorphisms. We collected physiological data from 43 subjects, including light-induced melatonin suppression, and performed haplotype analyses on the clock genes, PER2 and PER3, exhibiting geographical differentiation of allele frequencies. Among the haplotypes of PER3, no significant difference in light sensitivity was found. However, three common haplotypes of PER2 accounted for more than 96% of the chromosomes in subjects, and 1 of those 3 had a significantly low-sensitive response to light-stimulus (P < 0.05. The homozygote of the low-sensitive PER2 haplotype showed significantly lower percentages of melatonin suppression (P < 0.05, and the heterozygotes of the haplotypes varied their ratios, indicating that the physiological variation for light-sensitivity is evidently related to the PER2 polymorphism. Compared with global haplotype frequencies, the haplotype with a low-sensitive response was more frequent in Africans than in non-Africans, and came to the root in the phylogenetic tree, suggesting that the low light-sensitive haplotype is the ancestral type, whereas the other haplotypes with high sensitivity to light are the derived types. Hence, we speculate that the high light-sensitive haplotypes have spread throughout the world after the Out-of-Africa migration of modern humans.

Antenatal interpersonal sensitivity is more strongly associated than perinatal depressive symptoms with postnatal mother-infant interaction quality.

Science.gov (United States)

Raine, Karen; Cockshaw, Wendell; Boyce, Philip; Thorpe, Karen

2016-10-01

Maternal mental health has enduring effects on children's life chances and is a substantial cost driver for child health, education and social services. A key linking mechanism is the quality of mother-infant interaction. A body of work associates maternal depressive symptoms across the antenatal and postnatal (perinatal) period with less-than-optimal mother-infant interaction. Our study aims to build on previous research in the field through exploring the association of a maternal personality trait, interpersonal sensitivity, measured in early pregnancy, with subsequent mother-infant interaction quality. We analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine the association between antenatal interpersonal sensitivity and postnatal mother-infant interaction quality in the context of perinatal depressive symptoms. Interpersonal sensitivity was measured during early pregnancy and depressive symptoms in the antenatal year and across the first 21 months of the postnatal period. In a subsample of the ALSPAC, mother-infant interaction was measured at 12 months postnatal through a standard observation. For the subsample that had complete data at all time points (n = 706), hierarchical regression examined the contribution of interpersonal sensitivity to variance in mother-infant interaction quality. Perinatal depressive symptoms predicted little variance in mother-infant interaction. Antenatal interpersonal sensitivity explained a greater proportion of variance in mother-infant interaction quality. The personality trait, interpersonal sensitivity, measured in early pregnancy, is a more robust indicator of subsequent mother-infant-interaction quality than perinatal depressive symptoms, thus affording enhanced opportunity to identify vulnerable mother-infant relationships for targeted early intervention.

Respiratory sensitization and allergy: Current research approaches and needs

International Nuclear Information System (INIS)

Boverhof, Darrell R.; Billington, Richard; Gollapudi, B. Bhaskar; Hotchkiss, John A.; Krieger, Shannon M.; Poole, Alan; Wiescinski, Connie M.; Woolhiser, Michael R.

2008-01-01

There are currently no accepted regulatory models for assessing the potential of a substance to cause respiratory sensitization and allergy. In contrast, a number of models exist for the assessment of contact sensitization and allergic contact dermatitis (ACD). Research indicates that respiratory sensitizers may be identified through contact sensitization assays such as the local lymph node assay, although only a small subset of the compounds that yield positive results in these assays are actually respiratory sensitizers. Due to the increasing health concerns associated with occupational asthma and the impending directives on the regulation of respiratory sensitizers and allergens, an approach which can identify these compounds and distinguish them from contact sensitizers is required. This report discusses some of the important contrasts between respiratory allergy and ACD, and highlights several prominent in vivo, in vitro and in silico approaches that are being applied or could be further developed to identify compounds capable of causing respiratory allergy. Although a number of animal models have been used for researching respiratory sensitization and allergy, protocols and endpoints for these approaches are often inconsistent, costly and difficult to reproduce, thereby limiting meaningful comparisons of data between laboratories and development of a consensus approach. A number of emerging in vitro and in silico models show promise for use in the characterization of contact sensitization potential and should be further explored for their ability to identify and differentiate contact and respiratory sensitizers. Ultimately, the development of a consistent, accurate and cost-effective model will likely incorporate a number of these approaches and will require effective communication, collaboration and consensus among all stakeholders

Uncertainty and sensitivity analyses of ballast life-cycle cost and payback period

Energy Technology Data Exchange (ETDEWEB)

McMahon, James E.; Liu, Xiaomin; Turiel, Ike; Hakim, Sajid; Fisher, Diane

2000-06-01

The paper introduces an innovative methodology for evaluating the relative significance of energy-efficient technologies applied to fluorescent lamp ballasts. The method involves replacing the point estimates of life cycle cost of the ballasts with uncertainty distributions reflecting the whole spectrum of possible costs, and the assessed probability associated with each value. The results of uncertainty and sensitivity analyses will help analysts reduce effort in data collection and carry on analysis more efficiently. These methods also enable policy makers to gain an insightful understanding of which efficient technology alternatives benefit or cost what fraction of consumers, given the explicit assumptions of the analysis.

Long-Period Variability in o Ceti

Science.gov (United States)

Templeton, Matthew R.; Karovska, Margarita

2009-02-01

We carried out a new and sensitive search for long-period variability in the prototype of the Mira class of long-period pulsating variables, o Ceti (Mira A), the closest and brightest Mira variable. We conducted this search using an unbroken light curve from 1902 to the present, assembled from the visual data archives of five major variable star observing organizations from around the world. We applied several time-series analysis techniques to search for two specific kinds of variability: long secondary periods (LSPs) longer than the dominant pulsation period of ~333 days, and long-term period variation in the dominant pulsation period itself. The data quality is sufficient to detect coherent periodic variations with photometric amplitudes of 0.05 mag or less. We do not find evidence for coherent LSPs in o Ceti to a limit of 0.1 mag, where the amplitude limit is set by intrinsic, stochastic, low-frequency variability of approximately 0.1 mag. We marginally detect a slight modulation of the pulsation period similar in timescale to that observed in the Miras with meandering periods, but with a much lower period amplitude of ±2 days. However, we do find clear evidence of a low-frequency power-law component in the Fourier spectrum of o Ceti's long-term light curve. The amplitude of this stochastic variability is approximately 0.1 mag at a period of 1000 days, and it exhibits a turnover for periods longer than this. This spectrum is similar to the red noise spectra observed in red supergiants.

Identifying Moderators of the Link Between Parent and Child Anxiety Sensitivity: The Roles of Gender, Positive Parenting, and Corporal Punishment.

Science.gov (United States)

Graham, Rebecca A; Weems, Carl F

2015-07-01

A substantial body of literature suggests that anxiety sensitivity is a risk factor for the development of anxiety problems and research has now begun to examine the links between parenting, parent anxiety sensitivity and their child's anxiety sensitivity. However, the extant literature has provided mixed findings as to whether parent anxiety sensitivity is associated with child anxiety sensitivity, with some evidence suggesting that other factors may influence the association. Theoretically, specific parenting behaviors may be important to the development of child anxiety sensitivity and also in understanding the association between parent and child anxiety sensitivity. In this study, 191 families (n = 255 children and adolescents aged 6-17 and their parents) completed measures of child anxiety sensitivity (CASI) and parenting (APQ-C), and parents completed measures of their own anxiety sensitivity (ASI) and their parenting (APQ-P). Corporal punishment was associated with child anxiety sensitivity and the child's report of their parent's positive parenting behaviors moderated the association between parent and child anxiety sensitivity. The child's gender was also found to moderate the association between parent and child anxiety sensitivity, such that there was a positive association between girls' and their parents anxiety sensitivity and a negative association in boys. The findings advance the understanding of child anxiety sensitivity by establishing a link with corporal punishment and by showing that the association between parent and child anxiety sensitivity may depend upon the parenting context and child's gender.

A case of contact dermatitis to dimethylfumarate in shoes identified in Italy

Directory of Open Access Journals (Sweden)

Franca Davanzo

2010-12-01

Full Text Available The present paper describes a case of shoe contact dermatitis from DMF identified by the Poison Control Centre of Milan (PCCM, Italy, in 2009. A 35 year old woman was affected by irritant reactions while wearing shoes contaminated with DMF. Exposure to these shoes was limited to a 8 hour period and was not repeated. In the following days the patient suffered feet blistering and swelling limited to the area in contact with shoe vamp. Topical application of cortisone did not prevent development of bullous eczema. After 20 days from exposure, the lesions were healed but the skin remained red, dry and very sensitive. Chemical analyses of shoes quantified an average concentration of DMF of 383 mg/kg. The patient refused to be patch tested. The observation here reported confirm that DMF should be considered a possible causal agent in shoe contact dermatitis. Documentation of cases exposed to this chemical provide a relevant support to characterize clinical manifestations and to identifying contaminated articles.

Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

Energy Technology Data Exchange (ETDEWEB)

Skiöld, Sara [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Azimzadeh, Omid [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Merl-Pham, Juliane [Research Unit Protein Science, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg (Germany); Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet [Division of Radiotherapy, Radiumhemmet, Karolinska University Hospital, Stockholm (Sweden); Tapio, Soile [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Harms-Ringdahl, Mats [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Haghdoost, Siamak, E-mail: Siamak.Haghdoost@su.se [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden)

2015-06-15

Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy.

Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

International Nuclear Information System (INIS)

Skiöld, Sara; Azimzadeh, Omid; Merl-Pham, Juliane; Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet; Tapio, Soile; Harms-Ringdahl, Mats; Haghdoost, Siamak

2015-01-01

Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy

Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides

Science.gov (United States)

Birsoy, Kıvanç; Possemato, Richard; Lorbeer, Franziska K.; Bayraktar, Erol C.; Thiru, Prathapan; Yucel, Burcu; Wang, Tim; Chen, Walter W.; Clish, Clary B.; Sabatini, David M.

2014-04-01

As the concentrations of highly consumed nutrients, particularly glucose, are generally lower in tumours than in normal tissues, cancer cells must adapt their metabolism to the tumour microenvironment. A better understanding of these adaptations might reveal cancer cell liabilities that can be exploited for therapeutic benefit. Here we developed a continuous-flow culture apparatus (Nutrostat) for maintaining proliferating cells in low-nutrient media for long periods of time, and used it to undertake competitive proliferation assays on a pooled collection of barcoded cancer cell lines cultured in low-glucose conditions. Sensitivity to low glucose varies amongst cell lines, and an RNA interference (RNAi) screen pinpointed mitochondrial oxidative phosphorylation (OXPHOS) as the major pathway required for optimal proliferation in low glucose. We found that cell lines most sensitive to low glucose are defective in the OXPHOS upregulation that is normally caused by glucose limitation as a result of either mitochondrial DNA (mtDNA) mutations in complex I genes or impaired glucose utilization. These defects predict sensitivity to biguanides, antidiabetic drugs that inhibit OXPHOS, when cancer cells are grown in low glucose or as tumour xenografts. Notably, the biguanide sensitivity of cancer cells with mtDNA mutations was reversed by ectopic expression of yeast NDI1, a ubiquinone oxidoreductase that allows bypass of complex I function. Thus, we conclude that mtDNA mutations and impaired glucose utilization are potential biomarkers for identifying tumours with increased sensitivity to OXPHOS inhibitors.

Environmental sensitivity of the coastal islands of Ubatuba, SP, Brazil

Directory of Open Access Journals (Sweden)

Getulio Teixeira Batista

2008-08-01

Full Text Available The Environmental Sensitivity Index Maps for Oil Spills (ESI Maps, or SAO in Portuguese constitute an essential component and source of basic information for emergency planning, response decision support and damage evaluation in case of oil spills. This study aims at the elaboration of sensitivity maps for oil spills for the islands within the Ubatuba municipality, north coast of the State of São Paulo. The adopted methodology is based on the Technical Specifications for the production of Environmental Sensitivity Maps for oil spills (SAO maps proposed by the Brazilian Ministry of Environment. The study involved the gathering of secondary data, followed by field work carried out in the summer and winter periods of 2007; the elaboration of the cartographic base maps and, finally, the integration of the data to a GIS (Geographic Information System. As a result it was registered and mapped the physical (geology, geomorphology, oceanography and climatology, biological (fauna, flora and coastal environments and socioeconomic (anthropic influence, human use, artificial structures and impacts resources of Ubatuba coastal islands. Eleven beaches have been identified, located at six islands, with distinct topographic and geomorphologic features. The beaches were classified with sensitivity index 4, because they are sheltered from actions of waves and currents. Most of the mapped environments (44.8% were classified with sensitivity index 8, indicating high sensitivity of the islands. The oil spill impacts on coastal environments can be significantly minimized during the contingency actions when previous knowledge of the ecosystems that compose the islands environment is available, especially when it is integrated into GIS data basis, capable of displaying easy-to-use maps. The environmental sensitivity mapping is an important management instrument, especially when dealing with sensible and poorly studied areas such as the islands of Ubatuba.

Global sensitivity analysis for identifying important parameters of nitrogen nitrification and denitrification under model uncertainty and scenario uncertainty

Science.gov (United States)

Chen, Zhuowei; Shi, Liangsheng; Ye, Ming; Zhu, Yan; Yang, Jinzhong

2018-06-01

Nitrogen reactive transport modeling is subject to uncertainty in model parameters, structures, and scenarios. By using a new variance-based global sensitivity analysis method, this paper identifies important parameters for nitrogen reactive transport with simultaneous consideration of these three uncertainties. A combination of three scenarios of soil temperature and two scenarios of soil moisture creates a total of six scenarios. Four alternative models describing the effect of soil temperature and moisture content are used to evaluate the reduction functions used for calculating actual reaction rates. The results show that for nitrogen reactive transport problem, parameter importance varies substantially among different models and scenarios. Denitrification and nitrification process is sensitive to soil moisture content status rather than to the moisture function parameter. Nitrification process becomes more important at low moisture content and low temperature. However, the changing importance of nitrification activity with respect to temperature change highly relies on the selected model. Model-averaging is suggested to assess the nitrification (or denitrification) contribution by reducing the possible model error. Despite the introduction of biochemical heterogeneity or not, fairly consistent parameter importance rank is obtained in this study: optimal denitrification rate (Kden) is the most important parameter; reference temperature (Tr) is more important than temperature coefficient (Q10); empirical constant in moisture response function (m) is the least important one. Vertical distribution of soil moisture but not temperature plays predominant role controlling nitrogen reaction. This study provides insight into the nitrogen reactive transport modeling and demonstrates an effective strategy of selecting the important parameters when future temperature and soil moisture carry uncertainties or when modelers face with multiple ways of establishing nitrogen

Lexical Organization in Second Language Acquisition: Does the Critical Period Matter?

Science.gov (United States)

Cardimona, Kimberly; Smith, Pamela; Roberts, Lauren Sones

2016-01-01

This study examined lexical organization in English language learners (ELLs) who acquired their second language (L2) either during or after the period of maximal sensitivity related to the critical period hypothesis. Twenty-three native-Spanish-speaking ELLs completed psycholinguistic tasks to examine age effects in bilingual lexical organization.…

Consequences of implementing a cardiac troponin assay with improved sensitivity at Swedish coronary care units: an analysis from the SWEDEHEART registry.

Science.gov (United States)

Eggers, Kai M; Lindahl, Bertil; Melki, Dina; Jernberg, Tomas

2016-08-07

Cardiac troponin (cTn) assays with improved sensitivity are increasingly utilized for the assessment of patients admitted because of suspected acute coronary syndrome (ACS). However, data on the clinical consequences of the implementation of such assays are limited. In a retrospective register-based study (37 710 coronary care unit admissions; SWEDEHEART registry), we compared the case mix, the use of diagnostic procedures, treatments, and 1-year all-cause mortality 1 year before the implementation of a cTn assay with improved sensitivity (study period 1) and 1 year thereafter (study period 2). During study period 2, more at-risk patients were admitted and more patients had cTn levels above the myocardial infarction cut-off (ACS patients +13.1%; non-ACS patients +160.1%). cTn levels above this cut-off exhibited stronger associations with mortality risk in study period 2 (adjusted HR 4.45 [95% confidence interval, CI, 3.36-5.89]) compared with period 1 (adjusted HR 2.43 [95% CI 2.11-2.80]), similar as for the cTn ratio relative to the respective 99th percentile. While there was no multivariable-adjusted increase in the use of diagnostic procedures, significant trends towards more differentiated treatment depending on the cause of cTn elevation, i.e. ACS or non-ACS, were noted. The implementation of a cTn assay with improved sensitivity was associated with an increase in the number of patients who due to their cTn-status were identified as suitable for beneficial therapies. There was no inappropriate increase in hospital resource utilization. As such, cTn assays with improved sensitivity provide an opportunity to improve the clinical management of patients with suspected ACS. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Hereditary periodic fever syndromes

NARCIS (Netherlands)

McDermott, MF; Frenkel, J

Hereditary periodic fever syndromes are defined by recurrent attacks of generalised inflammation for which no infectious or auto-immune cause can be identified. For most of these disorders, the molecular basis has recently been elucidated. This has opened the prospect of novel therapeutic

Incidence of human brucellosis in the Kilimanjaro Region of Tanzania in the periods 2007–2008 and 2012–2014

Science.gov (United States)

Carugati, Manuela; Biggs, Holly M; Maze, Michael J; Stoddard, Robyn A; Cash-Goldwasser, Shama; Hertz, Julian T; Halliday, Jo E B; Saganda, Wilbrod; Lwezaula, Bingileki F; Kazwala, Rudovick R; Cleaveland, Sarah; Maro, Venance P; Rubach, Matthew P; Crump, John A

2018-01-01

Abstract Background Brucellosis causes substantial morbidity among humans and their livestock. There are few robust estimates of the incidence of brucellosis in sub-Saharan Africa. Using cases identified through sentinel hospital surveillance and health care utilization data, we estimated the incidence of brucellosis in Moshi Urban and Moshi Rural Districts, Kilimanjaro Region, Tanzania, for the periods 2007–2008 and 2012–2014. Methods Cases were identified among febrile patients at two sentinel hospitals and were defined as having either a 4-fold increase in Brucella microscopic agglutination test titres between acute and convalescent serum or a blood culture positive for Brucella spp. Findings from a health care utilization survey were used to estimate multipliers to account for cases not seen at sentinel hospitals. Results Of 585 patients enrolled in the period 2007–2008, 13 (2.2%) had brucellosis. Among 1095 patients enrolled in the period 2012–2014, 32 (2.9%) had brucellosis. We estimated an incidence (range based on sensitivity analysis) of brucellosis of 35 (range 32–93) cases per 100 000 persons annually in the period 2007–2008 and 33 (range 30–89) cases per 100 000 persons annually in the period 2012–2014. Conclusions We found a moderate incidence of brucellosis in northern Tanzania, suggesting that the disease is endemic and an important human health problem in this area. PMID:29697848

Utilization of critical periods during development to study the effects of low levels of environmental agents

International Nuclear Information System (INIS)

Russell, L.B.

1981-01-01

This chapter shows how careful definition of critical periods in the development of selected characters can result in experimental systems that may be highly useful in studying risk at low levels of exposure. Presents 3 systems that utilize critical periods to study low-level effects: 1) cell kinetics as an indicator of nervous-system maldevelopment; 2) oocyte depletion; and 3) homeotic shifts in the skeleton. Discusses application of the sensitive systems to the testing of chemicals and the role of sensitive stages in estimating risk. Suggests that tests such as the 3 discussed in this paper, which are developed with strict attention to specific critical periods, can provide rapid and sensitive means for revealing whether an agent is capable of causing developmental interference. Concludes that epidemiological investigations can lose much of their value unless critical periods are known for the endpoints being studied

Minimum period and the gap in periods of Cataclysmic binaries

International Nuclear Information System (INIS)

Paczynski, B.; Sienkiewicz, R.

1983-01-01

The 81 minute cutoff to the orbital periods of hydrogen-rich cataclysmic binaries is consistent with evolution of those systems being dominated by angular momentum losses due to gravitational radiation. Unfortunately, many uncertainties, mainly poorly known atmospheric opacities below 2000 K, make is physically impossible to verify the quadrupole formula for gravitational radiation by using the observed cutoff at 81 minutes. The upper boundary of the gap in orbital periods observed at about 3 hours is almost certainly due to enhanced angular momentum losses from cataclysmic binaries which have longer periods. The physical mechanism of those losses is not identified, but a possible importance of stellar winds is pointed out. The lower boundary of the gap may be explained with the oldest cataclysmic binaries, whose periods evolved past the minimum at 81 minutes and reached the value of 2 hours within about 12 x 10 9 years after the binary had formed. Those binaries should have secondary components of only 0.02 solar masses, and their periods could be used to estimate ages of the oldest cataclysmic stars, and presumably the age of Galaxy. An alternative explanation for the gap requires that binaries should be detached while crossing the gap. A possible mechanism for this phenomenon is discussed. It requires the secondary components to be about 0.2 solar masses in the binaries just below the gap

Temporal diagnostic analysis of the SWAT model to detect dominant periods of poor model performance

Science.gov (United States)

Guse, Björn; Reusser, Dominik E.; Fohrer, Nicola

2013-04-01

Hydrological models generally include thresholds and non-linearities, such as snow-rain-temperature thresholds, non-linear reservoirs, infiltration thresholds and the like. When relating observed variables to modelling results, formal methods often calculate performance metrics over long periods, reporting model performance with only few numbers. Such approaches are not well suited to compare dominating processes between reality and model and to better understand when thresholds and non-linearities are driving model results. We present a combination of two temporally resolved model diagnostic tools to answer when a model is performing (not so) well and what the dominant processes are during these periods. We look at the temporal dynamics of parameter sensitivities and model performance to answer this question. For this, the eco-hydrological SWAT model is applied in the Treene lowland catchment in Northern Germany. As a first step, temporal dynamics of parameter sensitivities are analyzed using the Fourier Amplitude Sensitivity test (FAST). The sensitivities of the eight model parameters investigated show strong temporal variations. High sensitivities were detected for two groundwater (GW_DELAY, ALPHA_BF) and one evaporation parameters (ESCO) most of the time. The periods of high parameter sensitivity can be related to different phases of the hydrograph with dominances of the groundwater parameters in the recession phases and of ESCO in baseflow and resaturation periods. Surface runoff parameters show high parameter sensitivities in phases of a precipitation event in combination with high soil water contents. The dominant parameters give indication for the controlling processes during a given period for the hydrological catchment. The second step included the temporal analysis of model performance. For each time step, model performance was characterized with a "finger print" consisting of a large set of performance measures. These finger prints were clustered into

Dynamical mechanisms for sensitive response of aperiodic firing cells to external stimulation

International Nuclear Information System (INIS)

Xie Yong; Xu Jianxue; Hu Sanjue; Kang Yanmei; Yang Hongjun; Duan Yubin

2004-01-01

An interesting phenomenon that aperiodic firing neurons have a higher sensitivity to drugs than periodic firing neurons have been reported for the chronically compressed dorsal root ganglion neurons in rats. In this study, the dynamical mechanisms for such a phenomenon are uncovered from the viewpoint of dynamical systems theory. We use the Rose-Hindmarsh neuron model to illustrate our opinions. Periodic orbit theory is introduced to characterize the dynamical behavior of aperiodic firing neurons. It is considered that bifurcations, crises and sensitive dependence of chaotic motions on control parameters can be the underlying mechanisms. And then, a similar analysis is applied to the modified Chay model describing the firing behavior of pancreatic beta cells. The same dynamical mechanisms can be obtained underlying that aperiodic firing cells are more sensitive to external stimulation than periodic firing ones. As a result, we conjecture that sensitive response of aperiodic firing cells to external stimulation is a universal property of excitable cells

Sensing Characteristics of Side-Hole Fiber-Based Long-Period Grating

Directory of Open Access Journals (Sweden)

Yi Xin

2013-01-01

Full Text Available Long-period gratings (LPGs have been fabricated in a side-hole fiber (SHF by using a pulsed CO2 laser. Sensing characteristics of this SHF-LPG to temperature surrounding refractive index and bend have been investigated. Experimental results show that resonant wavelength of the SHF-LPG has a blue shift with temperature with sensitivity of −0.11 nm/°C, a blue shift with increasing sensitivity with surrounding refractive index ranging from 1.335 to 1.44 (the maximum sensitivity is achieved when the surrounding refractive index reaches the effective index of the fiber cladding, and a red shift with bend-direction-dependent sensitivity up to 9.36 nm/m−1.

Meta-analysis of the relative sensitivity of semi-natural vegetation species to ozone

International Nuclear Information System (INIS)

Hayes, F.; Jones, M.L.M.; Mills, G.; Ashmore, M.

2007-01-01

This study identified 83 species from existing publications suitable for inclusion in a database of sensitivity of species to ozone (OZOVEG database). An index, the relative sensitivity to ozone, was calculated for each species based on changes in biomass in order to test for species traits associated with ozone sensitivity. Meta-analysis of the ozone sensitivity data showed a wide inter-specific range in response to ozone. Some relationships in comparison to plant physiological and ecological characteristics were identified. Plants of the therophyte lifeform were particularly sensitive to ozone. Species with higher mature leaf N concentration were more sensitive to ozone than those with lower leaf N concentration. Some relationships between relative sensitivity to ozone and Ellenberg habitat requirements were also identified. In contrast, no relationships between relative sensitivity to ozone and mature leaf P concentration, Grime's CSR strategy, leaf longevity, flowering season, stomatal density and maximum altitude were found. The relative sensitivity of species and relationships with plant characteristics identified in this study could be used to predict sensitivity to ozone of untested species and communities. - Meta-analysis of the relative sensitivity of semi-natural vegetation species to ozone showed some relationships with physiological and ecological characteristics

Toward sustainable environmental quality: Identifying priority research questions for Latin America.

Science.gov (United States)

Furley, Tatiana Heid; Brodeur, Julie; Silva de Assis, Helena C; Carriquiriborde, Pedro; Chagas, Katia R; Corrales, Jone; Denadai, Marina; Fuchs, Julio; Mascarenhas, Renata; Miglioranza, Karina Sb; Miguez Caramés, Diana Margarita; Navas, José Maria; Nugegoda, Dayanthi; Planes, Estela; Rodriguez-Jorquera, Ignacio Alejandro; Orozco-Medina, Martha; Boxall, Alistair Ba; Rudd, Murray A; Brooks, Bryan W

2018-05-01

The Global Horizon Scanning Project (GHSP) is an innovative initiative that aims to identify important global environmental quality research needs. Here we report 20 key research questions from Latin America (LA). Members of the Society of Environmental Toxicology and Chemistry (SETAC) LA and other scientists from LA were asked to submit research questions that would represent priority needs to address in the region. One hundred questions were received, then partitioned among categories, examined, and some rearranged during a workshop in Buenos Aires, Argentina. Twenty priority research questions were subsequently identified. These research questions included developing, improving, and harmonizing across LA countries methods for 1) identifying contaminants and degradation products in complex matrices (including biota); 2) advancing prediction of contaminant risks and effects in ecosystems, addressing lab-to-field extrapolation challenges, and understanding complexities of multiple stressors (including chemicals and climate change); and 3) improving management and regulatory tools toward achieving sustainable development. Whereas environmental contaminants frequently identified in these key questions were pesticides, pharmaceuticals, endocrine disruptors or modulators, plastics, and nanomaterials, commonly identified environmental challenges were related to agriculture, urban effluents, solid wastes, pulp and paper mills, and natural extraction activities. Several interesting research topics included assessing and preventing pollution impacts on conservation protected areas, integrating environment and health assessments, and developing strategies for identification, substitution, and design of less hazardous chemicals (e.g., green chemistry). Finally, a recurrent research need included developing an understanding of differential sensitivity of regional species and ecosystems to environmental contaminants and other stressors. Addressing these critical questions will

Time analysis in astronomy: Tools for periodicity searches

International Nuclear Information System (INIS)

Buccheri, R.; Sacco, B.

1985-01-01

The authors discuss periodicity searches in radio and gamma-ray astronomy with special considerations for pulsar searches. The basic methodologies of fast Fourier transform, Rayleigh test, and epoch folding are reviewed with the main objective to compare cost and sensitivities in different applications. It is found that FFT procedures are convenient in unbiased searches for periodicity in radio astronomy, while in spark chamber gamma-ray astronomy, where the measurements are spread over a long integration time, unbiased searches are very difficult with the existing computing facilities and analyses with a-priori knowledge on the period values to look for are better done using the Rayleigh test with harmonics folding (Z /sub n/ test)

Remarks on Risk-Sensitive Control Problems

International Nuclear Information System (INIS)

Menaldi, Jose-Luis; Robin, Maurice

2005-01-01

The main purpose of this paper is to investigate the asymptotic behavior of the discounted risk-sensitive control problem for periodic diffusion processes when the discount factor α goes to zero. If u α (θ,x) denotes the optimal cost function, θ being the risk factor, then it is shown that lim { α to 0}α u α (θ,x)=ξ(θ) where ξ(θ) is the average on ]0,θ[ of the optimal cost of the (usual) infinite horizon risk-sensitive control problem

Clinical study of carbapenem sensitive and resistant Gram-negative bacteremia in neutropenic and nonneutropenic patients: The first series from India.

Science.gov (United States)

Ghafur, A K; Vidyalakshmi, P R; Kannaian, P; Balasubramaniam, R

2014-01-01

Carbapenem resistance is a growing global concern. There is a lack of published clinical studies on the topic from Indian subcontinent. Aim of this study was to analyze clinical profile of patients with carbapenem sensitive and resistant bacteremia among neutropenic and nonneutropenic patients. Retrospective analysis of 141 patients who had carbapenem resistant or sensitive Gram-negative bacteremia, identified over a period of 1-year was done by medical records review, in Apollo Specialty Hospital, a 300-bedded tertiary care Oncology, neurosurgical and orthopedic center in South India. Of the total 141 patients with Gram-negative bacteremia, 44 had carbapenem resistant ones. Of these 44 patients, 17 were neutropenics (resistant neutropenic group) and 27 nonneutropenic patients (resistant nonneutropenic group). Of the 97 patients with carbapenem sensitive bacteremia, 43 were neutropenic (sensitive neutropenic group) and 54 nonneutropenics (sensitive nonneutropenic group). The 28 days mortality was significantly higher in carbapenem resistant bacteremic group compared to the sensitive one (P = 0.008). This is the first study from India comparing clinical features of patients with carbapenem sensitive and resistant blood stream infections. Patients with carbapenem resistant bacteremia had higher mortality compared to patients with sensitive bacteremia.

Sensitivity analysis of LOFT L2-5 test calculations

International Nuclear Information System (INIS)

Prosek, Andrej

2014-01-01

The uncertainty quantification of best-estimate code predictions is typically accompanied by a sensitivity analysis, in which the influence of the individual contributors to uncertainty is determined. The objective of this study is to demonstrate the improved fast Fourier transform based method by signal mirroring (FFTBM-SM) for the sensitivity analysis. The sensitivity study was performed for the LOFT L2-5 test, which simulates the large break loss of coolant accident. There were 14 participants in the BEMUSE (Best Estimate Methods-Uncertainty and Sensitivity Evaluation) programme, each performing a reference calculation and 15 sensitivity runs of the LOFT L2-5 test. The important input parameters varied were break area, gap conductivity, fuel conductivity, decay power etc. For the influence of input parameters on the calculated results the FFTBM-SM was used. The only difference between FFTBM-SM and original FFTBM is that in the FFTBM-SM the signals are symmetrized to eliminate the edge effect (the so called edge is the difference between the first and last data point of one period of the signal) in calculating average amplitude. It is very important to eliminate unphysical contribution to the average amplitude, which is used as a figure of merit for input parameter influence on output parameters. The idea is to use reference calculation as 'experimental signal', 'sensitivity run' as 'calculated signal', and average amplitude as figure of merit for sensitivity instead for code accuracy. The larger is the average amplitude the larger is the influence of varied input parameter. The results show that with FFTBM-SM the analyst can get good picture of the contribution of the parameter variation to the results. They show when the input parameters are influential and how big is this influence. FFTBM-SM could be also used to quantify the influence of several parameter variations on the results. However, the influential parameters could not be

Identifying indicators of illegal behaviour: carnivore killing in human-managed landscapes.

Science.gov (United States)

St John, Freya A V; Keane, Aidan M; Edwards-Jones, Gareth; Jones, Lauren; Yarnell, Richard W; Jones, Julia P G

2012-02-22

Managing natural resources often depends on influencing people's behaviour, however effectively targeting interventions to discourage environmentally harmful behaviours is challenging because those involved may be unwilling to identify themselves. Non-sensitive indicators of sensitive behaviours are therefore needed. Previous studies have investigated people's attitudes, assuming attitudes reflect behaviour. There has also been interest in using people's estimates of the proportion of their peers involved in sensitive behaviours to identify those involved, since people tend to assume that others behave like themselves. However, there has been little attempt to test the potential of such indicators. We use the randomized response technique (RRT), designed for investigating sensitive behaviours, to estimate the proportion of farmers in north-eastern South Africa killing carnivores, and use a modified logistic regression model to explore relationships between our best estimates of true behaviour (from RRT) and our proposed non-sensitive indicators (including farmers' attitudes, and estimates of peer-behaviour). Farmers' attitudes towards carnivores, question sensitivity and estimates of peers' behaviour, predict the likelihood of farmers killing carnivores. Attitude and estimates of peer-behaviour are useful indicators of involvement in illicit behaviours and may be used to identify groups of people to engage in interventions aimed at changing behaviour.

Privacy Protection on Multiple Sensitive Attributes

Science.gov (United States)

Li, Zhen; Ye, Xiaojun

In recent years, a privacy model called k-anonymity has gained popularity in the microdata releasing. As the microdata may contain multiple sensitive attributes about an individual, the protection of multiple sensitive attributes has become an important problem. Different from the existing models of single sensitive attribute, extra associations among multiple sensitive attributes should be invested. Two kinds of disclosure scenarios may happen because of logical associations. The Q&S Diversity is checked to prevent the foregoing disclosure risks, with an α Requirement definition used to ensure the diversity requirement. At last, a two-step greedy generalization algorithm is used to carry out the multiple sensitive attributes processing which deal with quasi-identifiers and sensitive attributes respectively. We reduce the overall distortion by the measure of Masking SA.

Identifying the Climatic Conditions in Iraq by Tracking Down Cooling Events in the North Atlantic Ocean in the Period 3000–0 BC

Directory of Open Access Journals (Sweden)

Muslih Khamis D.

2014-09-01

Full Text Available North Atlantic Oscillation (NAO, monthly averages of precipitation in the Baghdad station, and petrologic tracer proxy data for ocean properties in the North Atlantic (NA have been used in an attempt to identify climatic conditions in Iraq during the study period. The study showed that contemporary changes in precipitation in Iraq are associated with NAO, as a negative relationship is found between them. Moreover, the study found that there is a strong negative correlation between NAOI and SST in NA, where drift ice indices explain between 33–36% of the NAOI variability.

The sensitive period for male-to-female sex reversal begins at the embryonic stage in the Nile tilapia and is associated with the sexual genotype.

Science.gov (United States)

Gennotte, Vincent; Mélard, Charles; D'Cotta, Helena; Baroiller, Jean-François; Rougeot, Carole

2014-12-01

In this study, we sought to determine the mechanism of early sex reversal in a teleost by applying 4 hr feminization treatments to XY (17α-ethynylestradiol 2000 μg L(-1) ) and YY (6500 μg L(-1) ) Nile tilapia embryos on the first day post-fertilization (dpf). We then searched for changes in the expression profiles of some sex-differentiating genes in the brain (cyp19a1b, foxl2, and amh) and in sex steroids (testosterone, 17β-estradiol, and 11-ketotestosterone) concentrations during embryogenesis and gonad differentiation. No sex reversal was observed in YY individuals, whereas sex-reversal rates in XY progeny ranged from 0-60%. These results, together with the clearance profile of 17α-ethynylestradiol, confirmed the existence of an early sensitive period for sex determination that encompasses embryonic and larval development and is active prior to any sign of gonad differentiation. Estrogen treatment induced elevated expression of cyp19a1b and higher testosterone and 17β-estradiol concentrations at 4 dpf in both XY and YY individuals. foxl2 and amh were repressed at 4 dpf and their expression levels were not different between treated and control groups at 14 dpf, suggesting that foxl2 did not control cyp19a1b in the brains of tilapia embryos. Increased cyp19a1b expression in treated embryos could reflect early brain sexualization, although this difference alone cannot account for the observed sex reversal as the treatment was ineffective in YY individuals. The differential sensitivity of XY and YY genotypes to embryonic induced-feminization suggests that a sex determinant on the sex chromosomes, such as a Y repressor or an X activator, may influence sex reversal during the first steps of tilapia embryogenesis. © 2014 Wiley Periodicals, Inc.

Mixed models, linear dependency, and identification in age-period-cohort models.

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O'Brien, Robert M

2017-07-20

This paper examines the identification problem in age-period-cohort models that use either linear or categorically coded ages, periods, and cohorts or combinations of these parameterizations. These models are not identified using the traditional fixed effect regression model approach because of a linear dependency between the ages, periods, and cohorts. However, these models can be identified if the researcher introduces a single just identifying constraint on the model coefficients. The problem with such constraints is that the results can differ substantially depending on the constraint chosen. Somewhat surprisingly, age-period-cohort models that specify one or more of ages and/or periods and/or cohorts as random effects are identified. This is the case without introducing an additional constraint. I label this identification as statistical model identification and show how statistical model identification comes about in mixed models and why which effects are treated as fixed and which are treated as random can substantially change the estimates of the age, period, and cohort effects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Traditional Practices of Mothers in the Postpartum Period: Evidence ...

African Journals Online (AJOL)

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In various cultures, the postpartum period is a sensitive time and various ... femmes au cours des huit premières semaines du post-partum qui se sont ..... For instance, in cultures such as those in India,. China ..... Asia Pacific Journal of Clinical.

The readmission risk flag: using the electronic health record to automatically identify patients at risk for 30-day readmission.

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Baillie, Charles A; VanZandbergen, Christine; Tait, Gordon; Hanish, Asaf; Leas, Brian; French, Benjamin; Hanson, C William; Behta, Maryam; Umscheid, Craig A

2013-12-01

Identification of patients at high risk for readmission is a crucial step toward improving care and reducing readmissions. The adoption of electronic health records (EHR) may prove important to strategies designed to risk stratify patients and introduce targeted interventions. To develop and implement an automated prediction model integrated into our health system's EHR that identifies on admission patients at high risk for readmission within 30 days of discharge. Retrospective and prospective cohort. Healthcare system consisting of 3 hospitals. All adult patients admitted from August 2009 to September 2012. An automated readmission risk flag integrated into the EHR. Thirty-day all-cause and 7-day unplanned healthcare system readmissions. Using retrospective data, a single risk factor, ≥ 2 inpatient admissions in the past 12 months, was found to have the best balance of sensitivity (40%), positive predictive value (31%), and proportion of patients flagged (18%), with a C statistic of 0.62. Sensitivity (39%), positive predictive value (30%), proportion of patients flagged (18%), and C statistic (0.61) during the 12-month period after implementation of the risk flag were similar. There was no evidence for an effect of the intervention on 30-day all-cause and 7-day unplanned readmission rates in the 12-month period after implementation. An automated prediction model was effectively integrated into an existing EHR and identified patients on admission who were at risk for readmission within 30 days of discharge. © 2013 Society of Hospital Medicine.

High-Sensitivity GaN Microchemical Sensors

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Son, Kyung-ah; Yang, Baohua; Liao, Anna; Moon, Jeongsun; Prokopuk, Nicholas

2009-01-01

Systematic studies have been performed on the sensitivity of GaN HEMT (high electron mobility transistor) sensors using various gate electrode designs and operational parameters. The results here show that a higher sensitivity can be achieved with a larger W/L ratio (W = gate width, L = gate length) at a given D (D = source-drain distance), and multi-finger gate electrodes offer a higher sensitivity than a one-finger gate electrode. In terms of operating conditions, sensor sensitivity is strongly dependent on transconductance of the sensor. The highest sensitivity can be achieved at the gate voltage where the slope of the transconductance curve is the largest. This work provides critical information about how the gate electrode of a GaN HEMT, which has been identified as the most sensitive among GaN microsensors, needs to be designed, and what operation parameters should be used for high sensitivity detection.

Genetic and Pharmacological Screens Converge in Identifying FLIP, BCL2, and IAP Proteins as Key Regulators of Sensitivity to the TRAIL-Inducing Anticancer Agent ONC201/TIC10.

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Allen, Joshua E; Prabhu, Varun V; Talekar, Mala; van den Heuvel, A Pieter J; Lim, Bora; Dicker, David T; Fritz, Jennifer L; Beck, Adam; El-Deiry, Wafik S

2015-04-15

ONC201/TIC10 is a small-molecule inducer of the TRAIL gene under current investigation as a novel anticancer agent. In this study, we identify critical molecular determinants of ONC201 sensitivity offering potential utility as pharmacodynamic or predictive response markers. By screening a library of kinase siRNAs in combination with a subcytotoxic dose of ONC201, we identified several kinases that ablated tumor cell sensitivity, including the MAPK pathway-inducer KSR1. Unexpectedly, KSR1 silencing did not affect MAPK signaling in the presence or absence of ONC201, but instead reduced expression of the antiapoptotic proteins FLIP, Mcl-1, Bcl-2, cIAP1, cIAP2, and survivin. In parallel to this work, we also conducted a synergy screen in which ONC201 was combined with approved small-molecule anticancer drugs. In multiple cancer cell populations, ONC201 synergized with diverse drug classes, including the multikinase inhibitor sorafenib. Notably, combining ONC201 and sorafenib led to synergistic induction of TRAIL and its receptor DR5 along with a potent induction of cell death. In a mouse xenograft model of hepatocellular carcinoma, we demonstrated that ONC201 and sorafenib cooperatively and safely triggered tumor regressions. Overall, our results established a set of determinants for ONC201 sensitivity that may predict therapeutic response, particularly in settings of sorafenib cotreatment to enhance anticancer responses. ©2015 American Association for Cancer Research.

Genetic and pharmacological screens converge in identifying FLIP, BCL2 and IAP proteins as key regulators of sensitivity to the TRAIL-inducing anti-cancer agent ONC201/TIC10

Science.gov (United States)

Allen, Joshua E.; Prabhu, Varun V.; Talekar, Mala; van den Heuvel, AP; Lim, Bora; Dicker, David T.; Fritz, Jennifer L.; Beck, Adam; El-Deiry, Wafik S.

2015-01-01

ONC201/TIC10 is a small molecule inducer of the TRAIL gene under current investigation as a novel anticancer agent. In this study, we identify critical molecular determinants of ONC201 sensitivity offering potential utility as pharmacodynamic or predictive response markers. By screening a library of kinase siRNAs in combination with a subcytotoxic dose of ONC201, we identified several kinases that ablated tumor cell sensitivity, including the MAPK pathway inducer KSR1. Unexpectedly, KSR1 silencing did not affect MAPK signaling in the presence or absence of ONC201, but instead reduced expression of the anti-apoptotic proteins FLIP, Mcl-1, Bcl-2, cIAP1, cIAP2, and survivin. In parallel to this work, we also conducted a synergy screen in which ONC201 was combined with approved small molecule anticancer drugs. In multiple cancer cell populations, ONC201 synergized with diverse drug classes including the multi-kinase inhibitor sorafenib. Notably, combining ONC201 and sorafenib led to synergistic induction of TRAIL and its receptor DR5 along with a potent induction of cell death. In a mouse xenograft model of hepatocellular carcinoma, we demonstrated that ONC201 and sorafenib cooperatively and safely triggered tumor regressions. Overall, our results established a set of determinants for ONC201 sensitivity that may predict therapeutic response, particularly in settings of sorafenib co-treatment to enhance anticancer responses. PMID:25681273

Novel TRAIL sensitizer Taraxacum officinale F.H. Wigg enhances TRAIL-induced apoptosis in Huh7 cells.

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Yoon, Ji-Yong; Cho, Hyun-Soo; Lee, Jeong-Ju; Lee, Hyo-Jung; Jun, Soo Young; Lee, Jae-Hye; Song, Hyuk-Hwan; Choi, SangHo; Saloura, Vassiliki; Park, Choon Gil; Kim, Cheol-Hee; Kim, Nam-Soon

2016-04-01

TRAIL (TNF-related apoptosis inducing ligand) is a promising anti-cancer drug target that selectively induces apoptosis in cancer cells. However, many cancer cells are resistant to TRAIL-induced apoptosis. Therefore, reversing TRAIL resistance is an important step for the development of effective TRAIL-based anti-cancer therapies. We previously reported that knockdown of the TOR signaling pathway regulator-like (TIPRL) protein caused TRAIL-induced apoptosis by activation of the MKK7-c-Jun N-terminal Kinase (JNK) pathway through disruption of the MKK7-TIPRL interaction. Here, we identified Taraxacum officinale F.H. Wigg (TO) as a novel TRAIL sensitizer from a set of 500 natural products using an ELISA system and validated its activity by GST pull-down analysis. Furthermore, combination treatment of Huh7 cells with TRAIL and TO resulted in TRAIL-induced apoptosis mediated through inhibition of the MKK7-TIPRL interaction and subsequent activation of MKK7-JNK phosphorylation. Interestingly, HPLC analysis identified chicoric acid as a major component of the TO extract, and combination treatment with chicoric acid and TRAIL induced TRAIL-induced cell apoptosis via JNK activation due to inhibition of the MKK7-TIPRL interaction. Our results suggest that TO plays an important role in TRAIL-induced apoptosis, and further functional studies are warranted to confirm the importance of TO as a novel TRAIL sensitizer for cancer therapy. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Identifying significant environmental features using feature recognition.

Science.gov (United States)

2015-10-01

The Department of Environmental Analysis at the Kentucky Transportation Cabinet has expressed an interest in feature-recognition capability because it may help analysts identify environmentally sensitive features in the landscape, : including those r...

Diagnostic tools for identifying sleepy drivers in the field.

Science.gov (United States)

2013-05-06

The overarching goal of this project was to identify and evaluate cognitive and behavioral indices that are sensitive to sleep : deprivation and may help identify commercial motor vehicle drivers (CMV) who are at-risk for driving in a sleep deprived ...

Periodic matrix population models: growth rate, basic reproduction number, and entropy.

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Bacaër, Nicolas

2009-10-01

This article considers three different aspects of periodic matrix population models. First, a formula for the sensitivity analysis of the growth rate lambda is obtained that is simpler than the one obtained by Caswell and Trevisan. Secondly, the formula for the basic reproduction number R0 in a constant environment is generalized to the case of a periodic environment. Some inequalities between lambda and R0 proved by Cushing and Zhou are also generalized to the periodic case. Finally, we add some remarks on Demetrius' notion of evolutionary entropy H and its relationship to the growth rate lambda in the periodic case.

The irreversibility of sensitive period effects in language development: evidence from second language acquisition in international adoptees.

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Norrman, Gunnar; Bylund, Emanuel

2016-05-01

The question of a sensitive period in language acquisition has been subject to extensive research and debate for more than half a century. While it has been well established that the ability to learn new languages declines in early years, the extent to which this outcome depends on biological maturation in contrast to previously acquired knowledge remains disputed. In the present study, we addressed this question by examining phonetic discriminatory abilities in early second language (L2) speakers of Swedish, who had either maintained their first language (L1) (immigrants) or had lost it (international adoptees), using native speaker controls. Through this design, we sought to disentangle the effects of the maturational state of the learner on L2 development from the effects of L1 interference: if additional language development is indeed constrained by an interfering L1, then adoptees should outperform immigrant speakers. The results of an auditory lexical decision task, in which fine vowel distinctions in Swedish had been modified, showed, however, no difference between the L2 groups. Instead, both L2 groups scored significantly lower than the native speaker group. The three groups did not differ in their ability to discriminate non-modified words. These findings demonstrate that L1 loss is not a crucial condition for successfully acquiring an L2, which in turn is taken as support for a maturational constraints view on L2 acquisition. A video abstract of this article can be viewed at: https://youtu.be/1J9X50aePeU. © 2015 John Wiley & Sons Ltd.

The sensitivity and specificity of four questions (HARK to identify intimate partner violence: a diagnostic accuracy study in general practice

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Feder Gene

2007-08-01

Full Text Available Abstract Background Intimate partner violence (IPV including physical, sexual and emotional violence, causes short and long term ill-health. Brief questions that reliably identify women experiencing IPV who present in clinical settings are a pre-requisite for an appropriate response from health services to this substantial public health problem. We estimated the sensitivity and specificity of four questions (HARK developed from the Abuse Assessment screen, compared to a 30-item abuse questionnaire, the Composite Abuse Scale (CAS. Methods We administered the four HARK questions and the CAS to women approached by two researchers in general practice waiting rooms in Newham, east London. Inclusions: women aged more than 17 years waiting to see a doctor or nurse, who had been in an intimate relationship in the last year. Exclusions: women who were accompanied by children over four years of age or another adult, too unwell to complete the questionnaires, unable to understand English or unable to give informed consent. Results Two hundred and thirty two women were recruited. The response rate was 54%. The prevalence of current intimate partner violence, within the last 12 months, using the CAS cut off score of ≥3, was 23% (95% C.I. 17% to 28% with pre-test odds of 0.3 (95% C.I. 0.2 to 0.4. The receiver operator characteristic curve demonstrated that a HARK cut off score of ≥1 maximises the true positives whilst minimising the false positives. The sensitivity of the optimal HARK cut-off score of ≥1 was 81% (95% C.I. 69% to 90%, specificity 95% (95% C.I. 91% to 98%, positive predictive value 83% (95% C.I. 70% to 91%, negative predictive value 94% (95% C.I. 90% to 97%, likelihood ratio 16 (95% C.I. 8 to 31 and post-test odds 5. Conclusion The four HARK questions accurately identify women experiencing IPV in the past year and may help women disclose abuse in general practice. The HARK questions could be incorporated into the electronic medical record

Interference pattern period measurement at picometer level

Science.gov (United States)

Xiang, Xiansong; Wei, Chunlong; Jia, Wei; Zhou, Changhe; Li, Minkang; Lu, Yancong

2016-10-01

To produce large scale gratings by Scanning Beam Interference Lithography (SBIL), a light spot containing grating pattern is generated by two beams interfering, and a scanning stage is used to drive the substrate moving under the light spot. In order to locate the stage at the proper exposure positions, the period of the Interference pattern must be measured accurately. We developed a set of process to obtain the period value of two interfering beams at picometer level. The process includes data acquisition and data analysis. The data is received from a photodiode and a laser interferometer with sub-nanometer resolution. Data analysis differs from conventional analyzing methods like counting wave peaks or using Fourier transform to get the signal period, after a preprocess of filtering and envelope removing, the mean square error is calculated between the received signal and ideal sinusoid waves to find the best-fit frequency, thus an accuracy period value is acquired, this method has a low sensitivity to amplitude noise and a high resolution of frequency. With 405nm laser beams interfering, a pattern period value around 562nm is acquired by employing this process, fitting diagram of the result shows the accuracy of the period value reaches picometer level, which is much higher than the results of conventional methods.

Methods and tools for the evaluation of the sensitivity to natural radiations of advanced integrated circuits

International Nuclear Information System (INIS)

Peronnard, P.

2009-10-01

Atmospheric neutrons, whose fluxes and energies dependent on the altitude, the sun activity and the geographic coordinates, have been identified as being capable to provoke SEE (Single Event Effects), by indirect ionisation, in integrated devices issued from advanced manufacturing processes (nano-metric devices). This concerns not only avionics but also applications operating at ground level. The evaluation of the sensitivity to SEE provoked by natural radiation becomes thus a mandatory step during the selection of devices devoted to be included in applications requiring high reliability. The sensitivity to SEE can be mitigated by different approaches at different levels from manufacturing level (use of particular process technologies such as SOI - Silicon On Isolator -) to the system level (hardware/software redundancy). Independently of the adopted hardening approach, the so-called radiation ground testing are mandatory to evaluate the error rates of a device or a system. During such tests, the DUT (Device Under Test) is exposed to a flux of particles while it performs a given activity. For SEU (Single Event Upsets) radiation ground testing, two main strategies exist: static test: the circuit areas which are supposed to be sensitive to SEUs (registers, memories,...) are initialized with a reference pattern. The content of the sensitive area is periodically compared to the reference pattern to identify potential SEU. Dynamic test: the DUT performs an activity representative of the one it will execute during the final application. Static test: strategies are frequently adopted as they provide the intrinsic sensitivity, in terms of the average number of particles needed to provoke an SEU, of different sensitive areas of the device. From such a strategy can thus be obtained a 'worst case estimation' of the device sensitivity. This thesis aims at giving a description and validating the methodologies required to estimate the sensitivity to radiations of two types of

Validity of the Male Depression Risk Scale in a representative Canadian sample: sensitivity and specificity in identifying men with recent suicide attempt.

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Rice, Simon M; Ogrodniczuk, John S; Kealy, David; Seidler, Zac E; Dhillon, Haryana M; Oliffe, John L

2017-12-22

Clinical practice and literature has supported the existence of a phenotypic sub-type of depression in men. While a number of self-report rating scales have been developed in order to empirically test the male depression construct, psychometric validation of these scales is limited. To confirm the psychometric properties of the multidimensional Male Depression Risk Scale (MDRS-22) and to develop clinical cut-off scores for the MDRS-22. Data were obtained from an online sample of 1000 Canadian men (median age (M) = 49.63, standard deviation (SD) = 14.60). Confirmatory factor analysis (CFA) was used to replicate the established six-factor model of the MDRS-22. Psychometric values of the MDRS subscales were comparable to the widely used Patient Health Questionnaire-9. CFA model fit indices indicated adequate model fit for the six-factor MDRS-22 model. ROC curve analysis indicated the MDRS-22 was effective for identifying those with a recent (previous four-weeks) suicide attempt (area under curve (AUC) values = 0.837). The MDRS-22 cut-off identified proportionally more (84.62%) cases of recent suicide attempt relative to the PHQ-9 moderate range (53.85%). The MDRS-22 is the first male-sensitive depression scale to be psychometrically validated using CFA techniques in independent and cross-nation samples. Additional studies should identify differential item functioning and evaluate cross-cultural effects.

High Throughput Measurement of Locomotor Sensitization to Volatilized Cocaine in Drosophila melanogaster.

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Filošević, Ana; Al-Samarai, Sabina; Andretić Waldowski, Rozi

2018-01-01

Drosophila melanogaster can be used to identify genes with novel functional roles in neuronal plasticity induced by repeated consumption of addictive drugs. Behavioral sensitization is a relatively simple behavioral output of plastic changes that occur in the brain after repeated exposures to drugs of abuse. The development of screening procedures for genes that control behavioral sensitization has stalled due to a lack of high-throughput behavioral tests that can be used in genetically tractable organism, such as Drosophila . We have developed a new behavioral test, FlyBong, which combines delivery of volatilized cocaine (vCOC) to individually housed flies with objective quantification of their locomotor activity. There are two main advantages of FlyBong: it is high-throughput and it allows for comparisons of locomotor activity of individual flies before and after single or multiple exposures. At the population level, exposure to vCOC leads to transient and concentration-dependent increase in locomotor activity, representing sensitivity to an acute dose. A second exposure leads to further increase in locomotion, representing locomotor sensitization. We validate FlyBong by showing that locomotor sensitization at either the population or individual level is absent in the mutants for circadian genes period (per) , Clock (Clk) , and cycle (cyc) . The locomotor sensitization that is present in timeless (tim) and pigment dispersing factor (pdf) mutant flies is in large part not cocaine specific, but derived from increased sensitivity to warm air. Circadian genes are not only integral part of the neural mechanism that is required for development of locomotor sensitization, but in addition, they modulate the intensity of locomotor sensitization as a function of the time of day. Motor-activating effects of cocaine are sexually dimorphic and require a functional dopaminergic transporter. FlyBong is a new and improved method for inducing and measuring locomotor sensitization

High Throughput Measurement of Locomotor Sensitization to Volatilized Cocaine in Drosophila melanogaster

Directory of Open Access Journals (Sweden)

Ana Filošević

2018-02-01

Full Text Available Drosophila melanogaster can be used to identify genes with novel functional roles in neuronal plasticity induced by repeated consumption of addictive drugs. Behavioral sensitization is a relatively simple behavioral output of plastic changes that occur in the brain after repeated exposures to drugs of abuse. The development of screening procedures for genes that control behavioral sensitization has stalled due to a lack of high-throughput behavioral tests that can be used in genetically tractable organism, such as Drosophila. We have developed a new behavioral test, FlyBong, which combines delivery of volatilized cocaine (vCOC to individually housed flies with objective quantification of their locomotor activity. There are two main advantages of FlyBong: it is high-throughput and it allows for comparisons of locomotor activity of individual flies before and after single or multiple exposures. At the population level, exposure to vCOC leads to transient and concentration-dependent increase in locomotor activity, representing sensitivity to an acute dose. A second exposure leads to further increase in locomotion, representing locomotor sensitization. We validate FlyBong by showing that locomotor sensitization at either the population or individual level is absent in the mutants for circadian genes period (per, Clock (Clk, and cycle (cyc. The locomotor sensitization that is present in timeless (tim and pigment dispersing factor (pdf mutant flies is in large part not cocaine specific, but derived from increased sensitivity to warm air. Circadian genes are not only integral part of the neural mechanism that is required for development of locomotor sensitization, but in addition, they modulate the intensity of locomotor sensitization as a function of the time of day. Motor-activating effects of cocaine are sexually dimorphic and require a functional dopaminergic transporter. FlyBong is a new and improved method for inducing and measuring locomotor

Indexing molecules with chemical graph identifiers.

Science.gov (United States)

Gregori-Puigjané, Elisabet; Garriga-Sust, Rut; Mestres, Jordi

2011-09-01

Fast and robust algorithms for indexing molecules have been historically considered strategic tools for the management and storage of large chemical libraries. This work introduces a modified and further extended version of the molecular equivalence number naming adaptation of the Morgan algorithm (J Chem Inf Comput Sci 2001, 41, 181-185) for the generation of a chemical graph identifier (CGI). This new version corrects for the collisions recognized in the original adaptation and includes the ability to deal with graph canonicalization, ensembles (salts), and isomerism (tautomerism, regioisomerism, optical isomerism, and geometrical isomerism) in a flexible manner. Validation of the current CGI implementation was performed on the open NCI database and the drug-like subset of the ZINC database containing 260,071 and 5,348,089 structures, respectively. The results were compared with those obtained with some of the most widely used indexing codes, such as the CACTVS hash code and the new InChIKey. The analyses emphasize the fact that compound management activities, like duplicate analysis of chemical libraries, are sensitive to the exact definition of compound uniqueness and thus still depend, to a minor extent, on the type and flexibility of the molecular index being used. Copyright © 2011 Wiley Periodicals, Inc.

Developmental trajectories of anxiety symptoms in early adolescence: the influence of anxiety sensitivity.

Science.gov (United States)

Allan, Nicholas P; Capron, Daniel W; Lejuez, Carl W; Reynolds, Elizabeth K; MacPherson, Laura; Schmidt, Norman B

2014-05-01

Children and adolescents seem to suffer from anxiety disorders at rates similar to adults. Interestingly, anxiety symptoms appear to generally decline over time within children as evidenced by lower rates in early and middle adolescence. There is some evidence that there may be heterogeneous subpopulations of adolescent children with different trajectories of anxiety symptoms, including a class of adolescents with elevated levels of anxiety that do not dissipate over time. Anxiety sensitivity has been identified as an important risk factor in the development of anxiety psychopathology. This study prospectively examined the development of anxiety symptoms in a sample of 277 adolescents (M age = 11.52; 44 % female, 56 % male) over a 3 year period including the influence of anxiety sensitivity on this development. Further, this study investigated whether there were distinct classes of adolescents based on their anxiety symptom trajectories and including anxiety sensitivity as a predictor. Consistent with other reports, findings indicated an overall decline in anxiety symptoms over time in the sample. However, three classes of adolescents were found with distinct anxiety symptom trajectories and anxiety sensitivity was an important predictor of class membership. Adolescents with elevated anxiety sensitivity scores were more likely to be classified as having high and increasing anxiety symptoms over time versus having moderate to low and decreasing anxiety symptoms over time. There are important implications for identification of adolescents and children who are at risk for the development of an anxiety disorder.

TransCom 3 CO2 inversion intercomparison: 2. Sensitivity of annual mean results to data choices

International Nuclear Information System (INIS)

Law, Rachel M.; Yu-Han Chen

2003-01-01

TransCom 3 is an intercomparison project for CO 2 source inversions. Annual mean CO 2 concentration data are used to estimate CO 2 sources using 16 different atmospheric transport models. Here we test the sensitivity of the inversion to the concentration data. We examine data network choice, time period of data, baseline data selection and the choice of data uncertainty used. We find that in most cases regional source estimates lie within the source uncertainty range of the control inversion. This indicates that the estimated sources are relatively insensitive to the changes in data that were tested. In the data network tests, only the Australian region source estimates varied over a much larger range than that given by the control case uncertainty estimate. For the other regions, the sensitivity to data network was within or close to the uncertainty range. Most of the sensitivity was found to be associated with a small number of sites (e.g. Darwin, Easter Island). These sites are often identified by the inability of the inversion to fit the data at these locations. The model-mean inversion values are mostly insensitive to the time period of data used, with the exception of temperate North America and the tropical Indian ocean. Data selection has a small impact on source estimates for the mean across models, but individual model sensitivity can be large. The magnitude of data uncertainties controls the relative magnitude of the estimated source uncertainty and the spread in model source estimates. Smaller data uncertainties lead to larger differences in source estimates between models. Overall, the data sensitivity tests performed here support the robustness of the control inversion source estimates presented in Gurney et al. (2003. Tellus 55B, this issue). The test results also provide guidance in setting up and interpreting other inversions

[Effect of oral administration of ascorbic acid on insulin sensitivity and lipid profile in obese individuals].

Science.gov (United States)

Martínez-Abundis, E; Pascoe-González, S; González-Ortiz, M; Mora-Martínez, J M; Cabrera-Pivaral, C E

2001-01-01

The aim of this study was to identify the effect of an oral ascorbic acid (AA) supplement on lipid profile and insulin sensitivity in obese people. A randomized double-blind clinical trial placebo controlled was performed in 16 obese male volunteers [body mass index (BMI) 30-40 kg/m2]. Eight received orally 1 g of AA daily for four weeks and the other eight volunteers received placebo by the same scheme and period of time. Before and after the pharmacological intervention were measured total cholesterol, high-density-lipoprotein (HDL) cholesterol, triglycerides, glucose, creatinine and uric acid. Low-density-lipoprotein (LDL) cholesterol and very-low-density-lipoprotein (VLDL) triglycerides were calculated using formulas. In order to assess insulin sensitivity before and after the intervention, the steady-state glucose (SSG) was calculated from the insulin suppression test modified with octreotide. There were not significant differences in clinical characteristics between both groups. Basal metabolic profile and SSG were similar between both groups. There were not significant differences in both groups between before and after the intervention in metabolic profile and insulin sensitivity. AA did not modify the lipid profile nor insulin sensitivity in the group of obese people studied.

Nogo Receptor 1 Confines a Disinhibitory Microcircuit to the Critical Period in Visual Cortex.

Science.gov (United States)

Stephany, Céleste-Élise; Ikrar, Taruna; Nguyen, Collins; Xu, Xiangmin; McGee, Aaron W

2016-10-26

A characteristic of the developing mammalian visual system is a brief interval of plasticity, termed the "critical period," when the circuitry of primary visual cortex is most sensitive to perturbation of visual experience. Depriving one eye of vision (monocular deprivation [MD]) during the critical period alters ocular dominance (OD) by shifting the responsiveness of neurons in visual cortex to favor the nondeprived eye. A disinhibitory microcircuit involving parvalbumin-expressing (PV) interneurons initiates this OD plasticity. The gene encoding the neuronal nogo-66-receptor 1 (ngr1/rtn4r) is required to close the critical period. Here we combined mouse genetics, electrophysiology, and circuit mapping with laser-scanning photostimulation to investigate whether disinhibition is confined to the critical period by ngr1 We demonstrate that ngr1 mutant mice retain plasticity characteristic of the critical period as adults, and that ngr1 operates within PV interneurons to restrict the loss of intracortical excitatory synaptic input following MD in adult mice, and this disinhibition induces a "lower PV network configuration" in both critical-period wild-type mice and adult ngr1 -/- mice. We propose that ngr1 limits disinhibition to close the critical period for OD plasticity and that a decrease in PV expression levels reports the diminished recent cumulative activity of these interneurons. Life experience refines brain circuits throughout development during specified critical periods. Abnormal experience during these critical periods can yield enduring maladaptive changes in neural circuits that impair brain function. In the developing visual system, visual deprivation early in life can result in amblyopia (lazy-eye), a prevalent childhood disorder comprising permanent deficits in spatial vision. Here we identify that the nogo-66 receptor 1 gene restricts an early and essential step in OD plasticity to the critical period. These findings link the emerging circuit

A retrospective audit of the extent and nature of domestic violence cases identified over a three year period in the two district command units of the police service of Northern Ireland.

Science.gov (United States)

Stevenson, T R; Goodall, E A; Moore, C B T

2008-10-01

The work load of forensic medical officers (FMOs) who provide medical cover for the Coleraine and Limavady district command units (DCU) of the police service of Northern Ireland (PSNI) in dealing with domestic violence was investigated over a three year period from 1st April 2003 to 31st March 2006. A total of 128 cases involving domestic violence were identified during this three year period. There was a significant increase from 4% (32/791) in the first year to 6.6% (56/851, p<0.01) in the number of cases of identified domestic violence in the second year which dropped to 4.2% (40/956) in the third year. Victims were identified in 38% of these domestic violence cases with 62% being identified as assailants. It was noted that there was a significant difference in the proportion of male assailants (96.2%) from female assailants (3.8%). Fifty-four percent of victims were noted to have injuries in accordance with the more serious injury categories of assault of actual bodily harm (AOABH) and grievous bodily harm (GBH). Domestic incidents occurred at the home in 91% of cases, with the FMO being the primary contact in 97% of cases. Alcohol was implicated in 56% of all domestic violence cases recorded.

Vantage Sensitivity: Environmental Sensitivity to Positive Experiences as a Function of Genetic Differences.

Science.gov (United States)

Pluess, Michael

2017-02-01

A large number of gene-environment interaction studies provide evidence that some people are more likely to be negatively affected by adverse experiences as a function of specific genetic variants. However, such "risk" variants are surprisingly frequent in the population. Evolutionary analysis suggests that genetic variants associated with increased risk for maladaptive development under adverse environmental conditions are maintained in the population because they are also associated with advantages in response to different contextual conditions. These advantages may include (a) coexisting genetic resilience pertaining to other adverse influences, (b) a general genetic susceptibility to both low and high environmental quality, and (c) a coexisting propensity to benefit disproportionately from positive and supportive exposures, as reflected in the recent framework of vantage sensitivity. After introducing the basic properties of vantage sensitivity and highlighting conceptual similarities and differences with diathesis-stress and differential susceptibility patterns of gene-environment interaction, selected and recent empirical evidence for the notion of vantage sensitivity as a function of genetic differences is reviewed. The unique contribution that the new perspective of vantage sensitivity may make to our understanding of social inequality will be discussed after suggesting neurocognitive and molecular mechanisms hypothesized to underlie the propensity to benefit disproportionately from benevolent experiences. © 2015 Wiley Periodicals, Inc.

Criteria for confirming sequence periodicity identified by Fourier transform analysis: application to GCR2, a candidate plant GPCR?

Science.gov (United States)

Illingworth, Christopher J R; Parkes, Kevin E; Snell, Christopher R; Mullineaux, Philip M; Reynolds, Christopher A

2008-03-01

Methods to determine periodicity in protein sequences are useful for inferring function. Fourier transformation is one approach but care is required to ensure the periodicity is genuine. Here we have shown that empirically-derived statistical tables can be used as a measure of significance. Genuine protein sequences data rather than randomly generated sequences were used as the statistical backdrop. The method has been applied to G-protein coupled receptor (GPCR) sequences, by Fourier transformation of hydrophobicity values, codon frequencies and the extent of over-representation of codon pairs; the latter being related to translational step times. Genuine periodicity was observed in the hydrophobicity whereas the apparent periodicity (as inferred from previously reported measures) in the translation step times was not validated statistically. GCR2 has recently been proposed as the plant GPCR receptor for the hormone abscisic acid. It has homology to the Lanthionine synthetase C-like family of proteins, an observation confirmed by fold recognition. Application of the Fourier transform algorithm to the GCR2 family revealed strongly predicted seven fold periodicity in hydrophobicity, suggesting why GCR2 has been reported to be a GPCR, despite negative indications in most transmembrane prediction algorithms. The underlying multiple sequence alignment, also required for the Fourier transform analysis of periodicity, indicated that the hydrophobic regions around the 7 GXXG motifs commence near the C-terminal end of each of the 7 inner helices of the alpha-toroid and continue to the N-terminal region of the helix. The results clearly explain why GCR2 has been understandably but erroneously predicted to be a GPCR.

Spontaneous swallowing frequency has potential to identify dysphagia in acute stroke.

Science.gov (United States)

Crary, Michael A; Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael F

2013-12-01

Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. In a cohort of 63 acute stroke cases, swallow frequency rates (swallows per minute [SPM]) were compared with stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with versus without clinically significant dysphagia. Receiver operating characteristic curve analysis was used to identify the optimal threshold in SPM, which was compared with a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was used to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. Receiver operating characteristic curve analysis yielded a threshold of SPM≤0.40 that identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5- to 10-minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel.

Spontaneous Swallowing Frequency [Has Potential to] Identify Dysphagia in Acute Stroke

Science.gov (United States)

Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael

2014-01-01

Background and Purpose Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. Methods In a cohort of 63 acute stroke cases swallow frequency rates (swallows per minute: SPM) were compared to stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with vs. without clinically significant dysphagia. ROC analysis was used to identify the optimal threshold in SPM which was compared to a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was employed to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. Results SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. ROC analysis yielded a threshold of SPM ≤ 0.40 which identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5 to 10 minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Conclusions Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel. PMID:24149008

Intrauterine and genetic factors in early childhood sensitization

DEFF Research Database (Denmark)

Bønnelykke, Klaus

2010-01-01

The allergy-associated (atopic) diseases; asthma, eczema and rhinoconjunctivitis, are the most common chronic diseases in childhood. A large number of environmental and genetic risk factors have been suggested, but still our understanding of the underlying disease mechanisms and etiologies...... with production of specific IgE-antibodies against allergens. Sensitization may cause allergic symptoms, and sensitization early in life is a strong risk factor for later disease. Fetal and early postnatal life seems to be a critical period for development of atopic disease and may be an important “window...... of opportunity” for prevention. The aim of this thesis was to increase the understanding of sensitization in early life. We studied indicators of sensitization in the newborn, and early development of sensitization and disease associated with a newly discovered genetic risk factor. Such insight may increase our...

Maternal sensitivity and social support protect against childhood atopic dermatitis.

Science.gov (United States)

Letourneau, Nicole L; Kozyrskyj, Anita L; Cosic, Nela; Ntanda, Henry N; Anis, Lubna; Hart, Martha J; Campbell, Tavis S; Giesbrecht, Gerald F

2017-01-01

Many studies have identified associations between qualities of maternal-child relationships and childhood asthma, but few have examined associations with childhood atopic dermatitis (AD), a common precursor to asthma. Moreover, maternal psychological distress, including prenatal and postnatal depression, anxiety and stress, may increase risk, while social support from partners may reduce risk for childhood AD. We sought to uncover the association between maternal-infant relationship qualities (maternal sensitivity towards infant behavioral signals, controlling behavior, and unresponsiveness) and child AD after accounting for risk (i.e., prenatal and postnatal maternal depression, anxiety and stress) and protective (i.e., social support) factors. We conducted a secondary analysis of data collected on a subsample of 242 women and their infants enrolled during pregnancy in the ongoing Alberta Pregnancy Outcomes and Nutrition cohort study. Inclusion criteria required mothers to be >16 years of age, English speaking and depression, anxiety and stress in the prenatal and postnatal periods and physician diagnosis of childhood AD at 18 months were gathered via maternal report. Maternal sensitivity, unresponsiveness and controlling behaviours were assessed via videotaped observations using the Child-Adult Relationship Experimental (CARE)-Index at 6 months of infant age. Higher maternal sensitivity, or the inability of the mother to appropriately understand and respond to infant needs based on behavioral signals, predicted reduced odds of AD independent of and in combination with low prenatal and postnatal anxiety and high paternal support. After adjustment, higher maternal controlling behaviours and unresponsiveness also predicted greater odds of AD. Low maternal sensitivity is a risk factor for childhood AD, independently and in combination with perinatal anxiety and low social support. Thus, interventions that improve maternal-infant relationship quality, especially

CHEMICAL VAPOUR DEPOSITION FROM A RADIATION-SENSITIVE PRECURSOR

DEFF Research Database (Denmark)

2017-01-01

The present invention relates in one aspect to a method of depositing a thin film on a substrate by chemical vapour deposition (CVD) from a radiation-sensitive precursor substance. The method comprises the steps of: (i) placing the substrate in a reaction chamber of a CVD system; (ii) heating...... heating pulse followed by an idle period; (iii) during at least one of the idle periods, providing a pressure pulse of precursor substance inside the reaction chamber by feeding at least one precursor substance to the reaction chamber so as to establish a reaction partial pressure for thin film deposition...... is formed. According to a further aspect, the invention relates to a chemical vapour deposition (CVD) system for depositing a thin film onto a substrate using precursor substances containing at least one radiation sensitive species....

Identifying Gender-Sensitive Agroforestry Options: Methodological Considerations From the Field

Directory of Open Access Journals (Sweden)

Sarah-Lan Mathez-Stiefel

2016-11-01

Full Text Available Agroforestry is seen as a promising set of land use practices that can lead to increased ecological integrity and sustainable benefits in mountain areas. Agroforestry practices can also enhance smallholder farmers' resilience in the face of social and ecological change. There is a need for critical examination of existing practices to ensure that agroforestry recommendations for smallholder farmers are socially inclusive and grounded in local experience, knowledge, and perceptions. In this paper, we present a transdisciplinary systems approach to the identification and analysis of suitable agroforestry options, which takes into account gendered perceptions of the benefits and values of natural resources. The 4-step approach consists of an appraisal of local perceptions of the social-ecological context and dynamics, an inventory of existing agroforestry practices and species, a gendered valuation of agroforestry practices and species, and the development of locally adapted and gender-sensitive agroforestry options. In a study using this approach in the Peruvian Andes, data were collected through a combination of participatory tools for gender research and ethnobotanical methods. This paper shares lessons learned and offers recommendations for researchers and practitioners in the field of sustainable mountain development. We discuss methodological considerations in the identification of locally adapted agroforestry options, the understanding of local social-ecological systems, the facilitation of social learning processes, engagement in gender research, and the establishment of ethical research collaborations. The methodology presented here is especially recommended for the exploratory phase of any natural resource management initiative in mountain areas with high environmental and sociocultural variability.

Post discharge issues identified by a call-back program: identifying improvement opportunities.

Science.gov (United States)

Ojeda, Patricia I; Kara, Areeba

2017-12-01

The period following discharge from the hospital is one of heightened vulnerability. Discharge instructions serve as a guide during this transition. Yet, clinicians receive little feedback on the quality of this document that ties into the patients' experience. We reviewed the issues voiced by discharged patients via a call-back program and compared them to the discharge instructions they had received. At our institution, patients receive an automated call forty-eight hours following discharge inquiring about progress. If indicated by the response to the call, they are directed to a nurse who assists with problem solving. We reviewed the nursing documentation of these encounters for a period of nine months. The issues voiced were grouped into five categories: communication, medications, durable medical equipment/therapies, follow up and new or ongoing symptoms. The discharge instructions given to each patient were reviewed. We retrieved data on the number of discharges from each specialty from the hospital over the same period. A total of 592 patients voiced 685 issues. The numbers of patients discharged from medical or surgical services identified as having issues via the call-back line paralleled the proportions discharged from medical and surgical services from the hospital during the same period. Nearly a quarter of the issues discussed had been addressed in the discharge instructions. The most common category of issues was related to communication deficits including missing or incomplete information which made it difficult for the patient to enact or understand the plan of care. Medication prescription related issues were the next most common. Resource barriers and questions surrounding medications were often unaddressed. Post discharge issues affect patients discharged from all services equally. Data from call back programs may provide actionable targets for improvement, identify the inpatient team's 'blind spots' and be used to provide feedback to clinicians.

Parametric uncertainty and global sensitivity analysis in a model of the carotid bifurcation: Identification and ranking of most sensitive model parameters.

Science.gov (United States)

Gul, R; Bernhard, S

2015-11-01

In computational cardiovascular models, parameters are one of major sources of uncertainty, which make the models unreliable and less predictive. In order to achieve predictive models that allow the investigation of the cardiovascular diseases, sensitivity analysis (SA) can be used to quantify and reduce the uncertainty in outputs (pressure and flow) caused by input (electrical and structural) model parameters. In the current study, three variance based global sensitivity analysis (GSA) methods; Sobol, FAST and a sparse grid stochastic collocation technique based on the Smolyak algorithm were applied on a lumped parameter model of carotid bifurcation. Sensitivity analysis was carried out to identify and rank most sensitive parameters as well as to fix less sensitive parameters at their nominal values (factor fixing). In this context, network location and temporal dependent sensitivities were also discussed to identify optimal measurement locations in carotid bifurcation and optimal temporal regions for each parameter in the pressure and flow waves, respectively. Results show that, for both pressure and flow, flow resistance (R), diameter (d) and length of the vessel (l) are sensitive within right common carotid (RCC), right internal carotid (RIC) and right external carotid (REC) arteries, while compliance of the vessels (C) and blood inertia (L) are sensitive only at RCC. Moreover, Young's modulus (E) and wall thickness (h) exhibit less sensitivities on pressure and flow at all locations of carotid bifurcation. Results of network location and temporal variabilities revealed that most of sensitivity was found in common time regions i.e. early systole, peak systole and end systole. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of bentonite alteration due to interactions with iron. Sensitivity analyses to identify the important factors for the bentonite alteration

International Nuclear Information System (INIS)

Sasamoto, Hiroshi; Wilson, James; Sato, Tsutomu

2013-01-01

Performance assessment of geological disposal systems for high-level radioactive waste requires a consideration of long-term systems behaviour. It is possible that the alteration of swelling clay present in bentonite buffers might have an impact on buffer functions. In the present study, iron (as a candidate overpack material)-bentonite (I-B) interactions were evaluated as the main buffer alteration scenario. Existing knowledge on alteration of bentonite during I-B interactions was first reviewed, then the evaluation methodology was developed considering modeling techniques previously used overseas. A conceptual model for smectite alteration during I-B interactions was produced. The following reactions and processes were selected: 1) release of Fe 2+ due to overpack corrosion; 2) diffusion of Fe 2+ in compacted bentonite; 3) sorption of Fe 2+ on smectite edge and ion exchange in interlayers; 4) dissolution of primary phases and formation of alteration products. Sensitivity analyses were performed to identify the most important factors for the alteration of bentonite by I-B interactions. (author)

Individual modulation of pain sensitivity under stress.

Science.gov (United States)

Reinhardt, Tatyana; Kleindienst, Nikolaus; Treede, Rolf-Detlef; Bohus, Martin; Schmahl, Christian

2013-05-01

Stress has a strong influence on pain sensitivity. However, the direction of this influence is unclear. Recent studies reported both decreased and increased pain sensitivities under stress, and one hypothesis is that interindividual differences account for these differences. The aim of our study was to investigate the effect of stress on individual pain sensitivity in a relatively large female sample. Eighty female participants were included. Pain thresholds and temporal summation of pain were tested before and after stress, which was induced by the Mannheim Multicomponent Stress Test. In an independent sample of 20 women, correlation coefficients between 0.45 and 0.89 indicated relatively high test-retest reliability for pain measurements. On average, there were significant differences between pain thresholds under non-stress and stress conditions, indicating an increased sensitivity to pain under stress. No significant differences between non-stress and stress conditions were found for temporal summation of pain. On an individual basis, both decreased and increased pain sensitivities under stress conditions based on Jacobson's criteria for reliable change were observed. Furthermore, we found significant negative associations between pain sensitivity under non-stress conditions and individual change of pain sensitivity under stress. Participants with relatively high pain sensitivity under non-stress conditions became less sensitive under stress and vice versa. These findings support the view that pain sensitivity under stress shows large interindividual variability, and point to a possible dichotomy of altered pain sensitivity under stress. Wiley Periodicals, Inc.

Sensitivity analysis of an individual-based model for simulation of influenza epidemics.

Directory of Open Access Journals (Sweden)

Elaine O Nsoesie

Full Text Available Individual-based epidemiology models are increasingly used in the study of influenza epidemics. Several studies on influenza dynamics and evaluation of intervention measures have used the same incubation and infectious period distribution parameters based on the natural history of influenza. A sensitivity analysis evaluating the influence of slight changes to these parameters (in addition to the transmissibility would be useful for future studies and real-time modeling during an influenza pandemic.In this study, we examined individual and joint effects of parameters and ranked parameters based on their influence on the dynamics of simulated epidemics. We also compared the sensitivity of the model across synthetic social networks for Montgomery County in Virginia and New York City (and surrounding metropolitan regions with demographic and rural-urban differences. In addition, we studied the effects of changing the mean infectious period on age-specific epidemics. The research was performed from a public health standpoint using three relevant measures: time to peak, peak infected proportion and total attack rate. We also used statistical methods in the design and analysis of the experiments. The results showed that: (i minute changes in the transmissibility and mean infectious period significantly influenced the attack rate; (ii the mean of the incubation period distribution appeared to be sufficient for determining its effects on the dynamics of epidemics; (iii the infectious period distribution had the strongest influence on the structure of the epidemic curves; (iv the sensitivity of the individual-based model was consistent across social networks investigated in this study and (v age-specific epidemics were sensitive to changes in the mean infectious period irrespective of the susceptibility of the other age groups. These findings suggest that small changes in some of the disease model parameters can significantly influence the uncertainty

Optimal glucose management in the perioperative period.

Science.gov (United States)

Evans, Charity H; Lee, Jane; Ruhlman, Melissa K

2015-04-01

Hyperglycemia is a common finding in surgical patients during the perioperative period. Factors contributing to poor glycemic control include counterregulatory hormones, hepatic insulin resistance, decreased insulin-stimulated glucose uptake, use of dextrose-containing intravenous fluids, and enteral and parenteral nutrition. Hyperglycemia in the perioperative period is associated with increased morbidity, decreased survival, and increased resource utilization. Optimal glucose management in the perioperative period contributes to reduced morbidity and mortality. To readily identify hyperglycemia, blood glucose monitoring should be instituted for all hospitalized patients. Published by Elsevier Inc.

Low-frequency Periodic Error Identification and Compensation for Star Tracker Attitude Measurement

Institute of Scientific and Technical Information of China (English)

WANG Jiongqi; XIONG Kai; ZHOU Haiyin

2012-01-01

The low-frequency periodic error of star tracker is one of the most critical problems for high-accuracy satellite attitude determination.In this paper an approach is proposed to identify and compensate the low-frequency periodic error for star tracker in attitude measurement.The analytical expression between the estimated gyro drift and the low-frequency periodic error of star tracker is derived firstly.And then the low-frequency periodic error,which can be expressed by Fourier series,is identified by the frequency spectrum of the estimated gyro drift according to the solution of the first step.Furthermore,the compensated model of the low-frequency periodic error is established based on the identified parameters to improve the attitude determination accuracy.Finally,promising simulated experimental results demonstrate the validity and effectiveness of the proposed method.The periodic error for attitude determination is eliminated basically and the estimation precision is improved greatly.

Application of Sensitivity Analysis in Design of Sustainable Buildings

DEFF Research Database (Denmark)

Heiselberg, Per; Brohus, Henrik; Rasmussen, Henrik

2009-01-01

satisfies the design objectives and criteria. In the design of sustainable buildings, it is beneficial to identify the most important design parameters in order to more efficiently develop alternative design solutions or reach optimized design solutions. Sensitivity analyses make it possible to identify...... possible to influence the most important design parameters. A methodology of sensitivity analysis is presented and an application example is given for design of an office building in Denmark....

Redox regulation of cell proliferation: Bioinformatics and redox proteomics approaches to identify redox-sensitive cell cycle regulators.

Science.gov (United States)

Foyer, Christine H; Wilson, Michael H; Wright, Megan H

2018-03-29

Plant stem cells are the foundation of plant growth and development. The balance of quiescence and division is highly regulated, while ensuring that proliferating cells are protected from the adverse effects of environment fluctuations that may damage the genome. Redox regulation is important in both the activation of proliferation and arrest of the cell cycle upon perception of environmental stress. Within this context, reactive oxygen species serve as 'pro-life' signals with positive roles in the regulation of the cell cycle and survival. However, very little is known about the metabolic mechanisms and redox-sensitive proteins that influence cell cycle progression. We have identified cysteine residues on known cell cycle regulators in Arabidopsis that are potentially accessible, and could play a role in redox regulation, based on secondary structure and solvent accessibility likelihoods for each protein. We propose that redox regulation may function alongside other known posttranslational modifications to control the functions of core cell cycle regulators such as the retinoblastoma protein. Since our current understanding of how redox regulation is involved in cell cycle control is hindered by a lack of knowledge regarding both which residues are important and how modification of those residues alters protein function, we discuss how critical redox modifications can be mapped at the molecular level. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Periodicity and repeatability in data

Science.gov (United States)

Southwood, D.

Using magnetic data from the first two years in Saturn orbit, the basic periodicity of apparent is examined with the aim of elucidating the `cam' shaft model of Espinosa et al. (2003) identifying the nature of the `cam' and giving a definitive period for its rotation. An initial hypothesis, supported by the spectral analysis of analysis of the first 8 months in orbit Gianpieri et al. (2006), is made that the source of the period is linked to something inside the planet and therefore that the source inertia means that the period effectively does not change over the 2 years. Moreover one expects that the source phase is fixed. Using this approach, not only can the period identified by spectral analysis (647.1 + 0.6 min.) be verified but also by phase analysis between successive passes over the 2 years the period can be refined to 647.6 + 0.1 min. The signal itself is remarkably reproducible from pass to pass. It appears in all three components of the field and its polarisation is unambiguously not attributable to direct detection of an internal field. Not only does the signal not decay rapidly with distance from the planet, but although it has the m=1 symmetry of a tilted dipole, the field lines diverge from the planet indicating an exterior source. This feature led to the `cam' model. The polarisation and comparisons of passes with different latitude profiles show a surprising north-south symmetry in the azimuthal field. The absence of asymmetry with respect to the magnetic equator rules out a direct magnetospheric-ionospheric interaction source. Accordingly, it is proposed that the basic `cam' effect is generated by a single hemisphere anomaly which creates hemisphere to hemisphere field aligned currents. The existence of Saturn phase related anomaly appears to produce a basic asymmetry in the inner magnetosphere that sets the phase of both an inflowing and outflowing sector in a rotating circulation system.

TransCom 3 CO{sub 2} inversion intercomparison: 2. Sensitivity of annual mean results to data choices

Energy Technology Data Exchange (ETDEWEB)

Law, Rachel M. [CSIRO Atmospheric Research, Aspendale, VIC (Australia); Yu-Han Chen [Massachusetts Inst. of Technology, Cambridge, MA (United States). Dept. of Earth, Atmospheric, and Planetary Science; Gurney, Kevin R. [Colorado State Univ., Fort Collins, CO (United States). Dept. of Atmospheric Science; Baker, D. (TRANSCOM-3 Modelers) (and others)

2003-04-01

TransCom 3 is an intercomparison project for CO{sub 2} source inversions. Annual mean CO{sub 2} concentration data are used to estimate CO{sub 2} sources using 16 different atmospheric transport models. Here we test the sensitivity of the inversion to the concentration data. We examine data network choice, time period of data, baseline data selection and the choice of data uncertainty used. We find that in most cases regional source estimates lie within the source uncertainty range of the control inversion. This indicates that the estimated sources are relatively insensitive to the changes in data that were tested. In the data network tests, only the Australian region source estimates varied over a much larger range than that given by the control case uncertainty estimate. For the other regions, the sensitivity to data network was within or close to the uncertainty range. Most of the sensitivity was found to be associated with a small number of sites (e.g. Darwin, Easter Island). These sites are often identified by the inability of the inversion to fit the data at these locations. The model-mean inversion values are mostly insensitive to the time period of data used, with the exception of temperate North America and the tropical Indian ocean. Data selection has a small impact on source estimates for the mean across models, but individual model sensitivity can be large. The magnitude of data uncertainties controls the relative magnitude of the estimated source uncertainty and the spread in model source estimates. Smaller data uncertainties lead to larger differences in source estimates between models. Overall, the data sensitivity tests performed here support the robustness of the control inversion source estimates presented in Gurney et al. (2003. Tellus 55B, this issue). The test results also provide guidance in setting up and interpreting other inversions.

Increased skeletal muscle capillarization enhances insulin sensitivity

DEFF Research Database (Denmark)

Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth

2014-01-01

Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity....... Skeletal muscle specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist Prazosin to the drinking water of Sprague Dawley rats (n=33) while 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-week Prazosin treatment, which ensured...... that Prazosin was cleared from the blood stream. Whole-body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]-Glucose during the plateau phase of the clamp. Whole...

Prenatal Particulate Air Pollution and Asthma Onset in Urban Children. Identifying Sensitive Windows and Sex Differences.

Science.gov (United States)

Hsu, Hsiao-Hsien Leon; Chiu, Yueh-Hsiu Mathilda; Coull, Brent A; Kloog, Itai; Schwartz, Joel; Lee, Alison; Wright, Robert O; Wright, Rosalind J

2015-11-01

The influence of particulate air pollution on respiratory health starts in utero. Fetal lung growth and structural development occurs in stages; thus, effects on postnatal respiratory disorders may differ based on timing of exposure. We implemented an innovative method to identify sensitive windows for effects of prenatal exposure to particulate matter with a diameter less than or equal to 2.5 μm (PM2.5) on children's asthma development in an urban pregnancy cohort. Analyses included 736 full-term (≥37 wk) children. Each mother's daily PM2.5 exposure was estimated over gestation using a validated satellite-based spatiotemporal resolved model. Using distributed lag models, we examined associations between weekly averaged PM2.5 levels over pregnancy and physician-diagnosed asthma in children by age 6 years. Effect modification by sex was also examined. Most mothers were ethnic minorities (54% Hispanic, 30% black), had 12 or fewer years of education (66%), and did not smoke in pregnancy (80%). In the sample as a whole, distributed lag models adjusting for child age, sex, and maternal factors (education, race and ethnicity, smoking, stress, atopy, prepregnancy obesity) showed that increased PM2.5 exposure levels at 16-25 weeks gestation were significantly associated with early childhood asthma development. An interaction between PM2.5 and sex was significant (P = 0.01) with sex-stratified analyses showing that the association exists only for boys. Higher prenatal PM2.5 exposure at midgestation was associated with asthma development by age 6 years in boys. Methods to better characterize vulnerable windows may provide insight into underlying mechanisms.

Deaerating operation during startup periods in Japanese BWRs

International Nuclear Information System (INIS)

Maeda, K.

2002-01-01

The IGSCC has been mitigated by application of effective countermeasures on water chemistry environment. Hydrogen water chemistry (HWC) has been implemented to reduce the reactor water dissolved oxygen concentration and electrochemical corrosion potential (ECP) during plant operation to reduced crack growth rate of in sensitized stainless steel. But the HWC has not been implemented during startup periods. The crack growth rate of sensitized stainless steel will increase obviously during startup period by increasing in temperature under high dissolved oxygen conditions [1]. The deaerating operation has been applied routinely in Japanese BWRs to reduce reactor water dissolved oxygen quickly and easily before plant startup [2,3]. The main condenser is vacuumed up before start in the deaerating operation. The reactor is connected with the main condenser by opening the main steam bypass valves or the main steam drain valves. The deaerating operation is started with keeping the reactor water temperature about 70 to 90 degrees centigrade. The deaerating operation will come to an end when the reactor water dissolved concentration will decrease below 200 ppb. This paper shows the procedure and actual results of deaerating operation. (authors)

Early life adversity during the infant sensitive period for attachment: Programming of behavioral neurobiology of threat processing and social behavior

Directory of Open Access Journals (Sweden)

Maya Opendak

2017-06-01

Full Text Available Animals, including humans, require a highly coordinated and flexible system of social behavior and threat evaluation. However, trauma can disrupt this system, with the amygdala implicated as a mediator of these impairments in behavior. Recent evidence has further highlighted the context of infant trauma as a critical variable in determining its immediate and enduring consequences, with trauma experienced from an attachment figure, such as occurs in cases of caregiver-child maltreatment, as particularly detrimental. This review focuses on the unique role of caregiver presence during early-life trauma in programming deficits in social behavior and threat processing. Using data primarily from rodent models, we describe the interaction between trauma and attachment during a sensitive period in early life, which highlights the role of the caregiver’s presence in engagement of attachment brain circuitry and suppressing threat processing by the amygdala. These data suggest that trauma experienced directly from an abusive caregiver and trauma experienced in the presence of caregiver cues produce similar neurobehavioral deficits, which are unique from those resulting from trauma alone. We go on to integrate this information into social experience throughout the lifespan, including consequences for complex scenarios, such as dominance hierarchy formation and maintenance.

Global optimization and sensitivity analysis

International Nuclear Information System (INIS)

Cacuci, D.G.

1990-01-01

A new direction for the analysis of nonlinear models of nuclear systems is suggested to overcome fundamental limitations of sensitivity analysis and optimization methods currently prevalent in nuclear engineering usage. This direction is toward a global analysis of the behavior of the respective system as its design parameters are allowed to vary over their respective design ranges. Presented is a methodology for global analysis that unifies and extends the current scopes of sensitivity analysis and optimization by identifying all the critical points (maxima, minima) and solution bifurcation points together with corresponding sensitivities at any design point of interest. The potential applicability of this methodology is illustrated with test problems involving multiple critical points and bifurcations and comprising both equality and inequality constraints

Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS).

Science.gov (United States)

Kuemmerle-Deschner, Jasmin B; Ozen, Seza; Tyrrell, Pascal N; Kone-Paut, Isabelle; Goldbach-Mansky, Raphaela; Lachmann, Helen; Blank, Norbert; Hoffman, Hal M; Weissbarth-Riedel, Elisabeth; Hugle, Boris; Kallinich, Tilmann; Gattorno, Marco; Gul, Ahmet; Ter Haar, Nienke; Oswald, Marlen; Dedeoglu, Fatma; Cantarini, Luca; Benseler, Susanne M

2017-06-01

Cryopyrin-associated periodic syndrome (CAPS) is a rare, heterogeneous disease entity associated with NLRP3 gene mutations and increased interleukin-1 (IL-1) secretion. Early diagnosis and rapid initiation of IL-1 inhibition prevent organ damage. The aim of the study was to develop and validate diagnostic criteria for CAPS. An innovative process was followed including interdisciplinary team building, item generation: review of CAPS registries, systematic literature review, expert surveys, consensus conferences for item refinement, item reduction and weighting using 1000Minds decision software. Resulting CAPS criteria were tested in large cohorts of CAPS cases and controls using correspondence analysis. Diagnostic models were explored using sensitivity analyses. The international team included 16 experts. Systematic literature and registry review identified 33 CAPS-typical items; the consensus conferences reduced these to 14. 1000Minds exercises ranked variables based on importance for the diagnosis. Correspondence analysis determined variables consistently associated with the diagnosis of CAPS using 284 cases and 837 controls. Seven variables were significantly associated with CAPS (pCAPS-typical symptoms: urticaria-like rash, cold-triggered episodes, sensorineural hearing loss, musculoskeletal symptoms, chronic aseptic meningitis and skeletal abnormalities. Sensitivity was 81%, specificity 94%. It performed well for all CAPS subtypes and regardless of NLRP3 mutation. The novel approach integrated traditional methods of evidence synthesis with expert consensus, web-based decision tools and innovative statistical methods and may serve as model for other rare diseases. These criteria will enable a rapid diagnosis for children and adults with CAPS. 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/.

Description of 15 DNA-positive and antibody-negative "window-period" blood donations identified during prospective screening for Babesia microti.

Science.gov (United States)

Moritz, Erin D; Tonnetti, Laura; Hewins, Mary Ellen; Berardi, Victor P; Dodd, Roger Y; Stramer, Susan L

2017-07-01

Blood donation screening detecting only antibodies fails to identify donors in the earliest stage of infection, before a detectable immunologic response, that is, the "window period" (WP). We present data on WP donations identified during prospective screening for Babesia microti, a transfusion-transmissible parasite of increasing concern in the United States. Blood donations collected in Connecticut, Massachusetts, Minnesota, and Wisconsin were screened using polymerase chain reaction (PCR) and arrayed fluorescence immunoassay (AFIA) to detect B. microti DNA and antibodies, respectively. Parasite loads were estimated using quantitative PCR. Red blood cell (RBC) samples were inoculated into hamsters to assess infectivity. Donors screening reactive were indefinitely deferred, tested by supplemental methods, and followed to assess DNA and antibody clearance. Demographic data from WP donors (i.e., those screening PCR positive and AFIA negative) were compared to data from other positive donors. Of 220,479 donations screened from June 2012 to August 2016, a total of 700 were positive, of which 15 (2% of positive donations or 1 per 14,699 screened donations) were confirmed WP donations. The median estimated parasite load in WP donations was 350 parasites/mL, no different than AFIA-positive and PCR-positive donors. Parasite loads in RBC samples from WP units ranged from 14 to 11,022 parasites/mL; RBC samples from three of 10 (30%) WP donations infected hamsters. The mean age of WP donors was 48 years (range, 17-75 years); three (20%) were female. WP donor demographics did not differ significantly from demographics of other donors. We report one per 15,000 B. microti WP infections in blood donors in endemic areas, demonstrating the importance of nucleic acid testing to mitigate the risk of transfusion-transmitted babesiosis. © 2017 AABB.

Olfactory sensitivity of Pacific Lampreys to lamprey bile acids

Science.gov (United States)

Robinson, T. Craig; Sorensen, Peter W.; Bayer, Jennifer M.; Seelye, James G.

2009-01-01

Pacific lampreys Lampetra tridentata are in decline throughout much of their historical range in the Columbia River basin. In support of restoration efforts, we tested whether larval and adult lamprey bile acids serve as migratory and spawning pheromones in adult Pacific lampreys, as they do in sea lampreys Petromyzon marinus. The olfactory sensitivity of adult Pacific lampreys to lamprey bile acids was measured by electro-olfactogram recording from the time of their capture in the spring until their spawning in June of the following year. As controls, we tested L-arginine and a non-lamprey bile acid, taurolithocholic acid 3-sulfate (TLS). Migrating adult Pacific lampreys were highly sensitive to petromyzonol sulfate (a component of the sea lamprey migratory pheromone) and 3-keto petromyzonol sulfate (a component of the sea lamprey sex pheromone) when first captured. This sensitivity persisted throughout their long migratory and overwinter holding period before declining to nearly unmeasurable levels by the time of spawning. The absolute magnitudes of adult Pacific lamprey responses to lamprey bile acids were smaller than those of the sea lamprey, and unlike the sea lamprey, the Pacific lamprey did not appear to detect TLS. No sexual dimorphism was noted in olfactory sensitivity. Thus, Pacific lampreys are broadly similar to sea lampreys in showing sensitivity to the major lamprey bile acids but apparently differ in having a longer period of sensitivity to those acids. The potential utility of bile acid-like pheromones in the restoration of Pacific lampreys warrants their further investigation in this species.

Periodically poled silicon

Science.gov (United States)

Hon, Nick K.; Tsia, Kevin K.; Solli, Daniel R.; Khurgin, Jacob B.; Jalali, Bahram

2010-02-01

Bulk centrosymmetric silicon lacks second-order optical nonlinearity χ(2) - a foundational component of nonlinear optics. Here, we propose a new class of photonic device which enables χ(2) as well as quasi-phase matching based on periodic stress fields in silicon - periodically-poled silicon (PePSi). This concept adds the periodic poling capability to silicon photonics, and allows the excellent crystal quality and advanced manufacturing capabilities of silicon to be harnessed for devices based on χ(2)) effects. The concept can also be simply achieved by having periodic arrangement of stressed thin films along a silicon waveguide. As an example of the utility, we present simulations showing that mid-wave infrared radiation can be efficiently generated through difference frequency generation from near-infrared with a conversion efficiency of 50% based on χ(2) values measurements for strained silicon reported in the literature [Jacobson et al. Nature 441, 199 (2006)]. The use of PePSi for frequency conversion can also be extended to terahertz generation. With integrated piezoelectric material, dynamically control of χ(2)nonlinearity in PePSi waveguide may also be achieved. The successful realization of PePSi based devices depends on the strength of the stress induced χ(2) in silicon. Presently, there exists a significant discrepancy in the literature between the theoretical and experimentally measured values. We present a simple theoretical model that produces result consistent with prior theoretical works and use this model to identify possible reasons for this discrepancy.

Validation of case-finding algorithms derived from administrative data for identifying adults living with human immunodeficiency virus infection.

Directory of Open Access Journals (Sweden)

Tony Antoniou

Full Text Available OBJECTIVE: We sought to validate a case-finding algorithm for human immunodeficiency virus (HIV infection using administrative health databases in Ontario, Canada. METHODS: We constructed 48 case-finding algorithms using combinations of physician billing claims, hospital and emergency room separations and prescription drug claims. We determined the test characteristics of each algorithm over various time frames for identifying HIV infection, using data abstracted from the charts of 2,040 randomly selected patients receiving care at two medical practices in Toronto, Ontario as the reference standard. RESULTS: With the exception of algorithms using only a single physician claim, the specificity of all algorithms exceeded 99%. An algorithm consisting of three physician claims over a three year period had a sensitivity and specificity of 96.2% (95% CI 95.2%-97.9% and 99.6% (95% CI 99.1%-99.8%, respectively. Application of the algorithm to the province of Ontario identified 12,179 HIV-infected patients in care for the period spanning April 1, 2007 to March 31, 2009. CONCLUSIONS: Case-finding algorithms generated from administrative data can accurately identify adults living with HIV. A relatively simple "3 claims in 3 years" definition can be used for assembling a population-based cohort and facilitating future research examining trends in health service use and outcomes among HIV-infected adults in Ontario.

Evolution of periodicity in periodical cicadas.

Science.gov (United States)

Ito, Hiromu; Kakishima, Satoshi; Uehara, Takashi; Morita, Satoru; Koyama, Takuya; Sota, Teiji; Cooley, John R; Yoshimura, Jin

2015-09-14

Periodical cicadas (Magicicada spp.) in the USA are famous for their unique prime-numbered life cycles of 13 and 17 years and their nearly perfectly synchronized mass emergences. Because almost all known species of cicada are non-periodical, periodicity is assumed to be a derived state. A leading hypothesis for the evolution of periodicity in Magicicada implicates the decline in average temperature during glacial periods. During the evolution of periodicity, the determinant of maturation in ancestral cicadas is hypothesized to have switched from size dependence to time (period) dependence. The selection for the prime-numbered cycles should have taken place only after the fixation of periodicity. Here, we build an individual-based model of cicadas under conditions of climatic cooling to explore the fixation of periodicity. In our model, under cold environments, extremely long juvenile stages lead to extremely low adult densities, limiting mating opportunities and favouring the evolution of synchronized emergence. Our results indicate that these changes, which were triggered by glacial cooling, could have led to the fixation of periodicity in the non-periodical ancestors.

Dynamic modeling and sensitivity analysis of solar thermal energy conversion systems

Science.gov (United States)

Hamilton, C. L.

1977-01-01

Since the energy input to solar thermal conversion systems is both time variant and probabilistic, it is unlikely that simple steady-state methods for estimating lifetime performance will provide satisfactory results. The work described here uses dynamic modeling to begin identifying what must be known about input radiation and system dynamic characteristics to estimate performance reliably. Daily operation of two conceptual solar energy systems was simulated under varying operating strategies with time-dependent radiation intensity ranging from smooth input of several magnitudes to input of constant total energy whose intensity oscillated with periods from 1/4 hour to 6 hours. Integrated daily system output and efficiency were functions of both level and dynamic characteristics of insolation. Sensitivity of output to changes in total input was greater than one.

Using Long-Term Satellite Observations to Identify Sensitive Regimes and Active Regions of Aerosol Indirect Effects for Liquid Clouds Over Global Oceans

Science.gov (United States)

Zhao, Xuepeng; Liu, Yangang; Yu, Fangquan; Heidinger, Andrew K.

2018-01-01

Long-term (1981-2011) satellite climate data records of clouds and aerosols are used to investigate the aerosol-cloud interaction of marine water cloud from a climatology perspective. Our focus is on identifying the regimes and regions where the aerosol indirect effects (AIEs) are evident in long-term averages over the global oceans through analyzing the correlation features between aerosol loading and the key cloud variables including cloud droplet effective radius (CDER), cloud optical depth (COD), cloud water path (CWP), cloud top height (CTH), and cloud top temperature (CTT). An aerosol optical thickness (AOT) range of 0.13 change of long-term averaged CDER appears only in limited oceanic regions. The signature of aerosol invigoration of water clouds as revealed by the increase of cloud cover fraction (CCF) and CTH with increasing AOT at the middle/high latitudes of both hemispheres is identified for a pristine atmosphere (AOT polluted marine atmosphere (AOT > 0.3) in the tropical convergence zones. The regions where the second AIE is likely to manifest in the CCF change are limited to several oceanic areas with high CCF of the warm water clouds near the western coasts of continents. The second AIE signature as represented by the reduction of the precipitation efficiency with increasing AOT is more likely to be observed in the AOT regime of 0.08 < AOT < 0.4. The corresponding AIE active regions manifested themselves as the decline of the precipitation efficiency are mainly limited to the oceanic areas downwind of continental aerosols. The sensitive regime of the conventional AIE identified in this observational study is likely associated with the transitional regime from the aerosol-limited regime to the updraft-limited regime identified for aerosol-cloud interaction in cloud model simulations.

Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci

DEFF Research Database (Denmark)

Walford, Geoffrey A; Gustafsson, Stefan; Rybin, Denis

2016-01-01

of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-related traits Consortium. Discovery was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested...

Machine Learning Approaches for Predicting Human Skin Sensitization Hazard

Science.gov (United States)

One of ICCVAM’s top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary for a substance to elicit a skin sensitization reaction suggests that no single in chemico, in vit...

A spatio-temporal synchronization of periodic markets: evidence ...

African Journals Online (AJOL)

This study seeks to identify the 'rings' of periodic market days in Akwa Ibom State, using eighteen periodic markets as case study The entire landmass of the state was covered with a network of grids. These grids were numbered and a table of random numbers was used in selecting a target population of eighteen ...

FEAST: sensitive local alignment with multiple rates of evolution.

Science.gov (United States)

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/.

Methods for identifying 30 chronic conditions: application to administrative data.

Science.gov (United States)

Tonelli, Marcello; Wiebe, Natasha; Fortin, Martin; Guthrie, Bruce; Hemmelgarn, Brenda R; James, Matthew T; Klarenbach, Scott W; Lewanczuk, Richard; Manns, Braden J; Ronksley, Paul; Sargious, Peter; Straus, Sharon; Quan, Hude

2015-04-17

Multimorbidity is common and associated with poor clinical outcomes and high health care costs. Administrative data are a promising tool for studying the epidemiology of multimorbidity. Our goal was to derive and apply a new scheme for using administrative data to identify the presence of chronic conditions and multimorbidity. We identified validated algorithms that use ICD-9 CM/ICD-10 data to ascertain the presence or absence of 40 morbidities. Algorithms with both positive predictive value and sensitivity ≥70% were graded as "high validity"; those with positive predictive value ≥70% and sensitivity <70% were graded as "moderate validity". To show proof of concept, we applied identified algorithms with high to moderate validity to inpatient and outpatient claims and utilization data from 574,409 people residing in Edmonton, Canada during the 2008/2009 fiscal year. Of the 40 morbidities, we identified 30 that could be identified with high to moderate validity. Approximately one quarter of participants had identified multimorbidity (2 or more conditions), one quarter had a single identified morbidity and the remaining participants were not identified as having any of the 30 morbidities. We identified a panel of 30 chronic conditions that can be identified from administrative data using validated algorithms, facilitating the study and surveillance of multimorbidity. We encourage other groups to use this scheme, to facilitate comparisons between settings and jurisdictions.

Local sensitivity analysis for inverse problems solved by singular value decomposition

Science.gov (United States)

Hill, M.C.; Nolan, B.T.

2010-01-01

Local sensitivity analysis provides computationally frugal ways to evaluate models commonly used for resource management, risk assessment, and so on. This includes diagnosing inverse model convergence problems caused by parameter insensitivity and(or) parameter interdependence (correlation), understanding what aspects of the model and data contribute to measures of uncertainty, and identifying new data likely to reduce model uncertainty. Here, we consider sensitivity statistics relevant to models in which the process model parameters are transformed using singular value decomposition (SVD) to create SVD parameters for model calibration. The statistics considered include the PEST identifiability statistic, and combined use of the process-model parameter statistics composite scaled sensitivities and parameter correlation coefficients (CSS and PCC). The statistics are complimentary in that the identifiability statistic integrates the effects of parameter sensitivity and interdependence, while CSS and PCC provide individual measures of sensitivity and interdependence. PCC quantifies correlations between pairs or larger sets of parameters; when a set of parameters is intercorrelated, the absolute value of PCC is close to 1.00 for all pairs in the set. The number of singular vectors to include in the calculation of the identifiability statistic is somewhat subjective and influences the statistic. To demonstrate the statistics, we use the USDA’s Root Zone Water Quality Model to simulate nitrogen fate and transport in the unsaturated zone of the Merced River Basin, CA. There are 16 log-transformed process-model parameters, including water content at field capacity (WFC) and bulk density (BD) for each of five soil layers. Calibration data consisted of 1,670 observations comprising soil moisture, soil water tension, aqueous nitrate and bromide concentrations, soil nitrate concentration, and organic matter content. All 16 of the SVD parameters could be estimated by

Preliminary sensitivity analyses of corrosion models for BWIP [Basalt Waste Isolation Project] container materials

International Nuclear Information System (INIS)

Anantatmula, R.P.

1984-01-01

A preliminary sensitivity analysis was performed for the corrosion models developed for Basalt Waste Isolation Project container materials. The models describe corrosion behavior of the candidate container materials (low carbon steel and Fe9Cr1Mo), in various environments that are expected in the vicinity of the waste package, by separate equations. The present sensitivity analysis yields an uncertainty in total uniform corrosion on the basis of assumed uncertainties in the parameters comprising the corrosion equations. Based on the sample scenario and the preliminary corrosion models, the uncertainty in total uniform corrosion of low carbon steel and Fe9Cr1Mo for the 1000 yr containment period are 20% and 15%, respectively. For containment periods ≥ 1000 yr, the uncertainty in corrosion during the post-closure aqueous periods controls the uncertainty in total uniform corrosion for both low carbon steel and Fe9Cr1Mo. The key parameters controlling the corrosion behavior of candidate container materials are temperature, radiation, groundwater species, etc. Tests are planned in the Basalt Waste Isolation Project containment materials test program to determine in detail the sensitivity of corrosion to these parameters. We also plan to expand the sensitivity analysis to include sensitivity coefficients and other parameters in future studies. 6 refs., 3 figs., 9 tabs

[Impact of hypoxia in different periods of prenatal ontogenesis on ECoG of rabbit fetus].

Science.gov (United States)

Guseĭnov, A G; Mamedov, Kh B

2012-10-01

Sensitivity of ECoG of sensorimotor cortex of 28-day rabbit foetus in different periods (prefetal and fetal) of embryogenesis to hypoxia impact was studied. In the foetus subjected to hypoxia during prefetal period (8-18th days) in the spectrum of the general activity the increase of slow waves, occupying little portion of the spectrum, is noticed, while the main delta-rhythm has more clear pattern. At the same time, hypoxia, undertaken in the fetal period (18-28th days) does not have significant effect on ECoG indexes. On the basis of our own and literature data one can propose tha high sensitivity of ECoG to oxygen deficiency is due to low stability of the brain cortex itself and subcortical white matter to hypoxic inpairement in early embriogenesis.

Widely tunable asymmetric long-period fiber grating with high sensitivity using optical polymer on laser-ablated cladding.

Science.gov (United States)

Chen, Nan-Kuang; Hsu, Der-Yi; Chi, Sien

2007-08-01

We demonstrate high-efficiency, wideband-tunable, laser-ablated long-period fiber gratings that use an optical polymer overlay. Portions of the fiber cladding are periodically removed by CO(2) laser pulses to induce periodic index changes for coupling the core mode into cladding modes. An optical polymer with a high thermo-optic coefficient with a dispersion distinct from that of silica is used on a deep-ablated cladding structure so that the effective indices of cladding modes become dispersive and the resonant wavelengths can be efficiently tuned. The tuning efficiency can be as high as 15.8 nm/ degrees C, and the tuning range can be wider than 105 nm (1545-1650 nm).

Organic dye for highly efficient solid-state dye-sensitized solar cells

Energy Technology Data Exchange (ETDEWEB)

Schmidt-Mende, L.; Bach, U.; Humphry-Baker, R.; Ito, S.; Graetzel, M. [Institut des Sciences et Ingenierie Chimiques (ISIC), Laboratoire de Photonique et Interfaces (LPI), Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne (Switzerland); Horiuchi, T.; Miura, H. [Technology Research Laboratory, Corporate Research Center, Mitsubishi Paper Mills Limited, 46, Wadai, Tsukuba City, Ibaraki 300-4247 (Japan); Uchida, S. [Institute of Multidisciplinary Research for Advanced Materials (IMRAM), Tohoku University, 1-1 Katahira 2-chome, Aoba-ku, Sendai 980-8577 (Japan)

2005-04-04

The feasibility of solid-state dye-sensitized solar cells as a low-cost alternative to amorphous silicon cells is demonstrated. Such a cell with a record efficiency of over 4 % under simulated sunlight is reported, made possible by using a new organic metal-free indoline dye as the sensitizer with high absorption coefficient. (Abstract Copyright [2005], Wiley Periodicals, Inc.)

Sensitivity and Nonlinearity of Thermoacoustic Oscillations

Science.gov (United States)

Juniper, Matthew P.; Sujith, R. I.

2018-01-01

Nine decades of rocket engine and gas turbine development have shown that thermoacoustic oscillations are difficult to predict but can usually be eliminated with relatively small ad hoc design changes. These changes can, however, be ruinously expensive to devise. This review explains why linear and nonlinear thermoacoustic behavior is so sensitive to parameters such as operating point, fuel composition, and injector geometry. It shows how nonperiodic behavior arises in experiments and simulations and discusses how fluctuations in thermoacoustic systems with turbulent reacting flow, which are usually filtered or averaged out as noise, can reveal useful information. Finally, it proposes tools to exploit this sensitivity in the future: adjoint-based sensitivity analysis to optimize passive control designs and complex systems theory to warn of impending thermoacoustic oscillations and to identify the most sensitive elements of a thermoacoustic system.

A low-fat diet improves peripheral insulin sensitivity in patients with Type 1 diabetes

DEFF Research Database (Denmark)

Rosenfalck, A M; Almdal, T; Viggers, L

2006-01-01

To compare the effects on insulin sensitivity, body composition and glycaemic control of the recommended standard weight-maintaining diabetes diet and an isocaloric low-fat diabetes diet during two, 3-month periods in patients with Type 1 diabetes.......To compare the effects on insulin sensitivity, body composition and glycaemic control of the recommended standard weight-maintaining diabetes diet and an isocaloric low-fat diabetes diet during two, 3-month periods in patients with Type 1 diabetes....

Sensitivity of system stability to model structure

Science.gov (United States)

Hosack, G.R.; Li, H.W.; Rossignol, P.A.

2009-01-01

A community is stable, and resilient, if the levels of all community variables can return to the original steady state following a perturbation. The stability properties of a community depend on its structure, which is the network of direct effects (interactions) among the variables within the community. These direct effects form feedback cycles (loops) that determine community stability. Although feedback cycles have an intuitive interpretation, identifying how they form the feedback properties of a particular community can be intractable. Furthermore, determining the role that any specific direct effect plays in the stability of a system is even more daunting. Such information, however, would identify important direct effects for targeted experimental and management manipulation even in complex communities for which quantitative information is lacking. We therefore provide a method that determines the sensitivity of community stability to model structure, and identifies the relative role of particular direct effects, indirect effects, and feedback cycles in determining stability. Structural sensitivities summarize the degree to which each direct effect contributes to stabilizing feedback or destabilizing feedback or both. Structural sensitivities prove useful in identifying ecologically important feedback cycles within the community structure and for detecting direct effects that have strong, or weak, influences on community stability. The approach may guide the development of management intervention and research design. We demonstrate its value with two theoretical models and two empirical examples of different levels of complexity. ?? 2009 Elsevier B.V. All rights reserved.

Rock disposal problems identified

Energy Technology Data Exchange (ETDEWEB)

Knox, R

1978-06-01

Mathematical models are the only way of examining the return of radioactivity from nuclear waste to the environment over long periods of time. Work in Britain has helped identify areas where more basic data is required, but initial results look very promising for final disposal of high level waste in hard rock repositories. A report by the National Radiological Protection Board of a recent study, is examined.

Current knowledge of environmental exposure in children during the sensitive developmental periods

Directory of Open Access Journals (Sweden)

Norma Helena Perlroth

2017-01-01

Conclusion: To identify the causes and understand the mechanisms involved in the genesis of these diseases is a challenge for science, as there is still a lack of knowledge on children's susceptibility to many environmental contaminants. Prevention policies and more research on child environmental health, improving the recording and surveillance of environmental risks to children's health, should be an ongoing priority in the public health field.

An in vitro human skin test for assessing sensitization potential.

Science.gov (United States)

Ahmed, S S; Wang, X N; Fielding, M; Kerry, A; Dickinson, I; Munuswamy, R; Kimber, I; Dickinson, A M

2016-05-01

Sensitization to chemicals resulting in an allergy is an important health issue. The current gold-standard method for identification and characterization of skin-sensitizing chemicals was the mouse local lymph node assay (LLNA). However, for a number of reasons there has been an increasing imperative to develop alternative approaches to hazard identification that do not require the use of animals. Here we describe a human in-vitro skin explant test for identification of sensitization hazards and the assessment of relative skin sensitizing potency. This method measures histological damage in human skin as a readout of the immune response induced by the test material. Using this approach we have measured responses to 44 chemicals including skin sensitizers, pre/pro-haptens, respiratory sensitizers, non-sensitizing chemicals (including skin-irritants) and previously misclassified compounds. Based on comparisons with the LLNA, the skin explant test gave 95% specificity, 95% sensitivity, 95% concordance with a correlation coefficient of 0.9. The same specificity and sensitivity were achieved for comparison of results with published human sensitization data with a correlation coefficient of 0.91. The test also successfully identified nickel sulphate as a human skin sensitizer, which was misclassified as negative in the LLNA. In addition, sensitizers and non-sensitizers identified as positive or negative by the skin explant test have induced high/low T cell proliferation and IFNγ production, respectively. Collectively, the data suggests the human in-vitro skin explant test could provide the basis for a novel approach for characterization of the sensitizing activity as a first step in the risk assessment process. Copyright © 2015 John Wiley & Sons, Ltd.

Polarization-sensitive color in butterfly scales: polarization conversion from ridges with reflecting elements.

Science.gov (United States)

Zhang, Ke; Tang, Yiwen; Meng, Jinsong; Wang, Ge; Zhou, Han; Fan, Tongxiang; Zhang, Di

2014-11-03

Polarization-sensitive color originates from polarization-dependent reflection or transmission, exhibiting abundant light information, including intensity, spectral distribution, and polarization. A wide range of butterflies are physiologically sensitive to polarized light, but the origins of polarized signal have not been fully understood. Here we systematically investigate the colorful scales of six species of butterfly to reveal the physical origins of polarization-sensitive color. Microscopic optical images under crossed polarizers exhibit their polarization-sensitive characteristic, and micro-structural characterizations clarify their structural commonality. In the case of the structural scales that have deep ridges, the polarization-sensitive color related with scale azimuth is remarkable. Periodic ridges lead to the anisotropic effective refractive indices in the parallel and perpendicular grating orientations, which achieves form-birefringence, resulting in the phase difference of two different component polarized lights. Simulated results show that ridge structures with reflecting elements reflect and rotate the incident p-polarized light into s-polarized light. The dimensional parameters and shapes of grating greatly affect the polarization conversion process, and the triangular deep grating extends the outstanding polarization conversion effect from the sub-wavelength period to the period comparable to visible light wavelength. The parameters of ridge structures in butterfly scales have been optimized to fulfill the polarization-dependent reflection for secret communication. The structural and physical origin of polarization conversion provides a more comprehensive perspective on the creation of polarization-sensitive color in butterfly wing scales. These findings show great potential in anti-counterfeiting technology and advanced optical material design.

Price Sensitivity of Demand for Prescription Drugs

DEFF Research Database (Denmark)

Skipper, Lars; Simonsen, Marianne; Skipper, Niels

This paper investigates price sensitivity of demand for prescription drugs using drug purchase records for at 20% random sample of the Danish population. We identify price responsiveness by exploiting exogenous variation in prices caused by kinked reimbursement schemes and implement a regression ...... education and income are, however, more responsive to the price. Also, essential drugs that prevent deterioration in health and prolong life have lower associated average price sensitivity....

A Synthetic Lethality Screen Using a Focused siRNA Library to Identify Sensitizers to Dasatinib Therapy for the Treatment of Epithelial Ovarian Cancer.

Directory of Open Access Journals (Sweden)

Harsh B Pathak

Full Text Available Molecular targeted therapies have been the focus of recent clinical trials for the treatment of patients with recurrent epithelial ovarian cancer (EOC. The majority have not fared well as monotherapies for improving survival of these patients. Poor bioavailability, lack of predictive biomarkers, and the presence of multiple survival pathways can all diminish the success of a targeted agent. Dasatinib is a tyrosine kinase inhibitor of the Src-family kinases (SFK and in preclinical studies shown to have substantial activity in EOC. However, when evaluated in a phase 2 clinical trial for patients with recurrent or persistent EOC, it was found to have minimal activity. We hypothesized that synthetic lethality screens performed using a cogently designed siRNA library would identify second-site molecular targets that could synergize with SFK inhibition and improve dasatinib efficacy. Using a systematic approach, we performed primary siRNA screening using a library focused on 638 genes corresponding to a network centered on EGFR, HER2, and the SFK-scaffolding proteins BCAR1, NEDD9, and EFS to screen EOC cells in combination with dasatinib. We followed up with validation studies including deconvolution screening, quantitative PCR to confirm effective gene silencing, correlation of gene expression with dasatinib sensitivity, and assessment of the clinical relevance of hits using TCGA ovarian cancer data. A refined list of five candidates (CSNK2A1, DAG1, GRB2, PRKCE, and VAV1 was identified as showing the greatest potential for improving sensitivity to dasatinib in EOC. Of these, CSNK2A1, which codes for the catalytic alpha subunit of protein kinase CK2, was selected for additional evaluation. Synergistic activity of the clinically relevant inhibitor of CK2, CX-4945, with dasatinib in reducing cell proliferation and increasing apoptosis was observed across multiple EOC cell lines. This overall approach to improving drug efficacy can be applied to other

Periodic optical variability of radio-detected ultracool dwarfs

International Nuclear Information System (INIS)

Harding, L. K.; Golden, A.; Singh, Navtej; Sheehan, B.; Butler, R. F.; Hallinan, G.; Boyle, R. P.; Zavala, R. T.

2013-01-01

A fraction of very low mass stars and brown dwarfs are known to be radio active, in some cases producing periodic pulses. Extensive studies of two such objects have also revealed optical periodic variability, and the nature of this variability remains unclear. Here, we report on multi-epoch optical photometric monitoring of six radio-detected dwarfs, spanning the ∼M8-L3.5 spectral range, conducted to investigate the ubiquity of periodic optical variability in radio-detected ultracool dwarfs. This survey is the most sensitive ground-based study carried out to date in search of periodic optical variability from late-type dwarfs, where we obtained 250 hr of monitoring, delivering photometric precision as low as ∼0.15%. Five of the six targets exhibit clear periodicity, in all cases likely associated with the rotation period of the dwarf, with a marginal detection found for the sixth. Our data points to a likely association between radio and optical periodic variability in late-M/early-L dwarfs, although the underlying physical cause of this correlation remains unclear. In one case, we have multiple epochs of monitoring of the archetype of pulsing radio dwarfs, the M9 TVLM 513–46546, spanning a period of 5 yr, which is sufficiently stable in phase to allow us to establish a period of 1.95958 ± 0.00005 hr. This phase stability may be associated with a large-scale stable magnetic field, further strengthening the correlation between radio activity and periodic optical variability. Finally, we find a tentative spin-orbit alignment of one component of the very low mass binary, LP 349–25.

Periodic optical variability of radio-detected ultracool dwarfs

Energy Technology Data Exchange (ETDEWEB)

Harding, L. K.; Golden, A.; Singh, Navtej; Sheehan, B.; Butler, R. F. [Centre for Astronomy, National University of Ireland, Galway, University Road, Galway (Ireland); Hallinan, G. [Cahill Center for Astrophysics, California Institute of Technology, 1200 East California Boulevard, MC 249-17, Pasadena, CA 91125 (United States); Boyle, R. P. [Vatican Observatory Research Group, Steward Observatory, University of Arizona, Tucson, AZ 85721 (United States); Zavala, R. T., E-mail: lkh@astro.caltech.edu [United States Naval Observatory, Flagstaff Station, Flagstaff, AZ 86001 (United States)

2013-12-20

A fraction of very low mass stars and brown dwarfs are known to be radio active, in some cases producing periodic pulses. Extensive studies of two such objects have also revealed optical periodic variability, and the nature of this variability remains unclear. Here, we report on multi-epoch optical photometric monitoring of six radio-detected dwarfs, spanning the ∼M8-L3.5 spectral range, conducted to investigate the ubiquity of periodic optical variability in radio-detected ultracool dwarfs. This survey is the most sensitive ground-based study carried out to date in search of periodic optical variability from late-type dwarfs, where we obtained 250 hr of monitoring, delivering photometric precision as low as ∼0.15%. Five of the six targets exhibit clear periodicity, in all cases likely associated with the rotation period of the dwarf, with a marginal detection found for the sixth. Our data points to a likely association between radio and optical periodic variability in late-M/early-L dwarfs, although the underlying physical cause of this correlation remains unclear. In one case, we have multiple epochs of monitoring of the archetype of pulsing radio dwarfs, the M9 TVLM 513–46546, spanning a period of 5 yr, which is sufficiently stable in phase to allow us to establish a period of 1.95958 ± 0.00005 hr. This phase stability may be associated with a large-scale stable magnetic field, further strengthening the correlation between radio activity and periodic optical variability. Finally, we find a tentative spin-orbit alignment of one component of the very low mass binary, LP 349–25.

Sensitization predicts asthma development among wheezing toddlers in secondary healthcare.

Science.gov (United States)

Boersma, Nienke A; Meijneke, Ruud W H; Kelder, Johannes C; van der Ent, Cornelis K; Balemans, Walter A F

2017-06-01

Some wheezing toddlers develop asthma later in childhood. Sensitization is known to predict asthma in birth cohorts. However, its predictive value in secondary healthcare is uncertain. This study examines the predictive value of sensitization to inhalant allergens among wheezing toddlers in secondary healthcare for the development of asthma at school age (≥6 years). Preschool children (1-3 years) who presented with wheezing in secondary healthcare were screened on asthma at school age with the International Study of Asthma and Allergies in Childhood questionnaire. The positive and negative predictive value (PPV and NPV) of specific IgE to inhalant allergens (cut-off concentration 0.35 kU/L) and several non-invasive variables from a child's history (such as hospitalization, eczema, and parental atopy) were calculated. The additional predictive value of sensitization when combined with non-invasive predictors was examined in multivariate analysis and by ROC curves. Of 116 included children, 63% developed asthma at school age. Sensitization to inhalant allergens was a strong asthma predictor. The odds ratio (OR), PPV and NPV were 7.4%, 86%, and 55%, respectively. Eczema (OR 3.4) and hospital admission (OR 2.6) were significant non-invasive determinants. Adding sensitization to these non-invasive predictors in multivariate analysis resulted in a significantly better asthma prediction. The area under the ROC curve increased from 0.70 with only non-invasive predictors to 0.79 after adding sensitization. Sensitization to inhalant allergens is a strong predictor of school age asthma in secondary healthcare and has added predictive value when combined with non-invasive determinants. Pediatr Pulmonol. 2017;52:729-736. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Identification and quality assessment of beverages using a long period grating fibre-optic sensor modified with a mesoporous thin film

Directory of Open Access Journals (Sweden)

Sergiy Korposh

2014-08-01

Full Text Available In this study, an optical fibre long period grating (LPG sensor functionalised with a mesoporous thin film was employed for the identification and quality assessment of beverages. The principle of the discrimination of beverages using an LPG sensor is based on the measurement of the change in refractive index of a sensitive film, induced by the binding of the chemical compounds present in the beverage. The sensitive film deposited onto the LPG consisted of poly(allylamine hydrochloride (PAH and silica nanospheres (SiO2 NPs with diameters ranging from 40 nm to 50 nm. PAH imparts selectivity, while the SiO2 NPs endow the film with high porosity and enhanced sensitivity. In this study, five different types of beverages, red and white wines, brandy, nihonshyu (sake, a Japanese rice wine, and shochu (a Japanese distilled beverage, prepared via distillation and fermentation, were used to assess the capability of the sensor to identify the origin of the beverages. In addition, a selection of red wines was used to evaluate the use of the sensor in the assessment of the quality of beverages. The results obtained were benchmarked against those obtained using gas chromatography–mass spectrometry for the determination of volatile compounds contributing to the flavours of a set of red wines. Principal component analysis (PCA was employed for data analysis. This approach enabled both quality assessment of beverages and identification of the methods and materials used for their preparation. Keywords: Long period grating, Mesoporous thin film, Layer-by-layer, Quality assessment, Beverages

The Effect of Applied Tensile Stress on Localized Corrosion in Sensitized AA5083

Science.gov (United States)

2015-09-01

corrosion, but if exposed to elevated temperature for prolonged periods of time the alloy becomes sensitized. Since the β phase is more anodic than the...degree of localized corrosion for sensitized AA5083 under an applied tensile stress. AA5083 is an aluminum -magnesium alloy that experiences severe...direction. 14. SUBJECT TERMS Aluminum alloy , AA5083, IGSCC, intergranular stress corrosion cracking, localized corrosion, sensitized aluminum 15

IDENTIFIABILITY VERSUS HETEROGENEITY IN GROUNDWATER MODELING SYSTEMS

Directory of Open Access Journals (Sweden)

A M BENALI

2003-06-01

Full Text Available Review of history matching of reservoirs parameters in groundwater flow raises the problem of identifiability of aquifer systems. Lack of identifiability means that there exists parameters to which the heads are insensitive. From the guidelines of the study of the homogeneous case, we inspect the identifiability of the distributed transmissivity field of heterogeneous groundwater aquifers. These are derived from multiple realizations of a random function Y = log T  whose probability distribution function is normal. We follow the identifiability of the autocorrelated block transmissivities through the measure of the sensitivity of the local derivatives DTh = (∂hi  ∕ ∂Tj computed for each sample of a population N (0; σY, αY. Results obtained from an analysis of Monte Carlo type suggest that the more a system is heterogeneous, the less it is identifiable.

The ultra-sensitive Nodewalk technique identifies stochastic from virtual, population-based enhancer hubs regulating MYC in 3D: Implications for the fitness of cancer cells

KAUST Repository

Sumida, Noriyuki; Sifakis, Emmanouil; Scholz, Barbara A; Fernandez Woodbridge, Alejandro; Kiani, Narsis A.; Gomez-Cabrero, David; Svensson, J Peter; Tegner, Jesper; Gondor, Anita; Ohlsson, Rolf

2018-01-01

The relationship between stochastic transcriptional bursts and dynamic 3D chromatin states is not well understood due to poor sensitivity and/or resolution of current chromatin structure-based assays. Consequently, it is not well established if enhancers operate individually and/or in clusters to coordinate gene transcription. In the current study, we introduce Nodewalk, which uniquely combines high sensitivity with high resolution to enable the analysis of chromatin networks in minute input material. The >10,000-fold increase in sensitivity over other many-to-all competing methods uncovered that active chromatin hubs identified in large input material, corresponding to 10 000 cells, flanking the MYC locus are primarily virtual. Thus, the close agreement between chromatin interactomes generated from aliquots corresponding to less than 10 cells with randomly re-sampled interactomes, we find that numerous distal enhancers positioned within flanking topologically associating domains (TADs) converge on MYC in largely mutually exclusive manners. Moreover, when comparing with several enhancer baits, the assignment of the MYC locus as the node with the highest dynamic importance index, indicates that it is MYC targeting its enhancers, rather than vice versa. Dynamic changes in the configuration of the boundary between TADs flanking MYC underlie numerous stochastic encounters with a diverse set of enhancers to depict the plasticity of its transcriptional regulation. Such an arrangement might increase the fitness of the cancer cell by increasing the probability of MYC transcription in response to a wide range of environmental cues encountered by the cell during the neoplastic process.

The ultra-sensitive Nodewalk technique identifies stochastic from virtual, population-based enhancer hubs regulating MYC in 3D: Implications for the fitness of cancer cells

KAUST Repository

Sumida, Noriyuki

2018-03-27

The relationship between stochastic transcriptional bursts and dynamic 3D chromatin states is not well understood due to poor sensitivity and/or resolution of current chromatin structure-based assays. Consequently, it is not well established if enhancers operate individually and/or in clusters to coordinate gene transcription. In the current study, we introduce Nodewalk, which uniquely combines high sensitivity with high resolution to enable the analysis of chromatin networks in minute input material. The >10,000-fold increase in sensitivity over other many-to-all competing methods uncovered that active chromatin hubs identified in large input material, corresponding to 10 000 cells, flanking the MYC locus are primarily virtual. Thus, the close agreement between chromatin interactomes generated from aliquots corresponding to less than 10 cells with randomly re-sampled interactomes, we find that numerous distal enhancers positioned within flanking topologically associating domains (TADs) converge on MYC in largely mutually exclusive manners. Moreover, when comparing with several enhancer baits, the assignment of the MYC locus as the node with the highest dynamic importance index, indicates that it is MYC targeting its enhancers, rather than vice versa. Dynamic changes in the configuration of the boundary between TADs flanking MYC underlie numerous stochastic encounters with a diverse set of enhancers to depict the plasticity of its transcriptional regulation. Such an arrangement might increase the fitness of the cancer cell by increasing the probability of MYC transcription in response to a wide range of environmental cues encountered by the cell during the neoplastic process.

Self-similarities of periodic structures for a discrete model of a two-gene system

International Nuclear Information System (INIS)

Souza, S.L.T. de; Lima, A.A.; Caldas, I.L.; Medrano-T, R.O.; Guimarães-Filho, Z.O.

2012-01-01

We report self-similar properties of periodic structures remarkably organized in the two-parameter space for a two-gene system, described by two-dimensional symmetric map. The map consists of difference equations derived from the chemical reactions for gene expression and regulation. We characterize the system by using Lyapunov exponents and isoperiodic diagrams identifying periodic windows, denominated Arnold tongues and shrimp-shaped structures. Period-adding sequences are observed for both periodic windows. We also identify Fibonacci-type series and Golden ratio for Arnold tongues, and period multiple-of-three windows for shrimps. -- Highlights: ► The existence of noticeable periodic windows has been reported recently for several nonlinear systems. ► The periodic window distributions appear highly organized in two-parameter space. ► We characterize self-similar properties of Arnold tongues and shrimps for a two-gene model. ► We determine the period of the Arnold tongues recognizing a Fibonacci-type sequence. ► We explore self-similar features of the shrimps identifying multiple period-three structures.

Self-similarities of periodic structures for a discrete model of a two-gene system

Energy Technology Data Exchange (ETDEWEB)

Souza, S.L.T. de, E-mail: thomaz@ufsj.edu.br [Departamento de Física e Matemática, Universidade Federal de São João del-Rei, Ouro Branco, MG (Brazil); Lima, A.A. [Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, MG (Brazil); Caldas, I.L. [Instituto de Física, Universidade de São Paulo, São Paulo, SP (Brazil); Medrano-T, R.O. [Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo, Diadema, SP (Brazil); Guimarães-Filho, Z.O. [Aix-Marseille Univ., CNRS PIIM UMR6633, International Institute for Fusion Science, Marseille (France)

2012-03-12

We report self-similar properties of periodic structures remarkably organized in the two-parameter space for a two-gene system, described by two-dimensional symmetric map. The map consists of difference equations derived from the chemical reactions for gene expression and regulation. We characterize the system by using Lyapunov exponents and isoperiodic diagrams identifying periodic windows, denominated Arnold tongues and shrimp-shaped structures. Period-adding sequences are observed for both periodic windows. We also identify Fibonacci-type series and Golden ratio for Arnold tongues, and period multiple-of-three windows for shrimps. -- Highlights: ► The existence of noticeable periodic windows has been reported recently for several nonlinear systems. ► The periodic window distributions appear highly organized in two-parameter space. ► We characterize self-similar properties of Arnold tongues and shrimps for a two-gene model. ► We determine the period of the Arnold tongues recognizing a Fibonacci-type sequence. ► We explore self-similar features of the shrimps identifying multiple period-three structures.

A longitudinal study on the maternal–fetal relationship and postnatal maternal sensitivity

NARCIS (Netherlands)

Maas, A.J.B.M.; de Cock, E.S.A.; Vreeswijk, C.M.J.M.; Vingerhoets, A.J.J.M.; van Bakel, H.J.A.

2016-01-01

Objective: The present study examined whether early signs of maternal sensitivity can be detected during pregnancy by focusing on the maternal–fetal relationship and postnatal maternal sensitivity. Background: Earlier research has identified maternal sensitive behaviour as an important factor for

Outcomes sensitive to nursing service quality in ambulatory cancer chemotherapy: Systematic scoping review.

Science.gov (United States)

Griffiths, Peter; Richardson, Alison; Blackwell, Rebecca

2012-07-01

There is long standing interest in identifying patient outcomes that are sensitive to nursing care and an increasing number of systems that include outcomes in order to demonstrate or monitor the quality of nursing care. We undertook scoping reviews of the literature in order to identify patient outcomes sensitive to the quality of nursing services in ambulatory cancer chemotherapy settings to guide the development of an outcomes-based quality measurement system. A 2-stage scoping review to identify potential outcome areas which were subsequently assessed for their sensitivity to nursing was carried out. Data sources included the Cochrane Library, Medline, Embase, the British Nursing Index, Google and Google scholar. We identified a broad range of outcomes potentially sensitive to nursing. Individual trials support many nursing interventions but we found relatively little clear evidence of effect on outcomes derived from systematic reviews and no evidence associating characteristics of nursing services with outcomes. The purpose of identifying a set of outcomes as specifically nurse-sensitive for quality measurement is to give clear responsibility and create an expectation of strong clinical leadership by nurses in terms of monitoring and acting on results. It is important to select those outcomes that nurses have most impact upon. Patient experience, nausea, vomiting, mucositis and safe medication administration were outcome areas most likely to yield sensitive measures of nursing service quality in ambulatory cancer chemotherapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

Forage: a sensitive indicator of airborne radioactivity

International Nuclear Information System (INIS)

Jackson, W.M.; Noakes, J.E.; Spaulding, J.D.

1981-01-01

This paper presents the results of using Ge(Li) γ-ray spectroscopy to measure radioactivity concentration of forage in the vicinity of the Joseph M. Farley Nuclear Plant, Houston County, AL., over a 31/2 yr period. The report period includes 2 yr of pre-operational and 11/2 yr of operational sampling. Although the objective of forage sampling was the measurement of manmade airborne fallout radioactivity, several natural radioisotopes were also found to be present. A summary of natural radioactivity data for all samples measured during the period from August 1975 to December 1978 is given. Approximately 10 days after each of four Chinese atmospheric nuclear tests conducted during the sampling period fresh fission product fallout was measured on the forage. The information from these nuclear tests shows forage sampling to be a convenient and sensitive monitoring tool for airborne fallout radioactivity. (author)

Physical determinants of radiation sensitivity in bacterial spores

International Nuclear Information System (INIS)

Powers, E.L.

1982-01-01

Several factors modifying radiation sensitivity in dry bacterial spores are described and discussed. Vacuum inducing the loss of critical structural water, very low dose rates of radiation from which the cell may recover, radiations of high linear energy transfer, and the action of temperature over long periods of time on previously irradiated cells are recognized from extensive laboratory work as important in determining survival of spores exposed to low radiation doses at low temperatures for long periods of time. Some extensions of laboratory work are proposed

Transcriptome-wide analysis of the Trypanosoma cruzi proliferative cycle identifies the periodically expressed mRNAs and their multiple levels of control.

Directory of Open Access Journals (Sweden)

Santiago Chávez

Full Text Available Trypanosoma cruzi is the protozoan parasite causing American trypanosomiasis or Chagas disease, a neglected parasitosis with important human health impact in Latin America. The efficacy of current therapy is limited, and its toxicity is high. Since parasite proliferation is a fundamental target for rational drug design, we sought to progress into its understanding by applying a genome-wide approach. Treating a TcI linage strain with hydroxyurea, we isolated epimastigotes in late G1, S and G2/M cell cycle stages at 70% purity. The sequencing of each phase identified 305 stage-specific transcripts (1.5-fold change, p≤0.01, coding for conserved cell cycle regulated proteins and numerous proteins whose cell cycle dependence has not been recognized before. Comparisons with the parasite T. brucei and the human host reveal important differences. The meta-analysis of T. cruzi transcriptomic and ribonomic data indicates that cell cycle regulated mRNAs are subject to sub-cellular compartmentalization. Compositional and structural biases of these genes- including CAI, GC content, UTR length, and polycistron position- may contribute to their regulation. To discover nucleotide motifs responsible for the co-regulation of cell cycle regulated genes, we looked for overrepresented motifs at their UTRs and found a variant of the cell cycle sequence motif at the 3' UTR of most of the S and G2 stage genes. We additionally identified hairpin structures at the 5' UTRs of a high proportion of the transcripts, suggesting that periodic gene expression might also rely on translation initiation in T. cruzi. In summary, we report a comprehensive list of T. cruzi cell cycle regulated genes, including many previously unstudied proteins, we show evidence favoring a multi-step control of their expression, and we identify mRNA motifs that may mediate their regulation. Our results provide novel information of the T. cruzi proliferative proteins and the integrated levels of

A periodic table for cancer.

Science.gov (United States)

Epstein, Richard J

2015-01-01

Cancers exhibit differences in metastatic behavior and drug sensitivity that correlate with certain tumor-specific variables such as differentiation grade, growth rate/extent and molecular regulatory aberrations. In practice, patient management is based on the past results of clinical trials adjusted for these biomarkers. Here, it is proposed that treatment strategies could be fine-tuned upfront simply by quantifying tumorigenic spatial (cell growth) and temporal (genetic stability) control losses, as predicted by genetic defects of cell-cycle-regulatory gatekeeper and genome-stabilizing caretaker tumor suppressor genes, respectively. These differential quantifications of tumor dysfunction may in turn be used to create a tumor-specific 'periodic table' that guides rational formulation of survival-enhancing anticancer treatment strategies.

Multivariate Models for Prediction of Skin Sensitization Hazard in Humans

Science.gov (United States)

One of ICCVAM’s highest priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary for a substance to elicit a skin sensitization reaction suggests that no single alternative me...

A non-human primate model for gluten sensitivity.

Directory of Open Access Journals (Sweden)

Michael T Bethune

2008-02-01

Full Text Available Gluten sensitivity is widespread among humans. For example, in celiac disease patients, an inflammatory response to dietary gluten leads to enteropathy, malabsorption, circulating antibodies against gluten and transglutaminase 2, and clinical symptoms such as diarrhea. There is a growing need in fundamental and translational research for animal models that exhibit aspects of human gluten sensitivity.Using ELISA-based antibody assays, we screened a population of captive rhesus macaques with chronic diarrhea of non-infectious origin to estimate the incidence of gluten sensitivity. A selected animal with elevated anti-gliadin antibodies and a matched control were extensively studied through alternating periods of gluten-free diet and gluten challenge. Blinded clinical and histological evaluations were conducted to seek evidence for gluten sensitivity.When fed with a gluten-containing diet, gluten-sensitive macaques showed signs and symptoms of celiac disease including chronic diarrhea, malabsorptive steatorrhea, intestinal lesions and anti-gliadin antibodies. A gluten-free diet reversed these clinical, histological and serological features, while reintroduction of dietary gluten caused rapid relapse.Gluten-sensitive rhesus macaques may be an attractive resource for investigating both the pathogenesis and the treatment of celiac disease.

Switch of Sensitivity Dynamics Revealed with DyGloSA Toolbox for Dynamical Global Sensitivity Analysis as an Early Warning for System's Critical Transition

Science.gov (United States)

Baumuratova, Tatiana; Dobre, Simona; Bastogne, Thierry; Sauter, Thomas

2013-01-01

Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA – a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA) of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times). DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later) and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits. PMID:24367574

Switch of sensitivity dynamics revealed with DyGloSA toolbox for dynamical global sensitivity analysis as an early warning for system's critical transition.

Science.gov (United States)

Baumuratova, Tatiana; Dobre, Simona; Bastogne, Thierry; Sauter, Thomas

2013-01-01

Systems with bifurcations may experience abrupt irreversible and often unwanted shifts in their performance, called critical transitions. For many systems like climate, economy, ecosystems it is highly desirable to identify indicators serving as early warnings of such regime shifts. Several statistical measures were recently proposed as early warnings of critical transitions including increased variance, autocorrelation and skewness of experimental or model-generated data. The lack of automatized tool for model-based prediction of critical transitions led to designing DyGloSA - a MATLAB toolbox for dynamical global parameter sensitivity analysis (GPSA) of ordinary differential equations models. We suggest that the switch in dynamics of parameter sensitivities revealed by our toolbox is an early warning that a system is approaching a critical transition. We illustrate the efficiency of our toolbox by analyzing several models with bifurcations and predicting the time periods when systems can still avoid going to a critical transition by manipulating certain parameter values, which is not detectable with the existing SA techniques. DyGloSA is based on the SBToolbox2 and contains functions, which compute dynamically the global sensitivity indices of the system by applying four main GPSA methods: eFAST, Sobol's ANOVA, PRCC and WALS. It includes parallelized versions of the functions enabling significant reduction of the computational time (up to 12 times). DyGloSA is freely available as a set of MATLAB scripts at http://bio.uni.lu/systems_biology/software/dyglosa. It requires installation of MATLAB (versions R2008b or later) and the Systems Biology Toolbox2 available at www.sbtoolbox2.org. DyGloSA can be run on Windows and Linux systems, -32 and -64 bits.

Rapid and sensitive method to identify Mycobacterium avium subsp. paratuberculosis in cow's milk by DNA methylase genotyping.

Science.gov (United States)

Mundo, Silvia Leonor; Gilardoni, Liliana Rosa; Hoffman, Federico José; Lopez, Osvaldo Jorge

2013-03-01

Paratuberculosis is an infectious, chronic, and incurable disease that affects ruminants, caused by Mycobacterium avium subsp. paratuberculosis. This bacterium is shed primarily through feces of infected cows but can be also excreted in colostrum and milk and might survive pasteurization. Since an association of genomic sequences of M. avium subsp. paratuberculosis in patients with Crohn's disease has been described; it is of interest to rapidly detect M. avium subsp. paratuberculosis in milk for human consumption. IS900 insertion is used as a target for PCR amplification to identify the presence of M. avium subsp. paratuberculosis in biological samples. Two target sequences were selected: IS1 (155 bp) and IS2 (94 bp). These fragments have a 100% identity among all M. avium subsp. paratuberculosis strains sequenced. M. avium subsp. paratuberculosis was specifically concentrated from milk samples by immunomagnetic separation prior to performing PCR. The amplicons were characterized using DNA methylase Genotyping, i.e., the amplicons were methylated with 6-methyl-adenine and digested with restriction enzymes to confirm their identity. The methylated amplicons from 100 CFU of M. avium subsp. paratuberculosis can be visualized in a Western blot format using an anti-6-methyl-adenine monoclonal antibody. The use of DNA methyltransferase genotyping coupled to a scintillation proximity assay allows for the detection of up to 10 CFU of M. avium subsp. paratuberculosis per ml of milk. This test is rapid and sensitive and allows for automation and thus multiple samples can be tested at the same time.

Identifying specific interstellar polycyclic aromatic hydrocarbons

International Nuclear Information System (INIS)

Mulas, Giacomo; Malloci, Giuliano; Porceddu, Ignazio

2005-01-01

Interstellar Polycyclic Aromatic Hydrocarbons (PAHs) have been thought to be ubiquitous for more than twenty years, yet no single species in this class has been identified in the Interstellar Medium (ISM) to date. The unprecedented sensitivity and resolution of present Infrared Space Observatory (ISO) and forthcoming Herschel observations in the far infrared spectral range will offer a unique way out of this embarrassing impasse

Sensitive response of a model of symbiotic ecosystem to seasonal periodic drive

Energy Technology Data Exchange (ETDEWEB)

Rekker, A.; Lumi, N.; Mankin, R. [Institute of Mathematics and Natural Sciences, Tallinn University, 25 Narva Road, 10120 Tallinn (Estonia)

2014-11-12

A symbiotic ecosysytem (metapopulation) is studied by means of the stochastic Lotka-Volterra model with generalized Verhulst self-regulation. The effect of variable environment on the carrying capacities of populations is taken into account as an asymmetric dichotomous noise and as a deterministic periodic stimulus. In the framework of the mean-field theory an explicit self-consistency equation for the system in the long-time limit is presented. Also, expressions for the probability distribution and for the moments of the population size are found. In certain cases the mean population size exhibits large oscillations in time, even if the amplitude of the seasonal environmental drive is small. Particularly, it is shown that the occurrence of large oscillations of the mean population size can be controlled by noise parameters (such as amplitude and correlation time) and by the coupling strength of the symbiotic interaction between species.

Sensitive response of a model of symbiotic ecosystem to seasonal periodic drive

Science.gov (United States)

Rekker, A.; Lumi, N.; Mankin, R.

2014-11-01

A symbiotic ecosysytem (metapopulation) is studied by means of the stochastic Lotka-Volterra model with generalized Verhulst self-regulation. The effect of variable environment on the carrying capacities of populations is taken into account as an asymmetric dichotomous noise and as a deterministic periodic stimulus. In the framework of the mean-field theory an explicit self-consistency equation for the system in the long-time limit is presented. Also, expressions for the probability distribution and for the moments of the population size are found. In certain cases the mean population size exhibits large oscillations in time, even if the amplitude of the seasonal environmental drive is small. Particularly, it is shown that the occurrence of large oscillations of the mean population size can be controlled by noise parameters (such as amplitude and correlation time) and by the coupling strength of the symbiotic interaction between species.

Sensitive response of a model of symbiotic ecosystem to seasonal periodic drive

International Nuclear Information System (INIS)

Rekker, A.; Lumi, N.; Mankin, R.

2014-01-01

A symbiotic ecosysytem (metapopulation) is studied by means of the stochastic Lotka-Volterra model with generalized Verhulst self-regulation. The effect of variable environment on the carrying capacities of populations is taken into account as an asymmetric dichotomous noise and as a deterministic periodic stimulus. In the framework of the mean-field theory an explicit self-consistency equation for the system in the long-time limit is presented. Also, expressions for the probability distribution and for the moments of the population size are found. In certain cases the mean population size exhibits large oscillations in time, even if the amplitude of the seasonal environmental drive is small. Particularly, it is shown that the occurrence of large oscillations of the mean population size can be controlled by noise parameters (such as amplitude and correlation time) and by the coupling strength of the symbiotic interaction between species

Spontaneous baroreflex sensitivity estimates during graded bicycle exercise: a comparative study

International Nuclear Information System (INIS)

Vallais, Frederic; Baselli, Giuseppe; Lucini, Daniela; Pagani, Massimo; Porta, Alberto

2009-01-01

In the literature, several methods have been proposed for the assessment of the baroreflex sensitivity from spontaneous variability of heart period and systolic arterial pressure. The present study compares the most utilized approaches for the evaluation of the spontaneous baroreflex sensitivity (i.e. sequence-based, spectral, cross-spectral and model-based techniques) over a protocol capable of inducing a progressive decrease of the baroreflex sensitivity in the presence of a relevant respiratory drive (i.e. a stepwise dynamic bicycle exercise at 10%, 20% and 30% of the maximum nominal individual effort) in 16 healthy humans. Results demonstrated that the degree of correlation among the estimates is related to the structure of the model explicitly or implicitly assumed by the method and depends on the experimental condition (i.e. on the physiological mechanisms contemporaneously active with baroreflex, e.g. cardiopulmonary reflexes). However, even in the presence of a significant correlation, proportional and/or constant biases can be present, thus rendering spontaneous baroreflex estimates not interchangeable. We suggest that the comparison among different baroreflex sensitivity estimates might elucidate physiological mechanisms responsible for the relationship between heart period and systolic arterial pressure

Increased expression of alpha- and beta-globin mRNAs at the pituitary following exposure to estrogen during the critical period of neonatal sex differentiation in the rat

DEFF Research Database (Denmark)

Leffers, H; Navarro, V M; Nielsen, John E

2006-01-01

Deterioration of reproductive health in human and wildlife species during the past decades has drawn considerable attention to the potential adverse effects of exposure to xenosteroids during sensitive periods of sex development. The hypothalamic-pituitary (HP) unit is a key element in the neuroe......Deterioration of reproductive health in human and wildlife species during the past decades has drawn considerable attention to the potential adverse effects of exposure to xenosteroids during sensitive periods of sex development. The hypothalamic-pituitary (HP) unit is a key element......, we screened for differentially expressed genes at the pituitary and hypothalamus of rats after neonatal exposure to estradiol benzoate. Our analyses identified persistent up-regulation of alpha- and beta-globin mRNAs at the pituitary following neonatal estrogenization. This finding was confirmed...... by combination of RT-PCR analyses and in situ hybridization. Induction of alpha- and beta-globin mRNA expression at the pituitary by neonatal exposure to estrogen was demonstrated as dose-dependent and it was persistently detected up to puberty. In contrast, durable up-regulation of alpha- and beta-globin genes...

Recent approaches in sensitive enantioseparations by CE.

Science.gov (United States)

Sánchez-Hernández, Laura; Castro-Puyana, María; Marina, María Luisa; Crego, Antonio L

2012-01-01

The latest strategies and instrumental improvements for enhancing the detection sensitivity in chiral analysis by CE are reviewed in this work. Following the previous reviews by García-Ruiz et al. (Electrophoresis 2006, 27, 195-212) and Sánchez-Hernández et al. (Electrophoresis 2008, 29, 237-251; Electrophoresis 2010, 31, 28-43), this review includes those papers that were published during the period from June 2009 to May 2011. These works describe the use of offline and online sample treatment techniques, online sample preconcentration techniques based on electrophoretic principles, and alternative detection systems to UV-Vis to increase the detection sensitivity. The application of the above-mentioned strategies, either alone or combined, to improve the sensitivity in the enantiomeric analysis of a broad range of samples, such as pharmaceutical, biological, food and environmental samples, enables to decrease the limits of detection up to 10⁻¹² M. The use of microchips to achieve sensitive chiral separations is also discussed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

“Drug mules” as a radiological challenge: Sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

Energy Technology Data Exchange (ETDEWEB)

Flach, Patricia M., E-mail: patricia.flach@irm.uzh.ch [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Department of Neuroradiology, Inselspital Bern, University of Bern, 3010 Bern (Switzerland); Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Department of Radiology, University Hospital USZ, University of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Ross, Steffen G. [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Ampanozi, Garyfalia; Ebert, Lars [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Germerott, Tanja; Hatch, Gary M. [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Thali, Michael J. [Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Bern, Buehlstrasse 20, 3012 Bern (Switzerland); Centre for Forensic Imaging and Virtopsy, Institute of Forensic Medicine, University of Zurich, Winterthurerstrasse 190/52, 8057 Zurich (Switzerland); Patak, Michael A. [Department of Radiology, Inselspital Bern, University of Bern, 3010 Bern (Switzerland); Department of Radiology, University Hospital USZ, University of Zurich, Raemistrasse 100, 8091 Zurich (Switzerland)

2012-10-15

Purpose: The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox{sup ®}) in the detection of internal cocaine containers. Methods: Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16–45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT = 35, nDR = 70, nLSDR = 30. An overall calculation of all “drug mules” and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. Results: There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. Conclusions: CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage.

“Drug mules” as a radiological challenge: Sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

International Nuclear Information System (INIS)

Flach, Patricia M.; Ross, Steffen G.; Ampanozi, Garyfalia; Ebert, Lars; Germerott, Tanja; Hatch, Gary M.; Thali, Michael J.; Patak, Michael A.

2012-01-01

Purpose: The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox ® ) in the detection of internal cocaine containers. Methods: Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16–45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT = 35, nDR = 70, nLSDR = 30. An overall calculation of all “drug mules” and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. Results: There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. Conclusions: CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage

PERIODIC AND APERIODIC VARIABILITY IN THE MOLECULAR CLOUD ρ OPHIUCHUS

International Nuclear Information System (INIS)

Parks, J. Robert; Plavchan, Peter; Gee, Alan H.; White, Russel J.

2014-01-01

Presented are the results of a near-IR photometric survey of 1678 stars in the direction of the ρ Ophiuchus (ρ Oph) star forming region using data from the 2MASS Calibration Database. For each target in this sample, up to 1584 individual J-, H-, and K s -band photometric measurements with a cadence of ∼1 day are obtained over three observing seasons spanning ∼2.5 yr; it is the most intensive survey of stars in this region to date. This survey identifies 101 variable stars with ΔK s -band amplitudes from 0.044 to 2.31 mag and Δ(J – K s ) color amplitudes ranging from 0.053 to 1.47 mag. Of the 72 young ρ Oph star cluster members included in this survey, 79% are variable; in addition, 22 variable stars are identified as candidate members. Based on the temporal behavior of the K s time-series, the variability is distinguished as either periodic, long time-scale or irregular. This temporal behavior coupled with the behavior of stellar colors is used to assign a dominant variability mechanism. A new period-searching algorithm finds periodic signals in 32 variable stars with periods between 0.49 to 92 days. The chief mechanism driving the periodic variability for 18 stars is rotational modulation of cool starspots while 3 periodically vary due to accretion-induced hot spots. The time-series for six variable stars contains discrete periodic ''eclipse-like'' features with periods ranging from 3 to 8 days. These features may be asymmetries in the circumstellar disk, potentially sustained or driven by a proto-planet at or near the co-rotation radius. Aperiodic, long time-scale variations in stellar flux are identified in the time-series for 31 variable stars with time-scales ranging from 64 to 790 days. The chief mechanism driving long time-scale variability is variable extinction or mass accretion rates. The majority of the variable stars (40) exhibit sporadic, aperiodic variability over no discernable time-scale. No chief variability mechanism

PERIODIC AND APERIODIC VARIABILITY IN THE MOLECULAR CLOUD ρ OPHIUCHUS

Energy Technology Data Exchange (ETDEWEB)

Parks, J. Robert; Plavchan, Peter; Gee, Alan H. [Infrared Processing and Analysis Center, California Institute of Technology, Mail Code 100-22, 770 South Wilson Avenue, Pasadena, CA 91125 (United States); White, Russel J., E-mail: parksj@chara.gsu.edu [Georgia State University, Department of Physics and Astronomy, 25 Park Place, Room 605, Atlanta, GA 30303 (United States)

2014-03-01

Presented are the results of a near-IR photometric survey of 1678 stars in the direction of the ρ Ophiuchus (ρ Oph) star forming region using data from the 2MASS Calibration Database. For each target in this sample, up to 1584 individual J-, H-, and K{sub s} -band photometric measurements with a cadence of ∼1 day are obtained over three observing seasons spanning ∼2.5 yr; it is the most intensive survey of stars in this region to date. This survey identifies 101 variable stars with ΔK{sub s} -band amplitudes from 0.044 to 2.31 mag and Δ(J – K{sub s} ) color amplitudes ranging from 0.053 to 1.47 mag. Of the 72 young ρ Oph star cluster members included in this survey, 79% are variable; in addition, 22 variable stars are identified as candidate members. Based on the temporal behavior of the K{sub s} time-series, the variability is distinguished as either periodic, long time-scale or irregular. This temporal behavior coupled with the behavior of stellar colors is used to assign a dominant variability mechanism. A new period-searching algorithm finds periodic signals in 32 variable stars with periods between 0.49 to 92 days. The chief mechanism driving the periodic variability for 18 stars is rotational modulation of cool starspots while 3 periodically vary due to accretion-induced hot spots. The time-series for six variable stars contains discrete periodic ''eclipse-like'' features with periods ranging from 3 to 8 days. These features may be asymmetries in the circumstellar disk, potentially sustained or driven by a proto-planet at or near the co-rotation radius. Aperiodic, long time-scale variations in stellar flux are identified in the time-series for 31 variable stars with time-scales ranging from 64 to 790 days. The chief mechanism driving long time-scale variability is variable extinction or mass accretion rates. The majority of the variable stars (40) exhibit sporadic, aperiodic variability over no discernable time-scale. No chief

Multivariate Models for Prediction of Human Skin Sensitization Hazard

Science.gov (United States)

Strickland, Judy; Zang, Qingda; Paris, Michael; Lehmann, David M.; Allen, David; Choksi, Neepa; Matheson, Joanna; Jacobs, Abigail; Casey, Warren; Kleinstreuer, Nicole

2016-01-01

One of ICCVAM’s top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary to produce skin sensitization suggests that no single alternative method will replace the currently accepted animal tests. ICCVAM is evaluating an integrated approach to testing and assessment based on the adverse outcome pathway for skin sensitization that uses machine learning approaches to predict human skin sensitization hazard. We combined data from three in chemico or in vitro assays—the direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT), and KeratinoSens™ assay—six physicochemical properties, and an in silico read-across prediction of skin sensitization hazard into 12 variable groups. The variable groups were evaluated using two machine learning approaches, logistic regression (LR) and support vector machine (SVM), to predict human skin sensitization hazard. Models were trained on 72 substances and tested on an external set of 24 substances. The six models (three LR and three SVM) with the highest accuracy (92%) used: (1) DPRA, h-CLAT, and read-across; (2) DPRA, h-CLAT, read-across, and KeratinoSens; or (3) DPRA, h-CLAT, read-across, KeratinoSens, and log P. The models performed better at predicting human skin sensitization hazard than the murine local lymph node assay (accuracy = 88%), any of the alternative methods alone (accuracy = 63–79%), or test batteries combining data from the individual methods (accuracy = 75%). These results suggest that computational methods are promising tools to effectively identify potential human skin sensitizers without animal testing. PMID:27480324

Comparative sensitivity of quantitative EEG (QEEG) spectrograms for detecting seizure subtypes.

Science.gov (United States)

Goenka, Ajay; Boro, Alexis; Yozawitz, Elissa

2018-02-01

To assess the sensitivity of Persyst version 12 QEEG spectrograms to detect focal, focal with secondarily generalized, and generalized onset seizures. A cohort of 562 seizures from 58 patients was analyzed. Successive recordings with 2 or more seizures during continuous EEG monitoring for clinical indications in the ICU or EMU between July 2016 and January 2017 were included. Patient ages ranged from 5 to 64 years (mean = 36 years). There were 125 focal seizures, 187 secondarily generalized and 250 generalized seizures from 58 patients analyzed. Seizures were identified and classified independently by two epileptologists. A correlate to the seizure pattern in the raw EEG was sought in the QEEG spectrograms in 4-6 h EEG epochs surrounding the identified seizures. A given spectrogram was interpreted as indicating a seizure, if at the time of a seizure it showed a visually significant departure from the pre-event baseline. Sensitivities for seizure detection using each spectrogram were determined for each seizure subtype. Overall sensitivities of the QEEG spectrograms for detecting seizures ranged from 43% to 72%, with highest sensitivity (402/562,72%) by the seizure detection trend. The asymmetry spectrogram had the highest sensitivity for detecting focal seizures (117/125,94%). The FFT spectrogram was most sensitive for detecting secondarily generalized seizures (158/187, 84%). The seizure detection trend was the most sensitive for generalized onset seizures (197/250,79%). Our study suggests that different seizure types have specific patterns in the Persyst QEEG spectrograms. Identifying these patterns in the EEG can significantly increase the sensitivity for seizure identification. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

A comparative study of the metabolic profile, insulin sensitivity and inflammatory response between organically and conventionally managed dairy cattle during the periparturient period.

Science.gov (United States)

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

2014-09-01

The number of organically managed cattle (OMC) within the European Union has increased tremendously in the last decade. However, there are still some concerns about animals under this farming system meeting their dietary requirements for milk production. The aim of this study was to compare the metabolic adaptations to the onset of lactation in three different herds, one conventional and two organic ones. Twenty-two conventionally managed cattle (CMC) and 20 from each organic farm were sampled throughout the periparturient period. These samplings were grouped into four different stages: (i) far-off dry, (ii) close-up dry, (iii) fresh and (iv) peak of lactation and compared among them. In addition, the results of periparturient animals were also compared within each management type with a control group (animals between the 4th and 5th months of pregnancy). Metabolic profiles were used to assess the health status of the herds, along with the quantification of the acute phase proteins haptoglobin and serum amyloid A, insulin and the calculation of different surrogate indices of insulin sensitivity. Generalised linear mixed models with repeated measurements were used to study the effect of the stage, management type or their interaction on the serum variables studied. The prevalence of subclinical ketosis was higher in OMC, although they showed better insulin sensitivity, a lower degree of inflammation and less liver injury, without a higher risk of macromineral deficiencies. Therefore, attention should be paid on organic farms to the nutritional management of cows around the time of calving in order to prevent the harmful consequences of excessive negative energy balance. Moreover, it must be taken into account that most of the common practices used to treat this condition in CMC are not allowed on a systematic basis in OMC.

Interference and Sensitivity Analysis.

Science.gov (United States)

VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J; Halloran, M Elizabeth

2014-11-01

Causal inference with interference is a rapidly growing area. The literature has begun to relax the "no-interference" assumption that the treatment received by one individual does not affect the outcomes of other individuals. In this paper we briefly review the literature on causal inference in the presence of interference when treatments have been randomized. We then consider settings in which causal effects in the presence of interference are not identified, either because randomization alone does not suffice for identification, or because treatment is not randomized and there may be unmeasured confounders of the treatment-outcome relationship. We develop sensitivity analysis techniques for these settings. We describe several sensitivity analysis techniques for the infectiousness effect which, in a vaccine trial, captures the effect of the vaccine of one person on protecting a second person from infection even if the first is infected. We also develop two sensitivity analysis techniques for causal effects in the presence of unmeasured confounding which generalize analogous techniques when interference is absent. These two techniques for unmeasured confounding are compared and contrasted.

Transcranial magnetic stimulation (TMS): compared sensitivity of different motor response parameters in ALS.

Science.gov (United States)

Pouget, J; Trefouret, S; Attarian, S

2000-06-01

Owing to the low sensitivity of clinical signs in assessing upper motor neuron (UMN) involvement in ALS, there is a need for investigative tools capable of detecting abnormal function of the pyramidal tract. Transcranial magnetic stimulation (TMS) may contribute to the diagnosis by reflecting a UMN dysfunction that is not clinically detectable. Several parameters for the motor responses to TMS can be evaluated with different levels of significance in healthy subjects compared with ALS patients. The central motor conduction time, however, is not sensitive in detecting subclinical UMN defects in individual ALS patients. The amplitude of the motor evoked potential (MEP), expressed as the percentage of the maximum wave, also has a low sensitivity. In some cases, the corticomotor threshold is decreased early in the disease course as a result of corticomotor neuron hyperexcitability induced by glutamate. Later, the threshold increases, indicating a loss of UMN. In our experience, a decreased silent period duration appears to be the most sensitive parameter when using motor TMS in ALS. TMS is also a sensitive technique for investigating the corticobulbar tract, which is difficult to study by other methods. TMS is a widely available, painless and safe technique with a good sensitivity that can visualize both corticospinal and corticobulbar tract abnormalities. The sensitivity can be improved further by taking into account the several MEP parameters, including latency and cortical silent period decreased duration.

Validation of search filters for identifying pediatric studies in PubMed

NARCIS (Netherlands)

Leclercq, Edith; Leeflang, Mariska M. G.; van Dalen, Elvira C.; Kremer, Leontien C. M.

2013-01-01

To identify and validate PubMed search filters for retrieving studies including children and to develop a new pediatric search filter for PubMed. We developed 2 different datasets of studies to evaluate the performance of the identified pediatric search filters, expressed in terms of sensitivity,

Sensitivity analysis of the reactor safety study. Final report

International Nuclear Information System (INIS)

Parkinson, W.J.; Rasmussen, N.C.; Hinkle, W.D.

1979-01-01

The Reactor Safety Study (RSS) or Wash 1400 developed a methodology estimating the public risk from light water nuclear reactors. In order to give further insights into this study, a sensitivity analysis has been performed to determine the significant contributors to risk for both the PWR and BWR. The sensitivity to variation of the point values of the failure probabilities reported in the RSS was determined for the safety systems identified therein, as well as for many of the generic classes from which individual failures contributed to system failures. Increasing as well as decreasing point values were considered. An analysis of the sensitivity to increasing uncertainty in system failure probabilities was also performed. The sensitivity parameters chosen were release category probabilities, core melt probability, and the risk parameters of early fatalities, latent cancers and total property damage. The latter three are adequate for describing all public risks identified in the RSS. The results indicate reductions of public risk by less than a factor of two for factor reductions in system or generic failure probabilities as high as one hundred. There also appears to be more benefit in monitoring the most sensitive systems to verify adherence to RSS failure rates than to backfitting present reactors. The sensitivity analysis results do indicate, however, possible benefits in reducing human error rates

Temporal correlations between sensitivity to radiation-induced mitotic delay and the S phase of the sea urchin egg

International Nuclear Information System (INIS)

Rustad, R.C.; Viswanathan, G.; Antonellis, B.C.

1979-01-01

Separate samples of eggs from the sea urchin Arbacia punctulata were gamma irradiated (4kR) at different times after fertilisation and division delay measured. The results demonstrated a characteristic post-fertilisation pattern of a rise in sensitivity to radiation-induced mitotic delay, followed by a biphasic decrease in sensitivity to a refractory period. Measurements of the cumulative incorporation of 3 H-TdR showed that the first period of decreasing radiation sensitivity was closely associated with the bulk synthesis of DNA (S phase). (U.K.)

EPA Releases Draft Policy to Reduce Animal Testing for Skin Sensitization

Science.gov (United States)

The document, Draft Interim Science Policy: Use of Alternative Approaches for Skin Sensitization as a Replacement for Laboratory Animal Testing, describes the science behind the non-animal alternatives that can now be used to identify skin sensitization.

Decoding facial expressions based on face-selective and motion-sensitive areas.

Science.gov (United States)

Liang, Yin; Liu, Baolin; Xu, Junhai; Zhang, Gaoyan; Li, Xianglin; Wang, Peiyuan; Wang, Bin

2017-06-01

Humans can easily recognize others' facial expressions. Among the brain substrates that enable this ability, considerable attention has been paid to face-selective areas; in contrast, whether motion-sensitive areas, which clearly exhibit sensitivity to facial movements, are involved in facial expression recognition remained unclear. The present functional magnetic resonance imaging (fMRI) study used multi-voxel pattern analysis (MVPA) to explore facial expression decoding in both face-selective and motion-sensitive areas. In a block design experiment, participants viewed facial expressions of six basic emotions (anger, disgust, fear, joy, sadness, and surprise) in images, videos, and eyes-obscured videos. Due to the use of multiple stimulus types, the impacts of facial motion and eye-related information on facial expression decoding were also examined. It was found that motion-sensitive areas showed significant responses to emotional expressions and that dynamic expressions could be successfully decoded in both face-selective and motion-sensitive areas. Compared with static stimuli, dynamic expressions elicited consistently higher neural responses and decoding performance in all regions. A significant decrease in both activation and decoding accuracy due to the absence of eye-related information was also observed. Overall, the findings showed that emotional expressions are represented in motion-sensitive areas in addition to conventional face-selective areas, suggesting that motion-sensitive regions may also effectively contribute to facial expression recognition. The results also suggested that facial motion and eye-related information played important roles by carrying considerable expression information that could facilitate facial expression recognition. Hum Brain Mapp 38:3113-3125, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Fabrication of Long Period Gratings by Periodically Removing the Coating of Cladding-Etched Single Mode Optical Fiber Towards Optical Fiber Sensor Development.

Science.gov (United States)

Ascorbe, Joaquin; Corres, Jesus M; Del Villar, Ignacio; Matias, Ignacio R

2018-06-07

Here, we present a novel method to fabricate long period gratings using standard single mode optical fibers (SMF). These optical devices were fabricated in a three-step process, which consisted of etching the SMF, then coating it with a thin-film and, the final step, which involved removing sections of the coating periodically by laser ablation. Tin dioxide was chosen as the material for this study and it was sputtered using a pulsed DC sputtering system. Theoretical simulations were performed in order to select the appropriate parameters for the experiments. The responses of two different devices to different external refractive indices was studied, and the maximum sensitivity obtained was 6430 nm/RIU for external refractive indices ranging from 1.37 to 1.39.

Fabrication of Long Period Gratings by Periodically Removing the Coating of Cladding-Etched Single Mode Optical Fiber Towards Optical Fiber Sensor Development

Directory of Open Access Journals (Sweden)

Joaquin Ascorbe

2018-06-01

Full Text Available Here, we present a novel method to fabricate long period gratings using standard single mode optical fibers (SMF. These optical devices were fabricated in a three-step process, which consisted of etching the SMF, then coating it with a thin-film and, the final step, which involved removing sections of the coating periodically by laser ablation. Tin dioxide was chosen as the material for this study and it was sputtered using a pulsed DC sputtering system. Theoretical simulations were performed in order to select the appropriate parameters for the experiments. The responses of two different devices to different external refractive indices was studied, and the maximum sensitivity obtained was 6430 nm/RIU for external refractive indices ranging from 1.37 to 1.39.

No Weight Catch-Up Growth of SGA Infants Is Associated with Impaired Insulin Sensitivity during the Early Postnatal Period

Directory of Open Access Journals (Sweden)

Tong-yan Han

2010-01-01

Full Text Available Objective. To investigate the relationship between weight catch-up growth and insulin sensitivity in small for gestational age (SGA infants. Methods. Forty-four singleton SGA subjects met the inclusion criteria and finished-3-month followup. Body weight, length, fasting glucose, and fasting insulin (FI levels were measured at 3 days and 3 months. Insulin sensitivity was evaluated by FI and homeostasis model assessment (HOMA. Results. According to the change of weight Z-score, forty-four subjects were divided into two groups: noncatch-up growth (NCUG and catch-up growth (CUG. By 3 months of age, the body weight, body length and BMI of NCUG group were significantly lower than those of CUG group. The FI and HOMA were significantly higher in NCUG group. The change of weight Z-score during 3 months was inversely related to the HOMA at 3 months. Conclusion. Our data exemplified that no weight catch-up growth during the first 3 months was associated with impaired insulin sensitivity in SGA infants.

Barriers to midwives and nurses addressing mental health issues with women during the perinatal period: The Mind Mothers study.

Science.gov (United States)

Higgins, Agnes; Downes, Carmel; Monahan, Mark; Gill, Ailish; Lamb, Stephen A; Carroll, Margaret

2018-01-03

To explore barriers to midwives and nurses addressing mental health issues with women during the perinatal period. Perinatal mental health is considered an important public health issue with health policy internationally identifying the importance of psychological support for women in the perinatal period. Midwives and primary care nurses are ideally positioned to detect mental distress early, but evidence suggests that they are reluctant to discuss mental health issues with women during pregnancy or in the postnatal period. The research used a descriptive design. A total of 809 midwives and nurses completed an anonymous, online or hard copy survey. Designed by the research team, the survey listed 26 potential barriers to the provision of perinatal mental health care. Participants identified organisational factors as presenting the greatest barriers. Organisational barriers included lack of perinatal mental health services, absence of care pathways, heavy workload, lack of time, lack of privacy and not seeing women regularly enough to build a relationship. Over 50% of participants identified practitioner-related barriers, such as lack of knowledge on perinatal mental health and cultural issues; lack of skill, in particular, skills to respond to a disclosure of a mental health issue; and fears of causing women offence and distress. Findings also indicated that the context of care and education influenced the degree to which participants perceived certain items as barriers. Midwives and primary care nurses encounter many organisational- and practitioner-related barriers that negatively impact on their ability to incorporate mental health care into their practice. Midwifery and nursing services need to develop strategies to address system- and practitioner-related barriers, including the development of services and care pathways, and the provision of culturally sensitive education on perinatal mental health in order to support practitioners to address issues with

Period and phase comparisons of near-decadal oscillations in solar, geomagnetic, and cosmic ray time series

Science.gov (United States)

Juckett, David A.

2001-09-01

A more complete understanding of the periodic dynamics of the Sun requires continued exploration of non-11-year oscillations in addition to the benchmark 11-year sunspot cycle. In this regard, several solar, geomagnetic, and cosmic ray time series were examined to identify common spectral components and their relative phase relationships. Several non-11-year oscillations were identified within the near-decadal range with periods of ~8, 10, 12, 15, 18, 22, and 29 years. To test whether these frequency components were simply low-level noise or were related to a common source, the phases were extracted for each component in each series. The phases were nearly identical across the solar and geomagnetic series, while the corresponding components in four cosmic ray surrogate series exhibited inverted phases, similar to the known phase relationship with the 11-year sunspot cycle. Cluster analysis revealed that this pattern was unlikely to occur by chance. It was concluded that many non-11-year oscillations truly exist in the solar dynamical environment and that these contribute to the complex variations observed in geomagnetic and cosmic ray time series. Using the different energy sensitivities of the four cosmic ray surrogate series, a preliminary indication of the relative intensities of the various solar-induced oscillations was observed. It provides evidence that many of the non-11-year oscillations result from weak interplanetary magnetic field/solar wind oscillations that originate from corresponding variations in the open-field regions of the Sun.

Ethical problems and moral sensitivity in physiotherapy: a descriptive study.

Science.gov (United States)

Kulju, Kati; Suhonen, Riitta; Leino-Kilpi, Helena

2013-08-01

This study identified and described ethical problems encountered by physiotherapists in their practice and physiotherapists' moral sensitivity in ethical situations. A questionnaire-based survey was constructed to identify ethical problems, and the Moral Sensitivity Questionnaire Revised version was used to measure moral sensitivity. Physiotherapists (n = 116) working in public health services responded to the questionnaire. Based on the results, most of the physiotherapists encounter ethical problems weekly. They concern mainly financial considerations, equality and justice, professionalism, unethical conduct of physiotherapists or other professions and patients' self-determination. The dimension of moral strength was emphasised in physiotherapists' self-evaluations of their moral sensitivity. As a conclusion, ethical problems do occur not only at individual level but also at organisational and society level. Physiotherapists seem to have moral strength for speaking on behalf of the patient. Scarce resources make them feel insufficient but much could still be done to provide quality care in co-operation with other health-care professionals.

Insulin resistance in obese children and adolescents: HOMA-IR cut-off levels in the prepubertal and pubertal periods.

Science.gov (United States)

Kurtoğlu, Selim; Hatipoğlu, Nihal; Mazıcıoğlu, Mümtaz; Kendirici, Mustafa; Keskin, Mehmet; Kondolot, Meda

2010-01-01

Childhood obesity is associated with an increased risk for insulin resistance. The underlying mechanism for the physiological increase in insulin levels in puberty is not clearly understood. The aim of the present study was to determine the cut-off values for homeostasis model assessment for insulin resistance (HOMA-IR) in obese children and adolescents according to gender and pubertal status. Two hundred and eight obese children and adolescents (141 girls, 127 boys) aged between 5 and 18 years were included in the study. The children were divided into prepubertal and pubertal groups. A standard oral glucose tolerance test (OGTT) was carried out in all children. A total insulin level exceeding 300 μU/mL in the blood samples, collected during the test period, was taken as the insulin resistance criterion. Cut-off values for HOMA-IR were calculated by receiver operating characteristic (ROC) analysis. In the prepubertal period, the rate of insulin resistance was found to be 37% in boys and 27.8% in girls,while in the pubertal period, this rate was 61.7% in boys and 66.7% in girls. HOMA-IR cut-off values for insulin resistance in the prepubertal period were calculated to be 2.67 (sensitivity 88.2%, specificity 65.5%) in boys and 2.22 (sensitivity 100%, specificity 42.3%) in girls, and in the pubertal period, they were 5.22 (sensitivity 56%, specificity 93.3%) in boys and 3.82 (sensitivity 77.1%, specificity 71.4%) in girls. Since gender, obesity and pubertal status are factors affecting insulin resistance, cut-off values which depend on gender and pubertal status, should be used in evaluation of insulin resistance.

A sensitive HIV-1 envelope induced fusion assay identifies fusion enhancement of thrombin

International Nuclear Information System (INIS)

Cheng, De-Chun; Zhong, Guo-Cai; Su, Ju-Xiang; Liu, Yan-Hong; Li, Yan; Wang, Jia-Ye; Hattori, Toshio; Ling, Hong; Zhang, Feng-Min

2010-01-01

To evaluate the interaction between HIV-1 envelope glycoprotein (Env) and target cell receptors, various cell-cell-fusion assays have been developed. In the present study, we established a novel fusion system. In this system, the expression of the sensitive reporter gene, firefly luciferase (FL) gene, in the target cells was used to evaluate cell fusion event. Simultaneously, constitutively expressed Renilla luciferase (RL) gene was used to monitor effector cell number and viability. FL gave a wider dynamic range than other known reporters and the introduction of RL made the assay accurate and reproducible. This system is especially beneficial for investigation of potential entry-influencing agents, for its power of ruling out the false inhibition or enhancement caused by the artificial cell-number variation. As a case study, we applied this fusion system to observe the effect of a serine protease, thrombin, on HIV Env-mediated cell-cell fusion and have found the fusion enhancement activity of thrombin over two R5-tropic HIV strains.

A nitrate sensitive planar optode; performance and interferences

DEFF Research Database (Denmark)

Pedersen, Lasse; Dechesne, Arnaud; Smets, Barth F.

2015-01-01

We present a newly developed nitrate sensitive planar optode. It exhibits a linear response to nitrate from 1 to 50 mM at pH 8.0, a fast response time below 10 s and a good lifetime, allowing for fast two dimensional nitrate measurements over long periods of time. Interference from nitrite...

Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers - prehaptens and prohaptens.

Science.gov (United States)

Karlberg, Ann-Therese; Börje, Anna; Duus Johansen, Jeanne; Lidén, Carola; Rastogi, Suresh; Roberts, David; Uter, Wolfgang; White, Ian R

2013-12-01

Experimental and clinical studies have shown that fragrance substances can act as prehaptens or prohaptens. They form allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, thus, increasing the risk of sensitization. In the present review a series of fragrance substances with well documented abiotic and/or biotic activation are given as indicative and illustrative examples of the general problem. Commonly used fragrance substances, also found in essential oils, autoxidize on contact with air, forming potent sensitizers that can be an important source for contact allergy to fragrances and fragranced products. Some of them can act as prohaptens and be activated in the skin as well. The experimental findings are confirmed in large clinical studies. When substances with structural alerts for acting as prohaptens and/or prehaptens are identified, the possibility of generating new potent allergens should be considered. Predictive testing should include activation steps. Further experimental and clinical research regarding activation of fragrance substances is needed to increase consumer safety. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Validity of pre and post-term birth rates based on the date of last menstrual period compared to early obstetric ultrasonography

Directory of Open Access Journals (Sweden)

Maria Nilza Lima Medeiros

2015-04-01

Full Text Available The aim of this study was to assess the validity of the last menstrual period (LMP estimate in determining pre and post-term birth rates, in a prenatal cohort from two Brazilian cities, São Luís and Ribeirão Preto. Pregnant women with a single fetus and less than 20 weeks' gestation by obstetric ultrasonography who received prenatal care in 2010 and 2011 were included. The LMP was obtained on two occasions (at 22-25 weeks gestation and after birth. The sensitivity of LMP obtained prenatally to estimate the preterm birth rate was 65.6% in São Luís and 78.7% in Ribeirão Preto and the positive predictive value was 57.3% in São Luís and 73.3% in Ribeirão Preto. LMP errors in identifying preterm birth were lower in the more developed city, Ribeirão Preto. The sensitivity and positive predictive value of LMP for the estimate of the post-term birth rate was very low and tended to overestimate it. LMP can be used with some errors to identify the preterm birth rate when obstetric ultrasonography is not available, but is not suitable for predicting post-term birth.

The role of sensitivity analysis in assessing uncertainty

International Nuclear Information System (INIS)

Crick, M.J.; Hill, M.D.

1987-01-01

Outside the specialist world of those carrying out performance assessments considerable confusion has arisen about the meanings of sensitivity analysis and uncertainty analysis. In this paper we attempt to reduce this confusion. We then go on to review approaches to sensitivity analysis within the context of assessing uncertainty, and to outline the types of test available to identify sensitive parameters, together with their advantages and disadvantages. The views expressed in this paper are those of the authors; they have not been formally endorsed by the National Radiological Protection Board and should not be interpreted as Board advice

Longitudinal Changes in Behavioral Approach System Sensitivity and Brain Structures Involved in Reward Processing during Adolescence

Science.gov (United States)

Urosevic, Snezana; Collins, Paul; Muetzel, Ryan; Lim, Kelvin; Luciana, Monica

2012-01-01

Adolescence is a period of radical normative changes and increased risk for substance use, mood disorders, and physical injury. Researchers have proposed that increases in reward sensitivity (i.e., sensitivity of the behavioral approach system [BAS]) and/or increases in reactivity to all emotional stimuli (i.e., reward and threat sensitivities)…

Sensitivity of tomato cultivars to sulfur dioxide

Energy Technology Data Exchange (ETDEWEB)

Howe, T.K.; Woltz, S.S.

1982-04-01

The sensitivity of 26 cultivars of tomato (Lycopersicon esculentum Mill.) were compared at 2 concentrations of SO/sub 2/in specially designed exposure greenhouses. Cultivars studied included fresh market, processing, and specialty types. Insensitive and sensitive cultivars were identified by assessment of acute SO/sub 2/-induced foliar necrosis. Cultivars found to be insensitive to SO/sub 2/ included: 'Ace', 'Bonanza', 'Heinz 1350', 'Tarquinia Tondino', and 'VF 145-B 7879'. Cultivars found to be sensitive to SO/sub 2/ included: 'Bellarina', 'Chico III', 'Flora-Dade', 'Red Cherry Large' 'Sub-Arctic Delight', and 'Vetomold. 10 figures, 1 table.

Central sensitization does not identify patients with carpal tunnel syndrome who are likely to achieve short-term success with physical therapy.

Science.gov (United States)

Fernández-de-Las-Peñas, César; Cleland, Joshua A; Ortega-Santiago, Ricardo; de-la-Llave-Rincon, Ana Isabel; Martínez-Perez, Almudena; Pareja, Juan A

2010-11-01

The aim of the current study was to identify whether hyperexcitability of the central nervous system is a prognostic factor for individuals with carpal tunnel syndrome (CTS) likely to experience rapid and clinical self-reported improvement following a physical therapy program including soft tissue mobilization and nerve slider neurodynamic interventions. Women presenting with clinical and electrophysiological findings of CTS were involved in a prospective single-arm trial. Participants underwent a standardized examination and then a physical therapy session. The physical therapy sessions included both soft tissue mobilization directed at the anatomical sites of potential median nerve entrapment and a passive nerve slider neurodynamic technique targeted to the median nerve. Pressure pain thresholds (PPT) over the median, radial and ulnar nerves, C5-C6 zygapophyseal joint, carpal tunnel and tibialis anterior muscle were assessed bilaterally. Additionally, thermal detection and pain thresholds were measured over the carpal tunnel and thenar eminence bilaterally to evaluate central nervous system excitability. Subjects were classified as responders (having achieved a successful outcome) or non-responders based on self-perceived recovery. Variables were entered into a stepwise logistic regression model to determine the most accurate variables for determining prognosis. Data from 72 women were included in the analysis, of which 35 experienced a successful outcome (48.6%). Three variables including PPT over the C5-C6 joint affected side 66 points were identified. If 2 out of 3 variables were present (LR + 14.8), the likelihood of success increased from 48.6 to 93.3%. We identified 3 factors that may be associated with a rapid clinical response to both soft tissue mobilization and nerve slider neurodynamic techniques targeted to the median nerve in women presenting with CTS. Our results support that widespread central sensitization may not be present in women with CTS who

Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA.

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Orr Ashenberg

2017-03-01

Full Text Available The innate-immune restriction factor MxA inhibits influenza replication by targeting the viral nucleoprotein (NP. Human influenza virus is more resistant than avian influenza virus to inhibition by human MxA, and prior work has compared human and avian viral strains to identify amino-acid differences in NP that affect sensitivity to MxA. However, this strategy is limited to identifying sites in NP where mutations that affect MxA sensitivity have fixed during the small number of documented zoonotic transmissions of influenza to humans. Here we use an unbiased deep mutational scanning approach to quantify how all single amino-acid mutations to NP affect MxA sensitivity in the context of replication-competent virus. We both identify new sites in NP where mutations affect MxA resistance and re-identify mutations known to have increased MxA resistance during historical adaptations of influenza to humans. Most of the sites where mutations have the greatest effect are almost completely conserved across all influenza A viruses, and the amino acids at these sites confer relatively high resistance to MxA. These sites cluster in regions of NP that appear to be important for its recognition by MxA. Overall, our work systematically identifies the sites in influenza nucleoprotein where mutations affect sensitivity to MxA. We also demonstrate a powerful new strategy for identifying regions of viral proteins that affect inhibition by host factors.

The role of sensitivity analysis in probabilistic safety assessment

International Nuclear Information System (INIS)

Hirschberg, S.; Knochenhauer, M.

1987-01-01

The paper describes several items suitable for close examination by means of application of sensitivity analysis, when performing a level 1 PSA. Sensitivity analyses are performed with respect to; (1) boundary conditions, (2) operator actions, and (3) treatment of common cause failures (CCFs). The items of main interest are identified continuously in the course of performing a PSA, as well as by scrutinising the final results. The practical aspects of sensitivity analysis are illustrated by several applications from a recent PSA study (ASEA-ATOM BWR 75). It is concluded that sensitivity analysis leads to insights important for analysts, reviewers and decision makers. (orig./HP)

Flux quantization in periodic networks containing tiles with irrational ratio of areas

International Nuclear Information System (INIS)

Santhanam, P.; Chi, C.C.; Molzen, W.W.

1988-01-01

We report measurements of the superconducting-normal transition boundary T/sub c/(H) of two-dimensional periodic networks with two different space-group symmetries in a magnetic field. Each network is a mixture of squares and equilateral triangles. In both cases, we observe maxima in T/sub c/(H) with one major period, which does not correspond to the area of either the square or the triangle. We interpret the results in terms of flux configurations whose energies are sensitive to the geometry of a given network

Transitions in sensitive period attachment learning in infancy: the role of corticosterone.

Science.gov (United States)

Sullivan, Regina M; Holman, Parker J

2010-05-01

Survival of altricial infants, including humans and rats, depends on attachment to the caregiver - a process that requires infants to recognize, learn, and remember their attachment figure. The demands of a dynamic environment combined with a maturing organism require frequent neurobehavioral reorganization. This restructuring of behavior and its supporting neural circuitry can be viewed through the unique lens of attachment learning in rats in which preference learning is enhanced and aversion learning is attenuated. Behavioral restructuring is well adapted to securing the crucial infant-caregiver relationship regardless of the quality of care. With maturation and the end of the infant-caregiver attachment learning period, the complex interplay of neural structures, hormones, and social behavior coordinates the developing rat's eventual transition to life outside of the nest. Nevertheless, early-life environmental and physiological stressors can alter the resilient nature of this system, particularly with respect to the amygdala, and these changes may provide important clues to understanding the lasting effects of early stress. (c) 2009 Elsevier Ltd. All rights reserved.

Sensitivity Analysis Of Financing Demand In Syariah Banking

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DR. HJ. ROSYETTI

2017-11-01

Full Text Available This study aims to analyze the Sensitivity of Demand Financing in syariah banking with a focus on the elasticity of financing demand income elasticity and cross elasticity. The type of data used in this study is secondary data quantitative and time series obtained from the publication of BPS BI and OJK. The data analysis technique begins by estimating multiple linear regression equations using the Eviews Application further measuring the sensitivity using elasticity. The research variables consist of revenue gross domestic product and conventional bank interest rate as independent variables and demand for financing as a dependent variable. The results obtained for the results gross domestic product and interest rate of conventional banks simultaneously affect the demand for financing in Islamic banking with a significant level of 5 obtained probability value F statistic amp945 005. Partially revenue share and gross domestic product have a significant effect on demand for financing. While the variable interest rate of conventional banks partially does not have a significant effect on demand for financing in Islamic banking. The ability of the three independent variables to explain the dependent variable of 99.06 the rest of 0.04 influenced by other factors outside this study. The sensitive value of demand for financing in syariah banking during the observation period was 3.94 amp400P 1 so that it can be said that demand for financing in syariah banking is elastic. The elasticity of income demand for financing in syariah banking during the observation period of 3.08 amp400I 1 is categorized as luxuries goods. The cross elasticity value of financing demand in syariah banking during the observation period is 0.52 or positive amp400C 0 it can be categorized that the interest rate of a conventional bank is a substitute of profit sharing.

Identifying heat-related deaths by using medical examiner and vital statistics data: Surveillance analysis and descriptive epidemiology - Oklahoma, 1990-2011.

Science.gov (United States)

Johnson, Matthew G; Brown, Sheryll; Archer, Pam; Wendelboe, Aaron; Magzamen, Sheryl; Bradley, Kristy K

2016-10-01

Approximately 660 deaths occur annually in the United States associated with excess natural heat. A record heat wave in Oklahoma during 2011 generated increased interest concerning heat-related mortality among public health preparedness partners. We aimed to improve surveillance for heat-related mortality and better characterize heat-related deaths in Oklahoma during 1990-2011, and to enhance public health messaging during future heat emergencies. Heat-related deaths were identified by querying vital statistics (VS) and medical examiner (ME) data during 1990-2011. Case inclusion criteria were developed by using heat-related International Classification of Diseases codes, cause-of-death nomenclature, and ME investigation narrative. We calculated sensitivity and predictive value positive (PVP) for heat-related mortality surveillance by using VS and ME data and performed a descriptive analysis. During the study period, 364 confirmed and probable heat-related deaths were identified when utilizing both data sets. ME reports had 87% sensitivity and 74% PVP; VS reports had 80% sensitivity and 52% PVP. Compared to Oklahoma's general population, decedents were disproportionately male (67% vs. 49%), aged ≥65 years (46% vs. 14%), and unmarried (78% vs. 47%). Higher rates of heat-related mortality were observed among Blacks. Of 95 decedents with available information, 91 (96%) did not use air conditioning. Linking ME and VS data sources together and using narrative description for case classification allows for improved case ascertainment and surveillance data quality. Males, Blacks, persons aged ≥65 years, unmarried persons, and those without air conditioning carry a disproportionate burden of the heat-related deaths in Oklahoma. Published by Elsevier Inc.

Quasi-periodic luminosity variations in dwarf novae

International Nuclear Information System (INIS)

Robinson, E.L.; Nather, R.E.

1979-01-01

We have identified quasi-periodic oscillations in the light curves of five dwarf novae--U Gem, SS Cyg, RU Peg, KT Per, and VW Hyi-- and in the light curve of the quasi-periodic X-ray source Sco X-1. The mean periods of the quasi-periodic oscillations range from 32 s in SS Cyg to 147 s in KT Per and 165 s in Sco X-l. Their amplitudes are typically 0.005--0.0l mag. The properties of the quasi-periodic oscillations are represented well by a second-order autoregressive process. Use of this representation shows that the length of time over which the quasi-periodic oscillations maintain coherence is very short, typically 3--5 cycles of the oscillations. Thus the quasi-periodic oscillations can be distinguished from the short-period coherent oscillations in dwarf novae, which are usually interpreted as white dwarf pulsations, because t the periods of the quasi-periodic oscillations are 3--4 times longer and their coherence time is much shorter. The quasi-periodic oscillations occur in dwarf novae only during their eruptions and occur in Sco X-l only when the system is bright. The presence of the oscillations does not depend on the subclass to which a dwarf nova belongs or on the morphology of the individual eruptions. We argue that their short periods, their short coherence times, and their presence in Sco X-l require that the quasi-periodic oscillations be produced by the accretion disk, and not by the stars or by the boundary between the a accretion disk and its central star

A quantitative analysis of 2-D gels identifies proteins in which labeling is increased following long-term sensitization in Aplysia

International Nuclear Information System (INIS)

Castellucci, V.F.; Kennedy, T.E.; Kandel, E.R.; Goelet, P.

1988-01-01

Long-term memory for sensitization of the gill- and siphon-withdrawal reflex in Aplysia, produced by 4 days of training, is associated with increased synaptic efficacy of the connection between the sensory and motor neurons. This training is also accompanied by neuronal growth; there is an increase in the number of synaptic varicosities per sensory neuron and in the number of active zones. Such structural changes may be due to changes in the rates of synthesis of certain proteins. We have searched for proteins in which the rates of [ 35 S]methionine labeling are altered during the maintenance phase of long-term memory for sensitization by using computer-assisted quantitative 2-D gel analysis. This method has allowed us to detect 4 proteins in which labeling is altered after 4 days of sensitization training

SENSITIVITY OF MORNINGGLORY PLANTS AND THEIR PROGENIES TO GLUFOSINATE AMMONIUM

OpenAIRE

BRITO, I.P.F.S.; MORAES, C.P.; MARCHESI, B.B.; CARBONARI, C.A.; VELINI, E.D.

2017-01-01

ABSTRACT The sensitivity of weed species to herbicides is variable, and the behavior can be repeated or not in the next generation. The objective of this study was to evaluate the response of morningglory plants to different doses of glufosinate ammonium and the sensitivity of plant populations and their progenies to the herbicide. Three studies were conducted, all in a greenhouse and repeated in two periods. In the first study, two experiments were conducted to examine the dose-response curv...

Sensitivity of intermittent streams to climate variations in the USA

Science.gov (United States)

Eng, Kenny; Wolock, David M.; Dettinger, Mike

2015-01-01

There is a great deal of interest in the literature on streamflow changes caused by climate change because of the potential negative effects on aquatic biota and water supplies. Most previous studies have primarily focused on perennial streams, and there have been only a few studies examining the effect of climate variability on intermittent streams. Our objectives in this study were to (1) identify regions of similar zero-flow behavior, and (2) evaluate the sensitivity of intermittent streams to historical variability in climate in the United States. This study was carried out at 265 intermittent streams by evaluating: (1) correlations among time series of flow metrics (number of zero-flow events, the average of the central 50% and largest 10% of flows) with climate (magnitudes, durations and intensity), and (2) decadal changes in the seasonality and long-term trends of these flow metrics. Results identified five distinct seasonality patterns in the zero-flow events. In addition, strong associations between the low-flow metrics and historical changes in climate were found. The decadal analysis suggested no significant seasonal shifts or decade-to-decade trends in the low-flow metrics. The lack of trends or changes in seasonality is likely due to unchanged long-term patterns in precipitation over the time period examined.

The economic burden of nurse-sensitive adverse events in 22 medical-surgical units: retrospective and matching analysis.

Science.gov (United States)

Tchouaket, Eric; Dubois, Carl-Ardy; D'Amour, Danielle

2017-07-01

The aim of this study was to assess the economic burden of nurse-sensitive adverse events in 22 acute-care units in Quebec by estimating excess hospital-related costs and calculating resulting additional hospital days. Recent changes in the worldwide economic and financial contexts have made the cost of patient safety a topical issue. Yet, our knowledge about the economic burden of safety of nursing care is quite limited in Canada in general and Quebec in particular. Retrospective analysis of charts of 2699 patients hospitalized between July 2008 - August 2009 for at least 2 days of 30-day periods in 22 medical-surgical units in 11 hospitals in Quebec. Data were collected from September 2009 to August 2010. Nurse-sensitive adverse events analysed were pressure ulcers, falls, medication administration errors, pneumonia and urinary tract infections. Descriptive statistics identified numbers of cases for each nurse-sensitive adverse event. A literature analysis was used to estimate excess median hospital-related costs of treatments with these nurse-sensitive adverse events. Costs were calculated in 2014 Canadian dollars. Additional hospital days were estimated by comparing lengths of stay of patients with nurse-sensitive adverse events with those of similar patients without nurse-sensitive adverse events. This study found that five adverse events considered nurse-sensitive caused nearly 1300 additional hospital days for 166 patients and generated more than Canadian dollars 600,000 in excess treatment costs. The results present the financial consequences of the nurse-sensitive adverse events. Government should invest in prevention and in improvements to care quality and patient safety. Managers need to strengthen safety processes in their facilities and nurses should take greater precautions. © 2017 John Wiley & Sons Ltd.

Leaf Spectral Characteristics and Its Sensitivity to N, P, K in Different Fruit Growth Periods of Armeniaca vulgaris 'Luntaibaixing'%轮台白杏果实不同生育期叶片光谱特性及对氮磷钾的敏感性

Institute of Scientific and Technical Information of China (English)

胡珍珠; 潘存德; 高淑然

2012-01-01

[目的]通过分析果实不同生育期叶片光谱反射率对N、P、K的响应,探寻采用叶片光谱指数诊断N、P、K的敏感期,为轮台白杏简便快捷的非破坏性营养诊断提供最佳时间窗.[方法]基于“3414”肥料效应田间试验,利用Unispec - SC光谱仪测定轮台白杏在不同N、P、K施肥水平下果实膨大期、着色期、成熟期、收后期叶片光谱反射率.[结果]轮台白杏果实不同生育期叶片光谱反射率变异依赖于波长,变异最小的波段位于可见光范围,且光谱反射率呈现膨大期＞成熟期＞收后期＞着色期.在不同N、P、K施肥水平下,轮台白杏果实不同生育期叶片光谱指数(ND705)之间均存在显著差异(P＜0.05)或极显著差异(P＜0.01).[结论]果实着色期是轮台白杏N素叶片光谱营养诊断的敏感期,果实膨大期是P、K素叶片光谱营养诊断的敏感期.%[Objective] Sensitive stages of leaf spectral index used for N, P, K diagnosis were explored by analyzing the effect of N, P, K on leaf spectral reflectance in different fruit growth periods to provide the best temporal window for noninvasive, simple and rapid nutritional diagnosis of Armeniaca wlgaris ' Luntaibaixing'. [ Method] Based on "3414" fertilizer effect field experiments, leaf spectral reflectance in the fruit swollen period, fruit coloured period, fruit mature period, fruit harvest period under diverse N, P, K fertilization levels were measured with Unispec - SC. [ Result]The variation of leaf spectral reflectance of A. Vulgaris ' Luntaibaixing' in different fruit growth periods relied on the wavelength, the smallest variance which appeared in the visible light range and the leaf spectral reflectance was fruit swollen period > fruit mature period > fruit harvest period > fruit coloured period. The difference of leaf spectral index ND705 in different fruit growth periods under diverse N, P, K fertilization levels were significant or extremely remarkable

A Long-Period Grating Sensor for Wind Turbine Blades

DEFF Research Database (Denmark)

Glavind, Lars

This PhD project concerns the applied research for providing a novel sensor for measurements on wind turbine blades, based on Long-Period Gratings. The idea is based on the utilization of a special asymmetrical optical fibre with Long-Period Gratings for directional sensitive bend sensing...... blade material, where a suitable process and recoating material were investigated. The sensor was implemented and tested on a full scale wind turbine blade placed on a test rig. This first prototype has demonstrated the capability of the sensor for wind turbine blade monitoring, particular...... the possibility to distinguish between the flap- and edge-wise bend directions on the wind turbine blade, providing a selective sensor. The sensor has proven to be very robust and suitable for this application....

Numerical modeling and sensitivity analysis of seawater intrusion in a dual-permeability coastal karst aquifer with conduit networks

Directory of Open Access Journals (Sweden)

Z. Xu

2018-01-01

important parameters identified from sensitivity results, including salinity at the submarine spring with rainfall recharge, sea level rise, and a longer simulation time under an extended low rainfall period.

The prevalence and incidence of glaucoma in Denmark in a fifteen year period

DEFF Research Database (Denmark)

Kolko, Miriam; Horwitz, Anna; Thygesen, John

2015-01-01

PURPOSE: The purpose of the present study was to describe the prevalence, incidence and geographic variation of glaucoma in Denmark in the period from 1996 to 2011. Moreover, the aim was to identify the treatment patterns of glaucoma within the studied period. METHODS: All Danish citizens were...... included throughout the study period. The National Prescription Registry was used to identify all claimed prescriptions for glaucoma medication. RESULTS: A total of 116,592 incident glaucoma patients were identified. Average age at onset was 66 years (range: 0-105 years), 55% were women. The prevalence...... of glaucoma increased from 0.79% to 1.72% during the investigated period. In 2011 glaucoma affected 3.76% of the population above 50 years and 10% in patients above 80 years. The age-specific incidence rate of glaucoma seemed to be constant and the increasing prevalence was primarily attributed to an aging...

Sensory sensitivity and identification and hedonic assessment ofolfactory stimuli

Directory of Open Access Journals (Sweden)

Borys Ruszpel

2012-06-01

Full Text Available Conducted research had an exploratory character. It was focused on connections between temperament and olfactory functioning – in particular, identification and affective assessment of olfactory stimuli. Main research question dealt with potential correlations between sensory sensitivity (dimension of temperamental questionnaire FCZ‑KT with declarative and objective ability to identify presented odours and their assessment. Fifty four schoolgirls from one of the Warsaw sec‑ ondary schools participated in the research and they were asked for filling in the FCZ‑KT questionnaire and evaluating each of 16 smell samples. Analyses revealed a significant positive correlation between declared familiarity and accurate odours’ identification (odours that were subjectively known were recognized more accurately than unknown and a posi‑ tive correlation between declared familiarity and affective assessment (odours that were known were assessed as more pleasant than unknown. Sensory sensitivity was not correlated neither with declarative nor real ability to identify smells, however sensory sensitivity was positively correlated with affective assessment (the higher scores on sensory sensitivity dimension, the more pleasantly assessed odours in general. Analyses revealed a number of connections between other dimensions of FCZ‑KT questionnaire (perseverance, liveliness, stamina and the ability (both objective and subjective to correctly identify odours which were most difficult to recognize. Completed project might be perceived as a starting point for further research concerning relationships between temperament, olfactory functioning, and food preferences among patients diagnosed with eating disorders such as anorexia nervosa, bulimia nervosa, and obesity.

Exquisite light sensitivity of Drosophila melanogaster cryptochrome.

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Pooja Vinayak

Full Text Available Drosophila melanogaster shows exquisite light sensitivity for modulation of circadian functions in vivo, yet the activities of the Drosophila circadian photopigment cryptochrome (CRY have only been observed at high light levels. We studied intensity/duration parameters for light pulse induced circadian phase shifts under dim light conditions in vivo. Flies show far greater light sensitivity than previously appreciated, and show a surprising sensitivity increase with pulse duration, implying a process of photic integration active up to at least 6 hours. The CRY target timeless (TIM shows dim light dependent degradation in circadian pacemaker neurons that parallels phase shift amplitude, indicating that integration occurs at this step, with the strongest effect in a single identified pacemaker neuron. Our findings indicate that CRY compensates for limited light sensitivity in vivo by photon integration over extraordinarily long times, and point to select circadian pacemaker neurons as having important roles.

[Sensitization to chymopapain in patients treated with chemonucleolysis].

Science.gov (United States)

García-Ortega, P; Ramírez Ferreiras, W; Sancho, A; Urías, S; Cisteró, A

1991-03-23

Chemonucleolysis (intradisk administration of chymopapain) is a procedure to treat intervertebral disk hernia. Recently, its use has been questioned due to the development of anaphylactic reactions in patients sensitized to chymopapain. The prevalence of sensitization to chymopapain has been evaluated before and after chemonucleolysis, and the possibility to establish risk groups through the allergy history has been assessed. 104 consecutive patients who were candidates to chemonucleolysis were evaluated with an allergy questionnaire, cutaneous tests to aeroallergens and to chymopapain, and chymopapain-specific IgE. The two latter tests were repeated one month after chemonucleolysis. Only 2 patients (1.9%) showed evidence of chymopapain sensitization before the procedure. Sixteen patients (16%) were sensitized after chemonucleolysis. None of the possible risk factors evaluated in the allergy questionnaire (atopy, drug allergy, papaya occupational exposure or use of additives, cosmetics or drugs containing papaine) were significantly related with the risk of sensitization to chymopapain. The prevalence of chymopapain sensitization in the study group was low. The allergy questionnaire (atopy, drug allergy, use of papaya, occupational history did not identify sensitized patients. Cutaneous tests and specific IgE are the best method to detect chymopapain sensitization. The remarkable rate of sensitization after chemonucleolysis may partially limit the usefulness of the procedure.

Two statistics for evaluating parameter identifiability and error reduction

Science.gov (United States)

Doherty, John; Hunt, Randall J.

2009-01-01

Two statistics are presented that can be used to rank input parameters utilized by a model in terms of their relative identifiability based on a given or possible future calibration dataset. Identifiability is defined here as the capability of model calibration to constrain parameters used by a model. Both statistics require that the sensitivity of each model parameter be calculated for each model output for which there are actual or presumed field measurements. Singular value decomposition (SVD) of the weighted sensitivity matrix is then undertaken to quantify the relation between the parameters and observations that, in turn, allows selection of calibration solution and null spaces spanned by unit orthogonal vectors. The first statistic presented, "parameter identifiability", is quantitatively defined as the direction cosine between a parameter and its projection onto the calibration solution space. This varies between zero and one, with zero indicating complete non-identifiability and one indicating complete identifiability. The second statistic, "relative error reduction", indicates the extent to which the calibration process reduces error in estimation of a parameter from its pre-calibration level where its value must be assigned purely on the basis of prior expert knowledge. This is more sophisticated than identifiability, in that it takes greater account of the noise associated with the calibration dataset. Like identifiability, it has a maximum value of one (which can only be achieved if there is no measurement noise). Conceptually it can fall to zero; and even below zero if a calibration problem is poorly posed. An example, based on a coupled groundwater/surface-water model, is included that demonstrates the utility of the statistics. ?? 2009 Elsevier B.V.

OSL sensitivity changes during single aliquot procedures: Computer simulations

DEFF Research Database (Denmark)

McKeever, S.W.S.; Agersnap Larsen, N.; Bøtter-Jensen, L.

1997-01-01

We present computer simulations of sensitivity changes obtained during single aliquot, regeneration procedures. The simulations indicate that the sensitivity changes are the combined result of shallow trap and deep trap effects. Four separate processes have been identified. Although procedures can...... be suggested to eliminate the shallow trap effects, it appears that the deep trap effects cannot be removed. The character of the sensitivity changes which result from these effects is seen to be dependent upon several external parameters, including the extent of bleaching of the OSL signal, the laboratory...

Robust modal curvature features for identifying multiple damage in beams

Science.gov (United States)

Ostachowicz, Wiesław; Xu, Wei; Bai, Runbo; Radzieński, Maciej; Cao, Maosen

2014-03-01

Curvature mode shape is an effective feature for damage detection in beams. However, it is susceptible to measurement noise, easily impairing its advantage of sensitivity to damage. To deal with this deficiency, this study formulates an improved curvature mode shape for multiple damage detection in beams based on integrating a wavelet transform (WT) and a Teager energy operator (TEO). The improved curvature mode shape, termed the WT - TEO curvature mode shape, has inherent capabilities of immunity to noise and sensitivity to damage. The proposed method is experimentally validated by identifying multiple cracks in cantilever steel beams with the mode shapes acquired using a scanning laser vibrometer. The results demonstrate that the improved curvature mode shape can identify multiple damage accurately and reliably, and it is fairly robust to measurement noise.

Assessing flood risk at the global scale: model setup, results, and sensitivity

International Nuclear Information System (INIS)

Ward, Philip J; Jongman, Brenden; Weiland, Frederiek Sperna; Winsemius, Hessel C; Bouwman, Arno; Ligtvoet, Willem; Van Beek, Rens; Bierkens, Marc F P

2013-01-01

Globally, economic losses from flooding exceeded $19 billion in 2012, and are rising rapidly. Hence, there is an increasing need for global-scale flood risk assessments, also within the context of integrated global assessments. We have developed and validated a model cascade for producing global flood risk maps, based on numerous flood return-periods. Validation results indicate that the model simulates interannual fluctuations in flood impacts well. The cascade involves: hydrological and hydraulic modelling; extreme value statistics; inundation modelling; flood impact modelling; and estimating annual expected impacts. The initial results estimate global impacts for several indicators, for example annual expected exposed population (169 million); and annual expected exposed GDP ($1383 billion). These results are relatively insensitive to the extreme value distribution employed to estimate low frequency flood volumes. However, they are extremely sensitive to the assumed flood protection standard; developing a database of such standards should be a research priority. Also, results are sensitive to the use of two different climate forcing datasets. The impact model can easily accommodate new, user-defined, impact indicators. We envisage several applications, for example: identifying risk hotspots; calculating macro-scale risk for the insurance industry and large companies; and assessing potential benefits (and costs) of adaptation measures. (letter)

The sensitivity and specificity of the social communication questionnaire for autism spectrum with respect to age.

Science.gov (United States)

Barnard-Brak, Lucy; Brewer, Adam; Chesnut, Steven; Richman, David; Schaeffer, Anna Marie

2016-08-01

The age neutrality of the Social Communication Questionnaire (SCQ) was examined as a common screener for ASD. Mixed findings have been reported regarding the recommended cutoff score's ability to accurately classify an individual as at-risk for autism spectrum disorder (ASD) (sensitivity) versus accurately classifying an individual as not at-risk for ASD (specificity). With a sample from the National Database for Autism Research, this study examined the SCQ's sensitivity versus specificity. Analyses indicated that the actual sensitivity and specificity scores were lower than initially reported by the creators of the SCQ. Autism Res 2016, 9: 838-845. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Platelet function in the postprandial period

Directory of Open Access Journals (Sweden)

Sinzinger Helmut

2012-09-01

Full Text Available Abstract Background Postprandial hyperlipidemia and hyperglycemia have been related to cardiovascular events. Among different underlying mechanisms platelet activation seems to be responsible too. No comparable data between various tests in normo- vs. hyperlipidemics before and at different time intervals are available after a fat meal. We aimed to compare 9 of them within the same patients at several time points in postprandial hyperlipidemia. Results For some tests baseline values between the groups were significantly different (TXB2, platelet sensitivity, sedimentation and WU-test. However, hyperlipidemia revealed a variable influence on the tests examined. Some of the available tests apparently sensitive to show platelet activation reflect the increase in triglycerides (TG, such as the sedimentation index. ADP-induced platelet aggregatory activity in count adjusted washed isolated platelet samples during postprandial hyperlipidemia indicates mildly enhanced platelet activity, but does not seem to induce significant changes in aggregation. In patients with severe hypertriglyceridemia (> 400 mg/dl fasting changes in platelet function are more pronounced due to delayed decay and may last up to 16 hours paralleling TG reaching the prevalue. The overwhelming majority of platelet function tests do not significantly respond to postprandial hyperlipidemia. The correlation between the tests applied is poor. For standardization purpose, platelet aggregation tests, aimed to examine proaggregatory capacity in atherosclerosis, should only be performed at the same time of the day after a fasting period > 6 hours. The great variation in preanalytical work-up on comparison of various tests, large number of platelet tests available and their respective potential value are discussed. Conclusions At present, the suspicion that platelet function is significantly activated in the postprandial period cannot be supported by any of the tests used. The

Accuracy of magnetic resonance in identifying traumatic intraarticular knee lesions

International Nuclear Information System (INIS)

Vaz, Carlos Eduardo Sanches; Camargo, Olavo Pires de; Santana, Paulo Jose de; Valezi, Antonio Carlos

2005-01-01

Purpose: To evaluate the diagnostic accuracy of magnetic resonance imaging of the knee in identifying traumatic intraarticular knee lesions. Method: 300 patients with a clinical diagnosis of traumatic intraarticular knee lesions underwent prearthoscopic magnetic resonance imaging. The sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for a positive test, likelihood ratio for a negative test, and accuracy of magnetic resonance imaging were calculated relative to the findings during arthroscopy in the studied structures of the knee (medial meniscus, lateral meniscus, anterior cruciate ligament, posterior cruciate ligament, and articular cartilage). Results: Magnetic resonance imaging produced the following results regarding detection of lesions: medial meniscus: sensitivity 97.5%, specificity 92.9%, positive predictive value 93.9%, positive negative value 97%, likelihood positive ratio 13.7, likelihood negative ratio 0.02, and accuracy 95.3%; lateral meniscus: sensitivity 91.9%, specificity 93.6%, positive predictive value 92.7%, positive negative value 92.9%, likelihood positive ratio 14.3, likelihood negative ratio 0.08, and accuracy 93.6%; anterior cruciate ligament: sensitivity 99.0%, specificity 95.9%, positive predictive value 91.9%, positive negative value 99.5%, likelihood positive ratio 21.5, likelihood negative ratio 0.01, and accuracy 96.6%; posterior cruciate ligament: sensitivity 100%, specificity 99%, positive predictive value 80.0%, positive negative value 100%, likelihood positive ratio 100, likelihood negative ratio 0.01, and accuracy 99.6%; articular cartilage: sensitivity 76.1%, specificity 94.9%, positive predictive value 94.7%, positive negative value 76.9%, likelihood positive ratio 14.9, likelihood negative ratio 0.25, and accuracy 84.6%. Conclusion: Magnetic resonance imaging is a satisfactory diagnostic tool for evaluating meniscal and ligamentous lesions of the knee, but it is unable to clearly

Accuracy of magnetic resonance in identifying traumatic intraarticular knee lesions

Directory of Open Access Journals (Sweden)

Vaz Carlos Eduardo Sanches

2005-01-01

Full Text Available PURPOSE: To evaluate the diagnostic accuracy of magnetic resonance imaging of the knee in identifying traumatic intraarticular knee lesions. METHOD: 300 patients with a clinical diagnosis of traumatic intraarticular knee lesions underwent prearthoscopic magnetic resonance imaging. The sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for a positive test, likelihood ratio for a negative test, and accuracy of magnetic resonance imaging were calculated relative to the findings during arthroscopy in the studied structures of the knee (medial meniscus, lateral meniscus, anterior cruciate ligament, posterior cruciate ligament, and articular cartilage. RESULTS: Magnetic resonance imaging produced the following results regarding detection of lesions: medial meniscus: sensitivity 97.5%, specificity 92.9%, positive predictive value 93.9%, positive negative value 97%, likelihood positive ratio 13.7, likelihood negative ratio 0.02, and accuracy 95.3%; lateral meniscus: sensitivity 91.9%, specificity 93.6%, positive predictive value 92.7%, positive negative value 92.9%, likelihood positive ratio 14.3, likelihood negative ratio 0.08, and accuracy 93.6%; anterior cruciate ligament: sensitivity 99.0%, specificity 95.9%, positive predictive value 91.9%, positive negative value 99.5%, likelihood positive ratio 21.5, likelihood negative ratio 0.01, and accuracy 96.6%; posterior cruciate ligament: sensitivity 100%, specificity 99%, positive predictive value 80.0%, positive negative value 100%, likelihood positive ratio 100, likelihood negative ratio 0.01, and accuracy 99.6%; articular cartilage: sensitivity 76.1%, specificity 94.9%, positive predictive value 94.7%, positive negative value 76.9%, likelihood positive ratio 14.9, likelihood negative ratio 0.25, and accuracy 84.6%. CONCLUSION: Magnetic resonance imaging is a satisfactory diagnostic tool for evaluating meniscal and ligamentous lesions of the knee, but it is

PLANET HUNTERS: ASSESSING THE KEPLER INVENTORY OF SHORT-PERIOD PLANETS

International Nuclear Information System (INIS)

Schwamb, Megan E.; Lintott, Chris J.; Lynn, Stuart; Smith, Arfon M.; Simpson, Robert J.; Fischer, Debra A.; Giguere, Matthew J.; Brewer, John M.; Parrish, Michael; Schawinski, Kevin

2012-01-01

We present the results from a search of data from the first 33.5 days of the Kepler science mission (Quarter 1) for exoplanet transits by the Planet Hunters citizen science project. Planet Hunters enlists members of the general public to visually identify transits in the publicly released Kepler light curves via the World Wide Web. Over 24,000 volunteers reviewed the Kepler Quarter 1 data set. We examine the abundance of ≥2 R ⊕ planets on short-period ( ⊕ Planet Hunters ≥85% efficient at identifying transit signals for planets with periods less than 15 days for the Kepler sample of target stars. Our high efficiency rate for simulated transits along with recovery of the majority of Kepler ≥4 R ⊕ planets suggests that the Kepler inventory of ≥4 R ⊕ short-period planets is nearly complete.

Application of Sensitivity Analysis in Design of Integrated Building Concepts

DEFF Research Database (Denmark)

Heiselberg, Per; Brohus, Henrik; Hesselholt, Allan Tind

2007-01-01

analysis makes it possible to identify the most important parameters in relation to building performance and to focus design and optimization of integrated building concepts on these fewer, but most important parameters. The sensitivity analyses will typically be performed at a reasonably early stage...... the design requirements and objectives. In the design of integrated building concepts it is beneficial to identify the most important design parameters in order to more efficiently develop alternative design solutions or more efficiently perform an optimization of the building performance. The sensitivity...

Insulin resistance in obesity can be reliably identified from fasting plasma insulin.

Science.gov (United States)

ter Horst, K W; Gilijamse, P W; Koopman, K E; de Weijer, B A; Brands, M; Kootte, R S; Romijn, J A; Ackermans, M T; Nieuwdorp, M; Soeters, M R; Serlie, M J

2015-12-01

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), Pobese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

RETRAN sensitivity studies of light water reactor transients. Final report

International Nuclear Information System (INIS)

Burrell, N.S.; Gose, G.C.; Harrison, J.F.; Sawtelle, G.R.

1977-06-01

This report presents the results of sensitivity studies performed using the RETRAN/RELAP4 transient analysis code to identify critical parameters and models which influence light water reactor transient predictions. Various plant transients for both boiling water reactors and pressurized water reactors are examined. These studies represent the first detailed evaluation of the RETRAN/RELAP4 transient code capability in predicting a variety of plant transient responses. The wide range of transients analyzed in conjunction with the parameter and modeling studies performed identify several sensitive areas as well as areas requiring future study and model development

Communication with spatial periodic chaos synchronization

International Nuclear Information System (INIS)

Zhou, J.; Huang, H.B.; Qi, G.X.; Yang, P.; Xie, X.

2005-01-01

Based on the spatial periodic chaos synchronization in coupled ring and linear arrays, we proposed a random high-dimensional chaotic encryption scheme. The transmitter can choose hyperchaotic signals randomly from the ring at any different time and simultaneously transmit the information of chaotic oscillators in the ring to receiver through public channel, so that the message can be masked by different hyperchaotic signals in different time intervals during communication, and the receiver can decode the message based on chaos synchronization but the attacker does not know the random hyperchaotic dynamics and cannot decode the message. Furthermore, the high sensitivity to the symmetry of the coupling structure makes the attacker very difficult to obtain any useful message from the channel

Arc-Induced Long Period Gratings from Standard to Polarization-Maintaining and Photonic Crystal Fibers

Directory of Open Access Journals (Sweden)

Flavio Esposito

2018-03-01

Full Text Available In this work, we report about our recent results concerning the fabrication of Long Period Grating (LPG sensors in several optical fibers, through the Electric Arc Discharge (EAD technique. In particular, the following silica fibers with both different dopants and geometrical structures are considered: standard Ge-doped, photosensitive B/Ge codoped, P-doped, pure-silica core with F-doped cladding, Panda type Polarization-maintaining, and Hollow core Photonic crystal fiber. An adaptive platform was developed and the appropriate “recipe” was identified for each fiber, in terms of both arc discharge parameters and setup arrangement, for manufacturing LPGs with strong and narrow attenuation bands, low insertion losses, and short length. As the fabricated devices have appealing features from the application point of view, the sensitivity characteristics towards changes in different external perturbations (i.e., surrounding refractive index, temperature, and strain are investigated and compared, highlighting the effects of different fiber composition and structure.

Administrative Algorithms to identify Avascular necrosis of bone among patients undergoing upper or lower extremity magnetic resonance imaging: a validation study.

Science.gov (United States)

Barbhaiya, Medha; Dong, Yan; Sparks, Jeffrey A; Losina, Elena; Costenbader, Karen H; Katz, Jeffrey N

2017-06-19

Studies of the epidemiology and outcomes of avascular necrosis (AVN) require accurate case-finding methods. The aim of this study was to evaluate performance characteristics of a claims-based algorithm designed to identify AVN cases in administrative data. Using a centralized patient registry from a US academic medical center, we identified all adults aged ≥18 years who underwent magnetic resonance imaging (MRI) of an upper/lower extremity joint during the 1.5 year study period. A radiologist report confirming AVN on MRI served as the gold standard. We examined the sensitivity, specificity, positive predictive value (PPV) and positive likelihood ratio (LR + ) of four algorithms (A-D) using International Classification of Diseases, 9th edition (ICD-9) codes for AVN. The algorithms ranged from least stringent (Algorithm A, requiring ≥1 ICD-9 code for AVN [733.4X]) to most stringent (Algorithm D, requiring ≥3 ICD-9 codes, each at least 30 days apart). Among 8200 patients who underwent MRI, 83 (1.0% [95% CI 0.78-1.22]) had AVN by gold standard. Algorithm A yielded the highest sensitivity (81.9%, 95% CI 72.0-89.5), with PPV of 66.0% (95% CI 56.0-75.1). The PPV of algorithm D increased to 82.2% (95% CI 67.9-92.0), although sensitivity decreased to 44.6% (95% CI 33.7-55.9). All four algorithms had specificities >99%. An algorithm that uses a single billing code to screen for AVN among those who had MRI has the highest sensitivity and is best suited for studies in which further medical record review confirming AVN is feasible. Algorithms using multiple billing codes are recommended for use in administrative databases when further AVN validation is not feasible.

POWRS: position-sensitive motif discovery.

Directory of Open Access Journals (Sweden)

Ian W Davis

Full Text Available Transcription factors and the short, often degenerate DNA sequences they recognize are central regulators of gene expression, but their regulatory code is challenging to dissect experimentally. Thus, computational approaches have long been used to identify putative regulatory elements from the patterns in promoter sequences. Here we present a new algorithm "POWRS" (POsition-sensitive WoRd Set for identifying regulatory sequence motifs, specifically developed to address two common shortcomings of existing algorithms. First, POWRS uses the position-specific enrichment of regulatory elements near transcription start sites to significantly increase sensitivity, while providing new information about the preferred localization of those elements. Second, POWRS forgoes position weight matrices for a discrete motif representation that appears more resistant to over-generalization. We apply this algorithm to discover sequences related to constitutive, high-level gene expression in the model plant Arabidopsis thaliana, and then experimentally validate the importance of those elements by systematically mutating two endogenous promoters and measuring the effect on gene expression levels. This provides a foundation for future efforts to rationally engineer gene expression in plants, a problem of great importance in developing biotech crop varieties.BSD-licensed Python code at http://grassrootsbio.com/papers/powrs/.

Intermittent and sustained periodic windows in networked chaotic Rössler oscillators

International Nuclear Information System (INIS)

He, Zhiwei; Sun, Yong; Zhan, Meng

2013-01-01

Route to chaos (or periodicity) in dynamical systems is one of fundamental problems. Here, dynamical behaviors of coupled chaotic Rössler oscillators on complex networks are investigated and two different types of periodic windows with the variation of coupling strength are found. Under a moderate coupling, the periodic window is intermittent, and the attractors within the window extremely sensitively depend on the initial conditions, coupling parameter, and topology of the network. Therefore, after adding or removing one edge of network, the periodic attractor can be destroyed and substituted by a chaotic one, or vice versa. In contrast, under an extremely weak coupling, another type of periodic window appears, which insensitively depends on the initial conditions, coupling parameter, and network. It is sustained and unchanged for different types of network structure. It is also found that the phase differences of the oscillators are almost discrete and randomly distributed except that directly linked oscillators more likely have different phases. These dynamical behaviors have also been generally observed in other networked chaotic oscillators

Generalized tolerance sensitivity and DEA metric sensitivity

OpenAIRE

Neralić, Luka; E. Wendell, Richard

2015-01-01

This paper considers the relationship between Tolerance sensitivity analysis in optimization and metric sensitivity analysis in Data Envelopment Analysis (DEA). Herein, we extend the results on the generalized Tolerance framework proposed by Wendell and Chen and show how this framework includes DEA metric sensitivity as a special case. Further, we note how recent results in Tolerance sensitivity suggest some possible extensions of the results in DEA metric sensitivity.

Generalized tolerance sensitivity and DEA metric sensitivity

Directory of Open Access Journals (Sweden)

Luka Neralić

2015-03-01

Full Text Available This paper considers the relationship between Tolerance sensitivity analysis in optimization and metric sensitivity analysis in Data Envelopment Analysis (DEA. Herein, we extend the results on the generalized Tolerance framework proposed by Wendell and Chen and show how this framework includes DEA metric sensitivity as a special case. Further, we note how recent results in Tolerance sensitivity suggest some possible extensions of the results in DEA metric sensitivity.

Replicate periodic windows in the parameter space of driven oscillators

Energy Technology Data Exchange (ETDEWEB)

Medeiros, E.S., E-mail: esm@if.usp.br [Instituto de Fisica, Universidade de Sao Paulo, Sao Paulo (Brazil); Souza, S.L.T. de [Universidade Federal de Sao Joao del-Rei, Campus Alto Paraopeba, Minas Gerais (Brazil); Medrano-T, R.O. [Departamento de Ciencias Exatas e da Terra, Universidade Federal de Sao Paulo, Diadema, Sao Paulo (Brazil); Caldas, I.L. [Instituto de Fisica, Universidade de Sao Paulo, Sao Paulo (Brazil)

2011-11-15

Highlights: > We apply a weak harmonic perturbation to control chaos in two driven oscillators. > We find replicate periodic windows in the driven oscillator parameter space. > We find that the periodic window replication is associated with the chaos control. - Abstract: In the bi-dimensional parameter space of driven oscillators, shrimp-shaped periodic windows are immersed in chaotic regions. For two of these oscillators, namely, Duffing and Josephson junction, we show that a weak harmonic perturbation replicates these periodic windows giving rise to parameter regions correspondent to periodic orbits. The new windows are composed of parameters whose periodic orbits have the same periodicity and pattern of stable and unstable periodic orbits already existent for the unperturbed oscillator. Moreover, these unstable periodic orbits are embedded in chaotic attractors in phase space regions where the new stable orbits are identified. Thus, the observed periodic window replication is an effective oscillator control process, once chaotic orbits are replaced by regular ones.

Stress-induced sensitization: the hypothalamic-pituitary-adrenal axis and beyond.

Science.gov (United States)

Belda, Xavier; Fuentes, Silvia; Daviu, Nuria; Nadal, Roser; Armario, Antonio

2015-01-01

Exposure to certain acute and chronic stressors results in an immediate behavioral and physiological response to the situation followed by a period of days when cross-sensitization to further novel stressors is observed. Cross-sensitization affects to different behavioral and physiological systems, more particularly to the hypothalamus-pituitary-adrenal (HPA) axis. It appears that the nature of the initial (triggering) stressor plays a major role, HPA cross-sensitization being more widely observed with systemic or high-intensity emotional stressors. Less important appears to be the nature of the novel (challenging) stressor, although HPA cross-sensitization is better observed with short duration (5-15 min) challenging stressors. In some studies with acute immune stressors, HPA sensitization appears to develop over time (incubation), but most results indicate a strong initial sensitization that progressively declines over the days. Sensitization can affect other physiological system (i.e. plasma catecholamines, brain monoamines), but it is not a general phenomenon. When studied concurrently, behavioral sensitization appears to persist longer than that of the HPA axis, a finding of interest regarding long-term consequences of traumatic stress. In many cases, behavioral and physiological consequences of prior stress can only be observed following imposition of a new stressor, suggesting long-term latent effects of the initial exposure.

Sanitizing sensitive association rules using fuzzy correlation scheme

International Nuclear Information System (INIS)

Hameed, S.; Shahzad, F.; Asghar, S.

2013-01-01

Data mining is used to extract useful information hidden in the data. Sometimes this extraction of information leads to revealing sensitive information. Privacy preservation in Data Mining is a process of sanitizing sensitive information. This research focuses on sanitizing sensitive rules discovered in quantitative data. The proposed scheme, Privacy Preserving in Fuzzy Association Rules (PPFAR) is based on fuzzy correlation analysis. In this work, fuzzy set concept is integrated with fuzzy correlation analysis and Apriori algorithm to mark interesting fuzzy association rules. The identified rules are called sensitive. For sanitization, we use modification technique where we substitute maximum value of fuzzy items with zero, which occurs most frequently. Experiments demonstrate that PPFAR method hides sensitive rules with minimum modifications. The technique also maintains the modified data's quality. The PPFAR scheme has applications in various domains e.g. temperature control, medical analysis, travel time prediction, genetic behavior prediction etc. We have validated the results on medical dataset. (author)

Manufacturing a Long-Period Grating with Periodic Thermal Diffusion Technology on High-NA Fiber and Its Application as a High-Temperature Sensor.

Science.gov (United States)

Shen, Xiang; Dai, Bin; Xing, Yingbin; Yang, Luyun; Li, Haiqing; Li, Jinyan; Peng, Jingang

2018-05-08

We demonstrated a kind of long-period fiber grating (LPFG), which is manufactured with a thermal diffusion treatment. The LPFG was inscribed on an ultrahigh-numerical-aperture (UHNA) fiber, highly doped with Ge and P, which was able to easily diffuse at high temperatures within a few seconds. We analyzed how the elements diffused at a high temperature over 1300 °C in the UHNA fiber. Then we developed a periodically heated technology with a CO₂ laser, which was able to cause the diffusion of the elements to constitute the modulations of an LPFG. With this technology, there is little damage to the outer structure of the fiber, which is different from the traditional LPFG, as it is periodically tapered. Since the LPFG itself was manufactured under high temperature, it can withstand higher temperatures than traditional LPFGs. Furthermore, the LPFG presents a higher sensitivity to high temperature due to the large amount of Ge doping, which is approximately 100 pm/°C. In addition, the LPFG shows insensitivity to the changing of the environment’s refractive index and strain.

Using the Delphi method to develop nursing-sensitive quality indicators for the NICU.

Science.gov (United States)

Chen, Lin; Huang, Li-Hua; Xing, Mei-Yuan; Feng, Zhi-Xian; Shao, Le-Wen; Zhang, Mei-Yun; Shao, Rong-Ya

2017-02-01

To develop nursing-sensitive quality indicators consistent with current medical practices in Chinese neonatal intensive care units. The development of nursing-sensitive quality indicators has become a top priority in nursing management. To the best of our knowledge, there has been no objective, scientific and sensitive evaluation of the quality of neonatal intensive care unit nursing in China. A modified Delphi technique was used to seek opinions from experts about what should be used and prioritised as indicators of quality care in neonatal intensive care unit nursing. Based on a literature review, we identified 21 indicators of nursing-sensitive quality in the neonatal intensive care unit. Our group of 11 consultants chose 13 indicators to be discussed using the Delphi method. In October and November 2014, 39 neonatal intensive care unit experts in 18 tertiary hospitals spread across six provinces participated in two rounds of Delphi panels. Of the 13 indicators discussed, 11 were identified as indicators of nursing-sensitive quality in the neonatal intensive care unit: rate of nosocomial infections, rate of accidental endotracheal extubation, rate of errors in medication administration, rate of treatment for pain, rate of peripheral venous extravasation, rate of compliance with handwashing techniques, incidence of pressure ulcers, incidence of noise, the bed-to-care ratio, the proportion of nurses with greater than five years neonatal intensive care unit experience and incidence of retinopathy. The 11 neonatal intensive care unit nursing-sensitive indicators identified by the Delphi method integrated with basic Chinese practices provide a basis for nursing management and the monitoring of nursing quality. This study identified nursing-sensitive quality indicators for neonatal intensive care unit care that are suitable for current clinical practice in China. © 2016 John Wiley & Sons Ltd.

Coastal sensitivity mapping of Gulf of Kachchh and Gulf of Cambay, India

Digital Repository Service at National Institute of Oceanography (India)

ManiMurali, R.; Boora, P.; Vethamony, P.

and managers of coastal zones are also useful for identifying sensitive resources before a spill occurs (Jenson, 1998). In this way, protection priorities could be identified and established and cleanup strategies could be designed in advance. To deal... regions to oil spills. This research focuses on improving information about coastal environment mapping from remote sensing and GIS technology to generate maps of environmental sensitivity index for oil spill in Gulf of Kachchh and Gulf of Cambay...

Gender-Sensitive Post-Disaster Assessments

OpenAIRE

World Bank

2012-01-01

This note on gender-sensitive post-disaster assessments is the eighth in a series of guidance notes on gender issues in disaster risk management (DRM) in the East Asia and the Pacific region. Targeting World Bank staff, clients and development partners, this note gives an overview of the main reasons for assessing gender impacts as part of a post-disaster needs assessment, identifies the k...

Uniformity and stability of LiF sensitivity - a review of fourteen years' monitoring experience

International Nuclear Information System (INIS)

Grogan, D.; Bradley, R.P.; Mattioli, A.

1990-01-01

The Personnel Dosimetry Services of the Bureau of Radiation and Medical Devices have utilised an increasingly large pool of thermoluminescence dosimetry (TLD) plaques since 1976. Between 1975 and 1981, the volume increased from 60,000 to 180,000 to implement a change from films to TLDs. As of 1989, 317,000 plaques are in service. Most, but not all, of the thick and thin LiF-100 chips contained on each dosemeter plaque have been individually calibrated. Because the TLDs have been obtained over a period of fourteen years, it is possible to quantify the variation of response sensitivities for each batch purchased. A continued increase in sensitivity has been noted. Furthermore, because detailed records of use have been maintained, it is also possible to quantify information relating the purchased batch sensitivities to other parameters such as cumulative exposure, time of use, and number of readings. Some selected examples are given. Of most interest is the variation of sensitivity factors for individual LiF crystals in relation to the above parameters. Results for periods of one to fourteen years are presented. (author)

Ethical sensitivity in professional practice: concept analysis.

Science.gov (United States)

Weaver, Kathryn; Morse, Janice; Mitcham, Carl

2008-06-01

This paper is a report of a concept analysis of ethical sensitivity. Ethical sensitivity enables nurses and other professionals to respond morally to the suffering and vulnerability of those receiving professional care and services. Because of its significance to nursing and other professional practices, ethical sensitivity deserves more focused analysis. A criteria-based method oriented toward pragmatic utility guided the analysis of 200 papers and books from the fields of nursing, medicine, psychology, dentistry, clinical ethics, theology, education, law, accounting or business, journalism, philosophy, political and social sciences and women's studies. This literature spanned 1970 to 2006 and was sorted by discipline and concept dimensions and examined for concept structure and use across various contexts. The analysis was completed in September 2007. Ethical sensitivity in professional practice develops in contexts of uncertainty, client suffering and vulnerability, and through relationships characterized by receptivity, responsiveness and courage on the part of professionals. Essential attributes of ethical sensitivity are identified as moral perception, affectivity and dividing loyalties. Outcomes include integrity preserving decision-making, comfort and well-being, learning and professional transcendence. Our findings promote ethical sensitivity as a type of practical wisdom that pursues client comfort and professional satisfaction with care delivery. The analysis and resulting model offers an inclusive view of ethical sensitivity that addresses some of the limitations with prior conceptualizations.

Longitudinal Changes in Behavioral Approach System Sensitivity and Brain Structures Involved in Reward Processing during Adolescence

OpenAIRE

Urošević, Snežana; Collins, Paul; Muetzel, Ryan; Lim, Kelvin; Luciana, Monica

2012-01-01

Adolescence is a period of radical normative changes and increased risk for substance use, mood disorders, and physical injury. Researchers have proposed that increases in reward sensitivity, i.e., sensitivity of the behavioral approach system (BAS), and/or increases in reactivity to all emotional stimuli (i.e., reward and threat sensitivities) lead to these phenomena. The present study is the first longitudinal investigation of changes in reward (i.e., BAS) sensitivity in 9 to 23-year-olds a...

Analytical approximations for the amplitude and period of a relaxation oscillator

Directory of Open Access Journals (Sweden)

Golkhou Vahid

2009-01-01

Full Text Available Abstract Background Analysis and design of complex systems benefit from mathematically tractable models, which are often derived by approximating a nonlinear system with an effective equivalent linear system. Biological oscillators with coupled positive and negative feedback loops, termed hysteresis or relaxation oscillators, are an important class of nonlinear systems and have been the subject of comprehensive computational studies. Analytical approximations have identified criteria for sustained oscillations, but have not linked the observed period and phase to compact formulas involving underlying molecular parameters. Results We present, to our knowledge, the first analytical expressions for the period and amplitude of a classic model for the animal circadian clock oscillator. These compact expressions are in good agreement with numerical solutions of corresponding continuous ODEs and for stochastic simulations executed at literature parameter values. The formulas are shown to be useful by permitting quick comparisons relative to a negative-feedback represillator oscillator for noise (10× less sensitive to protein decay rates, efficiency (2× more efficient, and dynamic range (30 to 60 decibel increase. The dynamic range is enhanced at its lower end by a new concentration scale defined by the crossing point of the activator and repressor, rather than from a steady-state expression level. Conclusion Analytical expressions for oscillator dynamics provide a physical understanding for the observations from numerical simulations and suggest additional properties not readily apparent or as yet unexplored. The methods described here may be applied to other nonlinear oscillator designs and biological circuits.

Analysis of Publically Available Skin Sensitization Data from REACH Registrations 2008–2014

Science.gov (United States)

Luechtefeld, Thomas; Maertens, Alexandra; Russo, Daniel P.; Rovida, Costanza; Zhu, Hao; Hartung, Thomas

2017-01-01

Summary The public data on skin sensitization from REACH registrations already included 19,111 studies on skin sensitization in December 2014, making it the largest repository of such data so far (1,470 substances with mouse LLNA, 2,787 with GPMT, 762 with both in vivo and in vitro and 139 with only in vitro data). 21% were classified as sensitizers. The extracted skin sensitization data was analyzed to identify relationships in skin sensitization guidelines, visualize structural relationships of sensitizers, and build models to predict sensitization. A chemical with molecular weight > 500 Da is generally considered non-sensitizing owing to low bioavailability, but 49 sensitizing chemicals with a molecular weight > 500 Da were found. A chemical similarity map was produced using PubChem’s 2D Tanimoto similarity metric and Gephi force layout visualization. Nine clusters of chemicals were identified by Blondel’s module recognition algorithm revealing wide module-dependent variation. Approximately 31% of mapped chemicals are Michael’s acceptors but alone this does not imply skin sensitization. A simple sensitization model using molecular weight and five ToxTree structural alerts showed a balanced accuracy of 65.8% (specificity 80.4%, sensitivity 51.4%), demonstrating that structural alerts have information value. A simple variant of k-nearest neighbors outperformed the ToxTree approach even at 75% similarity threshold (82% balanced accuracy at 0.95 threshold). At higher thresholds, the balanced accuracy increased. Lower similarity thresholds decrease sensitivity faster than specificity. This analysis scopes the landscape of chemical skin sensitization, demonstrating the value of large public datasets for health hazard prediction. PMID:26863411

Non-animal sensitization testing: state-of-the-art.

Science.gov (United States)

Vandebriel, Rob J; van Loveren, Henk

2010-05-01

Predictive tests to identify the sensitizing properties of chemicals are carried out using animals. In the European Union timelines for phasing out many standard animal tests were established for cosmetics. Following this policy, the new European Chemicals Legislation (REACH) favors alternative methods, if validated and appropriate. In this review the authors aim to provide a state-of-the art overview of alternative methods (in silico, in chemico, and in vitro) to identify contact and respiratory sensitizing capacity and in some occasions give a measure of potency. The past few years have seen major advances in QSAR (quantitative structure-activity relationship) models where especially mechanism-based models have great potential, peptide reactivity assays where multiple parameters can be measured simultaneously, providing a more complete reactivity profile, and cell-based assays. Several cell-based assays are in development, not only using different cell types, but also several specifically developed assays such as three-dimenionally (3D)-reconstituted skin models, an antioxidant response reporter assay, determination of signaling pathways, and gene profiling. Some of these assays show relatively high sensitivity and specificity for a large number of sensitizers and should enter validation (or are indeed entering this process). Integrating multiple assays in a decision tree or integrated testing system is a next step, but has yet to be developed. Adequate risk assessment, however, is likely to require significantly more time and efforts.

Variably protease-sensitive prionopathy in the UK: a retrospective review 1991-2008

NARCIS (Netherlands)

Head, M.W.; Yull, H.M.; Ritchie, D.L.; Langeveld, J.P.M.; Fletcher, N.A.; Knight, R.S.; Ironside, J.W.

2013-01-01

Variably protease-sensitive prionopathy is a newly described human prion disease of unknown aetiology lying out with the hitherto recognized phenotypic spectrum of Creutzfeldt-Jakob disease. Two cases that conform to the variably protease-sensitive prionopathy phenotype have been identified

Inverse crystallization if Abrikosov vortex system at periodic pinning

CERN Document Server

Zyubin, M V; Kashurnikov, V A

2002-01-01

The vortex system in the quasi-two-dimensional HTSC plate is considered in the case of the periodic pinning. The M(H) magnetization curves by various values of the external magnetic field and different temperatures are calculated through the Monte Carlo method. It is shown that in the case of the periodic pinning the crystallization of the vortex system is possible by the temperature increase. A number of peculiarities conditioned by the impact of the pinning centers periodic lattice are identified on the magnetization curves. The pictures of the vortex distribution corresponding to various points on the M(H) curve are obtained

Toward sustainable environmental quality: Identifying priority research questions for Latin America

Science.gov (United States)

Furley, Tatiana Heid; Brodeur, Julie; Silva de Assis, Helena C; Carriquiriborde, Pedro; Chagas, Katia R; Corrales, Jone; Denadai, Marina; Fuchs, Julio; Mascarenhas, Renata; Miglioranza, Karina SB; Miguez Caramés, Diana Margarita; Navas, José Maria; Nugegoda, Dayanthi; Planes, Estela; Rodriguez‐Jorquera, Ignacio Alejandro; Orozco‐Medina, Martha; Boxall, Alistair BA; Rudd, Murray A

2018-01-01

ABSTRACT The Global Horizon Scanning Project (GHSP) is an innovative initiative that aims to identify important global environmental quality research needs. Here we report 20 key research questions from Latin America (LA). Members of the Society of Environmental Toxicology and Chemistry (SETAC) LA and other scientists from LA were asked to submit research questions that would represent priority needs to address in the region. One hundred questions were received, then partitioned among categories, examined, and some rearranged during a workshop in Buenos Aires, Argentina. Twenty priority research questions were subsequently identified. These research questions included developing, improving, and harmonizing across LA countries methods for 1) identifying contaminants and degradation products in complex matrices (including biota); 2) advancing prediction of contaminant risks and effects in ecosystems, addressing lab‐to‐field extrapolation challenges, and understanding complexities of multiple stressors (including chemicals and climate change); and 3) improving management and regulatory tools toward achieving sustainable development. Whereas environmental contaminants frequently identified in these key questions were pesticides, pharmaceuticals, endocrine disruptors or modulators, plastics, and nanomaterials, commonly identified environmental challenges were related to agriculture, urban effluents, solid wastes, pulp and paper mills, and natural extraction activities. Several interesting research topics included assessing and preventing pollution impacts on conservation protected areas, integrating environment and health assessments, and developing strategies for identification, substitution, and design of less hazardous chemicals (e.g., green chemistry). Finally, a recurrent research need included developing an understanding of differential sensitivity of regional species and ecosystems to environmental contaminants and other stressors. Addressing these critical

Acetylsalicylic acid-triggered 15-HETE generation by peripheral leukocytes for identifying ASA sensitivity.

Science.gov (United States)

Korosec, Peter; Tisler, Ursa; Bajrovic, Nissera; Silar, Mira; Mrhar, Ales; Kosnik, Mitja

2011-10-01

Exposure to acetylsalicylic acid (ASA) may exacerbate respiratory or skin diseases or induce anaphylactoid reactions in apparently healthy individuals. We wanted to evaluate the clinical and diagnostic utility of measuring ASA-induced 15-hydroxyeicosatetraenoic acid (15-HETE) generation. We performed a prospective single-blind study with 26 subjects undergoing clinical evaluation and/or ASA provocation testing. We also included 12 control subjects. Peripheral blood leukocytes were incubated with 500 μM ASA and 15-HETE release was measured by competitive ELISA. We found that 18 subjects were ASA-tolerant and 8 were ASA-intolerant. The mean increase in 15-HETE in intolerant subjects was 34% and this was comparable to the mean increase of 30% observed in ASA-tolerant subjects. A similar mean increase was also observed in control subjects. The ROC calculation showed that the optimal diagnostic threshold would be an increase of greater than 33%. However, the sensitivity of this increase was only 63% and the specificity was 50%. Our data suggest that further studies are needed before the ASA-induced 15-HETE test can be used in clinical practice. Copyright © 2011 Elsevier Ltd. All rights reserved.

Sensitivity-based virtual fields for the non-linear virtual fields method

Science.gov (United States)

Marek, Aleksander; Davis, Frances M.; Pierron, Fabrice

2017-09-01

The virtual fields method is an approach to inversely identify material parameters using full-field deformation data. In this manuscript, a new set of automatically-defined virtual fields for non-linear constitutive models has been proposed. These new sensitivity-based virtual fields reduce the influence of noise on the parameter identification. The sensitivity-based virtual fields were applied to a numerical example involving small strain plasticity; however, the general formulation derived for these virtual fields is applicable to any non-linear constitutive model. To quantify the improvement offered by these new virtual fields, they were compared with stiffness-based and manually defined virtual fields. The proposed sensitivity-based virtual fields were consistently able to identify plastic model parameters and outperform the stiffness-based and manually defined virtual fields when the data was corrupted by noise.

Sensitization of TRPA1 by Protein Kinase A.

Directory of Open Access Journals (Sweden)

Jannis E Meents

Full Text Available The TRPA1 ion channel is expressed in nociceptive (pain-sensitive somatosensory neurons and is activated by a wide variety of chemical irritants, such as acrolein in smoke or isothiocyanates in mustard. Here, we investigate the enhancement of TRPA1 function caused by inflammatory mediators, which is thought to be important in lung conditions such as asthma and COPD. Protein kinase A is an important kinase acting downstream of inflammatory mediators to cause sensitization of TRPA1. By using site-directed mutagenesis, patch-clamp electrophysiology and calcium imaging we identify four amino acid residues, S86, S317, S428, and S972, as the principal targets of PKA-mediated phosphorylation and sensitization of TRPA1.

Multiple Chemical Sensitivity

DEFF Research Database (Denmark)

Dantoft, Thomas Meinertz

Multiple chemical sensitivity (MCS) is a chronic disorder characterized by reports of symptoms from various organ systems attributed by the individuals to exposure to common odors and airborne chemicals in doses far below those known to induce toxic effects. There exists a general lack of knowledge......, significantly reduced levels of IL-13 in the MCS group and no group differences in the allergen specific IgE measures. The differences were independent of factors such as sex, age, Body Mass Index, asthma, smoking, depression, anxiety and allergen-specific IgE. In conclusion, the study identified a distinct...

Sensitivity of intermittent streams to climate variations in the United States

Science.gov (United States)

Eng, K.

2015-12-01

There is growing interest in the effects of climate change on streamflows because of the potential negative effects on aquatic biota and water supplies. Previous studies of climate controls on flows have primarily focused on perennial streams, and few studies have examined the effect of climate variability on intermittent streams. Our objectives in this study were to (1) identify regions showing similar patterns of intermittency, and (2) evaluate the sensitivity of intermittent streams to historical variability in climate in the United States. This study was carried out at 265 intermittent streams by evaluating: (1) correlations among time series of flow metrics (number of zero-flow events, the average of the central 50% and largest 10% of flows) with precipitation (magnitudes, durations and intensity) and temperature, and (2) decadal changes in the seasonality and long-term trends of these flow metrics. Results identified five distinct seasonal patterns of flow intermittency: fall, fall-to-winter, non-seasonal, summer, and summer-to-winter intermittent streams. In addition, strong associations between the low-flow metrics and historical climate variability were found. However, the lack of trends in historical variations in precipitation results in no significant seasonal shifts or decade-to-decade trends in the low-flow metrics over the period of record (1950 to 2013).

Prognostic Factors for Hormone Sensitive Metastatic Prostate Cancer: Impact of Disease Volume

Science.gov (United States)

Alhanafy, Alshimaa Mahmoud; Zanaty, Fouad; Ibrahem, Reda; Omar, Suzan

2018-04-27

Background and Aim: The optimal management of metastatic hormone-sensitive prostate cancer has been controversial in recent years with introduction of upfront chemohormonal treatment based on results of several Western studies. This changing landscape has renewed interest in the concept “disease volume”, the focus of the present study is the Egyptian patients. Methods: Patients with hormone sensitive metastatic prostate cancer presenting at Menoufia University Hospital, Egypt, during the period from June 2013 to May 2016, were enrolled. All received hormonal treatment. Radiologic images were evaluated and patients were stratified according to their disease volume into high or low, other clinical and pathological data that could affect survival also being collected and analyzed. Results: A total of 128 patients were included, with a median age of 70 years (53.9% ≥70). About 46% had co-morbidities, 62% having high volume disease. During the median follow up period of 28 months about half of the patients progressed and one third received chemotherapy. On univariate analysis, disease volume, performance status (PS), prostate specific antigen level (PSA) and presence of pain at presentation were identified as factors influencing overall survival. Multivariate analysis revealed the independent predictor factors for survival to be PS, PSA and disease volume. The median overall survival with 27 months was high volume versus 49 with low volume disease (hazard ratio 2.1; 95% CI 1.2 - 4.4; P=0.02). Median progression free survival was 19 months in the high volume, as compared with 48 months in the low volume disease patients (hazard ratio, 2.44; 95% CI, 1.42 – 7.4; P=0.009). Conclusions: Disease volume is a reliable predictor of survival which should be incorporated with other important factors as; patient performance status and comorbidities in treatment decision-making. Creative Commons Attribution License

The incubation period distribution of tuberculosis estimated with a molecular epidemiological approach.

NARCIS (Netherlands)

Borgdorff, M.W.; Sebek, M.; Geskus, R.B.; Kremer, K.; Kalisvaart, N.; Soolingen, D. van

2011-01-01

BACKGROUND: There is limited information on the distribution of incubation periods of tuberculosis (TB). METHODS: In The Netherlands, patients whose Mycobacterium tuberculosis isolates have identical DNA fingerprints in the period 1993-2007 were interviewed to identify epidemiological links between

Financial Profitability and Sensitivity Analysis of Palm Oil Plantation in Indonesia

Directory of Open Access Journals (Sweden)

Tereza Svatoňová

2015-01-01

Full Text Available Oil palm cultivation in Indonesia is increasing. This study investigates the financial and economic aspects of establishing an oil palm plantation using data collected in 2014. The financial case study is undertaken from the perspective of company in North Sumatra, Indonesia. A spreadsheet model was used to develop and calculate the net present value (NPV, return of investment (ROI, internal rate of return (IRR and payback period (PP. Sensitivity analysis of the NPV to the default discount rate (10% was included. A 8,000 ha plantation over 25 years was estimated to result in a positive NPV of USD 10,670 with a ROI 73.50% and an IRR at 14.83% and payback period of 6.75 years. Establishing an oil palm plantation seems to be very profitable investment on the basis of the assumptions made. System is tested on sensitivity in different capital and recurrent costs and in selling price of raw material, while change in selling price of FFB is more sensitive to NPV than change in investment and recurrent costs Discount rate is also one of the factors affecting NPV and system is tested between 5–15% change in discount rate.

Body weight and sensitivity of screening mammography

DEFF Research Database (Denmark)

Njor, Sisse H.; von Euler-Chelpin, My; Tjønneland, Anne

2016-01-01

benefit more from screening than other women. Methods: We combined data from the Danish Diet, Cancer and Health study and the organised population-based screening mammography programme in Copenhagen, Denmark. Women were categorised according to body mass index (BMI) (...Aim: Obese women tend to participate less in breast cancer screening than normal weight women. However, obese women have fattier breast than normal weight women, and screening mammography works better in fatty than in dense breasts. One might, therefore, hypothesise that obese women would actually......, and 35+). We measured recall rate, sensitivity and specificity for subsequent screens with a 2-year follow-up period. Results: The study included 6787 women. The recall rate varied from 1.4% for women with BMI women with BMI 35+, test for trend p = 0.86. Sensitivity varied from 42% (95...

The incubation period distribution of tuberculosis estimated with a molecular epidemiological approach

NARCIS (Netherlands)

Borgdorff, Martien W.; Sebek, Maruschka; Geskus, Ronald B.; Kremer, Kristin; Kalisvaart, Nico; van Soolingen, Dick

2011-01-01

There is limited information on the distribution of incubation periods of tuberculosis (TB). In The Netherlands, patients whose Mycobacterium tuberculosis isolates have identical DNA fingerprints in the period 1993-2007 were interviewed to identify epidemiological links between cases. We determined

Performance of terahertz metamaterials as high-sensitivity sensor

Science.gov (United States)

He, Yanan; Zhang, Bo; Shen, Jingling

2017-09-01

A high-sensitivity sensor based on the resonant transmission characteristics of terahertz (THz) metamaterials was investigated, with the proposal and fabrication of rectangular bar arrays of THz metamaterials exhibiting a period of 180 μm on a 25 μm thick flexible polyimide. Varying the size of the metamaterial structure revealed that the length of the rectangular unit modulated the resonant frequency, which was verified by both experiment and simulation. The sensing characteristics upon varying the surrounding media in the sample were tested by simulation and experiment. Changing the surrounding medium from that of air to that of alcohol or oil produced resonant frequency redshifts of 80 GHz or 150 GHz, respectively, which indicates that the sensor possessed a high sensitivity of 667 GHz per unit of refractive index. Finally, the influence of the sample substrate thickness on the sensor sensitivity was investigated by simulation. It may be a reference for future sensor design.

Salinity measurement in water environment with a long period grating based interferometer

International Nuclear Information System (INIS)

Possetti, G R C; Kamikawachi, R C; Muller, M; Fabris, J L; Prevedello, C L

2009-01-01

In this work, a comparative study of the behaviour of an in-fibre Mach–Zehnder interferometer for salinity measurement in a water solution is presented. The fibre transducer is composed of two nearly identical long period gratings forming an in-series 7.38 cm long device written in the same fibre optic. Two inorganic and one organic salts (NaCl, KCl, NaCOOH) were characterized within the concentration range from 0 to 150 g L −1 . For the long period grating interferometer, the average obtained sensitivities were −6.61, −5.58 and −3.83 pm/(g L −1 ) for the above salts, respectively, or equivalently −40.8, −46.5 and −39.1 nm RIU −1 . Salinity measured by means of fibre refractometry is compared with measurements obtained using an Abbe refractometer as well as via electrical conductivity. For the long period grating refractometer, the best resolutions attained were 1.30, 1.54 and 2.03 g of salt per litre for NaCl, KCl and NaCOOH, respectively, about two times better than the resolutions obtained by the Abbe refractometer. An average thermal sensitivity of 53 pm °C −1 was measured for the grating transducer immersed in water, indicating the need for the thermal correction of the sensor. Resolutions for the same ionic constituent in different salts are also analysed

Differential sensitivity of coral larvae to natural levels of ultraviolet radiation during the onset of larval competence.

KAUST Repository

Aranda, Manuel

2011-07-01

Scleractinian corals are the major builders of the complex structural framework of coral reefs. They live in tropical waters around the globe where they are frequently exposed to potentially harmful ultraviolet radiation (UVR). The eggs and early embryonic stages of some coral species are highly buoyant and remain near the sea surface for prolonged periods of time and may therefore be the most sensitive life stages with respect to UVR. Here, we analysed gene expression changes in five developmental stages of the Caribbean coral Montastraea faveolata to natural levels of UVR using high-density cDNA microarrays (10 930 clones). We found that larvae exhibit low sensitivity to natural levels of UVR during early development as reflected by comparatively few transcriptomic changes in response to UVR. However, we identified a time window of high UVR sensitivity that coincides with the motile planula stage and the onset of larval competence. These processes have been shown to be affected by UVR exposure, and the transcriptional changes we identified explain these observations well. Our analysis of differentially expressed genes indicates that UVR alters the expression of genes associated with stress response, the endoplasmic reticulum, Ca(2+) homoeostasis, development and apoptosis during the motile planula stage and affects the expression of neurogenesis-related genes that are linked to swimming and settlement behaviour at later stages. Taken together, our study provides further data on the impact of natural levels of UVR on coral larvae. Furthermore, our results might allow a better prediction of settlement and recruitment rates after coral spawning events if UVR climate data are taken into account.

System reliability assessment via sensitivity analysis in the Markov chain scheme

International Nuclear Information System (INIS)

Gandini, A.

1988-01-01

Methods for reliability sensitivity analysis in the Markov chain scheme are presented, together with a new formulation which makes use of Generalized Perturbation Theory (GPT) methods. As well known, sensitivity methods are fundamental in system risk analysis, since they allow to identify important components, so to assist the analyst in finding weaknesses in design and operation and in suggesting optimal modifications for system upgrade. The relationship between the GPT sensitivity expression and the Birnbaum importance is also given [fr

Global sensitivity analysis of DRAINMOD-FOREST, an integrated forest ecosystem model

Science.gov (United States)

Shiying Tian; Mohamed A. Youssef; Devendra M. Amatya; Eric D. Vance

2014-01-01

Global sensitivity analysis is a useful tool to understand process-based ecosystem models by identifying key parameters and processes controlling model predictions. This study reported a comprehensive global sensitivity analysis for DRAINMOD-FOREST, an integrated model for simulating water, carbon (C), and nitrogen (N) cycles and plant growth in lowland forests. The...

GenMol trademark supramolecular descriptors predicting reliable sensitivity of energetic compounds

Energy Technology Data Exchange (ETDEWEB)

Benazet, Stephane; Jacob, Guy [SNPE Materiaux Energetiques, Vert Le Petit (France); Pepe, Gerard [CINaM UPR-CNRS 3118, Campus de Luminy Case, Marseille (France)

2009-04-15

Structure/activity relationship methodology has been applied to the problem of the prediction of the energetic molecule's sensitivity. This parameter knowledge is of great importance to increase the safety of operations in the field of synthesis and manipulation of such compounds. It has been shown that descriptors of the solid state interactions and surface topology issued from GenMol {sup trademark} software calculations greatly enhanced the correlation between measured and predicted sensitivity. As the structural parameters used to establish the descriptors are experimental ones, their physical significance is particularly preserved which allows to give a good prediction for impact or friction sensitivity by the so defined descriptors. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

Relationship between the electrostatic sensitivity of nitramines and their molecular structure

Energy Technology Data Exchange (ETDEWEB)

Hossein Keshavarz, Mohammad [Department of Chemistry, Malek-ashtar University of Technology, Shahin-shahr (Iran); Moghadas, Mohammad Hassan [Department of Mechanical Engineering, Malek-ashtar University of Technology, Shahin-shahr (Iran); Kavosh Tehrani, Masoud [Department of Physics, Malek-ashtar University of Technology, Shahin-shahr (Iran)

2009-04-15

In this paper, a new approach is introduced to predict the electrostatic sensitivity of nitramines on the basis of their molecular structure. The ratio of carbon to oxygen and the existence of two specific structural parameters can be used for the prediction of the electrostatic sensitivity of nitramines. The results are also compared with quantum mechanical computations from [9] so that the new method gives better predictions with respect to the measured data. Electrostatic sensitivities calculated by the new method for two new nitramines CL-20 [2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane] and TNAZ [1,3,3-trinitroazatidine] are also close to the experimental data. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

Deep sequencing identifies ethnicity-specific bacterial signatures in the oral microbiome.

Directory of Open Access Journals (Sweden)

Matthew R Mason

Full Text Available Oral infections have a strong ethnic predilection; suggesting that ethnicity is a critical determinant of oral microbial colonization. Dental plaque and saliva samples from 192 subjects belonging to four major ethnicities in the United States were analyzed using terminal restriction fragment length polymorphism (t-RFLP and 16S pyrosequencing. Ethnicity-specific clustering of microbial communities was apparent in saliva and subgingival biofilms, and a machine-learning classifier was capable of identifying an individual's ethnicity from subgingival microbial signatures. The classifier identified African Americans with a 100% sensitivity and 74% specificity and Caucasians with a 50% sensitivity and 91% specificity. The data demonstrates a significant association between ethnic affiliation and the composition of the oral microbiome; to the extent that these microbial signatures appear to be capable of discriminating between ethnicities.

Influence of parameter values on the oscillation sensitivities of two p53-Mdm2 models.

Science.gov (United States)

Cuba, Christian E; Valle, Alexander R; Ayala-Charca, Giancarlo; Villota, Elizabeth R; Coronado, Alberto M

2015-09-01

Biomolecular networks that present oscillatory behavior are ubiquitous in nature. While some design principles for robust oscillations have been identified, it is not well understood how these oscillations are affected when the kinetic parameters are constantly changing or are not precisely known, as often occurs in cellular environments. Many models of diverse complexity level, for systems such as circadian rhythms, cell cycle or the p53 network, have been proposed. Here we assess the influence of hundreds of different parameter sets on the sensitivities of two configurations of a well-known oscillatory system, the p53 core network. We show that, for both models and all parameter sets, the parameter related to the p53 positive feedback, i.e. self-promotion, is the only one that presents sizeable sensitivities on extrema, periods and delay. Moreover, varying the parameter set values to change the dynamical characteristics of the response is more restricted in the simple model, whereas the complex model shows greater tunability. These results highlight the importance of the presence of specific network patterns, in addition to the role of parameter values, when we want to characterize oscillatory biochemical systems.

[Study on sensitivity of climatic factors on influenza A (H1N1) based on classification and regression tree and wavelet analysis].

Science.gov (United States)

Xiao, Hong; Lin, Xiao-ling; Dai, Xiang-yu; Gao, Li-dong; Chen, Bi-yun; Zhang, Xi-xing; Zhu, Pei-juan; Tian, Huai-yu

2012-05-01

To analyze the periodicity of pandemic influenza A (H1N1) in Changsha in year 2009 and its correlation with sensitive climatic factors. The information of 5439 cases of influenza A (H1N1) and synchronous meteorological data during the period between May 22th and December 31st in year 2009 (223 days in total) in Changsha city were collected. The classification and regression tree (CART) was employed to screen the sensitive climatic factors on influenza A (H1N1); meanwhile, cross wavelet transform and wavelet coherence analysis were applied to assess and compare the periodicity of the pandemic disease and its association with the time-lag phase features of the sensitive climatic factors. The results of CART indicated that the daily minimum temperature and daily absolute humidity were the sensitive climatic factors for the popularity of influenza A (H1N1) in Changsha. The peak of the incidence of influenza A (H1N1) was in the period between October and December (Median (M) = 44.00 cases per day), simultaneously the daily minimum temperature (M = 13°C) and daily absolute humidity (M = 6.69 g/m(3)) were relatively low. The results of wavelet analysis demonstrated that a period of 16 days was found in the epidemic threshold in Changsha, while the daily minimum temperature and daily absolute humidity were the relatively sensitive climatic factors. The number of daily reported patients was statistically relevant to the daily minimum temperature and daily absolute humidity. The frequency domain was mostly in the period of (16 ± 2) days. In the initial stage of the disease (from August 9th and September 8th), a 6-day lag was found between the incidence and the daily minimum temperature. In the peak period of the disease, the daily minimum temperature and daily absolute humidity were negatively relevant to the incidence of the disease. In the pandemic period, the incidence of influenza A (H1N1) showed periodic features; and the sensitive climatic factors did have a "driving

Robust prediction of anti-cancer drug sensitivity and sensitivity-specific biomarker.

Directory of Open Access Journals (Sweden)

Heewon Park

Full Text Available The personal genomics era has attracted a large amount of attention for anti-cancer therapy by patient-specific analysis. Patient-specific analysis enables discovery of individual genomic characteristics for each patient, and thus we can effectively predict individual genetic risk of disease and perform personalized anti-cancer therapy. Although the existing methods for patient-specific analysis have successfully uncovered crucial biomarkers, their performance takes a sudden turn for the worst in the presence of outliers, since the methods are based on non-robust manners. In practice, clinical and genomic alterations datasets usually contain outliers from various sources (e.g., experiment error, coding error, etc. and the outliers may significantly affect the result of patient-specific analysis. We propose a robust methodology for patient-specific analysis in line with the NetwrokProfiler. In the proposed method, outliers in high dimensional gene expression levels and drug response datasets are simultaneously controlled by robust Mahalanobis distance in robust principal component space. Thus, we can effectively perform for predicting anti-cancer drug sensitivity and identifying sensitivity-specific biomarkers for individual patients. We observe through Monte Carlo simulations that the proposed robust method produces outstanding performances for predicting response variable in the presence of outliers. We also apply the proposed methodology to the Sanger dataset in order to uncover cancer biomarkers and predict anti-cancer drug sensitivity, and show the effectiveness of our method.

Sensitivity of permanent meadows areas. Preliminary report

International Nuclear Information System (INIS)

Pourcelot, L.

2006-01-01

The objective of this work proposed in the framework of the S.E.N.S.I.B. project on the permanent meadows areas is to compare the sensitivity of these surfaces and cheese maker sector which are associated with them, and to identify the processes which determine this sensitivity. The realization of this objective will lean on certain data of activities acquired recently by the I.R.S.N. (compartments: soils, herb, milk and cheese), as well as on new measures, on three sites: Saint-Laurent-de-Geris ( West), Beaune-Le-Froid ( center), and Massif of Jura (East). Two scales of transfers observation and sensitivity are retained. In a first time, the sensitivity of meadows areas will studied at the regional scale, from data acquired in the Massif du Jura ( between 300 and 1200 metres up). In a second time, a study will allow to compare the sensitivity of three areas retained (West, Center, East) at the national scale. The expertise will be focused on the factors of sensitivity of the transfer soil-herb and the factors of sensitivity bound to the cheese makers sectors. The data of the already available zones of study create strong variabilities of the rates of 137 Cs transfer in the interfaces soil / herb and herb / milk, letting suppose that the nature of soils, the quantity and the quality of food ingested by the cattle constitutes dominating factors of sensitivity. Besides, the size of the basin of milk collection, extremely variable from a site of study in the other one, has to influence the contamination of cheeses and as such, it establishes an important factor of sensitivity of the cheese makers sector. (N.C.)

Identifying Mother-Child Interaction Styles Using a Person-Centered Approach.

Science.gov (United States)

Nelson, Jackie A; O'Brien, Marion; Grimm, Kevin J; Leerkes, Esther M

2014-05-01

Parent-child conflict in the context of a supportive relationship has been discussed as a potentially constructive interaction pattern; the current study is the first to test this using a holistic analytic approach. Interaction styles, defined as mother-child conflict in the context of maternal sensitivity, were identified and described with demographic and stress-related characteristics of families. Longitudinal associations were tested between interaction styles and children's later social competence. Participants included 814 partnered mothers with a first-grade child. Latent profile analysis identified agreeable , dynamic , and disconnected interaction styles. Mothers' intimacy with a partner, depressive symptoms, and authoritarian childrearing beliefs, along with children's later conflict with a best friend and externalizing problems, were associated with group membership. Notably, the dynamic style, characterized by high sensitivity and high conflict, included families who experienced psychological and relational stressors. Findings are discussed with regard to how family stressors shape parent-child interaction patterns.

Electric fuses operation, a review: 2. Arcing period

International Nuclear Information System (INIS)

Bussière, W

2012-01-01

In the electric fuse operation the arcing period follows immediately the pre-arcing period depicted in Part 1 (Part 1. Pre-arcing period). The transition between these two operation steps is not fully understood at this time. To simplify the beginning of the arcing period can be identified with the electric arc ignition i.e. with the electrodes voltage drop. The consecutive plasma is of metallic type at the beginning of the arcing period and of metallic plus silica type with varying mixture up to the end of the arcing period. The energy brought by the fault current is withdrawn by means of the interaction between the electric arc and the arc quenching material (usually silica sand) whose morphometric properties influence the properties of the plasma column: composition, thermodynamic properties and transport coefficients of the plasma column depend on the porosity (and other morphometric properties) of the filler. The fuse element erosion also known as burn-back is responsible for the lengthening of the plasma column and the variations of the electric field. The whole of these processes is depicted by means of experimental results or modellings when possible.

Peculiarities in mice embriogenesis under serotonin effect in pre- and post-irradiation period in prenervous period of development

International Nuclear Information System (INIS)

Konstantinova, M.M.; Panaeva, S.V.; Podmareva, O.N.; Turpaev, T.M.

1995-01-01

Effect of serotonin and X-ray irradiation on mice embriogenesis in prenervous period of development is studied. The above factors were applied separately and in combination (in various doses, with change of sequence). It is shown that development of embriotoxic effect of serotonin is determined by embryos age. Six-day embryos are most sensitive. Eight-day embryos are characterized by absence of toxic effect of serotonin doses applied. The eighth day embryos are most radiosensitive, whereas the six-day ones are less radiosensitive. Serotonin administered to mice females before and after irradiation on the eight day of pregnancy produced radioprotective and therapeutic effect, and on the sixth-seventh days intensified negative radiation consequences. 15 refs.; 2 tabs

Patterns of sensitization in infants and its relation to atopic dermatitis

DEFF Research Database (Denmark)

Jøhnke, Hanne; Norberg, Lene Annette; Vach, Werner

2006-01-01

Longitudinal studies in infant populations using validated diagnostic criteria of atopic dermatitis and sensitization are rarely reported, and disease definitions, testing procedures, age of study population and evaluation of objective markers vary between countries and studies. The objectives...... of this prospective birth cohort study were to investigate: (i) the prevalence, the cumulative incidence and the pattern of transient and persistent sensitization to common food- and aeroallergens in unselected infants, (ii) the association between sensitization and the development of atopic dermatitis (AD) and (iii......) the association between selected perinatal risk factors with respect to AD and post-natal sensitization. During a one-year period a cohort of 562 unselected newborns was established and followed up at the age of 3, 6, 9, 12 and 18 months of age. At all time points infants were examined clinically and by histamine...

Acute total sleep deprivation potentiates amphetamine-induced locomotor-stimulant effects and behavioral sensitization in mice.

Science.gov (United States)

Saito, Luis P; Fukushiro, Daniela F; Hollais, André W; Mári-Kawamoto, Elisa; Costa, Jacqueline M; Berro, Laís F; Aramini, Tatiana C F; Wuo-Silva, Raphael; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

2014-02-01

It has been demonstrated that a prolonged period (48 h) of paradoxical sleep deprivation (PSD) potentiates amphetamine (AMP)-induced behavioral sensitization, an animal model of addiction-related neuroadaptations. In the present study, we examined the effects of an acute short-term deprivation of total sleep (TSD) (6h) on AMP-induced behavioral sensitization in mice and compared them to the effects of short-term PSD (6 h). Three-month-old male C57BL/6J mice underwent TSD (experiment 1-gentle handling method) or PSD (experiment 2-multiple platforms method) for 6 h. Immediately after the sleep deprivation period, mice were tested in the open field for 10 min under the effects of saline or 2.0 mg/kg AMP. Seven days later, to assess behavioral sensitization, all of the mice received a challenge injection of 2.0 mg/kg AMP and were tested in the open field for 10 min. Total, peripheral, and central locomotion, and grooming duration were measured. TSD, but not PSD, potentiated the hyperlocomotion induced by an acute injection of AMP and this effect was due to an increased locomotion in the central squares of the apparatus. Similarly, TSD facilitated the development of AMP-induced sensitization, but only in the central locomotion parameter. The data indicate that an acute period of TSD may exacerbate the behavioral effects of AMP in mice. Because sleep architecture is composed of paradoxical and slow wave sleep, and 6-h PSD had no effects on AMP-induced hyperlocomotion or sensitization, our data suggest that the deprivation of slow wave sleep plays a critical role in the mechanisms that underlie the potentiating effects of TSD on both the acute and sensitized addiction-related responses to AMP. Copyright © 2013 Elsevier Inc. All rights reserved.

Verification and sensitivity analysis on the elastic stiffness of the leaf type holddown spring assembly

International Nuclear Information System (INIS)

Song, Kee Nam

1998-01-01

The elastic formula of leaf type hold down spring(HDS) assembly is verified by comparing the values of elastic stiffness with the characteristic test results of the HDS's specimens. The comparisons show that the derived elastic stiffness formula is useful in reliably estimating the elastic stiffness of leaf type HDS assembly. The elastic stiffness sensitivity of leaf type HDS assembly is analyzed using the formula and its gradient vectors obtained from the mid-point formula. As a result of sensitivity analysis, the elastic stiffness sensitivity with respect to each design variable is quantified and design variables of large sensitivity are identified. Among the design variables, leaf thickness is identified as the most sensitive design variable to the elastic of leaf type HDS assembly. In addition, the elastic stiffness sensitivity, with respect to design variable, is in power-law type correlation to the base thickness of the leaf. (author)

Importance and sensitivity of parameters affecting the Zion Seismic Risk

International Nuclear Information System (INIS)

George, L.L.; O'Connell, W.J.

1985-06-01

This report presents the results of a study on the importance and sensitivity of structures, systems, equipment, components and design parameters used in the Zion Seismic Risk Calculations. This study is part of the Seismic Safety Margins Research Program (SSMRP) supported by the NRC Office of Nuclear Regulatory Research. The objective of this study is to provide the NRC with results on the importance and sensitivity of parameters used to evaluate seismic risk. These results can assist the NRC in making decisions dealing with the allocation of research resources on seismic issues. This study uses marginal analysis in addition to importance and sensitivity analysis to identify subject areas (input parameter areas) for improvements that reduce risk, estimate how much the improvement dfforts reduce risk, and rank the subject areas for improvements. Importance analysis identifies the systems, components, and parameters that are important to risk. Sensitivity analysis estimates the change in risk per unit improvement. Marginal analysis indicates the reduction in risk or uncertainty for improvement effort made in each subject area. The results described in this study were generated using the SEISIM (Systematic Evaluation of Important Safety Improvement Measures) and CHAIN computer codes. Part 1 of the SEISIM computer code generated the failure probabilities and risk values. Part 2 of SEISIM, along with the CHAIN computer code, generated the importance and sensitivity measures

Importance and sensitivity of parameters affecting the Zion Seismic Risk

Energy Technology Data Exchange (ETDEWEB)

George, L.L.; O' Connell, W.J.

1985-06-01

This report presents the results of a study on the importance and sensitivity of structures, systems, equipment, components and design parameters used in the Zion Seismic Risk Calculations. This study is part of the Seismic Safety Margins Research Program (SSMRP) supported by the NRC Office of Nuclear Regulatory Research. The objective of this study is to provide the NRC with results on the importance and sensitivity of parameters used to evaluate seismic risk. These results can assist the NRC in making decisions dealing with the allocation of research resources on seismic issues. This study uses marginal analysis in addition to importance and sensitivity analysis to identify subject areas (input parameter areas) for improvements that reduce risk, estimate how much the improvement dfforts reduce risk, and rank the subject areas for improvements. Importance analysis identifies the systems, components, and parameters that are important to risk. Sensitivity analysis estimates the change in risk per unit improvement. Marginal analysis indicates the reduction in risk or uncertainty for improvement effort made in each subject area. The results described in this study were generated using the SEISIM (Systematic Evaluation of Important Safety Improvement Measures) and CHAIN computer codes. Part 1 of the SEISIM computer code generated the failure probabilities and risk values. Part 2 of SEISIM, along with the CHAIN computer code, generated the importance and sensitivity measures.

Adaptive Management Plan for Sensitive Plant Species on the Nevada Test Site

International Nuclear Information System (INIS)

Wills, C. A.

2001-01-01

The Nevada Test Site supports numerous plant species considered sensitive because of their past or present status under the Endangered Species Act and with federal and state agencies. In 1998, the U.S. Department of Energy, Nevada Operation Office (DOE/NV) prepared a Resource Management Plan which commits to protects and conserve these sensitive plant species and to minimize accumulative impacts to them. This document presents the procedures of a long-term adaptive management plan which is meant to ensure that these goals are met. It identifies the parameters that are measured for all sensitive plant populations during long-term monitoring and the adaptive management actions which may be taken if significant threats to these populations are detected. This plan does not, however, identify the current list of sensitive plant species know to occur on the Nevada Test Site. The current species list and progress on their monitoring is reported annually by DOE/NV in the Resource Management Plan

Sensitivity and uncertainty analysis of the PATHWAY radionuclide transport model

International Nuclear Information System (INIS)

Otis, M.D.

1983-01-01

Procedures were developed for the uncertainty and sensitivity analysis of a dynamic model of radionuclide transport through human food chains. Uncertainty in model predictions was estimated by propagation of parameter uncertainties using a Monte Carlo simulation technique. Sensitivity of model predictions to individual parameters was investigated using the partial correlation coefficient of each parameter with model output. Random values produced for the uncertainty analysis were used in the correlation analysis for sensitivity. These procedures were applied to the PATHWAY model which predicts concentrations of radionuclides in foods grown in Nevada and Utah and exposed to fallout during the period of atmospheric nuclear weapons testing in Nevada. Concentrations and time-integrated concentrations of iodine-131, cesium-136, and cesium-137 in milk and other foods were investigated. 9 figs., 13 tabs

Periodic Early Childhood Hearing Screening: The EHDI Perspective

Science.gov (United States)

Hoffman, Jeff; Houston, K. Todd; Munoz, Karen F.; Bradham, Tamala S.

2011-01-01

State coordinators of early hearing detection and intervention (EHDI) programs completed a strengths, weaknesses, opportunities, and threats, or SWOT, analysis that examined 12 areas within state EHDI programs. Concerning periodic early childhood hearing screening, 47 coordinators listed 241 items and themes were identified within each SWOT…

Genetic Variants Associated With Glycine Metabolism and Their Role in Insulin Sensitivity and Type 2 Diabetes

NARCIS (Netherlands)

Xie, W.J.; Wood, A.R.; Lyssenko, V.; Weedon, M.N.; Knowles, J.W.; Alkayyali, S.; Assimes, T.L.; Quertermous, T.; Abbasi, F.; Paananen, J.; Haring, H.; Hansen, T.; Pedersen, O.; Smith, U.; Laakso, M.; Dekker, J.M.; Nolan, J.J.; Groop, L.; Ferrannini, E.; Adam, K.P.; Gall, W.E.; Frayling, T.M.; Walker, M.

2013-01-01

Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp.

Geochemical sensitivity analysis: Identification of important geochemical parameters for performance assessment studies

International Nuclear Information System (INIS)

Siegel, M.; Guzowski, R.; Rechard, R.; Erickson, K.

1986-01-01

The EPA Standard for geologic disposal of high level waste requires demonstration that the cumulative discharge of individual radioisotopes over a 10,000 year period at points 5 kilometers from the engineered barrier system will not exceed the limits prescribed in 40 CFR Part 191. The roles of the waste package, engineered facility, hydrogeology and geochemical processes in limiting radionuclide releases all must be considered in calculations designed to assess compliance of candidate repositories with the EPA Standard. In this talk, they will discuss the geochemical requirements of calculations used in these compliance assessments. In addition, they will describe the complementary roles of (1) simple models designed to bound the radionuclide discharge over the widest reasonable range of geochemical conditions and scenarios and (2) detailed geochemical models which can provide insights into the actual behavior of the radionuclides in the ground water. Finally, they will discuss development of sensitivity/uncertainty techniques designed to identify important site-specific geochemical parameters and processes using data from a basalt formation

Depth of source from long period P-waves

International Nuclear Information System (INIS)

Roy, Falguni