WorldWideScience

Sample records for multiple proxy responses

  1. Analyzing differences between patient and proxy on Patient Reported Outcomes in multiple sclerosis.

    Science.gov (United States)

    Sonder, Judith M; Holman, Rebecca; Knol, Dirk L; Bosma, Libertje V A E; Polman, Chris H; Uitdehaag, Bernard M J

    2013-11-15

    Proxy respondents, partners of multiple sclerosis (MS) patients, can provide valuable information on the MS patients' disease. In an earlier publication we found relatively good agreement on patient reported outcomes (PROs) measuring physical impact and functioning, but we found large differences on (neuro)psychological scales. We aim to identify patient and proxy related variables explaining differences between patients' and proxies' ratings on five PROs. We report on data from 175 MS patients and proxy respondents. Regression analyses were performed, using as dependent variable the mean differences on five scales: Physical and Psychological scale of the Multiple Sclerosis Impact Scale (MSIS-29), the Multiple Sclerosis Walking Scale (MSWS), Guy's Neurological Disability Scale (GNDS) and the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ). The independent variables were patient, proxy and disease related variables. Caregiver strain was significantly related to differences between patient and proxy scores for all five PROs. A higher level of patient anxiety on the HADS was linked to larger differences on all PROs except the GNDS. In addition, cognitive functioning, proxy depression, walking ability, proxy gender and MS related disability were contributing to the discrepancies. We found several patient and proxy factors that may contribute to discrepancies between patient and proxy scores on MS PROs. The most important factor is caregiver burden. © 2013 Elsevier B.V. All rights reserved.

  2. Multiple water isotope proxy reconstruction of extremely low last glacial temperatures in Eastern Beringia (Western Arctic)

    NARCIS (Netherlands)

    Porter, Trevor J.; Froese, Duane G.; Feakins, Sarah J.; Bindeman, Ilya N.; Mahony, Matthew E.; Pautler, Brent G.; Reichart, Gert-Jan; Sanborn, Paul T.; Simpson, Myrna J.; Weijers, Johan W H

    2016-01-01

    Precipitation isotopes are commonly used for paleothermometry in high latitude regions. Here we present multiple water isotope proxies from the same sedimentary context - perennially frozen loess deposits in the Klondike Goldfields in central Yukon, Canada, representing parts of Marine Isotope

  3. Multiple water isotope proxy reconstruction of extremely low last glacial temperatures in Eastern Beringia (Western Arctic)

    NARCIS (Netherlands)

    Porter, T.J.; Froese, D.G.; Feakins, S.J.; Bindeman, I.N.; Mahony, M.E.; Pautler, B.G.; Reichart, G.-J.; Sanborn, P.T.; Simpson, M.J.; Weijers, J.W.H.

    2016-01-01

    Precipitation isotopes are commonly used for paleothermometry in high latitude regions. Here we present multiple water isotope proxies from the same sedimentary context – perennially frozen loess deposits in the Klondike Goldfields in central Yukon, Canada, representing parts of Marine Isotope

  4. ePRISM: A case study in multiple proxy and mixed temporal resolution integration

    Science.gov (United States)

    Robinson, Marci M.; Dowsett, Harry J.

    2010-01-01

    As part of the Pliocene Research, Interpretation and Synoptic Mapping (PRISM) Project, we present the ePRISM experiment designed I) to provide climate modelers with a reconstruction of an early Pliocene warm period that was warmer than the PRISM interval (similar to 3.3 to 3.0 Ma), yet still similar in many ways to modern conditions and 2) to provide an example of how best to integrate multiple-proxy sea surface temperature (SST) data from time series with varying degrees of temporal resolution and age control as we begin to build the next generation of PRISM, the PRISM4 reconstruction, spanning a constricted time interval. While it is possible to tie individual SST estimates to a single light (warm) oxygen isotope event, we find that the warm peak average of SST estimates over a narrowed time interval is preferential for paleoclimate reconstruction as it allows for the inclusion of more records of multiple paleotemperature proxies.

  5. Longitudinal proxy measurements in multiple sclerosis: patient-proxy agreement on the impact of MS on daily life over a period of two years

    Directory of Open Access Journals (Sweden)

    Thompson Alan J

    2008-02-01

    Full Text Available Abstract Background The use of self-report measurements in clinical settings is increasing. However, in patients with limitations that interfere with reliable self-assessment such as cognitive impairment or mood disturbances, as may be the case in multiple sclerosis (MS, data collection might be problematic. In these situations, information obtained from proxy respondents (e.g. partners may replace self-ratings. The aim of this study was to examine the value of proxy ratings at separate points in time and to assess patient-proxy agreement on possible changes in disease impact of MS. Methods Fifty-six MS patients and their partners completed the Multiple Sclerosis Impact Scale (MSIS-29 at baseline and follow-up, two years later. Patient-proxy agreement was assessed at both time points by calculating intraclass correlation coefficients (ICCs, exact and global agreement and the mean directional differences between groups. Agreement of change over time was assessed by calculating ICCs between change scores. In parallel, global ratings of both patients and proxy respondents of the extent to which the patient had improved or deteriorated over the past two years were collected to validate possible changes on the MSIS-29. Results At both time points, agreement on the physical scale was higher than agreement on the psychological scale (ICCs at baseline were 0.81 for the physical scale and 0.72 for the psychological scale; at follow-up, the ICC values were 0.86 and 0.65 respectively. At follow-up, statistically significant mean differences between patients and proxies were noted for the physical scale (-4.8 ± 12.7, p = 0.006 and the psychological scale (-8.9 ± 18.8, p = 0.001. Agreement between change scores on the MSIS-29 was fair (ICC Conclusion Proxy respondents could act as a reliable source of information in cross-sectional studies. Moreover, results suggested that agreement on change over time might be better for proxy respondents compared to

  6. Multiple imputation using linked proxy outcome data resulted in important bias reduction and efficiency gains: a simulation study.

    Science.gov (United States)

    Cornish, R P; Macleod, J; Carpenter, J R; Tilling, K

    2017-01-01

    When an outcome variable is missing not at random (MNAR: probability of missingness depends on outcome values), estimates of the effect of an exposure on this outcome are often biased. We investigated the extent of this bias and examined whether the bias can be reduced through incorporating proxy outcomes obtained through linkage to administrative data as auxiliary variables in multiple imputation (MI). Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) we estimated the association between breastfeeding and IQ (continuous outcome), incorporating linked attainment data (proxies for IQ) as auxiliary variables in MI models. Simulation studies explored the impact of varying the proportion of missing data (from 20 to 80%), the correlation between the outcome and its proxy (0.1-0.9), the strength of the missing data mechanism, and having a proxy variable that was incomplete. Incorporating a linked proxy for the missing outcome as an auxiliary variable reduced bias and increased efficiency in all scenarios, even when 80% of the outcome was missing. Using an incomplete proxy was similarly beneficial. High correlations (> 0.5) between the outcome and its proxy substantially reduced the missing information. Consistent with this, ALSPAC analysis showed inclusion of a proxy reduced bias and improved efficiency. Gains with additional proxies were modest. In longitudinal studies with loss to follow-up, incorporating proxies for this study outcome obtained via linkage to external sources of data as auxiliary variables in MI models can give practically important bias reduction and efficiency gains when the study outcome is MNAR.

  7. A multiple-proxy approach to understanding rapid Holocene climate change in Southeast Greenland

    Science.gov (United States)

    Davin, S. H.; Bradley, R. S.; Balascio, N. L.; de Wet, G.

    2012-12-01

    The susceptibility of the Arctic to climate change has made it an excellent workshop for paleoclimatological research. Although there have been previous studies concerning climate variability carried out in the Arctic, there remains a critical dearth of knowledge due the limited number of high-resolution Holocene climate-proxy records available from this region. This gap skews our understanding of observed and predicted climate change, and fuels uncertainty both in the realms of science and policy. This study takes a comprehensive approach to tracking Holocene climate variability in the vicinity of Tasiilaq, Southeast Greenland using a ~5.6 m sediment core from Lower Sermilik Lake. An age-depth model for the core has been established using 8 radiocarbon dates, the oldest of which was taken at 4 m down core and has been been dated to approximately 6.2 kyr BP. The bottom meter of the core below the final radiocarbon date contains a transition from cobbles and coarse sand to organic-rich laminations, indicating the termination of direct glacial influence and therefore likely marking the end of the last glacial period in this region. The remainder of the core is similarly organic-rich, with light-to-dark brown laminations ranging from 0.5 -1 cm in thickness and riddled with turbidites. Using this core in tandem with findings from an on-site assessment of the geomorphic history of the locale we attempt to assess and infer the rapid climatic shifts associated with the Holocene on a sub-centennial scale. Such changes include the termination of the last glacial period, the Mid-Holocene Climatic Optimum, the Neoglacial Period, the Medieval Climatic Optimum, and the Little Ice Age. A multiple proxy approach including magnetic susceptibility, bulk organic geochemistry, elemental profiles acquired by XRF scanning, grain-size, and spectral data will be used to characterize the sediment and infer paleoclimate conditions. Additionally, percent biogenic silica by weight has been

  8. Holocene seasonal variability inferred from multiple proxy records from Crevice Lake, Yellowstone National Park, USA

    Science.gov (United States)

    Whitlock, Cathy; Dean, Walter E.; Fritz, Sherilyn C.; Stevens, Lora R.; Stone, Jeffery R.; Power, Mitchell J.; Rosenbaum, Joseph R.; Pierce, Kenneth L.; Bracht-Flyr, Brandi B.

    2012-01-01

    the Roman Warm Period (~ 2000 cal yr BP) and Medieval Climate Anomaly (1200–800 cal yr BP). Long springs and mild summers occurred during the Little Ice Age, and these conditions persist to the present. Although the proxy data indicate effectively wet summer conditions in the early Holocene and drier conditions in the middle and late Holocene, none point specifically to changes in summer precipitation as the cause. Instead, summer conditions were governed by multi-seasonal controls on effective moisture that operated over multiple time scales.

  9. Latest Holocene Climate Variability revealed by a high-resolution multiple Proxy Record off Lisbon (Portugal)

    Science.gov (United States)

    Abrantes, F.; Lebreiro, S.; Ferreira, A.; Gil, I.; Jonsdottir, H.; Rodrigues, T.; Kissel, C.; Grimalt, J.

    2003-04-01

    The North Atlantic Oscillation (NAO) is known to have a major influence on the wintertime climate of the Atlantic basin and surrounding countries, determining precipitation and wind conditions at mid-latitudes. A comparison of Hurrel's NAO index to the mean winter (January-March) discharge of the Iberian Tagus River reveals a good negative correlation to negative NAO, while the years of largest upwelling anomalies, as referred in the literature, appear to be in good agreement with positive NAO. On this basis, a better understanding of the long-term variability of the NAO and Atlantic climate variability can be gained from high-resolution climate records from the Lisbon area. Climate variability of the last 2,000 years is assessed through a multiple proxy study of sedimentary sequences recovered from the Tagus prodelta deposition center, off Lisbon (Western Iberia). Physical properties, XRF and magnetic properties from core logging, grain size, δ18O, TOC, CaCO3, total alkenones, n-alkanes, alkenone SST, diatoms, benthic and planktonic foraminiferal assemblage compositions and fluxes are the proxies employed. The age model for site D13902 is based on AMS C-14 dates from mollusc and planktonic foraminifera shells, the reservoir correction for which was obtained by dating 3 pre-bomb, mollusc shells from the study area. Preliminary results indicate a Little Ice Age (LIA - 1300 - 1600 AD) alkenone derived SSTs around 15 degC followed by a sharp and rapid increase towards 19 degC. In spite the strong variability observed for most records, this low temperature interval is marked by a general increase in organic carbon, total alkenone concentration, diatom and foraminiferal abundances, as well as an increase in the sediment fine fraction and XRF determined Fe content, pointing to important river input and higher productivity. The Medieval Warm Period (1080 - 1300 AD) is characterized by 17-18 degC SSTs, increased mean grain size, but lower magnetic susceptibility and Fe

  10. Level of agreement between patient and proxy responses to the EQ-5D health questionnaire 12 months after injury.

    Science.gov (United States)

    Gabbe, Belinda J; Lyons, Ronan A; Sutherland, Ann M; Hart, Melissa J; Cameron, Peter A

    2012-04-01

    Health-related quality of life represents a patient's experiences and expectations and should be collected from the patient. In trauma, collection of information from the patient can be challenging, particularly for subgroups where cognitive impairment is prevalent, increasing reliance on proxy reporting. This study assessed the agreement between patient and proxy reporting of health-related quality of life 12 months after injury. The Victorian State Trauma Registry and Victorian Orthopaedic Trauma Outcomes Registry collect EQ-5D data at 12 months after injury. Cases where data were collected from the patient and proxy were extracted. Agreement between patient and proxy responses was compared using kappa (K) coefficients for the individual EQ-5D items, and Bland-Altman plots and Wilcoxon signed-rank tests for the EQ-5D summary score and visual analog scale (VAS). Agreement between patient and proxy respondents was substantial for the mobility (K = 0.61) and personal care items (K = 0.67) and moderate for the usual activities (K = 0.50), pain/discomfort (K = 0.42), and anxiety/depression items (K = 0.47). The mean difference between proxy and patient-reported scores for the VAS (0.74, 95% confidence interval: -2.73, 4.21) and the EQ-5D summary score (-0.02, 95% confidence interval: -0.07, 0.03) was small, but the limits of agreement were wide (-34.22 to 35.71 for VAS and -0.55 to 0.51 for summary score), suggesting no systematic bias. Although proxy and patient responses for the EQ-5D VAS may differ, the differences show random variability rather than systematic bias. Group comparisons using proxy responses are unlikely to be biased, but proxy responses should be used with caution when assessing individual patient recovery.

  11. Evaluation of patient and proxy responses on the activity measure for postacute care.

    Science.gov (United States)

    Jette, Alan M; Ni, Pengsheng; Rasch, Elizabeth K; Appelman, Jed; Sandel, M Elizabeth; Terdiman, Joseph; Chan, Leighton

    2012-03-01

    Our objective was to examine the agreement between adult patients with stroke and family member or clinician proxies in activity measure for postacute care (AM-PAC) summary scores for daily activity, basic mobility, and applied cognitive function. This study involved 67 patients with stroke admitted to a hospital within the Kaiser Permanente of Northern California system and were participants in a parent study on stroke outcomes. Each participant and proxy respondent completed the AM-PAC by personal or telephone interview at the point of hospital discharge or during ≥1 transitions to different postacute care settings. The results suggest that for patients with a stroke proxy, AM-PAC data are robust for family or clinician proxy assessment of basic mobility function and clinician proxy assessment of daily activity function, but less robust for family proxy assessment of daily activity function and for all proxy groups' assessments of applied cognitive function. The pattern of disagreement between patient and proxy was, on average, relatively small and random. There was little evidence of systematic bias between proxy and patient reports of their functional status. The degree of concordance between patient and proxy was similar for those with moderate to severe strokes compared with mild strokes. Patient and proxy ratings on the AM-PAC achieved adequate agreement for use in stroke research when using proxy respondents could reduce sample selection bias. The AM-PAC data can be implemented across institutional as well as community care settings while achieving precision and reducing respondent burden.

  12. Here be web proxies

    DEFF Research Database (Denmark)

    Weaver, Nicholas; Kreibich, Christian; Dam, Martin

    2014-01-01

    ,000 clients that include a novel proxy location technique based on traceroutes of the responses to TCP connection establishment requests, which provides additional clues regarding the purpose of the identified web proxies. Overall, we see 14% of Netalyzr-analyzed clients with results that suggest the presence...... of web proxies....

  13. Calibrating multiple isotopic proxies in a modern aragonite speleothem from northeast India

    Science.gov (United States)

    Ronay, E.; Oster, J. L.; Sharp, W. D.; Marks, N.; Erhardt, A.; Breitenbach, S. F. M.

    2017-12-01

    Uranium, strontium, and calcium isotope ratios in calcite speleothems are used as proxies for water-soil-rock interactions and prior calcite precipitation, and thus provide information about effective rainfall amount variations, primarily in semi-arid or highly seasonal regions. However, less is known about how these proxies function in humid regions and in aragonite speleothems. In this study, we use meteorological data to calibrate (234U/238U)i and 87Sr/86Sr in a modern aragonite speleothem from northeast India, the rainiest place on Earth, to determine how these proxies reflect effective monsoon rainfall amount. MAW-0201 is an annually laminated aragonite stalagmite that grew from 1960-2013 in Mawmluh Cave, Meghalaya, India. Rainfall here is extremely seasonal due to the Indian Summer Monsoon (ISM), which brings several meters of rain to the region each summer, but with inter-annual variability in total rainfall. The δ18O in Mawmluh dripwater and speleothems reflects moisture source and transport, rather than rainfall amount. Variations in Mg, U, and Ba concentrations in MAW-0201 show seasonal and multi-annual variability. U and Mg are closely correlated, but multi-year periods show significant anti-correlation. The Mg and U distribution coefficients in calcite and aragonite indicate correlated periods are times of prior calcite precipitation (PCP) and anti-correlated periods are times of prior aragonite precipitation (PAP) in the epikarst. We use δ44/40Ca to test this hypothesis, as Ca isotopes fractionate differently during calcite and aragonite precipitation and speleothem δ44/40Ca will record unique PAP and PCP fingerprints. We propose such shifts from PCP to PAP reflect hydrologic variability and/or flow path changes, which provide a useful tool for understanding epikarst hydrology but may also be a complicating factor in speleothem-based paleoclimate interpretations. Preliminary (234U/238U)i (always <1) and 87Sr/86Sr spanning 1991-2009 each show

  14. Comparison of 2010 Census Nonresponse Follow-Up Proxy Responses with Administrative Records Using Census Coverage Measurement Results

    Directory of Open Access Journals (Sweden)

    Mulry Mary H.

    2017-06-01

    Full Text Available The U.S. Census Bureau is currently conducting research on ways to use administrative records to reduce the cost and improve the quality of the 2020 Census Nonresponse Followup (NRFU at addresses that do not self-respond electronically or by mail. Previously, when a NRFU enumerator was unable to contact residents at an address, he/she found a knowledgeable person, such as a neighbor or apartment manager, who could provide the census information for the residents. This was called a proxy response. The Census Bureau’s recent advances in merging federal and third-party databases raise the question: Are proxy responses for NRFU addresses more accurate than the administrative records available for the housing unit? Our study attempts to answer this question by comparing the quality of proxy responses and the administrative records for those housing units in the same timeframe using the results of 2010 Census Coverage Measurement (CCM Program. The assessment of the quality of the proxy responses and the administrative records in the CCM sample of block clusters takes advantage of the extensive fieldwork, processing, and clerical matching conducted for the CCM.

  15. RESPONSE OF THREE PALEO-PRIMARY PRODUCTION PROXY MEASURES TO DEVELOPMENT OF AN URBAN ESTUARY

    Science.gov (United States)

    In this study we present a novel comparison of three proxy indicators of paleoproductivity, pigments, biogenic silica (BSi), and cysts of autotrophic dinoflagellates measured in cored sediments from New Bedford Harbor, Massachusetts. In addition to detailed historical reports we ...

  16. Appraising timing response of paleoenvironmental proxies to the Bond cycle in the western Mediterranean over the last 20 kyr

    Science.gov (United States)

    Rodrigo-Gámiz, Marta; Martínez-Ruiz, Francisca; Rodríguez-Tovar, Francisco J.; Pardo-Igúzquiza, Eulogio; Ortega-Huertas, Miguel

    2018-04-01

    The timing of climate responses to the Bond cycle is investigated in the western Mediterranean. Periodicities had been previously reported in a marine sediment record from this region spanning the last 20 kyr, and registered by diverse paleoenvironmental proxies, in particular those associated with terrigenous input, redox conditions, productivity, sea surface temperature (SST) and salinity. Further cross-spectral analyses on these time series reveal leads-lags in the 1400 year climate cycle. Considering as reference a terrigenous input proxy (the K/Al ratio), all the paleoenvironmental proxies displayed time shifts varying from ca. 700 year to ca. 350 year. SST and salinity variations show a first leaded response with the inflow of cold and less salty Atlantic waters. Followed by a time lead of 525 year, progresively arid conditions with an increase of eolian dust transport to the area, given by the Zr/Al signal, are observed. The intensification of dust transport could have triggered a latest biological response, lead by 350 year, with an increase of productivity, as suggested by the Ba/Al ratio. Lastly changes in the Mediterranean thermohaline circulation, indicated by a selected redox proxy (the U/Th ratio), are observed. These results support that the oceanic response triggered the atmospheric response to the Bond cycle in the western Mediterranean. Changes in the North Atlantic Oscillation mode and in the Inter-Tropical Convergence Zone migrations with variations in the monsoon activity or Saharan winds system, are considered as main forcing mechanisms, with a complex relationship of the involved phenomena.

  17. Holocene history and environmental reconstruction of a Hercynian mire and surrounding mountain landscape based on multiple proxies

    Science.gov (United States)

    Dudová, Lydie; Hájková, Petra; Opravilová, Věra; Hájek, Michal

    2014-07-01

    We discovered the first peat section covering the entire Holocene in the Hrubý Jeseník Mountains, representing an island of unique alpine vegetation whose history may display transitional features between the Hercynian and Carpathian regions. We analysed pollen, plant macrofossils (more abundant in bottom layers), testate amoebae (more abundant in upper layers), peat stratigraphy and chemistry. We found that the landscape development indeed differed from other Hercynian mountains located westward. This is represented by Pinus cembra and Larix during the Pleistocene/Holocene transition, the early expansion of spruce around 10,450 cal yr BP, and survival of Larix during the climatic optimum. The early Holocene climatic fluctuations are traced in our profile by species compositions of both the mire and surrounding forests. The mire started to develop as a calcium-rich percolation fen with some species recently considered to be postglacial relicts (Meesia triquetra, Betula nana), shifted into ombrotrophy around 7450 cal yr BP by autogenic succession and changed into a pauperised, nutrient-enriched spruce woodland due to modern forestry activities. We therefore concluded that its recent vegetation is not a product of natural processes. From a methodological viewpoint we demonstrated how using multiple biotic proxies and extensive training sets in transfer functions may overcome taphonomic problems.

  18. Longitudinal proxy measurements in multiple sclerosis: patient-proxy agreement on the impact of MS on daily life over a period of two years

    NARCIS (Netherlands)

    van der Linden, F.A.H.; Kragt, J.J.; van Bon, M.; Klein, M.; Thompson, A.J.; van der Ploeg, H.M.; Polman, C.H.; Uitdehaag, B.M.J.

    2008-01-01

    Background: The use of self-report measurements in clinical settings is increasing. However, in patients with limitations that interfere with reliable self-assessment such as cognitive impairment or mood disturbances, as may be the case in multiple sclerosis (MS), data collection might be

  19. Plant responses to multiple herbivory

    NARCIS (Netherlands)

    Li, Yehua

    2016-01-01

    This thesis explores whether aphid-infestation interferes with the plant response to chewing herbivores and whether this impacts performance and behaviour of individual chewing insect herbivores and their natural enemies, as well as the entire insect community. I investigated this using three

  20. Differences between Proxy and Patient Assessments of Cancer Care Experiences and Quality Ratings.

    Science.gov (United States)

    Roydhouse, Jessica K; Gutman, Roee; Keating, Nancy L; Mor, Vincent; Wilson, Ira B

    2018-04-01

    To assess the impact of proxy survey responses on cancer care experience reports and quality ratings. Secondary analysis of data from Cancer Care Outcomes Research and Surveillance (CanCORS). Recruitment occurred from 2003 to 2005. The study was a cross-sectional observational study. The respondents were patients with incident colorectal or lung cancer or their proxies. Analyses used linear regression models with an independent variable for proxy versus patient responses as well as study site and clinical covariates. The outcomes were experiences with medical care, nursing care, care coordination, and care quality rating. Multiple imputation was used for missing data. Among 6,471 respondents, 1,011 (16 percent) were proxies. The proportion of proxy respondents varied from 6 percent to 28 percent across study sites. Adjusted proxy scores were modestly higher for medical care experiences (+1.28 points [95 percent CI:+ 0.05 to +2.51]), but lower for nursing care (-2.81 [95 percent CI: -4.11 to -1.50]) and care coordination experiences (-2.98 [95 percent CI: -4.15 to -1.81]). There were no significant differences between adjusted patient and proxy ratings of quality. Proxy responses have small but statistically significant differences from patient responses. However, if ratings of care are used for financial incentives, such differences could be exaggerated across practices or areas if proxy use varies. © Health Research and Educational Trust.

  1. Reconstruction of late Quaternary marine and terrestrial environmental conditions of Northwest Africa and Southeast Australia : a multiple organic proxy study using marine sediments

    NARCIS (Netherlands)

    Alfama Lopes dos Santos, R.

    2012-01-01

    NW Africa and SE Australia are regions which are particularly vulnerable to climate change. In this thesis, organic proxies are used from marine sediment cores to reconstruct past environmental conditions from these areas. In sediments from NW Africa, the UK'37 showed an efficient proxy for sea

  2. Quality improvement through multiple response optimization

    International Nuclear Information System (INIS)

    Noorossana, R.; Alemzad, H.

    2003-01-01

    The performance of a product is often evaluated by several quality characteristics. Optimizing the manufacturing process with respect to only one quality characteristic will not always lead to the optimum values for other characteristics. Hence, it would be desirable to improve the overall quality of a product by improving quality characteristics, which are considered to be important. The problem consists of optimizing several responses using multiple objective decision making approach and design of experiments. A case study will be discussed to show the application of the proposal method

  3. Handwashing in 51 Countries: Analysis of Proxy Measures of Handwashing Behavior in Multiple Indicator Cluster Surveys and Demographic and Health Surveys, 2010–2013

    Science.gov (United States)

    Kumar, Swapna; Loughnan, Libbet; Luyendijk, Rolf; Hernandez, Orlando; Weinger, Merri; Arnold, Fred; Ram, Pavani K.

    2017-01-01

    Abstract. In 2009, a common set of questions addressing handwashing behavior was introduced into nationally representative Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS), providing large amounts of comparable data from numerous countries worldwide. The objective of this analysis is to describe global handwashing patterns using two proxy indicators for handwashing behavior from 51 DHS and MICS surveys conducted in 2010–2013: availability of soap anywhere in the dwelling and access to a handwashing place with soap and water. Data were also examined across geographic regions, wealth quintiles, and rural versus urban settings. We found large disparities for both indicators across regions, and even among countries within the same World Health Organization region. Within countries, households in lower wealth quintiles and in rural areas were less likely to have soap anywhere in the dwelling and at designated handwashing locations than households in higher wealth quintiles and urban areas. In addition, disparities existed among various geographic regions within countries. This analysis demonstrates the need to promote access to handwashing materials and placement at handwashing locations in the dwelling, particularly in poorer, rural areas where children are more vulnerable to handwashing-preventable syndromes such as pneumonia and diarrhea. PMID:28722572

  4. Handwashing in 51 Countries: Analysis of Proxy Measures of Handwashing Behavior in Multiple Indicator Cluster Surveys and Demographic and Health Surveys, 2010-2013.

    Science.gov (United States)

    Kumar, Swapna; Loughnan, Libbet; Luyendijk, Rolf; Hernandez, Orlando; Weinger, Merri; Arnold, Fred; Ram, Pavani K

    2017-08-01

    In 2009, a common set of questions addressing handwashing behavior was introduced into nationally representative Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS), providing large amounts of comparable data from numerous countries worldwide. The objective of this analysis is to describe global handwashing patterns using two proxy indicators for handwashing behavior from 51 DHS and MICS surveys conducted in 2010-2013: availability of soap anywhere in the dwelling and access to a handwashing place with soap and water. Data were also examined across geographic regions, wealth quintiles, and rural versus urban settings. We found large disparities for both indicators across regions, and even among countries within the same World Health Organization region. Within countries, households in lower wealth quintiles and in rural areas were less likely to have soap anywhere in the dwelling and at designated handwashing locations than households in higher wealth quintiles and urban areas. In addition, disparities existed among various geographic regions within countries. This analysis demonstrates the need to promote access to handwashing materials and placement at handwashing locations in the dwelling, particularly in poorer, rural areas where children are more vulnerable to handwashing-preventable syndromes such as pneumonia and diarrhea.

  5. Multiple oscillations during the Lateglacial as recorded in a multi-proxy, high-resolution record of the Moervaart palaeolake (NW Belgium)

    Science.gov (United States)

    Bos, Johanna A. A.; De Smedt, Philippe; Demiddele, Hendrik; Hoek, Wim Z.; Langohr, Roger; Marcelino, Vera; Van Asch, Nelleke; Van Damme, Dirk; Van der Meeren, Thijs; Verniers, Jacques; Boeckx, Pascal; Boudin, Mathieu; Court-Picon, Mona; Finke, Peter; Gelorini, Vanessa; Gobert, Stefan; Heiri, Oliver; Martens, Koen; Mostaert, Frank; Serbruyns, Lynn; Van Strydonck, Mark; Crombé, Philippe

    2017-04-01

    This paper presents the results of multi-disciplinary research carried out on the deposits of Moervaart depression, NW Belgium, one of the largest palaeolakes (∼25 km2) that existed during the Lateglacial interstadial in NW Europe. The multi-proxy study, including physical (organic matter and calcium carbonate, magnetic susceptibility, micromorphological), botanical (pollen, macrofossils, diatoms), zoological (ostracods, molluscs, chironomids) and chemical analyses (stable carbon and oxygen isotopes) has resulted in a detailed reconstruction of the Lateglacial landscape as well of the local conditions that prevailed in the lake itself. A chronology of the record was provided by radiocarbon dating and comparison with radiocarbon dates of the nearby Rieme site. These yielded a good match with the regional biostratigraphy. During the Lateglacial, vegetation and geomorphology of the landscape in general changed from a tundra landscape to a boreal forest. The vegetation development, however, was interrupted by a number of cold reversals. Three centennial-scale cold oscillations are present in the record: 1) the so-called Older Dryas corresponding to GI-1d in the Greenland ice-cores, 2) a short and pronounced cold event during the early Allerød, which could be correlated to GI-1c2 and 3) a cooling event during the late Allerød probably corresponding to the Intra Allerød Cold Period (IACP) or GI-1b. The latter most likely was responsible for the disappearance of the Moervaart palaeolake.

  6. Unearthing earthquakes and their tsunamis using multiple proxies: the 22 June 1932 event and a probable fourteenth-century predecessor on the Pacific coast of Mexico

    Czech Academy of Sciences Publication Activity Database

    Ramírez-Herrera, M.-T.; Corona, N.; Lagos, M.; Černý, Jan; Goguitchaichvili, A.; Goff, J.; Chaugé-Goff, C.; Machain, M. L.; Zawadzki, A.; Jacobsen, G.; Carranza-Edwards, A.; Lozano, S.; Blecher, L.

    2014-01-01

    Roč. 56, č. 13 (2014), s. 1584-1601 ISSN 0020-6814 Institutional support: RVO:67985831 Keywords : tsunami deposits * palaeotsunami * tropical environment * multi-proxy approach * Pacific coast * México Subject RIV: DC - Siesmology, Volcanology, Earth Structure Impact factor: 1.708, year: 2014

  7. Assessment of tree response to drought: validation of a methodology to identify and test proxies for monitoring past environmental changes in trees.

    Science.gov (United States)

    Tene, A; Tobin, B; Dyckmans, J; Ray, D; Black, K; Nieuwenhuis, M

    2011-03-01

    A thinning experiment stand at Avoca, Ballinvalley, on the east coast of the Republic of Ireland was used to test a developed methodology aimed at monitoring drought stress, based on the analysis of growth rings obtained by coring. The stand incorporated six plots representing three thinning regimes (light, moderate and heavy) and was planted in the spring of 1943 on a brown earth soil. Radial growth (early- and latewood) was measured for the purpose of this study. A multidisciplinary approach was used to assess historic tree response to climate: specifically, the application of statistical tools such as principal component and canonical correlation analysis to dendrochronology, stable isotopes, ring density proxy, blue reflectance and forest biometrics. Results showed that radial growth was a good proxy for monitoring changes to moisture deficit, while maximum density and blue reflectance were appropriate for assessing changes in accumulated temperature for the growing season. Rainfall also influenced radial growth changes but not significantly, and was a major factor in stable carbon and oxygen discrimination, mostly in the latewood formation phase. Stable oxygen isotope analysis was more accurate than radial growth analysis in drought detection, as it helped detect drought signals in both early- and latewood while radial growth analysis only detected the drought signal in earlywood. Many studies have shown that tree rings provide vital information for marking past climatic events. This work provides a methodology to better identify and understand how commonly measured tree proxies relate to environmental parameters, and can best be used to characterize and pinpoint drought events (variously described using parameters such as like moisture deficit, accumulated temperature, rainfall and potential evaporation).

  8. Can multiple-choice questions simulate free-response questions?

    OpenAIRE

    Lin, Shih-Yin; Singh, Chandralekha

    2016-01-01

    We discuss a study to evaluate the extent to which free-response questions could be approximated by multiple-choice equivalents. Two carefully designed research-based multiple-choice questions were transformed into a free-response format and administered on the final exam in a calculus-based introductory physics course. The original multiple-choice questions were administered in another similar introductory physics course on final exam. Findings suggest that carefully designed multiple-choice...

  9. Using module analysis for multiple choice responses

    DEFF Research Database (Denmark)

    Brewe, Eric; Bruun, Jesper; Bearden, Ian

    2016-01-01

    We describe a methodology for carrying out a network analysis of Force Concept Inventory (FCI) responses that aims to identify communities of incorrect responses. This method first treats FCI responses as a bipartite, student X response, network. We then use Locally Adaptive Network Sparsificatio...

  10. Measurement equivalence of the KINDL questionnaire across child self-reports and parent proxy-reports: a comparison between item response theory and ordinal logistic regression.

    Science.gov (United States)

    Jafari, Peyman; Sharafi, Zahra; Bagheri, Zahra; Shalileh, Sara

    2014-06-01

    Measurement equivalence is a necessary assumption for meaningful comparison of pediatric quality of life rated by children and parents. In this study, differential item functioning (DIF) analysis is used to examine whether children and their parents respond consistently to the items in the KINDer Lebensqualitätsfragebogen (KINDL; in German, Children Quality of Life Questionnaire). Two DIF detection methods, graded response model (GRM) and ordinal logistic regression (OLR), were applied for comparability. The KINDL was completed by 1,086 school children and 1,061 of their parents. While the GRM revealed that 12 out of the 24 items were flagged with DIF, the OLR identified 14 out of the 24 items with DIF. Seven items with DIF and five items without DIF were common across the two methods, yielding a total agreement rate of 50 %. This study revealed that parent proxy-reports cannot be used as a substitute for a child's ratings in the KINDL.

  11. Observations on Listener Responses from Multiple Perspectives

    NARCIS (Netherlands)

    de Kok, I.A.; Heylen, Dirk K.J.

    In this paper we present three studies that investigate the individual differences in nonverbal listening behavior. Besides collecting a corpus of listener responses, we asked people to watch a video of a speaker and indicate where they would produce a listener response. Also we asked people to

  12. Optimization of multi-response dynamic systems integrating multiple ...

    African Journals Online (AJOL)

    It also results in better optimization performance than back-propagation neural network-based approach and data mining-based approach reported by the past researchers. Keywords: multiple responses, multiple regression, weighted dynamic signal-to-noise ratio, performance measure modelling, response function ...

  13. Jemen - the Proxy War

    Directory of Open Access Journals (Sweden)

    Magdalena El Ghamari

    2015-12-01

    Full Text Available The military operation in Yemen is significant departure from Saudi Arabia's foreign policy tradition and customs. Riyadh has always relied on three strategies to pursue its interests abroad: wealth, establish a global network and muslim education and diplomacy and meadiation. The term "proxy war" has experienced a new popularity in stories on the Middle East. A proxy war is two opposing countries avoiding direct war, and instead supporting combatants that serve their interests. In some occasions, one country is a direct combatant whilst the other supporting its enemy. Various news sources began using the term to describe the conflict in Yemen immediately, as if on cue, after Saudi Arabia launched its bombing campaign against Houthi targets in Yemen on 25 March 2015. This is the reason, why author try to answer for following questions: Is the Yemen Conflict Devolves into Proxy War? and Who's fighting whom in Yemen's proxy war?" Research area includes the problem of proxy war in the Middle East. For sure, the real problem of proxy war must begin with the fact that the United States and its NATO allies opened the floodgates for regional proxy wars by the two major wars for regime change: in Iraq and Libya. Those two destabilising wars provided opportunities and motives for Sunni states across the Middle East to pursue their own sectarian and political power objectives through "proxy war".

  14. V S30, slope, H 800 and f 0: performance of various site-condition proxies in reducing ground-motion aleatory variability and predicting nonlinear site response

    Science.gov (United States)

    Derras, Boumédiène; Bard, Pierre-Yves; Cotton, Fabrice

    2017-09-01

    The aim of this paper is to investigate the ability of various site-condition proxies (SCPs) to reduce ground-motion aleatory variability and evaluate how SCPs capture nonlinearity site effects. The SCPs used here are time-averaged shear-wave velocity in the top 30 m ( V S30), the topographical slope (slope), the fundamental resonance frequency ( f 0) and the depth beyond which V s exceeds 800 m/s ( H 800). We considered first the performance of each SCP taken alone and then the combined performance of the 6 SCP pairs [ V S30- f 0], [ V S30- H 800], [ f 0-slope], [ H 800-slope], [ V S30-slope] and [ f 0- H 800]. This analysis is performed using a neural network approach including a random effect applied on a KiK-net subset for derivation of ground-motion prediction equations setting the relationship between various ground-motion parameters such as peak ground acceleration, peak ground velocity and pseudo-spectral acceleration PSA ( T), and M w, R JB, focal depth and SCPs. While the choice of SCP is found to have almost no impact on the median ground-motion prediction, it does impact the level of aleatory uncertainty. V S30 is found to perform the best of single proxies at short periods ( T < 0.6 s), while f 0 and H 800 perform better at longer periods; considering SCP pairs leads to significant improvements, with particular emphasis on [ V S30- H 800] and [ f 0-slope] pairs. The results also indicate significant nonlinearity on the site terms for soft sites and that the most relevant loading parameter for characterising nonlinear site response is the "stiff" spectral ordinate at the considered period.[Figure not available: see fulltext.

  15. Pattern-mixture models for analyzing normal outcome data with proxy respondents.

    Science.gov (United States)

    Shardell, Michelle; Hicks, Gregory E; Miller, Ram R; Langenberg, Patricia; Magaziner, Jay

    2010-06-30

    Studies of older adults often involve interview questions regarding subjective constructs such as perceived disability. In some studies, when subjects are unable (e.g. due to cognitive impairment) or unwilling to respond to these questions, proxies (e.g. relatives or other care givers) are recruited to provide responses in place of the subject. Proxies are usually not approached to respond on behalf of subjects who respond for themselves; thus, for each subject, data from only one of the subject or proxy are available. Typically, proxy responses are simply substituted for missing subject responses, and standard complete-data analyses are performed. However, this approach may introduce measurement error and produce biased parameter estimates. In this paper, we propose using pattern-mixture models that relate non-identifiable parameters to identifiable parameters to analyze data with proxy respondents. We posit three interpretable pattern-mixture restrictions to be used with proxy data, and we propose estimation procedures using maximum likelihood and multiple imputation. The methods are applied to a cohort of elderly hip-fracture patients. (c) 2010 John Wiley & Sons, Ltd.

  16. High pressure multiple shock response of aluminum

    International Nuclear Information System (INIS)

    Lawrence, R.J.; Asay, J.R.

    1977-01-01

    It is well known that both dynamic yield strength and rate-dependent material response exert direct influence on the development of surface and interface instabilities under conditions of strong shock loading. A detailed understanding of these phenomena is therefore an important aspect of the analysis of dynamic inertial confinement techniques which are being used in such applications as the generation of controlled thermonuclear fusion. In these types of applications the surfaces and interfaces under consideration can be subjected to cyclic loading characterized by shock pressures on the order of 100 GPa or more. It thus becomes important to understand how rate effects and material strength differ from the values observed in the low pressure regime where they are usually measured, as well as how they are altered by the loading history

  17. Modeling Rabbit Responses to Single and Multiple Aerosol ...

    Science.gov (United States)

    Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev

  18. Witnessing entanglement by proxy

    International Nuclear Information System (INIS)

    Bäuml, Stefan; Bruß, Dagmar; Kampermann, Hermann; Huber, Marcus; Winter, Andreas

    2016-01-01

    Entanglement is a ubiquitous feature of low temperature systems and believed to be highly relevant for the dynamics of condensed matter properties and quantum computation even at higher temperatures. The experimental certification of this paradigmatic quantum effect in macroscopic high temperature systems is constrained by the limited access to the quantum state of the system. In this paper we show how macroscopic observables beyond the mean energy of the system can be exploited as proxy witnesses for entanglement detection. Using linear and semi-definite relaxations we show that all previous approaches to this problem can be outperformed by our proxies, i.e. entanglement can be certified at higher temperatures without access to any local observable. For an efficient computation of proxy witnesses one can resort to a generalised grand canonical ensemble, enabling entanglement certification even in complex systems with macroscopic particle numbers. (paper)

  19. Multiple Response Regression for Gaussian Mixture Models with Known Labels.

    Science.gov (United States)

    Lee, Wonyul; Du, Ying; Sun, Wei; Hayes, D Neil; Liu, Yufeng

    2012-12-01

    Multiple response regression is a useful regression technique to model multiple response variables using the same set of predictor variables. Most existing methods for multiple response regression are designed for modeling homogeneous data. In many applications, however, one may have heterogeneous data where the samples are divided into multiple groups. Our motivating example is a cancer dataset where the samples belong to multiple cancer subtypes. In this paper, we consider modeling the data coming from a mixture of several Gaussian distributions with known group labels. A naive approach is to split the data into several groups according to the labels and model each group separately. Although it is simple, this approach ignores potential common structures across different groups. We propose new penalized methods to model all groups jointly in which the common and unique structures can be identified. The proposed methods estimate the regression coefficient matrix, as well as the conditional inverse covariance matrix of response variables. Asymptotic properties of the proposed methods are explored. Through numerical examples, we demonstrate that both estimation and prediction can be improved by modeling all groups jointly using the proposed methods. An application to a glioblastoma cancer dataset reveals some interesting common and unique gene relationships across different cancer subtypes.

  20. Munchausen by Proxy Syndrome

    Science.gov (United States)

    ... the Child Getting Help for the Parent or Caregiver Print Munchausen by proxy syndrome (MBPS) is a relatively rare form of child abuse that involves the exaggeration or fabrication of illnesses or symptoms by a primary caretaker. Also known as "medical child abuse," MBPS ...

  1. Ecological response to climate change and human activities indicated by n-alkane proxy during the mid- to late Holocene: a case study from an alpine lake

    Science.gov (United States)

    Zhang, C.; Zhao, C.

    2017-12-01

    Paleolimonological records provide long-term dynamics information of past climate, environment, human activities and ecological variations and give evolutionary perspectives to understand responses process of ecological shift to internal or external trigger. In this study, a powerful biomarkers, n-alkanes, was used to reconstruct the past 5000 years organic matter sources and ecological evolution history of Beilianchi Lake in the southwestern of Loess Plateau after preliminary investigation of modern samples. Climate-environment change and human activities were also traced by total organic matter (TOC), magnetic susceptibility (MS) and relevant proxies. The results showed that the ecosystem related to organic matter composition in Beilianchi Lake might be mainly controlled by climate change before 1400 cal B.P., whereas after that, it was significantly influenced by soil erosion induced by increasing population and enhanced human activities. Lake ecosystem experienced periodical change from relatively stable stage with combination of allochthonous-autochthonous organic sources prior to 1400 cal B.P. to extremely instability and final return to steady state with allochthonous-dominant organic source since 300 cal B.P.. During the period of instability, organic matter composition during 1400-800 cal B.P. indicated a obvious bimodal distribution based on probability density distribution analysis, which reflected the lake ecosystem might stay at bistable state and switched repeatedly from more-macrophytes state (regime A with low ACL) towards less-macrophytes state (regime B with high ACL) controlled by disturbance of soil erosion. The flickering during this period could serve as the early warning signal of transition towards more-macrophytes state or less-macrophytes state in lake ecosystems.

  2. Validity of proxies and correction for proxy use when evaluating social determinants of health in stroke patients.

    Science.gov (United States)

    Skolarus, Lesli E; Sánchez, Brisa N; Morgenstern, Lewis B; Garcia, Nelda M; Smith, Melinda A; Brown, Devin L; Lisabeth, Lynda D

    2010-03-01

    The purpose of this study was to evaluate stroke patient-proxy agreement with respect to social determinants of health, including depression, optimism, and spirituality, and to explore approaches to minimize proxy-introduced bias. Stroke patient-proxy pairs from the Brain Attack Surveillance in Corpus Christi Project were interviewed (n=34). Evaluation of agreement between patient-proxy pairs included calculation of intraclass correlation coefficients, linear regression models (ProxyResponse=alpha(0)+alpha(1)PatientResponse+delta, where alpha(0)=0 and alpha(1)=1 denotes no bias) and kappa statistics. Bias introduced by proxies was quantified with simulation studies. In the simulated data, we applied 4 approaches to estimate regression coefficients of stroke outcome social determinants of health associations when only proxy data were available for some patients: (1) substituting proxy responses in place of patient responses; (2) including an indicator variable for proxy use; (3) using regression calibration with external validation; and (4) internal validation. Agreement was fair for depression (intraclass correlation coefficient, 0.41) and optimism (intraclass correlation coefficient, 0.48) and moderate for spirituality (kappa, 0.48 to 0.53). Responses of proxies were a biased measure of the patients' responses for depression, with alpha(0)=4.88 (CI, 2.24 to 7.52) and alpha(1)=0.39 (CI, 0.09 to 0.69), and for optimism, with alpha(0)=3.82 (CI, -1.04 to 8.69) and alpha(1)=0.81 (CI, 0.41 to 1.22). Regression calibration with internal validation was the most accurate method to correct for proxy-induced bias. Fair/moderate patient-proxy agreement was observed for social determinants of health. Stroke researchers who plan to study social determinants of health may consider performing validation studies so corrections for proxy use can be made.

  3. Tree ring proxies show physiological responses of eastern red cedar to increased CO2 and SO4 concentrations over the 20th century

    Science.gov (United States)

    Thomas, R. B.; Spal, S.; Maxwell, S.; Nippert, J. B.

    2011-12-01

    stomatal control and lowering internal leaf CO2 concentrations. Thus, these tree-ring data show proxy evidence for physiological responses to increased CO2 over the previous century, but also provide a biotic signature illustrating the role of environmental legislation to alleviate environmental pollution at large spatial and temporal scales.

  4. Effectors from Wheat Rust Fungi Suppress Multiple Plant Defense Responses.

    Science.gov (United States)

    Ramachandran, Sowmya R; Yin, Chuntao; Kud, Joanna; Tanaka, Kiwamu; Mahoney, Aaron K; Xiao, Fangming; Hulbert, Scot H

    2017-01-01

    Fungi that cause cereal rust diseases (genus Puccinia) are important pathogens of wheat globally. Upon infection, the fungus secretes a number of effector proteins. Although a large repository of putative effectors has been predicted using bioinformatic pipelines, the lack of available high-throughput effector screening systems has limited functional studies on these proteins. In this study, we mined the available transcriptomes of Puccinia graminis and P. striiformis to look for potential effectors that suppress host hypersensitive response (HR). Twenty small (wheat, confirming its activity in a homologous system. Overall, this study provides the first evidence for the presence of effectors in Puccinia species suppressing multiple plant defense responses.

  5. Pavlovian conditioning of multiple opioid-like responses in mice.

    Science.gov (United States)

    Bryant, Camron D; Roberts, Kristofer W; Culbertson, Christopher S; Le, Alan; Evans, Christopher J; Fanselow, Michael S

    2009-07-01

    Conditional responses in rodents such as locomotion have been reported for drugs of abuse and similar to the placebo response in humans, may be associated with the expectation of reward. We examined several conditional opioid-like responses and the influence of drug expectation on conditioned place preference and concomitant conditional locomotion. Male C57BL/6J mice were conditioned with the selective mu opioid receptor agonist fentanyl (0.2mg/kg, i.p.) in a novel context and subsequently given a vehicle injection. In separate experiments, locomotor activity, Straub tail, hot plate sensitivity, and conditioned place preference (CPP) were measured. Mice exhibited multiple conditional opioid-like responses including conditional hyperlocomotion, a conditional pattern of opioid-like locomotion, Straub tail, analgesia, and place preference. Modulating drug expectation via administration of fentanyl to "demonstrator" mice in the home cage did not affect the expression of conditioned place preference or the concomitant locomotor activity in "observer" mice. In summary, Pavlovian conditioning of an opioid in a novel context induced multiple conditional opioid-like behaviors and provides a model for studying the neurobiological mechanisms of the placebo response in mice.

  6. Munchausen syndrome by proxy

    Directory of Open Access Journals (Sweden)

    Jovanović Aleksandar A.

    2005-01-01

    Full Text Available This review deals with bibliography on Munchausen syndrome by proxy (MSbP. The name of this disorder was introduced by English psychiatrist Roy Meadow who pointed to diagnostic difficulties as well as to serious medical and legal connotations of MSbP. MSbP was classified in DSM-IV among criteria sets provided for further study as "factitious disorder by proxy", while in ICD-10, though not explicitly cited, MSbP might be classified as "factitious disorders" F68.1. MSbP is a special form of abuse where the perpetrator induces somatic or mental symptoms of illness in the victim under his/her care and then persistently presents the victims for medical examinations and care. The victim is usually a preschool child and the perpetrator is the child's mother. Motivation for such pathological behavior of perpetrator is considered to be unconscious need to assume sick role by proxy while external incentives such as economic gain are absent. Conceptualization of MSbP development is still in the domain of psychodynamic speculation, its course is chronic and the prognosis is poor considering lack of consistent, efficient and specific treatment. The authors also present the case report of thirty-three year-old mother who had been abusing her nine year-old son both emotionally and physically over the last several years forcing him to, together with her, report to the police, medical and educational institutions that he had been the victim of rape, poisoning and beating by various individuals, especially teaching and medical staff. Mother manifested psychosis and her child presented with impaired cognitive development, emotional problems and conduct disorder.

  7. Reliability of psychophysiological responses across multiple motion sickness stimulation tests

    Science.gov (United States)

    Stout, C. S.; Toscano, W. B.; Cowings, P. S.

    1995-01-01

    Although there is general agreement that a high degree of variability exists between subjects in their autonomic nervous system responses to motion sickness stimulation, very little evidence exists that examines the reproducibility of autonomic responses within subjects during motion sickness stimulation. Our objectives were to examine the reliability of autonomic responses and symptom levels across five testing occasions using the (1) final minute of testing, (2) change in autonomic response and the change in symptom level, and (3) strength of the relationship between the change in symptom level and the change in autonomic responses across the entire motion sickness test. The results indicate that, based on the final minute of testing, the autonomic responses of heart rate, blood volume pulse, and respiration rate are moderately stable across multiple tests. Changes in heart rate, blood volume pulse, respiration rate, and symptoms throughout the test duration are less stable across the tests. Finally, autonomic responses and symptom levels are significantly related across the entire motion sickness test.

  8. Middle to Late Pleistocene multi-proxy record of environmental response to climate change from the Vienna Basin, Central Europe (Austria)

    Science.gov (United States)

    Salcher, Bernhard C.; Frank-Fellner, Christa; Lomax, Johanna; Preusser, Frank; Ottner, Franz; Scholger, Robert; Wagreich, Michael

    2017-10-01

    Tectonic basins can represent valuable archives of the environmental history. Presented here are the stratigraphy and multi-proxy analyses of two adjacent alluvial fans in the Quaternary active parts of the Vienna Basin, situated at the interface of the Atlantic, European continental and Mediterranean climate. Deposits comprise a sequence of coarse-grained fluvial deposits intercalated by laterally extensive horizons of pedogenically altered fine sediments. To establish palaeoenvironmental reconstructions, fine-grained sequences from a drill core and outcrop data were analysed according to its malacofauna, palaeopedology, susceptibility and sedimentology. The chronological framework is provided by 38 luminescence ages and supported by geomagnetic polarity investigations. Distinct warm periods each associated with a geomagnetic excursion, are recorded in three pedocomplexes formed during the Last Interglacial and two earlier interglacial periods, indicted to correlate with Marine Isotope Stage (MIS) 9 and MIS 11, respectively. Environmental conditions during the early last glacial period (MIS 5, c. 100-70 ka) are reconstructed from mollusc-shell rich overbank fines deposited along a former channel belt, covered by massive sheetflood deposits during MIS 2. Analysed warm phases suggest strong variations in humidity, ranging from steppe to forest dominated environments. The study presents one of the few numerically dated Middle Pleistocene multi-proxy records and one of the most comprehensive malacological datasets covering the early phases of last glacial period of continental Europe.

  9. Coding response to a case-mix measurement system based on multiple diagnoses.

    Science.gov (United States)

    Preyra, Colin

    2004-08-01

    To examine the hospital coding response to a payment model using a case-mix measurement system based on multiple diagnoses and the resulting impact on a hospital cost model. Financial, clinical, and supplementary data for all Ontario short stay hospitals from years 1997 to 2002. Disaggregated trends in hospital case-mix growth are examined for five years following the adoption of an inpatient classification system making extensive use of combinations of secondary diagnoses. Hospital case mix is decomposed into base and complexity components. The longitudinal effects of coding variation on a standard hospital payment model are examined in terms of payment accuracy and impact on adjustment factors. Introduction of the refined case-mix system provided incentives for hospitals to increase reporting of secondary diagnoses and resulted in growth in highest complexity cases that were not matched by increased resource use over time. Despite a pronounced coding response on the part of hospitals, the increase in measured complexity and case mix did not reduce the unexplained variation in hospital unit cost nor did it reduce the reliance on the teaching adjustment factor, a potential proxy for case mix. The main implication was changes in the size and distribution of predicted hospital operating costs. Jurisdictions introducing extensive refinements to standard diagnostic related group (DRG)-type payment systems should consider the effects of induced changes to hospital coding practices. Assessing model performance should include analysis of the robustness of classification systems to hospital-level variation in coding practices. Unanticipated coding effects imply that case-mix models hypothesized to perform well ex ante may not meet expectations ex post.

  10. Coding Response to a Case-Mix Measurement System Based on Multiple Diagnoses

    Science.gov (United States)

    Preyra, Colin

    2004-01-01

    Objective To examine the hospital coding response to a payment model using a case-mix measurement system based on multiple diagnoses and the resulting impact on a hospital cost model. Data Sources Financial, clinical, and supplementary data for all Ontario short stay hospitals from years 1997 to 2002. Study Design Disaggregated trends in hospital case-mix growth are examined for five years following the adoption of an inpatient classification system making extensive use of combinations of secondary diagnoses. Hospital case mix is decomposed into base and complexity components. The longitudinal effects of coding variation on a standard hospital payment model are examined in terms of payment accuracy and impact on adjustment factors. Principal Findings Introduction of the refined case-mix system provided incentives for hospitals to increase reporting of secondary diagnoses and resulted in growth in highest complexity cases that were not matched by increased resource use over time. Despite a pronounced coding response on the part of hospitals, the increase in measured complexity and case mix did not reduce the unexplained variation in hospital unit cost nor did it reduce the reliance on the teaching adjustment factor, a potential proxy for case mix. The main implication was changes in the size and distribution of predicted hospital operating costs. Conclusions Jurisdictions introducing extensive refinements to standard diagnostic related group (DRG)-type payment systems should consider the effects of induced changes to hospital coding practices. Assessing model performance should include analysis of the robustness of classification systems to hospital-level variation in coding practices. Unanticipated coding effects imply that case-mix models hypothesized to perform well ex ante may not meet expectations ex post. PMID:15230940

  11. Contrasting Responses of the Humboldt Current Ecosystem between the Holocene and MIS5e Interglacials Revealed from Multiple Sediment Records

    Science.gov (United States)

    Salvatteci, R.; Schneider, R. R.; Blanz, T.; Martinez, P.; Crosta, X.

    2016-12-01

    The Humboldt Current Ecosystem (HCE) off Peru yields about 10% of the global fish catch, producing more fish per unit area than any other region in the world. The high productivity is maintained by the upwelling of cold, nutrient-rich water from the oxygen minimum zone (OMZ), driven by strong trade winds. However, the potential impacts of climate change on upwelling dynamics and oceanographic conditions in the near future are uncertain, threatening local and global economies. Here, we unravel the response of the HCE to contrasting climatic conditions during the last two interglacials (i.e. Holocene and MIS5e) providing an independent insight about the relation between climatic factors and upwelling and productivity dynamics. For this purpose, we used multiple cores to reconstruct past changes in OMZ and upwelling intensity, productivity and fish biomass variability. Chronologies for the Holocene were obtained by multiple 14C ages and laminae correlations among cores, while for the MIS5e they were mainly done by correlation of prominent features in several proxies with other published records. We used a multiproxy approach including alkenones to reconstruct sea surface temperatures, δ15N as a proxy for water column denitrification, redox sensitive metals as proxies for sediment redox conditions, and diatom and fish debris assemblages to reconstruct ecological changes. The results show a very different response of the HCE to climate conditions during the last 2 interglacials, likely driven by changes in Tropical Pacific dynamics. During the Holocene we find that 1) the Late Holocene exhibits higher multi-centennial scale variability compared to the Early Holocene, 2) increased upwelling and a weak OMZ during the mid-Holocene, and 3) long term increase in productivity (diatoms and fishes) from the Early to the Late Holocene. During the MIS5e we find an 1) intense OMZ, 2) strong water column stratification, 3) high siliceous biomass, and 4) low fish biomass compared

  12. Quercus macrocarpa annual, early- and latewood widths as hydroclimatic proxies, southeastern Saskatchewan, Canada

    International Nuclear Information System (INIS)

    Vanstone, Jessica R; Sauchyn, David J

    2010-01-01

    Fluctuations in size of annual ring-widths of Quercus species suggest that environmental factors influence the size and density of vessels within the ring, either by acting as a limiting factor for growth or through fine tuning of the wood structure to environmental factors. The purpose of this study is to assess the potential of Q. macrocarpa to provide multiple dendroclimatic proxies for the Canadian Prairies, by investigating growth responses of annual, early- and latewood widths to regional climate variability. Results indicate that ring width chronologies, from southeastern Saskatchewan capture regional signals related to moisture and drought conditions. Correlations suggest that late-wood widths are more representative of annual ring-widths, than are early-wood widths, and are the best proxy of seasonal fluctuations in climate. Thus regression models that include latewood widths were able to account for more variance in the Palmer Drought Severity Index (PDSI) than when annual ring-widths are used as the only proxy. This study demonstrates that Q. macrocarpa can provide multiple dendroclimatic proxies for investigating large scale climatic fluctuations at annual and sub-annual time scales. It is novel in terms of sub-annual analysis of tree-rings in a region that previously lacked dendrochronological research.

  13. Visualization-based analysis of multiple response survey data

    Science.gov (United States)

    Timofeeva, Anastasiia

    2017-11-01

    During the survey, the respondents are often allowed to tick more than one answer option for a question. Analysis and visualization of such data have difficulties because of the need for processing multiple response variables. With standard representation such as pie and bar charts, information about the association between different answer options is lost. The author proposes a visualization approach for multiple response variables based on Venn diagrams. For a more informative representation with a large number of overlapping groups it is suggested to use similarity and association matrices. Some aggregate indicators of dissimilarity (similarity) are proposed based on the determinant of the similarity matrix and the maximum eigenvalue of association matrix. The application of the proposed approaches is well illustrated by the example of the analysis of advertising sources. Intersection of sets indicates that the same consumer audience is covered by several advertising sources. This information is very important for the allocation of the advertising budget. The differences between target groups in advertising sources are of interest. To identify such differences the hypothesis of homogeneity and independence are tested. Recent approach to the problem are briefly reviewed and compared. An alternative procedure is suggested. It is based on partition of a consumer audience into pairwise disjoint subsets and includes hypothesis testing of the difference between the population proportions. It turned out to be more suitable for the real problem being solved.

  14. Web Proxy Auto Discovery for the WLCG

    Science.gov (United States)

    Dykstra, D.; Blomer, J.; Blumenfeld, B.; De Salvo, A.; Dewhurst, A.; Verguilov, V.

    2017-10-01

    All four of the LHC experiments depend on web proxies (that is, squids) at each grid site to support software distribution by the CernVM FileSystem (CVMFS). CMS and ATLAS also use web proxies for conditions data distributed through the Frontier Distributed Database caching system. ATLAS & CMS each have their own methods for their grid jobs to find out which web proxies to use for Frontier at each site, and CVMFS has a third method. Those diverse methods limit usability and flexibility, particularly for opportunistic use cases, where an experiment’s jobs are run at sites that do not primarily support that experiment. This paper describes a new Worldwide LHC Computing Grid (WLCG) system for discovering the addresses of web proxies. The system is based on an internet standard called Web Proxy Auto Discovery (WPAD). WPAD is in turn based on another standard called Proxy Auto Configuration (PAC). Both the Frontier and CVMFS clients support this standard. The input into the WLCG system comes from squids registered in the ATLAS Grid Information System (AGIS) and CMS SITECONF files, cross-checked with squids registered by sites in the Grid Configuration Database (GOCDB) and the OSG Information Management (OIM) system, and combined with some exceptions manually configured by people from ATLAS and CMS who operate WLCG Squid monitoring. WPAD servers at CERN respond to http requests from grid nodes all over the world with a PAC file that lists available web proxies, based on IP addresses matched from a database that contains the IP address ranges registered to organizations. Large grid sites are encouraged to supply their own WPAD web servers for more flexibility, to avoid being affected by short term long distance network outages, and to offload the WLCG WPAD servers at CERN. The CERN WPAD servers additionally support requests from jobs running at non-grid sites (particularly for LHC@Home) which they direct to the nearest publicly accessible web proxy servers. The responses

  15. Seismic structural response analysis for multiple support excitation

    International Nuclear Information System (INIS)

    Shaw, D.E.

    1975-01-01

    In the seismic analysis of nuclear power plant equipment such as piping systems situations often arise in which piping systems span between adjacent structures or between different elevations in the same structure. Owing to the differences in the seismic time history response of different structures or different elevations of the same structure, the input support motion will differ for different supports. The concept of a frequency dependent participation factor and rotational response spectra accounting for phase differences between support excitations is developed by using classical equations of motion to formulate the seismic response of a structure subjected to multiple support excitation. The essence of the method lies in describing the seismic excitation of a multiply excited structure in terms of translational and rotational spectra used at every support and a frequency dependent spatial distribution function derived from the phase relationships of the different support time histories. In this manner it is shown that frequency dependent participation factors can be derived from the frequency dependent distribution functions. Examples are shown and discussed relative to closed form solutions and the state-of-the-art techniques presently being used for the solution of problems of multiply excited structures

  16. Transient response of the 'multiple water-bag' plasma

    International Nuclear Information System (INIS)

    Lim Cheeseng

    1989-01-01

    A charge activates impulsively and then decays temporally within a MWB (multiple water-bag)-modelled warm plasma. The transient problem is formulated and asymptotically resolved for large time. The response potential comprises two characteristically distinct quantities W and W N : W is a superposition of spherically expanding, moderately attenuated Kelvin waves contributed by certain points on a subset of dispersion curves; W N is a superposition, associated with two other dispersion curves, of three spherical wavefunctions, one of which incorporates the Fresnel integrals. A transient state feature of the MWB discretization is the partitioning of the response field by growing (fast) fronts, (trailing) slow caustics and a j -surfaces, the fastest among these being an a N- surface (thermal front) which pushes back a quasi-static exterior. Contrary to expectations, there is no response jump across any of those growing partitions. Wavefunctions near the slow caustics possess Airy factors. A rest state ultimately develops behind the slowest slow caustic. An application is made to the fluid plasma. (author)

  17. Excessive biologic response to IFNβ is associated with poor treatment response in patients with multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Richard A Rudick

    Full Text Available BACKGROUND: Interferon-beta (IFNβ is used to inhibit disease activity in multiple sclerosis (MS, but its mechanisms of action are incompletely understood, individual treatment response varies, and biological markers predicting response to treatment have yet to be identified. METHODS: The relationship between the molecular response to IFNβ and treatment response was determined in 85 patients using a longitudinal design in which treatment effect was categorized by brain magnetic resonance imaging as good (n = 70 or poor response (n = 15. Molecular response was quantified using a customized cDNA macroarray assay for 166 IFN-regulated genes (IRGs. RESULTS: The molecular response to IFNβ differed significantly between patients in the pattern and number of regulated genes. The molecular response was strikingly stable for individuals for as long as 24 months, however, suggesting an individual 'IFN response fingerprint'. Unexpectedly, patients with poor response showed an exaggerated molecular response. IRG induction ratios demonstrated an exaggerated molecular response at both the first and 6-month IFNβ injections. CONCLUSION: MS patients exhibit individually unique but temporally stable biological responses to IFNβ. Poor treatment response is not explained by the duration of biological effects or the specific genes induced. Rather, individuals with poor treatment response have a generally exaggerated biological response to type 1 IFN injections. We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity. The findings suggest a strategy for biologically based, rational use of IFNβ for individual MS patients.

  18. Prediction of response to interferon therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Søndergaard, Helle Bach; Koch-Henriksen, N

    2014-01-01

    OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the genes encoding interferon response factor (IRF)-5, IRF-8 and glypican-5 (GPC5) have been associated with disease activity in multiple sclerosis (MS) patients treated with interferon (IFN)-β. We analysed whether SNPs in the IRF5, IRF8 and GPC5...... genes are associated with clinical disease activity in MS patients beginning de novo treatment with IFN-β. METHODS: The SNPs rs2004640, rs3807306 and rs4728142 in IRF5, rs13333054 and rs17445836 in IRF8 and rs10492503 in GPC5 were genotyped in 575 patients with relapsing-remitting MS followed...... prospectively after the initiation of their first treatment with IFN-β. RESULTS: 62% of patients experienced relapses during the first 2 years of treatment, and 32% had disability progression during the first 5 years of treatment. Patients with a pretreatment annualized relapse rate >1 had an increased risk...

  19. Early response to therapy and survival in multiple myeloma.

    Science.gov (United States)

    Schaar, C G; Kluin-Nelemans, J C; le Cessie, S; Franck, P F H; te Marvelde, M C; Wijermans, P W

    2004-04-01

    Whether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M-protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON-16). M-proteins were collected monthly during melphalan-prednisone therapy (MP: melphalan 0.25 mg/kg, prednisone 1.0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease (n = 18), immunoglobulin M (IgM)-MM (n = 1) and no immunotyping (n = 1) were excluded. Of the 242 patients studied, 75% had IgG M-protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M-protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M-protein decrease of at least 30% after the first MP cycle, which became significant when an M-protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM.

  20. Dynamic response of multiple nanobeam system under a moving nanoparticle

    Directory of Open Access Journals (Sweden)

    Shahrokh Hosseini Hashemi

    2018-03-01

    Full Text Available In this article, nonlocal continuum based model of multiple nanobeam system (MNBS under a moving nanoparticle is investigated using Eringen’s nonlocal theory. Beam layers are assumed to be coupled by winkler elastic medium and the nonlocal Euler-Bernoulli beam theory is used to model each layer of beam. The Hamilton’s principle, Eigen function technique and the Laplace transform method are employed to solve the governing equations. Analytical solutions of the transverse displacements for MNBs with simply supported boundary condition are presented for double layered and three layered MNBSs. For higher number of layers, the governing set of equations is solved numerically and the results are presented. This study shows that small-scale parameter has a significant effect on dynamic response of MNBS under a moving nanoparticle. Sensitivity of dynamical deflection to variation of nonlocal parameter, stiffness of Winkler elastic medium and number of nanobeams are presented in nondimensional form for each layer. Keywords: Dynamic response, Analytical solution, Moving particle, Nanobeam, Multi-layered nanobeam

  1. Metabolic response to glatiramer acetate therapy in multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    Lidia De Riccardis

    2016-12-01

    Full Text Available Glatiramer acetate (GA; Copaxone is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS. Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4+, the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4+ T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4+ T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4+ T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

  2. Metabolic response to glatiramer acetate therapy in multiple sclerosis patients.

    Science.gov (United States)

    De Riccardis, Lidia; Ferramosca, Alessandra; Danieli, Antonio; Trianni, Giorgio; Zara, Vincenzo; De Robertis, Francesca; Maffia, Michele

    2016-12-01

    Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4 + , the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4 + T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs) and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4 + T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4 + T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

  3. Sepsis: Multiple Abnormalities, Heterogeneous Responses, and Evolving Understanding

    Science.gov (United States)

    Iskander, Kendra N.; Osuchowski, Marcin F.; Stearns-Kurosawa, Deborah J.; Kurosawa, Shinichiro; Stepien, David; Valentine, Catherine

    2013-01-01

    Sepsis represents the host's systemic inflammatory response to a severe infection. It causes substantial human morbidity resulting in hundreds of thousands of deaths each year. Despite decades of intense research, the basic mechanisms still remain elusive. In either experimental animal models of sepsis or human patients, there are substantial physiological changes, many of which may result in subsequent organ injury. Variations in age, gender, and medical comorbidities including diabetes and renal failure create additional complexity that influence the outcomes in septic patients. Specific system-based alterations, such as the coagulopathy observed in sepsis, offer both potential insight and possible therapeutic targets. Intracellular stress induces changes in the endoplasmic reticulum yielding misfolded proteins that contribute to the underlying pathophysiological changes. With these multiple changes it is difficult to precisely classify an individual's response in sepsis as proinflammatory or immunosuppressed. This heterogeneity also may explain why most therapeutic interventions have not improved survival. Given the complexity of sepsis, biomarkers and mathematical models offer potential guidance once they have been carefully validated. This review discusses each of these important factors to provide a framework for understanding the complex and current challenges of managing the septic patient. Clinical trial failures and the therapeutic interventions that have proven successful are also discussed. PMID:23899564

  4. UV-B absorbing pigments in spores: biochemical responses to shade in a high-latitude birch forest and implications for sporopollenin-based proxies of past environmental change

    Directory of Open Access Journals (Sweden)

    Terry V. Callaghan

    2011-08-01

    Full Text Available Current attempts to develop a proxy for Earth's surface ultraviolet-B (UV-B flux focus on the organic chemistry of pollen and spores because their constituent biopolymer, sporopollenin, contains UV-B absorbing pigments whose relative abundance may respond to the ambient UV-B flux. Fourier transform infrared (FTIR microspectroscopy provides a useful tool for rapidly determining the pigment content of spores. In this paper, we use FTIR to detect a chemical response of spore wall UV-B absorbing pigments that correspond with levels of shade beneath the canopy of a high-latitude Swedish birch forest. A 27% reduction in UV-B flux beneath the canopy leads to a significant (p<0.05 7.3% reduction in concentration of UV-B absorbing compounds in sporopollenin. The field data from this natural flux gradient in UV-B further support our earlier work on sporopollenin-based proxies derived from sedimentary records and herbaria collections.

  5. A diagnostic tree model for polytomous responses with multiple strategies.

    Science.gov (United States)

    Ma, Wenchao

    2018-04-23

    Constructed-response items have been shown to be appropriate for cognitively diagnostic assessments because students' problem-solving procedures can be observed, providing direct evidence for making inferences about their proficiency. However, multiple strategies used by students make item scoring and psychometric analyses challenging. This study introduces the so-called two-digit scoring scheme into diagnostic assessments to record both students' partial credits and their strategies. This study also proposes a diagnostic tree model (DTM) by integrating the cognitive diagnosis models with the tree model to analyse the items scored using the two-digit rubrics. Both convergent and divergent tree structures are considered to accommodate various scoring rules. The MMLE/EM algorithm is used for item parameter estimation of the DTM, and has been shown to provide good parameter recovery under varied conditions in a simulation study. A set of data from TIMSS 2007 mathematics assessment is analysed to illustrate the use of the two-digit scoring scheme and the DTM. © 2018 The British Psychological Society.

  6. The Last Millennium Reanalysis: Improvements to proxies and proxy modeling

    Science.gov (United States)

    Tardif, R.; Hakim, G. J.; Emile-Geay, J.; Noone, D.; Anderson, D. M.

    2017-12-01

    The Last Millennium Reanalysis (LMR) employs a paleoclimate data assimilation (PDA) approach to produce climate field reconstructions (CFRs). Here, we focus on two key factors in PDA generated CFRs: the set of assimilated proxy records and forward models (FMs) used to estimate proxies from climate model output. In the initial configuration of the LMR [Hakim et al., 2016], the proxy dataset of [PAGES2k Consortium, 2013] was used, along with univariate linear FMs calibrated against annually-averaged 20th century temperature datasets. In an updated configuration, proxy records from the recent dataset [PAGES2k Consortium, 2017] are used, while a hierarchy of statistical FMs are tested: (1) univariate calibrated on annual temperature as in the initial configuration, (2) univariate against temperature as in (1) but calibration performed using expert-derived seasonality for individual proxy records, (3) as in (2) but expert proxy seasonality replaced by seasonal averaging determined objectively as part of the calibration process, (4) linear objective seasonal FMs as in (3) but objectively selecting relationships calibrated either on temperature or precipitation, and (5) bivariate linear models calibrated on temperature and precipitation with objectively-derived seasonality. (4) and (5) specifically aim at better representing the physical drivers of tree ring width proxies. Reconstructions generated using the CCSM4 Last Millennium simulation as an uninformed prior are evaluated against various 20th century data products. Results show the benefits of using the new proxy collection, particularly on the detrended global mean temperature and spatial patterns. The positive impact of using proper seasonality and temperature/moisture sensitivities for tree ring width records is also notable. This updated configuration will be used for the first generation of LMR-generated CFRs to be publicly released. These also provide a benchmark for future efforts aimed at evaluating the

  7. Application and Network-Cognizant Proxies - Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Antonio Ortega; Daniel C. Lee

    2003-03-24

    OAK B264 Application and Network-Cognizant Proxies - Final Report. Current networks show increasing heterogeneity both in terms of their bandwidths/delays and the applications they are required to support. This is a trend that is likely to intensify in the future, as real-time services, such as video, become more widely available and networking access over wireless links becomes more widespread. For this reason they propose that application-specific proxies, intermediate network nodes that broker the interactions between server and client, will become an increasingly important network element. These proxies will allow adaptation to changes in network characteristics without requiring a direct intervention of either server or client. Moreover, it will be possible to locate these proxies strategically at those points where a mismatch occurs between subdomains (for example, a proxy could be placed so as to act as a bridge between a reliable network domain and an unreliable one). This design philosophy favors scalability in the sense that the basic network infrastructure can remain unchanged while new functionality can be added to proxies, as required by the applications. While proxies can perform numerous generic functions, such as caching or security, they concentrate here on media-specific, and in particular video-specific, tasks. The goal of this project was to demonstrate that application- and network-specific knowledge at a proxy can improve overall performance especially under changing network conditions. They summarize below the work performed to address these issues. Particular effort was spent in studying caching techniques and on video classification to enable DiffServ delivery. other work included analysis of traffic characteristics, optimized media scheduling, coding techniques based on multiple description coding, and use of proxies to reduce computation costs. This work covered much of what was originally proposed but with a necessarily reduced scope.

  8. Proxy comparisons for Paleogene sea water temperature reconstructions

    Science.gov (United States)

    de Bar, Marijke; de Nooijer, Lennart; Schouten, Stefan; Ziegler, Martin; Sluijs, Appy; Reichart, Gert-Jan

    2017-04-01

    , indicates that the fundamental mechanisms responsible for the proxy relation to temperature remained constant. de Bar, M. W., et al. (2016), Constraints on the application of long chain diol proxies in the Iberian Atlantic margin, Org. Geochem., 101, 184-195. Hollis, C. J., et al. (2012), Early Paleogene temperature history of the Southwest Pacific Ocean: Reconciling proxies and models, Earth Planet. Sci. Lett., 349, 53-66. Sluijs, A., et al. (2011), Southern ocean warming, sea level and hydrological change during the Paleocene-Eocene thermal maximum, Climate of the Past, 7(1), 47-61.

  9. Using Module Analysis for Multiple Choice Responses: A New Method Applied to Force Concept Inventory Data

    Science.gov (United States)

    Brewe, Eric; Bruun, Jesper; Bearden, Ian G.

    2016-01-01

    We describe "Module Analysis for Multiple Choice Responses" (MAMCR), a new methodology for carrying out network analysis on responses to multiple choice assessments. This method is used to identify modules of non-normative responses which can then be interpreted as an alternative to factor analysis. MAMCR allows us to identify conceptual…

  10. Can Free-Response Questions Be Approximated by Multiple-Choice Equivalents?

    OpenAIRE

    Lin, Shih-Yin; Singh, Chandralekha

    2016-01-01

    We discuss a study to evaluate the extent to which free-response questions can be approximated by multiple-choice equivalents. Two carefully designed research-based multiple-choice questions were transformed into a free-response format and administered on the final exam in a calculus-based introductory physics course. The original multiple-choice questions were administered in another, similar introductory physics course on the final exam. Our findings suggest that carefully designed multiple...

  11. Assessment of time to clinical response, a proxy for discharge readiness, among hospitalized patients with community-acquired pneumonia who received either ceftaroline fosamil or ceftriaxone in two phase III FOCUS trials.

    Science.gov (United States)

    Lodise, Thomas P; Anzueto, Antonio R; Weber, David J; Shorr, Andrew F; Yang, Min; Smith, Alexander; Zhao, Qi; Huang, Xingyue; File, Thomas M

    2015-02-01

    The primary driver of health care costs for patients with community-acquired pneumonia (CAP) is the hospital length of stay (LOS). Unfortunately, hospital LOS comparisons are difficult to make from phase III CAP trials because of their structured designs and prespecified treatment durations. However, an opportunity still exists to draw inferences about potential LOS differences between treatments through the use of surrogates for hospital discharge. The intent of this study was to quantify the time to a clinical response, a proxy for the time to discharge readiness, among hospitalized CAP patients who received either ceftaroline or ceftriaxone in two phase III CAP FOCUS clinical trials. On the basis of the Infectious Diseases Society of America and American Thoracic Society CAP management guidelines and recent FDA guidance documents for community-acquired bacterial pneumonia, a post hoc adjudication algorithm was constructed a priori to compare the time to a clinical response, a proxy for the time to discharge readiness, between patients who received ceftaroline or ceftriaxone. Overall, 1,116 patients (ceftaroline, n=562; ceftriaxone, n=554) from the pooled FOCUS trials met the selection criteria for this analysis. Kaplan-Meier analyses showed that ceftaroline was associated with a shorter time, measured in days, to meeting the clinical response criteria (P=0.03). Of the patients on ceftaroline, 61.0, 76.1, and 83.6% achieved a clinical response by days 3, 4, and 5, compared to 54.3, 69.8, and 79.3% of the ceftriaxone-treated patients. In the Cox regression, ceftaroline was associated with a shorter time to a clinical response (HR, 1.16, P=0.02). The methodology employed here provides a framework to draw comparative effectiveness inferences from phase III CAP efficacy trials. (The FOCUS trials whose data were analyzed in this study have been registered at ClinicalTrials.gov under registration no. NCT00621504 and NCT00509106.). Copyright © 2015, American Society

  12. Multi-proxy studies in palaeolimnology

    OpenAIRE

    Birks, Hilary H.; Birks, Harry John Betteley

    2006-01-01

    Multi-proxy studies are becoming increasingly common in palaeolimnology. Eight basic requirements and challenges for a multi-proxy study are outlined in this essay – definition of research questions, leadership, site selection and coring, data storage, chronology, presentation of results, numerical tools, and data interpretation. The nature of proxy data is discussed in terms of physical proxies and biotic proxies. Loss-on-ignition changes and the use of transfer functions are reviewed as exa...

  13. Applicability of a cognitive questionnaire in the elderly and proxy

    Directory of Open Access Journals (Sweden)

    Renata Areza Fegyveres

    Full Text Available Abstract The Informant Questionnaire on Cognitive Decline in the Elderly with the Proxy (IQCODE was developed as a screening tool for cognition alterations. Objectives: 1 To verify the applicability of IQCODE in the elderly with limited schooling, 2 To verify the reliability of the responses supplied by the aged and their proxies. Methods: Individuals of a Community Group were evaluated using the Mini-Mental State Examination (MMSE, IQCODE and Geriatric Depression Scale (GDS. The IQCODE was applied to informants and proxies. Results: We analyzed 44 individuals, aged between 58-82 years (M=66.8, SD=5.97 with mean elderly-schooling level of 3.75, SD=2.82 and 44 proxies aged 44.5 (SD=13.3, with mean schooling level of 8.25 (SD=4.3. The mean GDS was 8.22, SD=4.90 and 13 participants presented a score suggestive of depressive symptoms. The mean elderly IQCODE score was 3.26, SD=0.69 and 3.21, SD=0.65, for proxy responses. There was no statistical difference between these means. On the MMSE, the mean score was 24.20, SD=4.14 and 18 participants presented scores below the cut-off. The IQCODE answers by the elderly in this latter group were more congruent with MMSE than the answers of proxies. Conclusions: The applicability of the IQCODE in a population with little schooling was verified in that the proxy-report was similar to the elderly report. We can affirm that the elderly answers were more accurate than the proxies, as they were closer to MMSE score. The inclusion of a greater number of participants from community-dwelling settings is necessary to confirm the results obtained in this study.

  14. Qualitative and Quantitative Sentiment Proxies

    DEFF Research Database (Denmark)

    Zhao, Zeyan; Ahmad, Khurshid

    2015-01-01

    Sentiment analysis is a content-analytic investigative framework for researchers, traders and the general public involved in financial markets. This analysis is based on carefully sourced and elaborately constructed proxies for market sentiment and has emerged as a basis for analysing movements...

  15. Seismic response analysis of structural system subjected to multiple support excitation

    International Nuclear Information System (INIS)

    Wu, R.W.; Hussain, F.A.; Liu, L.K.

    1978-01-01

    In the seismic analysis of a multiply supported structural system subjected to nonuniform excitations at each support point, the single response spectrum, the time history, and the multiple response spectrum are the three commonly employed methods. In the present paper the three methods are developed, evaluated, and the limitations and advantages of each method assessed. A numerical example has been carried out for a typical piping system. Considerably smaller responses have been predicted by the time history method than that by the single response spectrum method. This is mainly due to the fact that the phase and amplitude relations between the support excitations are faithfully retained in the time history method. The multiple response spectrum prediction has been observed to compare favourably with the time history method prediction. Based on the present evaluation, the multiple response spectrum method is the most efficient method for seismic response analysis of structural systems subjected to multiple support excitation. (Auth.)

  16. Multiple-Choice versus Constructed-Response Tests in the Assessment of Mathematics Computation Skills.

    Science.gov (United States)

    Gadalla, Tahany M.

    The equivalence of multiple-choice (MC) and constructed response (discrete) (CR-D) response formats as applied to mathematics computation at grade levels two to six was tested. The difference between total scores from the two response formats was tested for statistical significance, and the factor structure of items in both response formats was…

  17. Pavlovian conditioning of multiple opioid-like responses in mice

    OpenAIRE

    Bryant, Camron D.; Roberts, Kristofer W.; Culbertson, Christopher S.; Le, Alan; Evans, Christopher J.; Fanselow, Michael S.

    2009-01-01

    Conditional responses in rodents such as locomotion have been reported for drugs of abuse and similar to the placebo response in humans, may be associated with the expectation of reward. We examined several conditional opioid-like responses and the influence of drug expectation on conditioned place preference and concomitant conditional locomotion. Male C57BL/6J mice were conditioned with the selective mu opioid receptor agonist fentanyl (0.2 mg/kg, i.p.) in a novel context and subsequently g...

  18. Optimization of multi-response dynamic systems integrating multiple ...

    African Journals Online (AJOL)

    regression and Taguchi's dynamic signal-to-noise ratio concept ..... algorithm for dynamic multi-response optimization based on goal programming approach. .... problem-solving confirmation, if no grave infringement of model suppositions is ...

  19. Bisensory stimulation increases gamma-responses over multiple cortical regions.

    Science.gov (United States)

    Sakowitz, O W; Quiroga, R Q; Schürmann, M; Başar, E

    2001-04-01

    In the framework of the discussion about gamma (approx. 40 Hz) oscillations as information carriers in the brain, we investigated the relationship between gamma responses in the EEG and intersensory association. Auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) were compared with bisensory evoked potentials (BEPs; simultaneous auditory and visual stimulation) in 15 subjects. Gamma responses in AEPs, VEPs and BEPs were assessed by means of wavelet decomposition. Overall maximum gamma-components post-stimulus were highest in BEPs (P < 0.01). Bisensory evoked gamma-responses also showed significant central, parietal and occipital amplitude-increases (P < 0.001, P < 0.01, P < 0.05, respectively; prestimulus interval as baseline). These were of greater magnitude when compared with the unisensory responses. As a correlate of the marked gamma responses to bimodal stimulation we suggest a process of 'intersensory association', i.e. one of the steps between sensory transmission and perception. Our data may be interpreted as a further example of function-related gamma responses in the EEG.

  20. Noninvasive optical monitoring multiple physiological parameters response to cytokine storm

    Science.gov (United States)

    Li, Zebin; Li, Ting

    2018-02-01

    Cancer and other disease originated by immune or genetic problems have become a main cause of death. Gene/cell therapy is a highlighted potential method for the treatment of these diseases. However, during the treatment, it always causes cytokine storm, which probably trigger acute respiratory distress syndrome and multiple organ failure. Here we developed a point-of-care device for noninvasive monitoring cytokine storm induced multiple physiological parameters simultaneously. Oxy-hemoglobin, deoxy-hemoglobin, water concentration and deep-tissue/tumor temperature variations were simultaneously measured by extended near infrared spectroscopy. Detection algorithms of symptoms such as shock, edema, deep-tissue fever and tissue fibrosis were developed and included. Based on these measurements, modeling of patient tolerance and cytokine storm intensity were carried out. This custom device was tested on patients experiencing cytokine storm in intensive care unit. The preliminary data indicated the potential of our device in popular and milestone gene/cell therapy, especially, chimeric antigen receptor T-cell immunotherapy (CAR-T).

  1. Drug response prediction in high-risk multiple myeloma

    DEFF Research Database (Denmark)

    Vangsted, A J; Helm-Petersen, S; Cowland, J B

    2018-01-01

    from high-risk patients by GEP70 at diagnosis from Total Therapy 2 and 3A to predict the response by the DRP score of drugs used in the treatment of myeloma patients. The DRP score stratified patients further. High-risk myeloma with a predicted sensitivity to melphalan by the DRP score had a prolonged...

  2. Shareholder Activism through the Proxy Process

    NARCIS (Netherlands)

    Renneboog, L.D.R.; Szilagyi, P.G.

    2009-01-01

    This paper provides evidence on the corporate governance role of shareholderinitiated proxy proposals. Previous studies debate over whether activists use proxy proposals to discipline firms or to simply advance their self-serving agendas, and whether proxy proposals are effective at all in

  3. Shareholder Activism Through the Proxy Process

    NARCIS (Netherlands)

    Renneboog, L.D.R.; Szilagyi, P.G.

    2009-01-01

    This paper provides evidence on the corporate governance role of shareholder-initiated proxy proposals. Previous studies debate over whether activists use proxy proposals to discipline firms or to simply advance their self-serving agendas, and whether proxy proposals are effective at all in

  4. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    OpenAIRE

    Dues, Dylan J.; Andrews, Emily K.; Schaar, Claire E.; Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxi...

  5. Proxy and patient reports of health-related quality of life in a national cancer survey.

    Science.gov (United States)

    Roydhouse, Jessica K; Gutman, Roee; Keating, Nancy L; Mor, Vincent; Wilson, Ira B

    2018-01-05

    Proxy respondents are frequently used in surveys, including those assessing health-related quality of life (HRQOL). In cancer, most research involving proxies has been undertaken with paired proxy-patient populations, where proxy responses are compared to patient responses for the same individual. In these populations, proxy-patient differences are small and suggest proxy underestimation of patient HRQOL. In practice, however, proxy responses will only be used when patient responses are not available. The difference between proxy and patient reports of patient HRQOL where patients are not able to report for themselves in cancer is not known. The objective of this study was to evaluate the difference between patient and proxy reports of patient HRQOL in a large national cancer survey, and determine if this difference could be mitigated by adjusting for clinical and sociodemographic information about patients. Data were from the Cancer Care Outcomes Research and Surveillance (CanCORS) study. Patients or their proxies were recruited within 3-6 months of diagnosis with lung or colorectal cancer. HRQOL was measured using the SF-12 mental and physical composite scales. Differences of ½ SD (=5 points) were considered clinically significant. The primary independent variable was proxy status. Linear regression models were used to adjust for patient sociodemographic and clinical covariates, including cancer stage, patient age and education, and patient co-morbidities. Of 6471 respondents, 1011 (16%) were proxies. Before adjustment, average proxy-reported scores were lower for both physical (-6.7 points, 95% CI -7.4 to -5.9) and mental (-6 points, 95% CI -6.7 to -5.2) health. Proxy-reported scores remained lower after adjustment (physical: -5.8 points, -6.6 to -5; mental: -5.8 points, -6.6 to 5). Proxy-patient score differences remained clinically and statistically significant, even after adjustment for sociodemographic and clinical variables. Proxy-reported outcome scores

  6. Responses of an isolation system with distinct multiple frequencies

    International Nuclear Information System (INIS)

    Wu, Ting-shu; Seidensticker, R.W.

    1991-01-01

    Base isolation systems are generally designed with a single natural frequency. A major concern for these isolation systems is that, if the dominant frequency of a future earthquake is equal or close to the system's natural frequency, the ground motion will be greatly amplified because of resonance,and the superstructure would suffer severe damages. This paper present an isolation system designed with two distinct frequencies. Its responses to different ground motions, including a harmonic motion, show that no excessive amplification will occur. Adoption of this isolation system would greatly enhance the safety of an isolated superstructure against future strong earthquakes. 3 refs., 4 figs., 2 tabs

  7. DMXAA: An antivascular agent with multiple host responses

    International Nuclear Information System (INIS)

    Baguley, Bruce C.; Ching, L.-M.

    2002-01-01

    Purpose: To measure host responses to the antivascular agent DMXAA (5,6-dimethylxanthenone-4-acetic acid) and to compare them with those of other antivascular agents. Methods: Induction of tumor necrosis was measured in s.c. murine Colon 38 carcinomas growing in normal or tumor necrosis factor (TNF) receptor-1 knockout mice. Plasma and tumor tissue TNF concentrations were measured by ELISA. Plasma concentrations of 5-hydroxyindoleacetic acid (as a measure of serotonin release) and nitrite (as a measure of nitric oxide release) were measured by high-performance liquid chromatography. Results: Administration of DMXAA to tumor-bearing mice increased plasma and tumor tissue-associated TNF, in addition to increasing plasma nitric oxide, distinguishing its action from that of mitotic poisons that had an antivascular action. Results from TNF receptor-1 knockout mice showed that TNF played an important role in both its antitumor action and its host toxicity. Release of serotonin occurred in response to mitotic poisons, as well as to DMXAA. Conclusions: The antivascular action of DMXAA involves in situ production in tumor tissue of a cascade of vasoactive events, including a direct effect on vascular endothelial cells and indirect vascular effects involving TNF, other cytokines, serotonin, and nitric oxide. Now that Phase I clinical trials of DMXAA are completed, the optimization of this cascade in cancer patients is a major challenge. Plasma 5-hydroxyindoleacetic acid concentrations may provide a useful surrogate marker for the antivascular effects of DMXAA and other antivascular agents

  8. A case report of Factitious Disorder (Munchausen Syndrome by proxy

    Directory of Open Access Journals (Sweden)

    Mehdi Shirzadifar

    2014-09-01

    Full Text Available Background: In Factitious Disorder by proxy, one person (perpetrator induces the disease in another person, thereby seeking emotional needs during the treatment process Diagnosis of this disorder is very difficult and there is not much consensus over it among experts. Lack of timely diagnosis of this disorder may lead to serious harms in patients. Case presentation: We will introduce a 19 year-old boy with mental retardation and history of multiple admissions to psychiatric, internal, urology and surgery wards. He has a 12 year-old sister and a 4 year-old brother, both with history of multiple admissions to pediatrics and internal wards. The father of family was 48 years old with chronic mental disorder, drug dependency and history of multiple admissions to medical, psychiatry and neurology wards. The mother of this family was diagnosed with munchausen syndrome by proxy.

  9. Multiple Resource Host Architecture (MRHA) for the Mobile Detection Assessment Response System (MDARS) Revision A

    National Research Council Canada - National Science Library

    Everett, H

    2000-01-01

    The Mobile Detection Assessment and Response System (MDARS) program employs multiple robotic security platforms operating under the high level control of a remote host, with the direct supervision of a human operator...

  10. Coupled multiple-response versus free-response conceptual assessment: An example from upper-division physics

    Directory of Open Access Journals (Sweden)

    Bethany R. Wilcox

    2014-10-01

    Full Text Available Free-response research-based assessments, like the Colorado Upper-division Electrostatics Diagnostic (CUE, provide rich, fine-grained information about students’ reasoning. However, because of the difficulties inherent in scoring these assessments, the majority of the large-scale conceptual assessments in physics are multiple choice. To increase the scalability and usability of the CUE, we set out to create a new version of the assessment that preserves the insights afforded by a free-response format while exploiting the logistical advantages of a multiple-choice assessment. We used our extensive database of responses to the free-response CUE to construct distractors for a new version where students can select multiple responses and receive partial credit based on the accuracy and consistency of their selections. Here, we describe the development of this modified CUE format, which we call coupled multiple response (CMR, and present data from direct comparisons of both versions. We find that the two formats have the same average score and perform similarly on multiple measures of validity and reliability, suggesting that the new version is a potentially viable alternative to the original CUE for the purpose of large-scale research-based assessment. We also compare the details of student responses on each of the two versions. While the CMR version does not capture the full scope of potential student responses, nearly three-quarters of our students’ responses to the free-response version contained one or more elements that matched options provided on the CMR version.

  11. On the Equivalence of Constructed-Response and Multiple-Choice Tests.

    Science.gov (United States)

    Traub, Ross E.; Fisher, Charles W.

    Two sets of mathematical reasoning and two sets of verbal comprehension items were cast into each of three formats--constructed response, standard multiple-choice, and Coombs multiple-choice--in order to assess whether tests with indentical content but different formats measure the same attribute, except for possible differences in error variance…

  12. Measuring SIP proxy server performance

    CERN Document Server

    Subramanian, Sureshkumar V

    2013-01-01

    Internet Protocol (IP) telephony is an alternative to the traditional Public Switched Telephone Networks (PSTN), and the Session Initiation Protocol (SIP) is quickly becoming a popular signaling protocol for VoIP-based applications. SIP is a peer-to-peer multimedia signaling protocol standardized by the Internet Engineering Task Force (IETF), and it plays a vital role in providing IP telephony services through its use of the SIP Proxy Server (SPS), a software application that provides call routing services by parsing and forwarding all the incoming SIP packets in an IP telephony network.SIP Pr

  13. Developing a proxy version of the Adult social care outcome toolkit (ASCOT).

    Science.gov (United States)

    Rand, Stacey; Caiels, James; Collins, Grace; Forder, Julien

    2017-05-19

    Social care-related quality of life is a key outcome indicator used in the evaluation of social care interventions and policy. It is not, however, always possible to collect quality of life data by self-report even with adaptations for people with cognitive or communication impairments. A new proxy-report version of the Adult Social Care Outcomes Toolkit (ASCOT) measure of social care-related quality of life was developed to address the issues of wider inclusion of people with cognitive or communication difficulties who may otherwise be systematically excluded. The development of the proxy-report ASCOT questionnaire was informed by literature review and earlier work that identified the key issues and challenges associated with proxy-reported outcomes. To evaluate the acceptability and content validity of the ASCOT-Proxy, qualitative cognitive interviews were conducted with unpaid carers or care workers of people with cognitive or communication impairments. The proxy respondents were invited to 'think aloud' while completing the questionnaire. Follow-up probes were asked to elicit further detail of the respondent's comprehension of the format, layout and content of each item and also how they weighed up the options to formulate a response. A total of 25 unpaid carers and care workers participated in three iterative rounds of cognitive interviews. The findings indicate that the items were well-understood and the concepts were consistent with the item definitions for the standard self-completion version of ASCOT with minor modifications to the draft ASCOT-Proxy. The ASCOT-Proxy allows respondents to rate the proxy-proxy and proxy-patient perspectives, which improved the acceptability of proxy report. A new proxy-report version of ASCOT was developed with evidence of its qualitative content validity and acceptability. The ASCOT-Proxy is ready for empirical testing of its suitability for data collection as a self-completion and/or interview questionnaire, and also

  14. Porcine humoral immune responses to multiple injections of murine monoclonal antibodies

    DEFF Research Database (Denmark)

    Lohse, Louise; Nielsen, Jens; Kamstrup, Søren

    2005-01-01

    In humans and cattle, multiple injections of murine monoclonal antibodies (m-mAbs) induce anti-mouse antibody responses. The objectives of the present. study were to investigate whether a similar response could be seen when pigs were subjected to m-mAb therapy, and to study the kinetics of such a...

  15. Coupled Multiple-Response versus Free-Response Conceptual Assessment: An Example from Upper-Division Physics

    Science.gov (United States)

    Wilcox, Bethany R.; Pollock, Steven J.

    2014-01-01

    Free-response research-based assessments, like the Colorado Upper-division Electrostatics Diagnostic (CUE), provide rich, fine-grained information about students' reasoning. However, because of the difficulties inherent in scoring these assessments, the majority of the large-scale conceptual assessments in physics are multiple choice. To increase…

  16. Experimental design and multiple response optimization. Using the desirability function in analytical methods development.

    Science.gov (United States)

    Candioti, Luciana Vera; De Zan, María M; Cámara, María S; Goicoechea, Héctor C

    2014-06-01

    A review about the application of response surface methodology (RSM) when several responses have to be simultaneously optimized in the field of analytical methods development is presented. Several critical issues like response transformation, multiple response optimization and modeling with least squares and artificial neural networks are discussed. Most recent analytical applications are presented in the context of analytLaboratorio de Control de Calidad de Medicamentos (LCCM), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, C.C. 242, S3000ZAA Santa Fe, ArgentinaLaboratorio de Control de Calidad de Medicamentos (LCCM), Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, C.C. 242, S3000ZAA Santa Fe, Argentinaical methods development, especially in multiple response optimization procedures using the desirability function. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Making assessments while taking repeated risks: a pattern of multiple response pathways.

    Science.gov (United States)

    Pleskac, Timothy J; Wershbale, Avishai

    2014-02-01

    Beyond simply a decision process, repeated risky decisions also require a number of cognitive processes including learning, search and exploration, and attention. In this article, we examine how multiple response pathways develop over repeated risky decisions. Using the Balloon Analogue Risk Task (BART) as a case study, we show that 2 different response pathways emerge over the course of the task. The assessment pathway is a slower, more controlled pathway where participants deliberate over taking a risk. The 2nd pathway is a faster, more automatic process where no deliberation occurs. Results imply the slower assessment pathway is taken as choice conflict increases and that the faster automatic response is a learned response. Based on these results, we modify an existing formal cognitive model of decision making during the BART to account for these dual response pathways. The slower more deliberative response process is modeled with a sequential sampling process where evidence is accumulated to a threshold, while the other response is given automatically. We show that adolescents with conduct disorder and substance use disorder symptoms not only evaluate risks differently during the BART but also differ in the rate at which they develop the more automatic response. More broadly, our results suggest cognitive models of judgment decision making need to transition from treating observed decisions as the result of a single response pathway to the result of multiple response pathways that change and develop over time.

  18. The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor

    Directory of Open Access Journals (Sweden)

    Sunmi Song

    2015-06-01

    Full Text Available The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood.

  19. The role of multiple negative social relationships in inflammatory cytokine responses to a laboratory stressor.

    Science.gov (United States)

    Song, Sunmi; Graham-Engeland, Jennifer E; Corwin, Elizabeth J; Ceballos, Rachel M; Taylor, Shelley E; Seeman, Teresa; Klein, Laura Cousino

    2015-01-01

    The present study examined the unique impact of perceived negativity in multiple social relationships on endocrine and inflammatory responses to a laboratory stressor. Via hierarchical cluster analysis, those who reported negative social exchanges across relationships with a romantic partner, family, and their closest friend had higher mean IL-6 across time and a greater increase in TNF-α from 15 min to 75 min post stress. Those who reported negative social exchanges across relationships with roommates, family, and their closest friend showed greater IL-6 responses to stress. Differences in mean IL-6 were accounted for by either depressed mood or hostility, whereas differences in the cytokine stress responses remained significant after controlling for those factors. Overall, this research provides preliminary evidence to suggest that having multiple negative relationships may exacerbate acute inflammatory responses to a laboratory stressor independent of hostility and depressed mood.

  20. Responses of stream microbes to multiple anthropogenic stressors in a mesocosm study.

    Science.gov (United States)

    Nuy, Julia K; Lange, Anja; Beermann, Arne J; Jensen, Manfred; Elbrecht, Vasco; Röhl, Oliver; Peršoh, Derek; Begerow, Dominik; Leese, Florian; Boenigk, Jens

    2018-08-15

    Stream ecosystems are affected by multiple anthropogenic stressors worldwide. Even though effects of many single stressors are comparatively well studied, the effects of multiple stressors are difficult to predict. In particular bacteria and protists, which are responsible for the majority of ecosystem respiration and element flows, are infrequently studied with respect to multiple stressors responses. We conducted a stream mesocosm experiment to characterize the responses of single and multiple stressors on microbiota. Two functionally important stream habitats, leaf litter and benthic phototrophic rock biofilms, were exposed to three stressors in a full factorial design: fine sediment deposition, increased chloride concentration (salinization) and reduced flow velocity. We analyzed the microbial composition in the two habitat types of the mesocosms using an amplicon sequencing approach. Community analysis on different taxonomic levels as well as principle component analyses (PCoAs) based on realtive abundances of operational taxonomic units (OTUs) showed treatment specific shifts in the eukaryotic biofilm community. Analysis of variance (ANOVA) revealed that Bacillariophyta responded positively salinity and sediment increase, while the relative read abundance of chlorophyte taxa decreased. The combined effects of multiple stressors were mainly antagonistic. Therefore, the community composition in multiply stressed environments resembled the composition of the unstressed control community in terms of OTU occurrence and relative abundances. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  1. 12 CFR 569.4 - Proxy soliciting material.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Proxy soliciting material. 569.4 Section 569.4 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY PROXIES § 569.4 Proxy soliciting material. No solicitation of a proxy shall be made by means of any statement, form of proxy...

  2. 12 CFR 569.2 - Form of proxies.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Form of proxies. 569.2 Section 569.2 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY PROXIES § 569.2 Form of proxies. Every form of proxy shall conform to the following requirements: (a) The proxy shall be revocable at will by...

  3. Electromagnetic velocity gauge: use of multiple gauges, time response, and flow perturbations

    International Nuclear Information System (INIS)

    Erickson, L.M.; Johnson, C.B.; Parker, N.L.; Vantine, H.C.; Weingart, R.C.; Lee, R.S.

    1981-01-01

    We have developed an in-situ electromagnetic velocity (EMV) gauge system for use in multiple-gauge studies of initiating and detonating explosives. We have also investigated the risetime of the gauge and the manner in which it perturbs a reactive flow. We report on the special precautions that are necessary in multiple gauge experiments to reduce lead spreading, simplify target fabrication problems and minimize cross talk through the conducting explosive. Agreement between measured stress records and calculations from multiple velocity gauge data give us confidence that our velocity gauges are recording properly. We have used laser velocity interferometry to measure the gauge risetime in polymethyl methacrylate (PMMA). To resolve the difference in the two methods, we have examined hydrodynamic and material rate effects. In addition, we considered the effects of shock tilt, electronic response and magntic diffusion on the gauge's response time

  4. Increased multiaxial lumbar motion responses during multiple-impulse mechanical force manually assisted spinal manipulation

    Directory of Open Access Journals (Sweden)

    Gunzburg Robert

    2006-04-01

    Full Text Available Abstract Background Spinal manipulation has been found to create demonstrable segmental and intersegmental spinal motions thought to be biomechanically related to its mechanisms. In the case of impulsive-type instrument device comparisons, significant differences in the force-time characteristics and concomitant motion responses of spinal manipulative instruments have been reported, but studies investigating the response to multiple thrusts (multiple impulse trains have not been conducted. The purpose of this study was to determine multi-axial segmental and intersegmental motion responses of ovine lumbar vertebrae to single impulse and multiple impulse spinal manipulative thrusts (SMTs. Methods Fifteen adolescent Merino sheep were examined. Tri-axial accelerometers were attached to intraosseous pins rigidly fixed to the L1 and L2 lumbar spinous processes under fluoroscopic guidance while the animals were anesthetized. A hand-held electromechanical chiropractic adjusting instrument (Impulse was used to apply single and repeated force impulses (13 total over a 2.5 second time interval at three different force settings (low, medium, and high along the posteroanterior axis of the T12 spinous process. Axial (AX, posteroanterior (PA, and medial-lateral (ML acceleration responses in adjacent segments (L1, L2 were recorded at a rate of 5000 samples per second. Peak-peak segmental accelerations (L1, L2 and intersegmental acceleration transfer (L1–L2 for each axis and each force setting were computed from the acceleration-time recordings. The initial acceleration response for a single thrust and the maximum acceleration response observed during the 12 multiple impulse trains were compared using a paired observations t-test (POTT, alpha = .05. Results Segmental and intersegmental acceleration responses mirrored the peak force magnitude produced by the Impulse Adjusting Instrument. Accelerations were greatest for AX and PA measurement axes. Compared to

  5. Linking and Psychological Functioning in a Chinese Sample: The Multiple Mediation of Response to Positive Affect

    Science.gov (United States)

    Yang, Hongfei; Li, Juan

    2016-01-01

    The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…

  6. Testing effect of a drug using multiple nested models for the dose–response

    DEFF Research Database (Denmark)

    Baayen, C.; Hougaard, P.; Pipper, C. B.

    2015-01-01

    of the assumed dose–response model. Bretz et al. (2005, Biometrics 61, 738–748) suggested a combined approach, which selects one or more suitable models from a set of candidate models using a multiple comparison procedure. The method initially requires a priori estimates of any non-linear parameters...

  7. Application of Item Response Theory to Modeling of Expanded Disability Status Scale in Multiple Sclerosis.

    NARCIS (Netherlands)

    Novakovic, A.M.; Krekels, E.H.; Munafo, A.; Ueckert, S.; Karlsson, M.O.

    2016-01-01

    In this study, we report the development of the first item response theory (IRT) model within a pharmacometrics framework to characterize the disease progression in multiple sclerosis (MS), as measured by Expanded Disability Status Score (EDSS). Data were collected quarterly from a 96-week phase III

  8. IsoGeneGUI : Multiple approaches for dose-response analysis of microarray data using R

    NARCIS (Netherlands)

    Otava, Martin; Sengupta, Rudradev; Shkedy, Ziv; Lin, Dan; Pramana, Setia; Verbeke, Tobias; Haldermans, Philippe; Hothorn, Ludwig A.; Gerhard, Daniel; Kuiper, Rebecca M.; Klinglmueller, Florian; Kasim, Adetayo

    2017-01-01

    The analysis of transcriptomic experiments with ordered covariates, such as dose-response data, has become a central topic in bioinformatics, in particular in omics studies. Consequently, multiple R packages on CRAN and Bioconductor are designed to analyse microarray data from various perspectives

  9. Acute and chronic cytokine responses to resistance exercise and training in people with multiple sclerosis

    DEFF Research Database (Denmark)

    Kjølhede, Tue; Dalgas, Ulrik; Brolin Gade, Anne

    2016-01-01

    Exercise is a well-established part of rehabilitation for people with multiple sclerosis (PwMS), and it has been hypothesized to stimulate an anti-inflammatory environment that might be disease modifying. Yet, investigations on exercise-induced immune responses are scarce and generally not paying...

  10. Proxy SDN Controller for Wireless Networks

    Directory of Open Access Journals (Sweden)

    Won-Suk Kim

    2016-01-01

    Full Text Available Management of wireless networks as well as wired networks by using software-defined networking (SDN has been highlighted continually. However, control features of a wireless network differ from those of a wired network in several aspects. In this study, we identify the various inefficient points when controlling and managing wireless networks by using SDN and propose SDN-based control architecture called Proxcon to resolve these problems. Proxcon introduces the concept of a proxy SDN controller (PSC for the wireless network control, and the PSC entrusted with the role of a main controller performs control operations and provides the latest network state for a network administrator. To address the control inefficiency, Proxcon supports offloaded SDN operations for controlling wireless networks by utilizing the PSC, such as local control by each PSC, hybrid control utilizing the PSC and the main controller, and locally cooperative control utilizing the PSCs. The proposed architecture and the newly supported control operations can enhance scalability and response time when the logically centralized control plane responds to the various wireless network events. Through actual experiments, we verified that the proposed architecture could address the various control issues such as scalability, response time, and control overhead.

  11. Deriving amplification factors from simple site parameters using generalized regression neural networks: implications for relevant site proxies

    Science.gov (United States)

    Boudghene Stambouli, Ahmed; Zendagui, Djawad; Bard, Pierre-Yves; Derras, Boumédiène

    2017-07-01

    Most modern seismic codes account for site effects using an amplification factor (AF) that modifies the rock acceleration response spectra in relation to a "site condition proxy," i.e., a parameter related to the velocity profile at the site under consideration. Therefore, for practical purposes, it is interesting to identify the site parameters that best control the frequency-dependent shape of the AF. The goal of the present study is to provide a quantitative assessment of the performance of various site condition proxies to predict the main AF features, including the often used short- and mid-period amplification factors, Fa and Fv, proposed by Borcherdt (in Earthq Spectra 10:617-653, 1994). In this context, the linear, viscoelastic responses of a set of 858 actual soil columns from Japan, the USA, and Europe are computed for a set of 14 real accelerograms with varying frequency contents. The correlation between the corresponding site-specific average amplification factors and several site proxies (considered alone or as multiple combinations) is analyzed using the generalized regression neural network (GRNN). The performance of each site proxy combination is assessed through the variance reduction with respect to the initial amplification factor variability of the 858 profiles. Both the whole period range and specific short- and mid-period ranges associated with the Borcherdt factors Fa and Fv are considered. The actual amplification factor of an arbitrary soil profile is found to be satisfactorily approximated with a limited number of site proxies (4-6). As the usual code practice implies a lower number of site proxies (generally one, sometimes two), a sensitivity analysis is conducted to identify the "best performing" site parameters. The best one is the overall velocity contrast between underlying bedrock and minimum velocity in the soil column. Because these are the most difficult and expensive parameters to measure, especially for thick deposits, other

  12. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways

    Science.gov (United States)

    Bergsma, Alexis L.; Senchuk, Megan M.; Van Raamsdonk, Jeremy M.

    2016-01-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage. PMID:27053445

  13. Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways.

    Science.gov (United States)

    Dues, Dylan J; Andrews, Emily K; Schaar, Claire E; Bergsma, Alexis L; Senchuk, Megan M; Van Raamsdonk, Jeremy M

    2016-04-01

    In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage.

  14. Role of Advance Care Planning in Proxy Decision Making Among Individuals With Dementia and Their Family Caregivers.

    Science.gov (United States)

    Kwak, Jung; De Larwelle, Jessica A; Valuch, Katharine O'Connell; Kesler, Toni

    2016-01-01

    Health care proxies make important end-of-life decisions for individuals with dementia. A cross-sectional survey was conducted to examine the role of advance care planning in proxy decision making for 141 individuals with cognitive impairment, Alzheimer's disease, or other types of dementia. Proxies who did not know the preferences of individuals with dementia for life support treatments reported greater understanding of their values. Proxies of individuals with dementia who did not want life support treatments anticipated receiving less support and were more uncertain in decision making. The greater knowledge proxies had about dementia trajectory, family support, and trust of physicians, the more informed, clearer, and less uncertain they were in decision making. In addition to advance care planning, multiple factors influence proxy decision making, which should be considered in developing interventions and future research to support informed decision making for individuals with dementia and their families. Copyright 2016, SLACK Incorporated.

  15. Transparent Proxy for Secure E-Mail

    Science.gov (United States)

    Michalák, Juraj; Hudec, Ladislav

    2010-05-01

    The paper deals with the security of e-mail messages and e-mail server implementation by means of a transparent SMTP proxy. The security features include encryption and signing of transported messages. The goal is to design and implement a software proxy for secure e-mail including its monitoring, administration, encryption and signing keys administration. In particular, we focus on automatic public key on-the-fly encryption and signing of e-mail messages according to S/MIME standard by means of an embedded computer system whose function can be briefly described as a brouter with transparent SMTP proxy.

  16. From process to proxy: Ecological challenges and opportunities of tree-ring based environmental reconstructions

    Science.gov (United States)

    Wilmking, Martin; Buras, Allan; Heinrich, Ingo; Scharnweber, Tobias; Simard, Sonia; Smiljanic, Marko; van der Maaten, Ernst; van der Maaten-Theunissen, Marieke

    2014-05-01

    Trees are sessile, long-living organisms and as such constantly need to adapt to changing environmental conditions. Accordingly, they often show high phenotypic plasticity (the ability to change phenotypic traits, such as allocation of resources) in response to environmental change. This high phenotypic plasticity is generally considered as one of the main ingredients for a sessile organism to survive and reach high ages. Precisely because of the ability of trees to reach old age and their in-ability to simply run away when conditions get worse, growth information recorded in tree rings has long been used as a major environmental proxy, covering time scales from decades to millennia. Past environmental conditions (e.g. climate) are recorded in i.e. annual tree-ring width, early- and latewood width, wood density, isotopic concentrations, cell anatomy or wood chemistry. One prerequisite for a reconstruction is that the relationship between the environmental variable influencing tree growth and the tree-growth variable itself is stable through time. This, however, might contrast the ecological theory of high plasticity and the trees ability to adapt to change. To untangle possible mechanisms leading to stable or unstable relationships between tree growth and environmental variables, it is helpful to have exact site information and several proxy variables of each tree-ring series available. Although we gain insight into the environmental history of a sampling site when sampling today, this is extremely difficult when using archeological wood. In this latter case, we face the additional challenge of unknown origin, provenance and (or) site conditions, making it even more important to use multiple proxy time-series from the same sample. Here, we review typical examples, where the relationship between tree growth and environmental variables seems 1) stable and 2) instable through time, and relate these two cases to ecological theory. Based on ecological theory, we then

  17. Analysis of the SOS response of Vibrio and other bacteria with multiple chromosomes.

    Science.gov (United States)

    Sanchez-Alberola, Neus; Campoy, Susana; Barbé, Jordi; Erill, Ivan

    2012-02-03

    The SOS response is a well-known regulatory network present in most bacteria and aimed at addressing DNA damage. It has also been linked extensively to stress-induced mutagenesis, virulence and the emergence and dissemination of antibiotic resistance determinants. Recently, the SOS response has been shown to regulate the activity of integrases in the chromosomal superintegrons of the Vibrionaceae, which encompasses a wide range of pathogenic species harboring multiple chromosomes. Here we combine in silico and in vitro techniques to perform a comparative genomics analysis of the SOS regulon in the Vibrionaceae, and we extend the methodology to map this transcriptional network in other bacterial species harboring multiple chromosomes. Our analysis provides the first comprehensive description of the SOS response in a family (Vibrionaceae) that includes major human pathogens. It also identifies several previously unreported members of the SOS transcriptional network, including two proteins of unknown function. The analysis of the SOS response in other bacterial species with multiple chromosomes uncovers additional regulon members and reveals that there is a conserved core of SOS genes, and that specialized additions to this basic network take place in different phylogenetic groups. Our results also indicate that across all groups the main elements of the SOS response are always found in the large chromosome, whereas specialized additions are found in the smaller chromosomes and plasmids. Our findings confirm that the SOS response of the Vibrionaceae is strongly linked with pathogenicity and dissemination of antibiotic resistance, and suggest that the characterization of the newly identified members of this regulon could provide key insights into the pathogenesis of Vibrio. The persistent location of key SOS genes in the large chromosome across several bacterial groups confirms that the SOS response plays an essential role in these organisms and sheds light into the

  18. Variable dead time counters. 1 - theoretical responses and the effects of neutron multiplication

    International Nuclear Information System (INIS)

    Lees, E.W.; Hooton, B.W.

    1978-10-01

    A theoretical expression is derived for calculating the response of any variable dead time counter (VDC) used in the passive assay of plutonium by neutron counting of the natural spontaneous fission activity. The effects of neutron multiplication in the sample arising from interactions of the original spontaneous fission neutrons is shown to modify the linear relationship between VDC signal and Pu mass. Numerical examples are shown for the Euratom VDC and a systematic investigation of the various factors affecting neutron multiplication is reported. Limited comparisons between the calculations and experimental data indicate provisional validity of the calculations. (author)

  19. Robotic Vehicle Proxy Simulation, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Energid Technologies proposes the development of a digital simulation that can replace robotic vehicles in field studies. This proxy simulation will model the...

  20. Extinction produces context inhibition and multiple-context extinction reduces response recovery in human predictive learning.

    Science.gov (United States)

    Glautier, Steven; Elgueta, Tito; Nelson, James Byron

    2013-12-01

    Two experiments with human participants were used to investigate recovery of an extinguished learned response after a context change using ABC designs. In an ABC design, the context changes over the three successive stages of acquisition (context A), extinction (context B), and test (context C). In both experiments, we found reduced recovery in groups that had extinction in multiple contexts, and that the extinction contexts acquired inhibitory strength. These results confirm those of previous investigations, that multiple-context extinction can produce less response recovery than single-context extinction, and they also provide new evidence for the involvement of contextual inhibitory processes in extinction in humans. The foregoing results are broadly in line with a protection-from-extinction account of response recovery. Yet, despite the fact that we detected contextual inhibition, predictions based on protection-from-extinction were not fully reliable for the single- and multiple-context group differences that we observed in (1) rates of extinction and (2) the strength of context inhibition. Thus, although evidence was obtained for a protection-from-extinction account of response recovery, this account can not explain all of the data.

  1. Web proxy auto discovery for the WLCG

    CERN Document Server

    Dykstra, D; Blumenfeld, B; De Salvo, A; Dewhurst, A; Verguilov, V

    2017-01-01

    All four of the LHC experiments depend on web proxies (that is, squids) at each grid site to support software distribution by the CernVM FileSystem (CVMFS). CMS and ATLAS also use web proxies for conditions data distributed through the Frontier Distributed Database caching system. ATLAS & CMS each have their own methods for their grid jobs to find out which web proxies to use for Frontier at each site, and CVMFS has a third method. Those diverse methods limit usability and flexibility, particularly for opportunistic use cases, where an experiment’s jobs are run at sites that do not primarily support that experiment. This paper describes a new Worldwide LHC Computing Grid (WLCG) system for discovering the addresses of web proxies. The system is based on an internet standard called Web Proxy Auto Discovery (WPAD). WPAD is in turn based on another standard called Proxy Auto Configuration (PAC). Both the Frontier and CVMFS clients support this standard. The input into the WLCG system comes from squids regis...

  2. Effects of extinction in multiple contexts on renewal of instrumental responses.

    Science.gov (United States)

    Bernal-Gamboa, Rodolfo; Nieto, Javier; Uengoer, Metin

    2017-09-01

    In two experiments with rats, we investigated the effects of using multiple contexts during extinction on renewal of lever-pressing behavior. During the first phase of both experiments, rats were reinforced to press a lever for food in Context A. Then, responses underwent extinction. For half of the animals, extinction sessions were conducted in a single context, whereas the other half received extinction in three different contexts. In Experiment 1, we observed that extinction in multiple contexts eliminated ABC renewal, but had no detectable impact on ABA renewal. Experiment 2 revealed that conducting extended extinction training in multiple contexts attenuated ABA renewal. Theoretical and clinical implications of the present findings are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Probing of multiple magnetic responses in magnetic inductors using atomic force microscopy.

    Science.gov (United States)

    Park, Seongjae; Seo, Hosung; Seol, Daehee; Yoon, Young-Hwan; Kim, Mi Yang; Kim, Yunseok

    2016-02-08

    Even though nanoscale analysis of magnetic properties is of significant interest, probing methods are relatively less developed compared to the significance of the technique, which has multiple potential applications. Here, we demonstrate an approach for probing various magnetic properties associated with eddy current, coil current and magnetic domains in magnetic inductors using multidimensional magnetic force microscopy (MMFM). The MMFM images provide combined magnetic responses from the three different origins, however, each contribution to the MMFM response can be differentiated through analysis based on the bias dependence of the response. In particular, the bias dependent MMFM images show locally different eddy current behavior with values dependent on the type of materials that comprise the MI. This approach for probing magnetic responses can be further extended to the analysis of local physical features.

  4. Detecting instabilities in tree-ring proxy calibration

    Directory of Open Access Journals (Sweden)

    H. Visser

    2010-06-01

    Full Text Available Evidence has been found for reduced sensitivity of tree growth to temperature in a number of forests at high northern latitudes and alpine locations. Furthermore, at some of these sites, emergent subpopulations of trees show negative growth trends with rising temperature. These findings are typically referred to as the "Divergence Problem" (DP. Given the high relevance of paleoclimatic reconstructions for policy-related studies, it is important for dendrochronologists to address this issue of potential model uncertainties associated with the DP. Here we address this issue by proposing a calibration technique, termed "stochastic response function" (SRF, which allows the presence or absence of any instabilities in growth response of trees (or any other climate proxy to their calibration target to be visualized and detected. Since this framework estimates confidence limits and subsequently provides statistical significance tests, the approach is also very well suited for proxy screening prior to the generation of a climate-reconstruction network.

    Two examples of tree growth/climate relationships are provided, one from the North American Arctic treeline and the other from the upper treeline in the European Alps. Instabilities were found to be present where stabilities were reported in the literature, and vice versa, stabilities were found where instabilities were reported. We advise to apply SRFs in future proxy-screening schemes, next to the use of correlations and RE/CE statistics. It will improve the strength of reconstruction hindcasts.

  5. Generation of synthetic time histories compatible with multiple-damping design response spectra

    International Nuclear Information System (INIS)

    Lilhanand, K.; Tseng, W.S.

    1987-01-01

    Seismic design of nuclear power plants as currently practiced requires time history analyses be performed to generate floor response spectra for seismic qualification of piping, equipment, and components. Since design response spectra are normally prescribed in the form of smooth spectra, the generation of synthetic time histories whose response spectra closely match the ''target'' design spectra of multiple damping values, is often required for the seismic time history analysis purpose. Various methods of generation of synthetic time histories compatible with target response spectra have been proposed in the literature. Since the mathematical problem of determining a time history from a given set of response spectral values is not unique, an exact solution is not possible, and all the proposed methods resort to some forms of approximate solutions. In this paper, a new iteration scheme, is described which effectively removes the difficulties encountered by the existing methods. This new iteration scheme can not only improve the accuracy of spectrum matching for a single-damping target spectrum, but also automate the spectrum matching for multiple-damping target spectra. The applicability and limitations as well as the method adopted to improve the numerical stability of this new iteration scheme are presented. The effectiveness of this new iteration scheme is illustrated by two example applications

  6. Evaluation of proxy-based millennial reconstruction methods

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Terry C.K.; Tsao, Min [University of Victoria, Department of Mathematics and Statistics, Victoria, BC (Canada); Zwiers, Francis W. [Environment Canada, Climate Research Division, Toronto, ON (Canada)

    2008-08-15

    A range of existing statistical approaches for reconstructing historical temperature variations from proxy data are compared using both climate model data and real-world paleoclimate proxy data. We also propose a new method for reconstruction that is based on a state-space time series model and Kalman filter algorithm. The state-space modelling approach and the recently developed RegEM method generally perform better than their competitors when reconstructing interannual variations in Northern Hemispheric mean surface air temperature. On the other hand, a variety of methods are seen to perform well when reconstructing surface air temperature variability on decadal time scales. An advantage of the new method is that it can incorporate additional, non-temperature, information into the reconstruction, such as the estimated response to external forcing, thereby permitting a simultaneous reconstruction and detection analysis as well as future projection. An application of these extensions is also demonstrated in the paper. (orig.)

  7. All of the above: When multiple correct response options enhance the testing effect.

    Science.gov (United States)

    Bishara, Anthony J; Lanzo, Lauren A

    2015-01-01

    Previous research has shown that multiple choice tests often improve memory retention. However, the presence of incorrect lures often attenuates this memory benefit. The current research examined the effects of "all of the above" (AOTA) options. When such options are correct, no incorrect lures are present. In the first three experiments, a correct AOTA option on an initial test led to a larger memory benefit than no test and standard multiple choice test conditions. The benefits of a correct AOTA option occurred even without feedback on the initial test; for both 5-minute and 48-hour retention delays; and for both cued recall and multiple choice final test formats. In the final experiment, an AOTA question led to better memory retention than did a control condition that had identical timing and exposure to response options. However, the benefits relative to this control condition were similar regardless of the type of multiple choice test (AOTA or not). Results suggest that retrieval contributes to multiple choice testing effects. However, the extra testing effect from a correct AOTA option, rather than being due to more retrieval, might be due simply to more exposure to correct information.

  8. Validation and analysis of the coupled multiple response Colorado upper-division electrostatics diagnostic

    Directory of Open Access Journals (Sweden)

    Bethany R. Wilcox

    2015-11-01

    Full Text Available Standardized conceptual assessment represents a widely used tool for educational researchers interested in student learning within the standard undergraduate physics curriculum. For example, these assessments are often used to measure student learning across educational contexts and instructional strategies. However, to support the large-scale implementation often required for cross-institutional testing, it is necessary for these instruments to have question formats that facilitate easy grading. Previously, we created a multiple-response version of an existing, validated, upper-division electrostatics diagnostic with the goal of increasing the instrument’s potential for large-scale implementation. Here, we report on the validity and reliability of this new version as an independent instrument. These findings establish the validity of the multiple-response version as measured by multiple test statistics including item difficulty, item discrimination, and internal consistency. Moreover, we demonstrate that the majority of student responses to the new version are internally consistent even when they are incorrect and provide an example of how the new format can be used to gain insight into student difficulties with specific content in electrostatics.

  9. The relationship between proxy reported health-related quality of life and parental distress: gender differences.

    Science.gov (United States)

    Davis, E; Davies, B; Waters, E; Priest, N

    2008-11-01

    Although primary caregiver proxy reports of health-related quality of life (HRQOL) are often used for healthcare decision making when child self-reports are unable to be collected (because of a variety of reasons such as child illness, disability or age), we have little understanding of the correlates of parent-proxy reports. The aim of this study was to examine the relationship between parental depression and parent-proxy reported QOL for primary caregivers (mothers and fathers), using a multidimensional HRQOL instrument. It was hypothesized that maternal depression would be negatively correlated with maternal reported HRQOL, but that paternal depression would not be correlated with paternal reported HRQOL. Data were from parents of children aged 4-5 years (n = 4983) involved in the Longitudinal Study of Australian Children. A questionnaire assessing parental depression (Kessler-6) and proxy reported HRQOL (Pediatric Quality of Life Inventory) was completed by the primary caregiver. For maternal primary caregivers, maternal depression was negatively correlated with all domains of maternal proxy reports of HRQOL (r = -0.24 to r = -0.36). For paternal primary caregivers, there was no relationship between paternal depression and paternal proxy reports of HRQOL. Multiple regression analyses demonstrated that maternal depression was a significant predictor of total HRQOL, accounting for 12% of the variance. For paternal mental health, depression did not predict parent-proxy reported total HRQOL. These results highlight the importance of assessing maternal mental health when measuring proxy reported QOL. Further research is needed in this area to examine the relationship between parental depression and proxy reported HRQOL (including both mothers and fathers, where possible), as well as child self-reported HRQOL.

  10. Inferring climate variability from skewed proxy records

    Science.gov (United States)

    Emile-Geay, J.; Tingley, M.

    2013-12-01

    Many paleoclimate analyses assume a linear relationship between the proxy and the target climate variable, and that both the climate quantity and the errors follow normal distributions. An ever-increasing number of proxy records, however, are better modeled using distributions that are heavy-tailed, skewed, or otherwise non-normal, on account of the proxies reflecting non-normally distributed climate variables, or having non-linear relationships with a normally distributed climate variable. The analysis of such proxies requires a different set of tools, and this work serves as a cautionary tale on the danger of making conclusions about the underlying climate from applications of classic statistical procedures to heavily skewed proxy records. Inspired by runoff proxies, we consider an idealized proxy characterized by a nonlinear, thresholded relationship with climate, and describe three approaches to using such a record to infer past climate: (i) applying standard methods commonly used in the paleoclimate literature, without considering the non-linearities inherent to the proxy record; (ii) applying a power transform prior to using these standard methods; (iii) constructing a Bayesian model to invert the mechanistic relationship between the climate and the proxy. We find that neglecting the skewness in the proxy leads to erroneous conclusions and often exaggerates changes in climate variability between different time intervals. In contrast, an explicit treatment of the skewness, using either power transforms or a Bayesian inversion of the mechanistic model for the proxy, yields significantly better estimates of past climate variations. We apply these insights in two paleoclimate settings: (1) a classical sedimentary record from Laguna Pallcacocha, Ecuador (Moy et al., 2002). Our results agree with the qualitative aspects of previous analyses of this record, but quantitative departures are evident and hold implications for how such records are interpreted, and

  11. Reliability of Autonomic Responses and Malaise Across Multiple Motion Sickness Stimulation Tests

    Science.gov (United States)

    Stout, Cynthia S.; Toscano, William B.; Cowings, Patricia S.

    1993-01-01

    There is general agreement that a high degree of variability exists between subjects in their autonomic nervous system responses to motion sickness stimulation. Additionally, a paucity of data exists that examines the variability within an individual across repeated motion sickness tests. Investigators have also examined the relationship of autonomic responses to motion sickness development. These investigations have used analyses at discrete points in time to describe this relationship. This approach fails to address the time course of autonomic responses and malaise development throughout the motion sickness test. Our objectives were to examine the reliability of autonomic responses and malaise using the final minute of the motion sickness test across five testing occasions, to examine the reliability of the change in autonomic responses and the change in malaise across five testing occasions, and to examine the relationship between changes in autonomic responses and changes in malaise level across the entire motion sickness test. Our results indicate that, based on the final minute of testing, the autonomic responses of heart rate, blood volume pulse, and respiration rate are moderately stable across multiple tests. Changes in heart rate, blood volume pulse, respiration rate, and malaise throughout the test duration were less stable across the tests. We attribute this instability to variations in individual susceptibility and the error associated with estimating a measure of autonomic gain.

  12. An experimental study of the response of the multiple support piping systems

    International Nuclear Information System (INIS)

    Chiba, T.; Koyanagi, R.

    1987-01-01

    From the test results, following remarks have been obtained. 1. Since the effect of internal pressure was not so small on the stress response, its effect should be considered in the design of piping systems. 2. The effect of the phase of excitations was fairly dominant to the response of piping systems. From this fact, the adopting of the support structures which have different dynamic characteristics may be one of the more realistic approaches to reduce the response of piping systems. 3. The acceleration responses near the support points are always underestimated because the natural modes of the analysis are zero at these support points. 4. If the pseudo-static response is dominant, the stress responses near the support points are always overestimated by the ABS method to support groups. In such case the SRSS method is recommended. 5. The 10% method to the closely spaced modes is conservative for the flexible piping. The closely spaced mode methods to these flexible piping systems should be used carefully. 6. The SRSS combination method is offered the reasonable results to the space, modes and support groups in the multiple response spectra method. (orig.)

  13. Photospheric activity of the Sun with VIRGO and GOLF. Comparison with standard activity proxies

    Science.gov (United States)

    Salabert, D.; García, R. A.; Jiménez, A.; Bertello, L.; Corsaro, E.; Pallé, P. L.

    2017-12-01

    We study the variability of solar activity using new photospheric proxies originally developed for the analysis of stellar magnetism with the CoRoT and Kepler photometric observations. These proxies were obtained by tracking the temporal modulations in the observations associated with the spots and magnetic features as the Sun rotates. We analyzed 21 yr of observations, spanning solar cycles 23 and 24, collected by the space-based photometric VIRGO and radial velocity GOLF instruments on board the SoHO satellite. We then calculated the photospheric activity proxy Sph is for each of the three VIRGO photometers and the associated Svel proxy from the radial velocity GOLF observations. Comparisons with several standard solar activity proxies sensitive to different layers of the Sun demonstrate that these new activity proxies, Sph and Svel, provide a new manner to monitor solar activity. We show that both the long- and short-term magnetic variabilities respectively associated with the 11-yr cycle and the quasi-biennial oscillation are well monitored, and that the magnetic field interaction between the subsurface, photosphere, and chromosphere of the Sun was modified between Cycle 24 and Cycle 23. Furthermore, the photometric proxies show a wavelength dependence of the response function of the solar photosphere among the three channels of the VIRGO photometers, providing inputs for the study of the stellar magnetism of Sun-like stars.

  14. Analysis of the SOS response of Vibrio and other bacteria with multiple chromosomes

    Directory of Open Access Journals (Sweden)

    Sanchez-Alberola Neus

    2012-02-01

    Full Text Available Abstract Background The SOS response is a well-known regulatory network present in most bacteria and aimed at addressing DNA damage. It has also been linked extensively to stress-induced mutagenesis, virulence and the emergence and dissemination of antibiotic resistance determinants. Recently, the SOS response has been shown to regulate the activity of integrases in the chromosomal superintegrons of the Vibrionaceae, which encompasses a wide range of pathogenic species harboring multiple chromosomes. Here we combine in silico and in vitro techniques to perform a comparative genomics analysis of the SOS regulon in the Vibrionaceae, and we extend the methodology to map this transcriptional network in other bacterial species harboring multiple chromosomes. Results Our analysis provides the first comprehensive description of the SOS response in a family (Vibrionaceae that includes major human pathogens. It also identifies several previously unreported members of the SOS transcriptional network, including two proteins of unknown function. The analysis of the SOS response in other bacterial species with multiple chromosomes uncovers additional regulon members and reveals that there is a conserved core of SOS genes, and that specialized additions to this basic network take place in different phylogenetic groups. Our results also indicate that across all groups the main elements of the SOS response are always found in the large chromosome, whereas specialized additions are found in the smaller chromosomes and plasmids. Conclusions Our findings confirm that the SOS response of the Vibrionaceae is strongly linked with pathogenicity and dissemination of antibiotic resistance, and suggest that the characterization of the newly identified members of this regulon could provide key insights into the pathogenesis of Vibrio. The persistent location of key SOS genes in the large chromosome across several bacterial groups confirms that the SOS response plays an

  15. Estimating effects of school quality using multiple proxies

    Czech Academy of Sciences Publication Activity Database

    Bernal, P.; Mittag, Nikolas; Qureshi, J. A.

    2016-01-01

    Roč. 39, April (2016), s. 1-10 ISSN 0927-5371 R&D Projects: GA ČR(CZ) GBP402/12/G130 Institutional support: RVO:67985998 Keywords : school quality * education * skill formation Subject RIV: AH - Economics Impact factor: 1.036, year: 2016

  16. 12 CFR 569.3 - Holders of proxies.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Holders of proxies. 569.3 Section 569.3 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY PROXIES § 569.3 Holders of proxies. No proxy of a mutual savings association with a term greater than eleven months or solicited at...

  17. Water Isotope Proxy-Proxy and Proxy-Model Convergence for Late Pleistocene East Asian Monsoon Rainfall Reconstructions

    Science.gov (United States)

    Clemens, S. C.; Holbourn, A.; Kubota, Y.; Lee, K. E.; Liu, Z.; Chen, G.

    2017-12-01

    Confidence in reconstruction of East Asian paleomonsoon rainfall using precipitation isotope proxies is a matter of considerable debate, largely due to the lack of correlation between precipitation amount and isotopic composition in the present climate. We present four new, very highly resolved records spanning the past 300,000 years ( 200 year sample spacing) from IODP Site U1429 in the East China Sea. We demonstrate that all the orbital- and millennial-scale variance in the onshore Yangtze River Valley speleothem δ18O record1 is also embedded in the offshore Site U1429 seawater δ18O record (derived from the planktonic foraminifer Globigerinoides ruber and sea surface temperature reconstructions). Signal replication in these two independent terrestrial and marine archives, both controlled by the same monsoon system, uniquely identifies δ18O of precipitation as the primary driver of the precession-band variance in both records. This proxy-proxy convergence also eliminates a wide array of other drivers that have been called upon as potential contaminants to the precipitation δ18O signal recorded by these proxies. We compare East Asian precipitation isotope proxy records to precipitation amount from a CCSM3 transient climate model simulation of the past 300,000 years using realistic insolation, ice volume, greenhouse gasses, and sea level boundary conditions. This model-proxy comparison suggests that both Yangtze River Valley precipitation isotope proxies (seawater and speleothem δ18O) track changes in summer-monsoon rainfall amount at orbital time scales, as do precipitation isotope records from the Pearl River Valley2 (leaf wax δ2H) and Borneo3 (speleothem δ18O). Notably, these proxy records all have significantly different spectral structure indicating strongly regional rainfall patterns that are also consistent with model results. Transient, isotope-enabled model simulations will be necessary to more thoroughly evaluate these promising results, and to

  18. Adaptive responses to salinity stress across multiple life stages in anuran amphibians.

    Science.gov (United States)

    Albecker, Molly A; McCoy, Michael W

    2017-01-01

    In many regions, freshwater wetlands are increasing in salinity at rates exceeding historic levels. Some freshwater organisms, like amphibians, may be able to adapt and persist in salt-contaminated wetlands by developing salt tolerance. Yet adaptive responses may be more challenging for organisms with complex life histories, because the same environmental stressor can require responses across different ontogenetic stages. Here we investigated responses to salinity in anuran amphibians: a common, freshwater taxon with a complex life cycle. We conducted a meta-analysis to define how the lethality of saltwater exposure changes across multiple life stages, surveyed wetlands in a coastal region experiencing progressive salinization for the presence of anurans, and used common garden experiments to investigate whether chronic salt exposure alters responses in three sequential life stages (reproductive, egg, and tadpole life stages) in Hyla cinerea , a species repeatedly observed in saline wetlands. Meta-analysis revealed differential vulnerability to salt stress across life stages with the egg stage as the most salt-sensitive. Field surveys revealed that 25% of the species known to occur in the focal region were detected in salt-intruded habitats. Remarkably, Hyla cinerea was found in large abundances in multiple wetlands with salinity concentrations 450% higher than the tadpole-stage LC 50 . Common garden experiments showed that coastal (chronically salt exposed) populations of H. cinerea lay more eggs, have higher hatching success, and greater tadpole survival in higher salinities compared to inland (salt naïve) populations. Collectively, our data suggest that some species of anuran amphibians have divergent and adaptive responses to salt exposure across populations and across different life stages. We propose that anuran amphibians may be a novel and amenable natural model system for empirical explorations of adaptive responses to environmental change.

  19. The e-MSWS-12: improving the multiple sclerosis walking scale using item response theory.

    Science.gov (United States)

    Engelhard, Matthew M; Schmidt, Karen M; Engel, Casey E; Brenton, J Nicholas; Patek, Stephen D; Goldman, Myla D

    2016-12-01

    The Multiple Sclerosis Walking Scale (MSWS-12) is the predominant patient-reported measure of multiple sclerosis (MS) -elated walking ability, yet it had not been analyzed using item response theory (IRT), the emerging standard for patient-reported outcome (PRO) validation. This study aims to reduce MSWS-12 measurement error and facilitate computerized adaptive testing by creating an IRT model of the MSWS-12 and distributing it online. MSWS-12 responses from 284 subjects with MS were collected by mail and used to fit and compare several IRT models. Following model selection and assessment, subpopulations based on age and sex were tested for differential item functioning (DIF). Model comparison favored a one-dimensional graded response model (GRM). This model met fit criteria and explained 87 % of response variance. The performance of each MSWS-12 item was characterized using category response curves (CRCs) and item information. IRT-based MSWS-12 scores correlated with traditional MSWS-12 scores (r = 0.99) and timed 25-foot walk (T25FW) speed (r =  -0.70). Item 2 showed DIF based on age (χ 2  = 19.02, df = 5, p Item 11 showed DIF based on sex (χ 2  = 13.76, df = 5, p = 0.02). MSWS-12 measurement error depends on walking ability, but could be lowered by improving or replacing items with low information or DIF. The e-MSWS-12 includes IRT-based scoring, error checking, and an estimated T25FW derived from MSWS-12 responses. It is available at https://ms-irt.shinyapps.io/e-MSWS-12 .

  20. Predicting hearing thresholds and occupational hearing loss with multiple-frequency auditory steady-state responses.

    Science.gov (United States)

    Hsu, Ruey-Fen; Ho, Chi-Kung; Lu, Sheng-Nan; Chen, Shun-Sheng

    2010-10-01

    An objective investigation is needed to verify the existence and severity of hearing impairments resulting from work-related, noise-induced hearing loss in arbitration of medicolegal aspects. We investigated the accuracy of multiple-frequency auditory steady-state responses (Mf-ASSRs) between subjects with sensorineural hearing loss (SNHL) with and without occupational noise exposure. Cross-sectional study. Tertiary referral medical centre. Pure-tone audiometry and Mf-ASSRs were recorded in 88 subjects (34 patients had occupational noise-induced hearing loss [NIHL], 36 patients had SNHL without noise exposure, and 18 volunteers were normal controls). Inter- and intragroup comparisons were made. A predicting equation was derived using multiple linear regression analysis. ASSRs and pure-tone thresholds (PTTs) showed a strong correlation for all subjects (r = .77 ≈ .94). The relationship is demonstrated by the equationThe differences between the ASSR and PTT were significantly higher for the NIHL group than for the subjects with non-noise-induced SNHL (p tool for objectively evaluating hearing thresholds. Predictive value may be lower in subjects with occupational hearing loss. Regardless of carrier frequencies, the severity of hearing loss affects the steady-state response. Moreover, the ASSR may assist in detecting noise-induced injury of the auditory pathway. A multiple linear regression equation to accurately predict thresholds was shown that takes into consideration all effect factors.

  1. Density dependence governs when population responses to multiple stressors are magnified or mitigated.

    Science.gov (United States)

    Hodgson, Emma E; Essington, Timothy E; Halpern, Benjamin S

    2017-10-01

    Population endangerment typically arises from multiple, potentially interacting anthropogenic stressors. Extensive research has investigated the consequences of multiple stressors on organisms, frequently focusing on individual life stages. Less is known about population-level consequences of exposure to multiple stressors, especially when exposure varies through life. We provide the first theoretical basis for identifying species at risk of magnified effects from multiple stressors across life history. By applying a population modeling framework, we reveal conditions under which population responses from stressors applied to distinct life stages are either magnified (synergistic) or mitigated. We find that magnification or mitigation critically depends on the shape of density dependence, but not the life stage in which it occurs. Stressors are always magnified when density dependence is linear or concave, and magnified or mitigated when it is convex. Using Bayesian numerical methods, we estimated the shape of density dependence for eight species across diverse taxa, finding support for all three shapes. © 2017 by the Ecological Society of America.

  2. Heinrich event 4 characterized by terrestrial proxies in southwestern Europe

    Directory of Open Access Journals (Sweden)

    J. M. López-García

    2013-05-01

    Full Text Available Heinrich event 4 (H4 is well documented in the North Atlantic Ocean as a cooling event that occurred between 39 and 40 Ka. Deep-sea cores around the Iberian Peninsula coastline have been analysed to characterize the H4 event, but there are no data on the terrestrial response to this event. Here we present for the first time an analysis of terrestrial proxies for characterizing the H4 event, using the small-vertebrate assemblage (comprising small mammals, squamates and amphibians from Terrassa Riera dels Canyars, an archaeo-palaeontological deposit located on the seaboard of the northeastern Iberian Peninsula. This assemblage shows that the H4 event is characterized in northeastern Iberia by harsher and drier terrestrial conditions than today. Our results were compared with other proxies such as pollen, charcoal, phytolith, avifauna and large-mammal data available for this site, as well as with the general H4 event fluctuations and with other sites where H4 and the previous and subsequent Heinrich events (H5 and H3 have been detected in the Mediterranean and Atlantic regions of the Iberian Peninsula. We conclude that the terrestrial proxies follow the same patterns as the climatic and environmental conditions detected by the deep-sea cores at the Iberian margins.

  3. MUNCHAUSEN SYNDROME BY PROXY IN PEDIATRIC DENTISTRY: MYTH OR REALITY?

    Directory of Open Access Journals (Sweden)

    Veronica PINTILICIUC-ŞERBAN

    2017-06-01

    Full Text Available Background and aims: Munchausen syndrome by proxy is a condition traditionally comprising physical and mental abuse and medical neglect as a form of psychogenic maltreatment of the child, secondary to fabrication of a pediatric illness by the parent or guardian. The aim of our paper is to assess whether such condition occurs in current pediatric dental practice and to evidence certain situations in which the pediatric dentist should suspect this form of child abuse. Problem statement: Munchausen syndrome by proxy in pediatric dentistry may lead to serious chronic disabilities of the abused or neglected child, being one of the causes of treatment failure. Discussion: Prompt detection of such condition should be regarded as one of the duties of the practitioner who should be trained to report the suspected cases to the governmental child protective agencies. This should be regarded as a form of child abuse and neglect, and the responsible caregiver could be held liable when such wrongful actions cause harm or endanger child’s welfare. Conclusion: Munchausen syndrome by proxy should be regarded as a reality in current pediatric dental practice and dental teams should be trained to properly recognize, assess and manage such complex situations.

  4. Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

    Science.gov (United States)

    Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

    2017-09-01

    Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of

  5. Exogenous ascorbic acid improves defence responses of sunflower (Helianthus annuus) exposed to multiple stresses.

    Science.gov (United States)

    Kaya, Armagan

    2017-09-01

    Ascorbic acid is an important antioxidant that plays role both on growth and development and also stress response of the plant. The purpose of this study was to determine the effect of ascorbate on physiological and biochemical changes of sunflower that was exposed to multiple stresses. Chlorophyll and carotenoid contents decreased and glutathione, ascorbate and malondialdehyde contents as well as antioxidant enzyme activities increased for sunflower plant that was exposed to 50 mM NaCl and pendimethalin at different concentrations. These changes were found to be more significant in groups simultaneously exposed to both stress factors. While malondialdehyde content decreased, chlorophyll, carotenoid, ascorbate, glutathione contents and antioxidant enzyme activities increased in plants treated exogenously with ascorbate, compared to the untreated samples. According to the findings of our study; compared to individual stress, the effect of stress is more pronounced in sunflower exposed to multiple stresses, and treatment with exogenous ascorbate reduces the negative effects of stress.

  6. A frequency domain global parameter estimation method for multiple reference frequency response measurements

    Science.gov (United States)

    Shih, C. Y.; Tsuei, Y. G.; Allemang, R. J.; Brown, D. L.

    1988-10-01

    A method of using the matrix Auto-Regressive Moving Average (ARMA) model in the Laplace domain for multiple-reference global parameter identification is presented. This method is particularly applicable to the area of modal analysis where high modal density exists. The method is also applicable when multiple reference frequency response functions are used to characterise linear systems. In order to facilitate the mathematical solution, the Forsythe orthogonal polynomial is used to reduce the ill-conditioning of the formulated equations and to decouple the normal matrix into two reduced matrix blocks. A Complex Mode Indicator Function (CMIF) is introduced, which can be used to determine the proper order of the rational polynomials.

  7. [Validity and reliability of the spanish EQ-5D-Y proxy version].

    Science.gov (United States)

    Gusi, N; Perez-Sousa, M A; Gozalo-Delgado, M; Olivares, P R

    2014-10-01

    A proxy version of the EQ-5D-Y, a questionnaire to evaluate the Health Related Quality of Life (HRQoL) in children and adolescents, has recently been developed. There are currently no data on the validity and reliability of this tool. The objective of this study was to analyze the validity and reliability of the EQ-5D-Y proxy version. A core set of self-report tools, including the Spanish version of the EQ-5D-Y were administered to a group of Spanish children and adolescents drawn from the general population. A similar core set of internationally standardized proxy tools, including the EQ-5D-Y proxy version were administered to their parents. Test-retest reliability was determined, and correlations with other generic measurements of HRQoL were calculated. Additionally, known group validity was examined by comparing groups with a priori expected differences in HRQoL. The agreement between the self-report and proxy version responses was also calculated. A total of 477 children and adolescents and their parents participated in the study. One week later, 158 participants completed the EQ-5D-Y/EQ-5D-Y proxy to facilitate reliability analysis. Agreement between the test-retest scores was higher than 88% for EQ-5D-Y self-report, and proxy version. Correlations with other health measurements showed similar convergent validity to that observed in the international EQ-5D-Y. Agreement between the self-report and proxy versions ranged from 72.9% to 97.1%. The results provide preliminary evidence of the reliability and validity of the EQ-5D-Y proxy version. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  8. Integration of multiple cues allows threat-sensitive anti-intraguild predator responses in predatory mites

    Science.gov (United States)

    Walzer, Andreas; Schausberger, Peter

    2013-01-01

    Intraguild (IG) prey is commonly confronted with multiple IG predator species. However, the IG predation (IGP) risk for prey is not only dependent on the predator species, but also on inherent (intraspecific) characteristics of a given IG predator such as its life-stage, sex or gravidity and the associated prey needs. Thus, IG prey should have evolved the ability to integrate multiple IG predator cues, which should allow both inter- and intraspecific threat-sensitive anti-predator responses. Using a guild of plant-inhabiting predatory mites sharing spider mites as prey, we evaluated the effects of single and combined cues (eggs and/or chemical traces left by a predator female on the substrate) of the low risk IG predator Neoseiulus californicus and the high risk IG predator Amblyseius andersoni on time, distance and path shape parameters of the larval IG prey Phytoseiulus persimilis. IG prey discriminated between traces of the low and high risk IG predator, with and without additional presence of their eggs, indicating interspecific threat-sensitivity. The behavioural changes were manifest in distance moved, activity and path shape of IG prey. The cue combination of traces and eggs of the IG predators conveyed other information than each cue alone, allowing intraspecific threat-sensitive responses by IG prey apparent in changed velocities and distances moved. We argue that graded responses to single and combined IG predator cues are adaptive due to minimization of acceptance errors in IG prey decision making. PMID:23750040

  9. Optimization of Multiple Responses of Ultrasonic Machining (USM Process: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Rina Chakravorty

    2013-04-01

    Full Text Available Ultrasonic machining (USM process has multiple performance measures, e.g. material removal rate (MRR, tool wear rate (TWR, surface roughness (SR etc., which are affected by several process parameters. The researchers commonly attempted to optimize USM process with respect to individual responses, separately. In the recent past, several systematic procedures for dealing with the multi-response optimization problems have been proposed in the literature. Although most of these methods use complex mathematics or statistics, there are some simple methods, which can be comprehended and implemented by the engineers to optimize the multiple responses of USM processes. However, the relative optimization performance of these approaches is unknown because the effectiveness of different methods has been demonstrated using different sets of process data. In this paper, the computational requirements for four simple methods are presented, and two sets of past experimental data on USM processes are analysed using these methods. The relative performances of these methods are then compared. The results show that weighted signal-to-noise (WSN ratio method and utility theory (UT method usually give better overall optimisation performance for the USM process than the other approaches.

  10. New aspects of the ionospheric response to the October 2003 superstorms from multiple-satellite observations

    Science.gov (United States)

    Lei, Jiuhou; Wang, Wenbin; Burns, Alan G.; Yue, Xinan; Dou, Xiankang; Luan, Xiaoli; Solomon, Stanley C.; Liu, Yong C.-M.

    2014-03-01

    The total electron content (TEC) data measured by the Jason, CHAMP, GRACE, and SAC-C satellites, the in situ electron densities from CHAMP and GRACE, and the vertical E × B drifts from the ROCSAT, have been utilized to examine the ionospheric response to the October 2003 superstorms. The combination of observations from multiple satellites provides a unique global view of ionospheric storm effects, especially over the Pacific Ocean and American regions, which were under sunlit conditions during the main phases of the October 2003 superstorms. The main results of this study are as follows: (1) There were substantial increases in TEC in the daytime at low and middle latitudes during both superstorms. (2) The enhancements were greater during the 30 October superstorm and occurred over a wider range of local times. (3) They also tended to peak at earlier local times during this second event. (4) These TEC enhancement events occurred at the local times when there were enhancements in the upward vertical drift. (5) The strong upward vertical drifts are attributed to penetration electric fields, suggesting that these penetration electric fields played a significant role in the electron density enhancements during these superstorms. Overall, the main contribution of this study is the simultaneous view of the storm time ionospheric response from multiple satellites, and the association of local time differences in ionospheric plasma response with measured vertical drift variations.

  11. Fighting terrorism in Africa by proxy

    DEFF Research Database (Denmark)

    Olsen, Gorm Rye

    2014-01-01

    The French intervention in Mali in early 2013 emphasizes that the decision-makers in Paris, Brussels, and Washington considered the establishment of the radical Islamist regime in Northern Mali a threat to their security interests. The widespread instability including the rise of radical Islamist...... groups in Somalia was perceived as a threat to western interests. It is the core argument of the paper if western powers decide to provide security in Africa, they will be inclined to use proxy instead of deploying own troops. Security provision by proxy in African means that African troops are doing...

  12. Community functional responses to soil and climate at multiple spatial scales: when does intraspecific variation matter?

    Directory of Open Access Journals (Sweden)

    Andrew Siefert

    Full Text Available Despite increasing evidence of the importance of intraspecific trait variation in plant communities, its role in community trait responses to environmental variation, particularly along broad-scale climatic gradients, is poorly understood. We analyzed functional trait variation among early-successional herbaceous plant communities (old fields across a 1200-km latitudinal extent in eastern North America, focusing on four traits: vegetative height, leaf area, specific leaf area (SLA, and leaf dry matter content (LDMC. We determined the contributions of species turnover and intraspecific variation to between-site functional dissimilarity at multiple spatial scales and community trait responses to edaphic and climatic factors. Among-site variation in community mean trait values and community trait responses to the environment were generated by a combination of species turnover and intraspecific variation, with species turnover making a greater contribution for all traits. The relative importance of intraspecific variation decreased with increasing geographic and environmental distance between sites for SLA and leaf area. Intraspecific variation was most important for responses of vegetative height and responses to edaphic compared to climatic factors. Individual species displayed strong trait responses to environmental factors in many cases, but these responses were highly variable among species and did not usually scale up to the community level. These findings provide new insights into the role of intraspecific trait variation in plant communities and the factors controlling its relative importance. The contribution of intraspecific variation to community trait responses was greatest at fine spatial scales and along edaphic gradients, while species turnover dominated at broad spatial scales and along climatic gradients.

  13. Treatment of patients with multiple myeloma over 65 yr: more tolerability or better response?

    Science.gov (United States)

    Tarkun, Pinar; Atalay, Figen; Atesoglu, Elif Birtas; Mehtap, Ozgur; Simsek, Melih; Terzi, Esra; Geduk, Ayfer; Balli, Fatih; Batman, Adnan; Baydemir, Canan; Hacihanefioglu, Abdullah

    2015-05-01

    Two-thirds of newly diagnosed patients with multiple myeloma (MM) are over 65 yr and/or physically unfit. Such patients are not eligible for high-dose chemotherapy or stem cell transplantation. The treatment aims in these patients should be to prolong survival by obtaining the best possible response, while maintaining good tolerability. The aim of our study was to evaluate the response to treatment and treatment-related toxicities in patients treated with conventional and novel protocols. The records of 138 elderly (≥65 yr) patients with MM were retrospectively evaluated. The median overall survival(OS) of the patients was 46 months. The median progression-free survival (PFS) was 18 months. The OS and PFS of the patients treated with the conventional protocols did not differ significantly from those treated with the novel protocols. The statistical analysis of the quality of the response to the treatment with the conventional and novel therapies showed that complete remission (CR), combined with a very good partial response (VGPR), was significantly higher in the latter. However, the toxicities were higher in the novel treatment group. The novel drug protocols significantly increased the quality of the responses of elderly patients with MM to therapy, but they did not increase the patients' tolerability. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. MR Imaging in Monitoring and Predicting Treatment Response in Multiple Sclerosis.

    Science.gov (United States)

    Río, Jordi; Auger, Cristina; Rovira, Àlex

    2017-05-01

    MR imaging is the most sensitive tool for identifying lesions in patients with multiple sclerosis (MS). MR imaging has also acquired an essential role in the detection of complications arising from these treatments and in the assessment and prediction of efficacy. In the future, other radiological measures that have shown prognostic value may be incorporated within the models for predicting treatment response. This article examines the role of MR imaging as a prognostic tool in patients with MS and the recommendations that have been proposed in recent years to monitor patients who are treated with disease-modifying drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Nonlinear response to the multiple sine wave excitation of a softening--hardening system

    International Nuclear Information System (INIS)

    Koplik, B.; Subudhi, M.; Curreri, J.

    1979-01-01

    In studying the earthquake response of the HTGR core, it was observed that the system can display softening--hardening characteristics. This is of great consequence in evaluating the structural safety aspects of the core. In order to obtain a better understanding of the governing parameters, an investigation was undertaken with a single-degree-of-freedom system having a softening--hardening spring characteristic and excited by multiple sine waves. A parametric study varying the input amplitudes and the spring characteristic was performed. Transients were introduced into the system, and the jump phenomena between the lower softening characteristics to the higher hardening curve was studied

  16. Cytokine profiles show heterogeneity of interferon-β response in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Hegen, Harald; Adrianto, Indra; Lessard, Christopher J

    2016-01-01

    OBJECTIVE: To evaluate serum cytokine profiles for their utility to determine the heterogeneous responses to interferon (IFN)-β treatment in patients with multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome receiving de novo IFN-β treatment...... were included in this prospective, observational study. Number of relapses and changes in disability were assessed 2 years prior to and 2 years after initiation of treatment. Sera were collected at baseline and after 3 months on therapy. Cytokine levels in sera were assessed by Luminex multiplex assays...

  17. Multiple Access Interference Reduction Using Received Response Code Sequence for DS-CDMA UWB System

    Science.gov (United States)

    Toh, Keat Beng; Tachikawa, Shin'ichi

    This paper proposes a combination of novel Received Response (RR) sequence at the transmitter and a Matched Filter-RAKE (MF-RAKE) combining scheme receiver system for the Direct Sequence-Code Division Multiple Access Ultra Wideband (DS-CDMA UWB) multipath channel model. This paper also demonstrates the effectiveness of the RR sequence in Multiple Access Interference (MAI) reduction for the DS-CDMA UWB system. It suggests that by using conventional binary code sequence such as the M sequence or the Gold sequence, there is a possibility of generating extra MAI in the UWB system. Therefore, it is quite difficult to collect the energy efficiently although the RAKE reception method is applied at the receiver. The main purpose of the proposed system is to overcome the performance degradation for UWB transmission due to the occurrence of MAI during multiple accessing in the DS-CDMA UWB system. The proposed system improves the system performance by improving the RAKE reception performance using the RR sequence which can reduce the MAI effect significantly. Simulation results verify that significant improvement can be obtained by the proposed system in the UWB multipath channel models.

  18. Munchausen Syndrome by Proxy: A Family Affair.

    Science.gov (United States)

    Mehl, Albert L.; And Others

    1990-01-01

    The article reports on a case of Munchausen syndrome by proxy in which chronic illicit insulin was administered to a one-year-old child by her mother. Factitious illnesses continued despite psychiatric intervention. Retrospective review of medical records suggested 30 previous episodes of factitious illness within the family. (DB)

  19. 78 FR 70987 - Proxy Advisory Firm Roundtable

    Science.gov (United States)

    2013-11-27

    ... Firm Roundtable AGENCY: Securities and Exchange Commission. ACTION: Notice of roundtable discussion... advisory firms. The panel will be asked to discuss topics including the current state of proxy advisory firm use by investment advisers and institutional investors and potential changes that have been...

  20. Munchausen syndrome by proxy: a family anthology.

    Science.gov (United States)

    Pickford, E; Buchanan, N; McLaughlan, S

    1988-06-20

    While the Munchausen-by-proxy syndrome is well recognized, the story of one family has been related to describe some remarkable features. These include the psychopathology of the mother, the involvement of both children in the family, the great difficulty in obtaining proof of child abuse and, finally, the prosecution of the mother in the criminal court.

  1. Impulsive response of an automatic transmission system with multiple clearances: Formulation, simulation and experiment

    Science.gov (United States)

    Crowther, Ashley R.; Singh, Rajendra; Zhang, Nong; Chapman, Chris

    2007-10-01

    Impulsive responses in geared systems with multiple clearances are studied when the mean torque excitation and system load change abruptly, with application to a vehicle driveline with an automatic transmission. First, torsional lumped-mass models of the planetary and differential gear sets are formulated using matrix elements. The model is then reduced to address tractable nonlinear problems while successfully retaining the main modes of interest. Second, numerical simulations for the nonlinear model are performed for transient conditions and a typical driving situation that induces an impulsive behaviour simulated. However, initial conditions and excitation and load profiles have to be carefully defined before the model can be numerically solved. It is shown that the impacts within the planetary or differential gears may occur under combinations of engine, braking and vehicle load transients. Our analysis shows that the shaping of the engine transient by the torque converter before reaching the clearance locations is more critical. Third, a free vibration experiment is developed for an analogous driveline with multiple clearances and three experiments that excite different response regimes have been carried out. Good correlations validate the proposed methodology.

  2. The Climate Response to Stratospheric Aerosol Geoengineering Can Be Tailored Using Multiple Injection Locations

    Energy Technology Data Exchange (ETDEWEB)

    MacMartin, Douglas G. [Mechanical and Aerospace Engineering, Cornell University, Ithaca NY USA; Department of Computing and Mathematical Sciences, California Institute of Technology, Pasadena CA USA; Kravitz, Ben [Atmospheric Sciences and Global Change Division, Pacific Northwest National Laboratory, Richland WA USA; Tilmes, Simone [Atmospheric Chemistry, Observations, and Modeling Laboratory, National Center for Atmospheric Research, Boulder CO USA; Climate and Global Dynamics Laboratory, National Center for Atmospheric Research, Boulder CO USA; Richter, Jadwiga H. [Climate and Global Dynamics Laboratory, National Center for Atmospheric Research, Boulder CO USA; Mills, Michael J. [Atmospheric Chemistry, Observations, and Modeling Laboratory, National Center for Atmospheric Research, Boulder CO USA; Lamarque, Jean-Francois [Atmospheric Chemistry, Observations, and Modeling Laboratory, National Center for Atmospheric Research, Boulder CO USA; Climate and Global Dynamics Laboratory, National Center for Atmospheric Research, Boulder CO USA; Tribbia, Joseph J. [Climate and Global Dynamics Laboratory, National Center for Atmospheric Research, Boulder CO USA; Vitt, Francis [Atmospheric Chemistry, Observations, and Modeling Laboratory, National Center for Atmospheric Research, Boulder CO USA

    2017-12-07

    The climate response to geoengineering with stratospheric aerosols has the potential to be designed to achieve some chosen objectives. By injecting different amounts of SO2 at multiple different latitudes, the spatial pattern of aerosol optical depth (AOD) can be partially controlled. We use simulations from the fully-coupled whole-atmosphere chemistry-climate model CESM1(WACCM), to demonstrate that three spatial degrees of freedom of AOD can be achieved by appropriately combining injection at different locations: an approximately spatially-uniform AOD distribution, the relative difference in AOD between Northern and Southern hemispheres, and the relative AOD in high versus low latitudes. For forcing levels that yield 1–2°C cooling, the AOD and surface temperature response are sufficiently linear in this model so that many climate effects can be predicted from single-latitude injection simulations. Optimized injection at multiple locations is predicted to improve compensation of CO2-forced climate change, relative to a case using only equatorial aerosol injection. The additional degrees of freedom can be used, for example, to balance interhemispheric temperature differences and the equator to pole temperature difference in addition to the global mean temperature; this is projected in this model to reduce the mean-square error in temperature compensation by 30%.

  3. Second and third responses to the same induction regimen in relapsing patients with multiple myeloma.

    Science.gov (United States)

    Paccagnella, A; Chiarion-Sileni, V; Soesan, M; Baggio, G; Bolzonella, S; De Besi, P; Casara, D; Frizzarin, M; Salvagno, L; Favaretto, A

    1991-09-01

    From September 1975 to December 1986, 115 consecutive previously untreated patients with multiple myeloma (MM) were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, melphalan, vincristine, and prednisone (M-2). No patients were excluded or lost during follow-up. Forty-three percent of the patients were Stage I plus II, and 57% were Stage III. Thirty-eight patients (33%) had blood urea nitrogen greater than or equal to 40 mg/dl (substage B). Reaching an objective response treatment was stopped, generally after 1 year, and restarted at relapse. After induction therapy, 94 patients (82%) responded and had a median duration of response (MDR) of 22 months. After first relapse, 26 of 38 patients (69%) responded again to the same regimen and had an MDR of 11 months. This response rate and MDR are significantly lower than the ones achieved in induction chemotherapy. After second relapse, 7 of 16 patients (44%) again responded with an MDR of 3.5 months. The median survival time (MST) was 50.5 months for all patients. The most relevant side effect was leukopenia. No case of secondary leukemia was noticed. The authors conclude that patients with MM can be treated safely without maintenance therapy after reaching remission because a high response rate can be obtained in first and even second relapse. The planned treatment pause at remission does not adversely affect the survival time. Secondary leukemia is infrequent after this policy. Quality of life improves during the treatment pause.

  4. Analyzing Multiple-Choice Questions by Model Analysis and Item Response Curves

    Science.gov (United States)

    Wattanakasiwich, P.; Ananta, S.

    2010-07-01

    In physics education research, the main goal is to improve physics teaching so that most students understand physics conceptually and be able to apply concepts in solving problems. Therefore many multiple-choice instruments were developed to probe students' conceptual understanding in various topics. Two techniques including model analysis and item response curves were used to analyze students' responses from Force and Motion Conceptual Evaluation (FMCE). For this study FMCE data from more than 1000 students at Chiang Mai University were collected over the past three years. With model analysis, we can obtain students' alternative knowledge and the probabilities for students to use such knowledge in a range of equivalent contexts. The model analysis consists of two algorithms—concentration factor and model estimation. This paper only presents results from using the model estimation algorithm to obtain a model plot. The plot helps to identify a class model state whether it is in the misconception region or not. Item response curve (IRC) derived from item response theory is a plot between percentages of students selecting a particular choice versus their total score. Pros and cons of both techniques are compared and discussed.

  5. A statistical-dynamical modeling approach for the simulation of local paleo proxy records using GCM output

    Energy Technology Data Exchange (ETDEWEB)

    Reichert, B.K.; Bengtsson, L. [Max-Planck-Institut fuer Meteorologie, Hamburg (Germany); Aakesson, O. [Sveriges Meteorologiska och Hydrologiska Inst., Norrkoeping (Sweden)

    1998-08-01

    Recent proxy data obtained from ice core measurements, dendrochronology and valley glaciers provide important information on the evolution of the regional or local climate. General circulation models integrated over a long period of time could help to understand the (external and internal) forcing mechanisms of natural climate variability. For a systematic interpretation of in situ paleo proxy records, a combined method of dynamical and statistical modeling is proposed. Local 'paleo records' can be simulated from GCM output by first undertaking a model-consistent statistical downscaling and then using a process-based forward modeling approach to obtain the behavior of valley glaciers and the growth of trees under specific conditions. The simulated records can be compared to actual proxy records in order to investigate whether e.g. the response of glaciers to climatic change can be reproduced by models and to what extent climate variability obtained from proxy records (with the main focus on the last millennium) can be represented. For statistical downscaling to local weather conditions, a multiple linear forward regression model is used. Daily sets of observed weather station data and various large-scale predictors at 7 pressure levels obtained from ECMWF reanalyses are used for development of the model. Daily data give the closest and most robust relationships due to the strong dependence on individual synoptic-scale patterns. For some local variables, the performance of the model can be further increased by developing seasonal specific statistical relationships. The model is validated using both independent and restricted predictor data sets. The model is applied to a long integration of a mixed layer GCM experiment simulating pre-industrial climate variability. The dynamical-statistical local GCM output within a region around Nigardsbreen glacier, Norway is compared to nearby observed station data for the period 1868-1993. Patterns of observed

  6. Cross-species multiple environmental stress responses: An integrated approach to identify candidate genes for multiple stress tolerance in sorghum (Sorghum bicolor (L. Moench and related model species.

    Directory of Open Access Journals (Sweden)

    Adugna Abdi Woldesemayat

    Full Text Available Crop response to the changing climate and unpredictable effects of global warming with adverse conditions such as drought stress has brought concerns about food security to the fore; crop yield loss is a major cause of concern in this regard. Identification of genes with multiple responses across environmental stresses is the genetic foundation that leads to crop adaptation to environmental perturbations.In this paper, we introduce an integrated approach to assess candidate genes for multiple stress responses across-species. The approach combines ontology based semantic data integration with expression profiling, comparative genomics, phylogenomics, functional gene enrichment and gene enrichment network analysis to identify genes associated with plant stress phenotypes. Five different ontologies, viz., Gene Ontology (GO, Trait Ontology (TO, Plant Ontology (PO, Growth Ontology (GRO and Environment Ontology (EO were used to semantically integrate drought related information.Target genes linked to Quantitative Trait Loci (QTLs controlling yield and stress tolerance in sorghum (Sorghum bicolor (L. Moench and closely related species were identified. Based on the enriched GO terms of the biological processes, 1116 sorghum genes with potential responses to 5 different stresses, such as drought (18%, salt (32%, cold (20%, heat (8% and oxidative stress (25% were identified to be over-expressed. Out of 169 sorghum drought responsive QTLs associated genes that were identified based on expression datasets, 56% were shown to have multiple stress responses. On the other hand, out of 168 additional genes that have been evaluated for orthologous pairs, 90% were conserved across species for drought tolerance. Over 50% of identified maize and rice genes were responsive to drought and salt stresses and were co-located within multifunctional QTLs. Among the total identified multi-stress responsive genes, 272 targets were shown to be co-localized within QTLs

  7. Additive effects prevail: The response of biota to multiple stressors in an intensively monitored watershed.

    Science.gov (United States)

    Gieswein, Alexander; Hering, Daniel; Feld, Christian K

    2017-09-01

    Freshwater ecosystems are impacted by a range of stressors arising from diverse human-caused land and water uses. Identifying the relative importance of single stressors and understanding how multiple stressors interact and jointly affect biology is crucial for River Basin Management. This study addressed multiple human-induced stressors and their effects on the aquatic flora and fauna based on data from standard WFD monitoring schemes. For altogether 1095 sites within a mountainous catchment, we used 12 stressor variables covering three different stressor groups: riparian land use, physical habitat quality and nutrient enrichment. Twenty-one biological metrics calculated from taxa lists of three organism groups (fish, benthic invertebrates and aquatic macrophytes) served as response variables. Stressor and response variables were subjected to Boosted Regression Tree (BRT) analysis to identify stressor hierarchy and stressor interactions and subsequently to Generalised Linear Regression Modelling (GLM) to quantify the stressors standardised effect size. Our results show that riverine habitat degradation was the dominant stressor group for the river fauna, notably the bed physical habitat structure. Overall, the explained variation in benthic invertebrate metrics was higher than it was in fish and macrophyte metrics. In particular, general integrative (aggregate) metrics such as % Ephemeroptera, Plecoptera and Trichoptera (EPT) taxa performed better than ecological traits (e.g. % feeding types). Overall, additive stressor effects dominated, while significant and meaningful stressor interactions were generally rare and weak. We concluded that given the type of stressor and ecological response variables addressed in this study, river basin managers do not need to bother much about complex stressor interactions, but can focus on the prevailing stressors according to the hierarchy identified. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. A multi-proxy approach to understanding complex responses of salt-lake catchments to climate variability and human pressure: A Late Quaternary case study from south-eastern, Spain

    Science.gov (United States)

    Jones, Samantha Elsie; Burjachs, Francesc; Ferrer-García, Carlos; Giralt, Santiago; Schulte, Lothar; Fernández-López de Pablo, Javier

    2018-03-01

    This article focuses on a former salt lake in the upper Vinalopó Valley in south-eastern Spain. The study spans the Late Pleistocene through to the Late Holocene, although with particular focus on the period between 11 ka cal BP and 3000 ka cal BP (which spans the Mesolithic and part of the Bronze Age). High resolution multi-proxy analysis (including pollen, non pollen palynomorphs, grain size, X-ray fluorescence and X-ray diffraction) was undertaken on the lake sediments. The results show strong sensitivity to both long term and small changes in the evaporation/precipitation ratio, affecting the surrounding vegetation composition, lake-biota and sediment geochemistry. To summarise the key findings the main general trends identified include: 1) Hyper-saline conditions and low lake levels at the end of the Late Glacial 2) Increasing wetness and temperatures which witnessed an expansion of mesophilic woodland taxa, lake infilling and the establishment of a more perennial lake system at the onset of the Holocene 3) An increase in solar insolation after 9 ka cal BP which saw the re-establishment of pine forests 4) A continued trend towards increasing dryness (climatic optimum) at 7 ka cal BP but with continued freshwater input 5) An increase in sclerophyllous open woody vegetation (anthropogenic?), and increasing wetness (climatic?) is represented in the lake record between 5.9 and 3 ka cal BP 6) The Holocene was also punctuated by several aridity pulses, the most prominent corresponding to the 8.2 ka cal BP event. These events, despite a paucity of well dated archaeological sites in the surrounding area, likely altered the carrying capacity of this area both regionally and locally, particularly during the Mesolithic-Neolithic transition, in terms of fresh water supply for human/animal consumption, wild plant food reserves and suitable land for crop growth.

  9. Spatial linkages between coral proxies of terrestrial runoff across a large embayment in Madagascar

    NARCIS (Netherlands)

    Grove, C.A.; Zinke, J.; Scheufen, T.; Maina, J.; Epping, E.; Boer, W.; Randriamanantsoa, B.; Brummer, G.-J.A.

    2012-01-01

    Coral cores provide vital climate reconstructions for site-specific temporal variability in river flow and sediment load. Yet, their ability to record spatial differences across multiple catchments is relatively unknown. Here, we investigate spatial linkages between four coral proxies of terrestrial

  10. The Proxy Challenge: Why bespoke proxy indicators can help solve the anti-corruption measurement problem

    OpenAIRE

    Johnsøn, Jesper; Mason, Phil

    2013-01-01

    Practitioners working in anti-corruption face perennial challenges in measuring changes in corruption levels and evaluating whether anti-corruption efforts are successful. These two challenges are linked but not inseparable. To make progress on the latter front, that is, evaluating whether anti-corruption efforts are having an impact, the U4 Anti-Corruption Resource Centre and the UK Department for International Development are launching an exploration into the use of proxy indicators. Proxy ...

  11. Multiple Rapid Swallow Responses During Esophageal High-Resolution Manometry Reflect Esophageal Body Peristaltic Reserve

    Science.gov (United States)

    Shaker, Anisa; Stoikes, Nathaniel; Drapekin, Jesse; Kushnir, Vladimir; Brunt, L. Michael; Gyawali, C. Prakash

    2014-01-01

    OBJECTIVES Dysphagia may develop following antireflux surgery as a consequence of poor esophageal peristaltic reserve. We hypothesized that suboptimal contraction response following multiple rapid swallows (MRS) could be associated with chronic transit symptoms following antireflux surgery. METHODS Wet swallow and MRS responses on esophageal high-resolution manometry (HRM) were characterized collectively in the esophageal body (distal contractile integral (DCI)), and individually in each smooth muscle contraction segment (S2 and S3 amplitudes) in 63 patients undergoing antireflux surgery and in 18 healthy controls. Dysphagia was assessed using symptom questionnaires. The MRS/wet swallow ratios were calculated for S2 and S3 peak amplitudes and DCI. MRS responses were compared in patients with and without late postoperative dysphagia following antireflux surgery. RESULTS Augmentation of smooth muscle contraction (MRS/wet swallow ratios > 1.0) as measured collectively by DCI was seen in only 11.1% with late postoperative dysphagia, compared with 63.6% in those with no dysphagia and 78.1% in controls (P≤0.02 for each comparison). Similar results were seen with S3 but not S2 peak amplitude ratios. Receiver operating characteristics identified a DCI MRS/wet swallow ratio threshold of 0.85 in segregating patients with late postoperative dysphagia from those with no postoperative dysphagia with a sensitivity of 0.67 and specificity of 0.64. CONCLUSIONS Lack of augmentation of smooth muscle contraction following MRS is associated with late postoperative dysphagia following antireflux surgery, suggesting that MRS responses could assess esophageal smooth muscle peristaltic reserve. Further research is warranted to determine if antireflux surgery needs to be tailored to the MRS response. PMID:24019081

  12. Properties of a novel linear sulfur response mode in a multiple flame photometric detector.

    Science.gov (United States)

    Clark, Adrian G; Thurbide, Kevin B

    2014-01-24

    A new linear sulfur response mode was established in the multiple flame photometric detector (mFPD) by monitoring HSO* emission in the red spectral region above 600nm. Optimal conditions for this mode were found by using a 750nm interference filter and oxygen flows to the worker flames of this device that were about 10mL/min larger than those used for monitoring quadratic S2* emission. By employing these parameters, this mode provided a linear response over about 4 orders of magnitude, with a detection limit near 5.8×10(-11)gS/s and a selectivity of sulfur over carbon of about 3.5×10(3). Specifically, the minimum detectable masses for 10 different sulfur analytes investigated ranged from 0.4 to 3.6ng for peak half-widths spanning 4-6s. The response toward ten different sulfur compounds was examined and produced an average reproducibility of 1.7% RSD (n=10) and an average equimolarity value of 1.0±0.1. In contrast to this, a conventional single flame S2* mode comparatively yielded respective values of 6.7% RSD (n=10) and 1.1±0.4. HSO* emission in the mFPD was also found to be relatively much less affected by response quenching due to hydrocarbons compared to a conventional single flame S2* emission mode. Results indicate that this new alternative linear mFPD response mode could be beneficial for sulfur monitoring applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. System Identification Based Proxy Model of a Reservoir under Water Injection

    Directory of Open Access Journals (Sweden)

    Berihun M. Negash

    2017-01-01

    Full Text Available Simulation of numerical reservoir models with thousands and millions of grid blocks may consume a significant amount of time and effort, even when high performance processors are used. In cases where the simulation runs are required for sensitivity analysis, dynamic control, and optimization, the act needs to be repeated several times by continuously changing parameters. This makes it even more time-consuming. Currently, proxy models that are based on response surface are being used to lessen the time required for running simulations during sensitivity analysis and optimization. Proxy models are lighter mathematical models that run faster and perform in place of heavier models that require large computations. Nevertheless, to acquire data for modeling and validation and develop the proxy model itself, hundreds of simulation runs are required. In this paper, a system identification based proxy model that requires only a single simulation run and a properly designed excitation signal was proposed and evaluated using a benchmark case study. The results show that, with proper design of excitation signal and proper selection of model structure, system identification based proxy models are found to be practical and efficient alternatives for mimicking the performance of numerical reservoir models. The resulting proxy models have potential applications for dynamic well control and optimization.

  14. Neurofilament light antibodies in serum reflect response to natalizumab treatment in multiple sclerosis.

    Science.gov (United States)

    Amor, Sandra; van der Star, Baukje J; Bosca, Isabel; Raffel, Joel; Gnanapavan, Sharmilee; Watchorn, Jonathan; Kuhle, Jens; Giovannoni, Gavin; Baker, David; Malaspina, Andrea; Puentes, Fabiola

    2014-09-01

    Increased levels of antibodies to neurofilament light protein (NF-L) in biological fluids have been found to reflect neuroinflammatory responses and neurodegeneration in multiple sclerosis (MS). To evaluate whether levels of serum antibodies against NF-L correlate with clinical variants and treatment response in MS. The autoantibody reactivity to NF-L protein was tested in serum samples from patients with relapsing-remitting MS (RRMS) (n=22) and secondary progressive MS (SPMS) (n=26). Two other cohorts of RRMS patients under treatment with natalizumab were analysed cross-sectionally (n=16) and longitudinally (n=24). The follow-up samples were taken at 6, 12, 18 and 24 months after treatment, and the NF-L antibody levels were compared against baseline levels. NF-L antibodies were higher in MS clinical groups than healthy controls and in RRMS compared to SPMS patients (ptreatment compared with baseline measurements (p=0.001). Drug efficacy in MS treatment indicates the potential use of monitoring the content of antibodies against the NF-L chain as a predictive biomarker of treatment response in MS. © The Author(s) 2014.

  15. Genetic and demographic responses of mosquitofish (Gambusia holbrooki) populations exposed to mercury for multiple generations

    Energy Technology Data Exchange (ETDEWEB)

    Tatara, C.P.; Mulvey, M.; Newman, M.C.

    1999-12-01

    Genetic and demographic responses of mosquitofish were examined after multiple generations of exposure to mercury. Previous studies of acute lethal exposures of mosquitofish to either mercury or arsenic demonstrated a consistent correlation between time to death and genotype at the glucosephosphate isomerase-2 (Gpi-2) locus. A mesocosm study involving mosquitofish populations exposed to mercury for 111 d showed significant female sexual selection and fecundity selection at the Gpi-2 locus. Here the mesocosm study was extended to populations exposed to mercury for several (approx. four) generations. After 2 years, control and mercury-exposed populations met Hardy-Weinberg expectations and showed no evidence of genetic bottlenecks. The mean number of heterozygous loci did not differ significantly between the mercury-exposed and control populations. Significant differences in allele frequencies at the Gpi-2 locus were observed between the mercury-exposed and control populations. Relative to the initial and control allele frequencies, the GPI-2{sup 100} allele frequency was lower, the Gpi-2{sup 66} allele frequency increased, but the Gpi-2{sup 38} allele frequency did not change in mercury-exposed populations. No significant differences were found in standard length, weight, sex ratio, or age class ratio between the control and mercury-exposed populations. Allele frequency changes at the Gpi-2 locus suggest population-level response to chronic mercury exposure. Changes in allele frequency may be useful as indicators of population response to contaminants, provided that the population in question is well understood.

  16. Inactivating UBE2M impacts the DNA damage response and genome integrity involving multiple cullin ligases.

    Directory of Open Access Journals (Sweden)

    Scott Cukras

    Full Text Available Protein neddylation is involved in a wide variety of cellular processes. Here we show that the DNA damage response is perturbed in cells inactivated with an E2 Nedd8 conjugating enzyme UBE2M, measured by RAD51 foci formation kinetics and cell based DNA repair assays. UBE2M knockdown increases DNA breakages and cellular sensitivity to DNA damaging agents, further suggesting heightened genomic instability and defective DNA repair activity. Investigating the downstream Cullin targets of UBE2M revealed that silencing of Cullin 1, 2, and 4 ligases incurred significant DNA damage. In particular, UBE2M knockdown, or defective neddylation of Cullin 2, leads to a blockade in the G1 to S progression and is associated with delayed S-phase dependent DNA damage response. Cullin 4 inactivation leads to an aberrantly high DNA damage response that is associated with increased DNA breakages and sensitivity of cells to DNA damaging agents, suggesting a DNA repair defect is associated. siRNA interrogation of key Cullin substrates show that CDT1, p21, and Claspin are involved in elevated DNA damage in the UBE2M knockdown cells. Therefore, UBE2M is required to maintain genome integrity by activating multiple Cullin ligases throughout the cell cycle.

  17. Inactivating UBE2M impacts the DNA damage response and genome integrity involving multiple cullin ligases.

    Science.gov (United States)

    Cukras, Scott; Morffy, Nicholas; Ohn, Takbum; Kee, Younghoon

    2014-01-01

    Protein neddylation is involved in a wide variety of cellular processes. Here we show that the DNA damage response is perturbed in cells inactivated with an E2 Nedd8 conjugating enzyme UBE2M, measured by RAD51 foci formation kinetics and cell based DNA repair assays. UBE2M knockdown increases DNA breakages and cellular sensitivity to DNA damaging agents, further suggesting heightened genomic instability and defective DNA repair activity. Investigating the downstream Cullin targets of UBE2M revealed that silencing of Cullin 1, 2, and 4 ligases incurred significant DNA damage. In particular, UBE2M knockdown, or defective neddylation of Cullin 2, leads to a blockade in the G1 to S progression and is associated with delayed S-phase dependent DNA damage response. Cullin 4 inactivation leads to an aberrantly high DNA damage response that is associated with increased DNA breakages and sensitivity of cells to DNA damaging agents, suggesting a DNA repair defect is associated. siRNA interrogation of key Cullin substrates show that CDT1, p21, and Claspin are involved in elevated DNA damage in the UBE2M knockdown cells. Therefore, UBE2M is required to maintain genome integrity by activating multiple Cullin ligases throughout the cell cycle.

  18. Interactions between SNPs affecting inflammatory response genes are associated with multiple myeloma disease risk and survival

    DEFF Research Database (Denmark)

    Nielsen, Kaspar René; Rodrigo-Domingo, Maria; Steffensen, Rudi

    2017-01-01

    The origin of multiple myeloma depends on interactions with stromal cells in the course of normal B-cell differentiation and evolution of immunity. The concept of the present study is that genes involved in MM pathogenesis, such as immune response genes, can be identified by screening for single......3L1 gene promoters. The occurrence of single polymorphisms, haplotypes and SNP-SNP interactions were statistically analyzed for association with disease risk and outcome following high-dose therapy. Identified genes that carried SNPs or haplotypes that were identified as risk or prognostic factors......= .005). The 'risk genes' were analyzed for expression in normal B-cell subsets (N = 6) from seven healthy donors and we found TNFA and IL-6 expressed both in naïve and in memory B cells when compared to preBI, II, immature and plasma cells. The 'prognosis genes' CHI3L1, IL-6 and IL-10 were differential...

  19. Time dependent response of low velocity impact induced composite conical shells under multiple delamination

    Science.gov (United States)

    Dey, Sudip; Karmakar, Amit

    2014-02-01

    This paper presents the time dependent response of multiple delaminated angle-ply composite pretwisted conical shells subjected to low velocity normal impact. The finite element formulation is based on Mindlin's theory incorporating rotary inertia and effects of transverse shear deformation. An eight-noded isoparametric plate bending element is employed to satisfy the compatibility of deformation and equilibrium of resultant forces and moments at the delamination crack front. A multipoint constraint algorithm is incorporated which leads to asymmetric stiffness matrices. The modified Hertzian contact law which accounts for permanent indentation is utilized to compute the contact force, and the time dependent equations are solved by Newmark's time integration algorithm. Parametric studies are conducted with respect to triggering parameters like laminate configuration, location of delamination, angle of twist, velocity of impactor, and impactor's displacement for centrally impacted shells.

  20. Magnetospheric Response Associated With Multiple Atmospheric Reflections of Precipitated Electrons in Aurora.

    Science.gov (United States)

    Khazanov, G. V.; Merkin, V. G.; Zesta, E.; Sibeck, D. G.; Grubbs, G. A., II; Chu, M.; Wiltberger, M. J.

    2017-12-01

    The magnetosphere and ionosphere are strongly coupled by precipitating electrons during storm times. Therefore, first principle simulations of precipitating electron fluxes are required to understand storm time variations of ionospheric conductances and related electric fields. As has been discussed by Khazanov et al. [2015 - 2017], the first step in such simulations is initiation of electron precipitation from the Earth's plasma sheet via wave particle interaction processes into both magnetically conjugate points, and the step 2 is the follow up of multiple atmospheric reflections of electron fluxes formed at the boundary between the ionosphere and magnetosphere of two magnetically conjugate points. To demonstrate this effect on the global magnetospheric response the Lyon-Fedder-Mobarry global magnetosphere model coupled with the Rice Convection Model of the inner magnetosphere has been used and run for the geomagnetic storm of 17 March 2013.

  1. Multiple system responses program: Identification of concerns related to a number of specific regulatory issues

    International Nuclear Information System (INIS)

    Murphy, G.A.; Casada, M.L.; Palko, L.E.; Roberts, M.W.

    1989-10-01

    This document describes the activities and results of the Multiple System Responses (MSR) program conducted by the Nuclear Operations Analysis Center (NOAC) at Oak Ridge National Laboratory (ORNL). The objective of the MSR program was to gather and review documentation for several unresolved safety issues and related programs of interest, and from that documentation, describe any additional potential safety concerns. The MSR program provides information that will aid the NRC staff in making an assessment of the relative safety significance of the concerns through the established prioritization process. Judgments were not made regarding the validity of the concerns expressed by others. Rather, the concerns were documented and potential safety issues were developed and defined as specifically as possible. Twenty-one potential safety issues were developed from the documented concerns. Additional information was gathered to support the NRC efforts in reviewing these issues for prioritization. 73 refs., 2 tabs

  2. Gender effects on treatment response to interferon-beta in multiple sclerosis

    DEFF Research Database (Denmark)

    Magyari, M; Koch-Henriksen, N; Laursen, B

    2014-01-01

    BACKGROUND: Gender appears to play a role in incidence and disease course of multiple sclerosis (MS). OBJECTIVE: The objective was to determine whether male and female patients with MS respond differently to interferon-beta treatment in terms of reduction in relapse rates. METHODS: We included all....... Patients served as their own controls, and relapse rates were compared between NAb-negative and NAb-positive periods. RESULTS: NAbs significantly abrogated the interferon-beta treatment efficacy in both genders. The all-over women:men relapse rate ratio irrespective of NAb status was 1.47 (95%CI; 1.......28-1.68). In a generalized linear Poisson models analysis with relapse counts as response variable, the main effects NAbs, sex, age at treatment start and number of relapses in 2 years before treatment start were strongly significant, but the effect of NAbs on relapse rates did not differ significantly between men and women...

  3. Global temperature response to the major volcanic eruptions in multiple reanalysis data sets

    Directory of Open Access Journals (Sweden)

    M. Fujiwara

    2015-12-01

    Full Text Available The global temperature responses to the eruptions of Mount Agung in 1963, El Chichón in 1982, and Mount Pinatubo in 1991 are investigated using nine currently available reanalysis data sets (JRA-55, MERRA, ERA-Interim, NCEP-CFSR, JRA-25, ERA-40, NCEP-1, NCEP-2, and 20CR. Multiple linear regression is applied to the zonal and monthly mean time series of temperature for two periods, 1979–2009 (for eight reanalysis data sets and 1958–2001 (for four reanalysis data sets, by considering explanatory factors of seasonal harmonics, linear trends, Quasi-Biennial Oscillation, solar cycle, and El Niño Southern Oscillation. The residuals are used to define the volcanic signals for the three eruptions separately, and common and different responses among the older and newer reanalysis data sets are highlighted for each eruption. In response to the Mount Pinatubo eruption, most reanalysis data sets show strong warming signals (up to 2–3 K for 1-year average in the tropical lower stratosphere and weak cooling signals (down to −1 K in the subtropical upper troposphere. For the El Chichón eruption, warming signals in the tropical lower stratosphere are somewhat smaller than those for the Mount Pinatubo eruption. The response to the Mount Agung eruption is asymmetric about the equator with strong warming in the Southern Hemisphere midlatitude upper troposphere to lower stratosphere. Comparison of the results from several different reanalysis data sets confirms the atmospheric temperature response to these major eruptions qualitatively, but also shows quantitative differences even among the most recent reanalysis data sets. The consistencies and differences among different reanalysis data sets provide a measure of the confidence and uncertainty in our current understanding of the volcanic response. The results of this intercomparison study may be useful for validation of climate model responses to volcanic forcing and for assessing proposed

  4. PROXY-BASED PATCHING STREAM TRANSMISSION STRATEGY IN MOBILE STREAMING MEDIA SYSTEM

    Institute of Scientific and Technical Information of China (English)

    Liao Jianxin; Lei Zhengxiong; Ma Xutao; Zhu Xiaomin

    2006-01-01

    A mobile transmission strategy, PMPatching (Proxy-based Mobile Patching) transmission strategy is proposed, it applies to the proxy-based mobile streaming media system in Wideband Code Division Multiple Access (WCDMA) network. Performance of the whole system can be improved by using patching stream to transmit anterior part of the suffix that had been played back, and by batching all the demands for the suffix arrived in prefix period and patching stream transmission threshold period. Experimental results show that this strategy can efficiently reduce average network transmission cost and number of channels consumed in central streaming media server.

  5. Multiple Sclerosis Patients with Markedly Low Intrathecal Antibody Response in Sri Lanka

    Directory of Open Access Journals (Sweden)

    S. M. K. Gamage

    2018-01-01

    Full Text Available Multiple sclerosis (MS is a heterogeneous disease which is poorly studied in Asia, where the disease is known to be rare with significant differences in clinical and radiological presentations and intrathecal antibody response. Therefore the objective of this study was to determine clinical presentation, radiological and neurophysiological characteristics, and oligoclonal band status in Sri Lankan MS patients, following careful exclusion of patients with neuromyelitis optica spectrum disorders and other conditions mimicking multiple sclerosis. Sixty-nine MS patients were recruited to the study adhering to McDonald 2010 criteria. Their clinical presentation, characteristics of central nervous system lesions in magnetic resonance imaging, visual evoked potential (VEP results, oligoclonal bands (OCB, and AQP4 antibody status were studied. Of 69 MS patients, 54%, 6%, and 1% were relapsing remitting, secondary progressive, and primary progressive, respectively, and 39% were patients with clinically isolated syndrome. The commonest clinical presentations were cerebral motor followed by cerebral sensory and optic neuritis. Majority had typical periventricular and infratentorial lesions in MRI. Though not clinically apparent, bilateral delay of P100 wave latency was present in 52%. OCB positivity was 42% and AQP4 antibody was positive in only one patient. In conclusion, this group of Sri Lankan MS patients shares most of the clinical and radiological features of Caucasian MS patients. However, the OCB positivity is lower in this group, when compared to the Caucasian MS populations.

  6. A Scalable proxy cache for Grid Data Access

    International Nuclear Information System (INIS)

    Cristian Cirstea, Traian; Just Keijser, Jan; Arthur Koeroo, Oscar; Starink, Ronald; Alan Templon, Jeffrey

    2012-01-01

    We describe a prototype grid proxy cache system developed at Nikhef, motivated by a desire to construct the first building block of a future https-based Content Delivery Network for grid infrastructures. Two goals drove the project: firstly to provide a “native view” of the grid for desktop-type users, and secondly to improve performance for physics-analysis type use cases, where multiple passes are made over the same set of data (residing on the grid). We further constrained the design by requiring that the system should be made of standard components wherever possible. The prototype that emerged from this exercise is a horizontally-scalable, cooperating system of web server / cache nodes, fronted by a customized webDAV server. The webDAV server is custom only in the sense that it supports http redirects (providing horizontal scaling) and that the authentication module has, as back end, a proxy delegation chain that can be used by the cache nodes to retrieve files from the grid. The prototype was deployed at Nikhef and tested at a scale of several terabytes of data and approximately one hundred fast cores of computing. Both small and large files were tested, in a number of scenarios, and with various numbers of cache nodes, in order to understand the scaling properties of the system. For properly-dimensioned cache-node hardware, the system showed speedup of several integer factors for the analysis-type use cases. These results and others are presented and discussed.

  7. Analysis of Brassica oleracea early stage abiotic stress responses reveals tolerance in multiple crop types and for multiple sources of stress.

    Science.gov (United States)

    Beacham, Andrew M; Hand, Paul; Pink, David Ac; Monaghan, James M

    2017-12-01

    Brassica oleracea includes a number of important crop types such as cabbage, cauliflower, broccoli and kale. Current climate conditions and weather patterns are causing significant losses in these crops, meaning that new cultivars with improved tolerance of one or more abiotic stress types must be sought. In this study, genetically fixed B. oleracea lines belonging to a Diversity Fixed Foundation Set (DFFS) were assayed for their response to seedling stage-imposed drought, flood, salinity, heat and cold stress. Significant (P ≤ 0.05) variation in stress tolerance response was found for each stress, for each of four measured variables (relative fresh weight, relative dry weight, relative leaf number and relative plant height). Lines tolerant to multiple stresses were found to belong to several different crop types. There was no overall correlation between the responses to the different stresses. Abiotic stress tolerance was identified in multiple B. oleracea crop types, with some lines exhibiting resistance to multiple stresses. For each stress, no one crop type appeared significantly more or less tolerant than others. The results are promising for the development of more environmentally robust lines of different B. oleracea crops by identifying tolerant material and highlighting the relationship between responses to different stresses. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  8. Legal requirements governing proxy voting in Denmark

    DEFF Research Database (Denmark)

    Werlauff, Erik

    2008-01-01

    The requirements in Danish company law concerning proxy voting in companies whose shares have been accepted for listing on a regulated market have been successively tightened in recent years, and corporate governance principles have also led to the introduction of several requirements concerning...... proxy holders. A thorough knowledge of these requirements is important not only for the listed companies but also for their advisers and investors in Denmark and abroad. This article considers these requirements as well as the additional requirements which will derive from Directive 2007....../36 on the exercise of shareholders' rights in listed companies, which must be implemented by 3 August 2009. It is pointed out that companies may provide with advantage in their articles of association for both the existing and the forthcoming requirements at this early stage....

  9. Response variability of different anodal transcranial direct current stimulation intensities across multiple sessions.

    Science.gov (United States)

    Ammann, Claudia; Lindquist, Martin A; Celnik, Pablo A

    It is well known that transcranial direct current stimulation (tDCS) is capable of modulating corticomotor excitability. However, a source of growing concern has been the observed inter- and intra-individual variability of tDCS-responses. Recent studies have assessed whether individuals respond in a predictable manner across repeated sessions of anodal tDCS (atDCS). The findings of these investigations have been inconsistent, and their methods have some limitations (i.e. lack of sham condition or testing only one tDCS intensity). To study inter- and intra-individual variability of atDCS effects at two different intensities on primary motor cortex (M1) excitability. Twelve subjects participated in a crossover study testing 7-min atDCS over M1 in three separate conditions (2 mA, 1 mA, sham) each repeated three times separated by 48 h. Motor evoked potentials were recorded before and after stimulation (up to 30min). Time of testing was maintained consistent within participants. To estimate the reliability of tDCS effects across sessions, we calculated the Intra-class Correlation Coefficient (ICC). AtDCS at 2 mA, but not 1 mA, significantly increased cortical excitability at the group level in all sessions. The overall ICC revealed fair to high reliability of tDCS effects for multiple sessions. Given that the distribution of responses showed important variability in the sham condition, we established a Sham Variability-Based Threshold to classify responses and to track individual changes across sessions. Using this threshold an intra-individual consistent response pattern was then observed only for the 2 mA condition. 2 mA anodal tDCS results in consistent intra- and inter-individual increases of M1 excitability. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Leaf movement, photosynthesis and resource use efficiency responses to multiple environmental stress in Glycine max (soybean)

    International Nuclear Information System (INIS)

    Rosa, L.M.G.

    1993-01-01

    Increases in the concentration of greenhouse gases in the atmosphere, may cause a significant increase in temperature, with implications for general wind patterns and precipitation. Reductions in stratospheric ozone will result in increased levels of UV-B reaching earth's surface. During their lifetime plants must deal with a variety of co-occurring environmental stresses. Accordingly, studies into plant responses to multiple environmental factors is important to our understanding of limits to their growth, productivity, and distribution. Heliotropic leaf movements are a generalized plant response to environmental stresses, and the pattern of these movements can be altered by resource availability (e.g., water, and nitrogen). Previous greenhouse and field studies have demonstrated damaging effects of UV-B radiation in crop species, including soybean. Documented in this paper are Leaf movement and gas exchange responses of four soybean cultivars with different sensitivity to UV-B radiation to enhanced levels of UV-B, and modifications of these responses caused by water stress and nitrogen fertilization. UV-B radiation had no effect on the patterns of leaf orientation in soybean; however, a ranking of the cultivars based on midday leaf angles was the same as the ranking of these cultivars based on their sensitivity to UV-B radiation. Water and nitrogen altered the leaf movement patterns of soybeans. Gas exchange parameters in all four cultivars responded in a similar fashion to changes in leaf water potential. Reductions in water availability resulted in lower discrimination. Nitrogen fertilization in cv Forrest, also resulted in lower discrimination, especially under low water regimes, indicating a higher water use efficiency for fertilized plants. UV-B radiation resulted in lower discrimination in the UV-B sensitive CNS cultivar, indicating a stronger stomatal limitation to photosynthesis under increased UV-B levels

  11. Harvard Law School Proxy Access Roundtable

    OpenAIRE

    Bebchuk, Lucian Arye; Hirst, Scott

    2010-01-01

    This paper contains the proceedings of the Proxy Access Roundtable that was held by the Harvard Law School Program on Corporate Governance on October 7, 2009. The Roundtable brought together prominent participants in the debate - representing a range of perspectives and experiences - for a day of discussion on the subject. The day’s first two sessions focused on the question of whether the Securities and Exchange Commission should provide an access regime, or whether it should leave the adopt...

  12. Munchausen syndrome by proxy and child's rights

    International Nuclear Information System (INIS)

    Al-Haidar, Fatima A.

    2008-01-01

    Munchausen syndrome by proxy (MSBP) is an extreme form of child abuse in which perpetrators induce life-threatening conditions in their children. A case of MSBP is described in detail. Difficulties in diagnosis and management in this part of the world are presented. Until now, no national legal guidelines exist in the Kingdom of Saudi Arabia (KSA) to child abuse in general and MSBP in particular. Urgent guidelines, policies and legal system are required in the KSA. (author)

  13. Forecasting Lightning Threat Using WRF Proxy Fields

    Science.gov (United States)

    McCaul, E. W., Jr.

    2010-01-01

    Objectives: Given that high-resolution WRF forecasts can capture the character of convective outbreaks, we seek to: 1. Create WRF forecasts of LTG threat (1-24 h), based on 2 proxy fields from explicitly simulated convection: - graupel flux near -15 C (captures LTG time variability) - vertically integrated ice (captures LTG threat area). 2. Calibrate each threat to yield accurate quantitative peak flash rate densities. 3. Also evaluate threats for areal coverage, time variability. 4. Blend threats to optimize results. 5. Examine sensitivity to model mesh, microphysics. Methods: 1. Use high-resolution 2-km WRF simulations to prognose convection for a diverse series of selected case studies. 2. Evaluate graupel fluxes; vertically integrated ice (VII). 3. Calibrate WRF LTG proxies using peak total LTG flash rate densities from NALMA; relationships look linear, with regression line passing through origin. 4. Truncate low threat values to make threat areal coverage match NALMA flash extent density obs. 5. Blend proxies to achieve optimal performance 6. Study CAPS 4-km ensembles to evaluate sensitivities.

  14. Detailed assessment of gene activation levels by multiple hypoxia-responsive elements under various hypoxic conditions.

    Science.gov (United States)

    Takeuchi, Yasuto; Inubushi, Masayuki; Jin, Yong-Nan; Murai, Chika; Tsuji, Atsushi B; Hata, Hironobu; Kitagawa, Yoshimasa; Saga, Tsuneo

    2014-12-01

    HIF-1/HRE pathway is a promising target for the imaging and the treatment of intractable malignancy (HIF-1; hypoxia-inducible factor 1, HRE; hypoxia-responsive element). The purposes of our study are: (1) to assess the gene activation levels resulting from various numbers of HREs under various hypoxic conditions, (2) to evaluate the bidirectional activity of multiple HREs, and (3) to confirm whether multiple HREs can induce gene expression in vivo. Human colon carcinoma HCT116 cells were transiently transfected by the constructs containing a firefly luciferase reporter gene and various numbers (2, 4, 6, 8, 10, and 12) of HREs (nHRE+, nHRE-). The relative luciferase activities were measured under various durations of hypoxia (6, 12, 18, and 24 h), O2 concentrations (1, 2, 4, 8, and 16 %), and various concentrations of deferoxamine mesylate (20, 40, 80, 160, and 320 µg/mL growth medium). The bidirectional gene activation levels by HREs were examined in the constructs (dual-luc-nHREs) containing firefly and Renilla luciferase reporter genes at each side of nHREs. Finally, to test whether the construct containing 12HRE and the NIS reporter gene (12HRE-NIS) can induce gene expression in vivo, SPECT imaging was performed in a mouse xenograft model. (1) gene activation levels by HREs tended to increase with increasing HRE copy number, but a saturation effect was observed in constructs with more than 6 or 8 copies of an HRE, (2) gene activation levels by HREs increased remarkably during 6-12 h of hypoxia, but not beyond 12 h, (3) gene activation levels by HREs decreased with increasing O2 concentrations, but could be detected even under mild hypoxia at 16 % O2, (4) the bidirectionally proportional activity of the HRE was confirmed regardless of the hypoxic severity, and (5) NIS expression driven by 12 tandem copies of an HRE in response to hypoxia could be visualized on in vivo SPECT imaging. The results of this study will help in the understanding and assessment of

  15. Spatial linkages between coral proxies of terrestrial runoff across a large embayment in Madagascar

    Directory of Open Access Journals (Sweden)

    C. A. Grove

    2012-08-01

    Full Text Available Coral cores provide vital climate reconstructions for site-specific temporal variability in river flow and sediment load. Yet, their ability to record spatial differences across multiple catchments is relatively unknown. Here, we investigate spatial linkages between four coral proxies of terrestrial runoff and their relationships between sites. Coral cores were drilled in and around Antongil Bay, the largest bay in Madagascar, and individually analysed for fifteen years of continuous luminescence (G / B, Ba / Ca, δ18Osw and δ13C data. Each coral core was drilled close to individual river mouths (≥ 7 km, and proxy data were compared to modelled river discharge and sediment runoff data for the three corresponding catchments. A reasonable agreement between terrestrial runoff proxies with modelled river discharge and sediment yield was observed. Some inconsistencies between proxy and modelled data are likely linked to proxy behaviour, watershed size and local environmental physiochemical parameters. In general, the further a coral resided from its river source, the weaker the proxy relationship was with modelled data and other corals, due to mixing gradients and currents. Nevertheless, we demonstrate that two coral Ba / Ca and luminescence (G / B records influenced by the same watershed are reproducible. Furthermore, a strong Ba / Ca relationship was observed between two cores from distant watersheds, with baseline averages in agreement with modelled sediment runoff data. As humic acids behave conservatively in the water column, luminescence (G / B data gave the highest regional correlations between cores, and showed the most consistent relationship with site specific modelled discharge. No statistical relationship was observed between cores in terms of interannual δ18Osw and δ13C, meaning corals were recording a localised signal at their respective sites, confounded by vital

  16. Dendritic cell, monocyte and T cell activation and response to glatiramer acetate in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Hesse, D; Limborg, S

    2012-01-01

    , monocytes and dendritic cells (DC) in relation to disease activity in MS patients treated with GA. Methods: Flow cytometry was used to study the activation of CD4+ T cells and T cell subsets (CD25high and CD26high cells), monocytes and DCs in a cross-sectional study of 39 untreated and 29 GA-treated MS......Background: Treatment with glatiramer acetate (GA) modestly decreases disease activity in multiple sclerosis (MS). The mechanism of action is incompletely understood and differences in the response to treatment between individuals may exist. Objective: To study the activation of CD4+ T cells...... (Bonferroni-corrected p=0.0005). The hazard ratio of relapse was 1.32 (95% confidence interval 1.05–1.64) per 1% increase in CD40+ DCs. Patients treated with GA had fewer CD4+ T cells expressing surface markers associated with T helper type 1 effector responses and more CD4+ T cells expressing surface markers...

  17. [Response and prognosis of patients with multiple myeloma induced by PAD/TAD].

    Science.gov (United States)

    Zeng, Tianmei; He, Haiyan; Shi, Haotian; Xi, Hao; Du, Juan; Zhang, Chunyang; Jiang, Hua; Fu, Weijun; Zhou, Fan; Hou, Jian

    2015-03-17

    To evaluate the impact of cytogenetic grouping and autologous stem cell transplantation on the prognosis of patients with multiple myeloma (MM) induced by PAD (velcade+epirubicin+dexamethasone) and TAD (thalidomide+epirubicin+dexamethasone). A total of 191 patients with a definite diagnosis of MM were enrolled from May 2008 to December 2013 into this prospective study. They were non-randomly induced by PAD (n = 132) or TAD (n = 59) plus autologous stem cell transplantation or chemotherapy. Response and survival rates were also analyzed between two groups. The overall response rates of PAD and TAD groups were 84.4% (108/128) and 69.5% (41/59) (P = 0.011) respectively. The very good partial remission (VGPR) rates were 70.3% (90/128) and 32.2% (19/59) (P TAD. After PAD induction, cytogenetic grouping may further distinguish the prognosis of MM patients. For FISH high-risk patients, their PFS is prolonged by autologous stem cell transplantation.

  18. Foraminifera Models to Interrogate Ostensible Proxy-Model Discrepancies During Late Pliocene

    Science.gov (United States)

    Jacobs, P.; Dowsett, H. J.; de Mutsert, K.

    2017-12-01

    Planktic foraminifera faunal assemblages have been used in the reconstruction of past oceanic states (e.g. the Last Glacial Maximum, the mid-Piacenzian Warm Period). However these reconstruction efforts have typically relied on inverse modeling using transfer functions or the modern analog technique, which by design seek to translate foraminifera into one or two target oceanic variables, primarily sea surface temperature (SST). These reconstructed SST data have then been used to test the performance of climate models, and discrepancies have been attributed to shortcomings in climate model processes and/or boundary conditions. More recently forward proxy models or proxy system models have been used to leverage the multivariate nature of proxy relationships to their environment, and to "bring models into proxy space". Here we construct ecological models of key planktic foraminifera taxa, calibrated and validated with World Ocean Atlas (WO13) oceanographic data. Multiple modeling methods (e.g. multilayer perceptron neural networks, Mahalanobis distance, logistic regression, and maximum entropy) are investigated to ensure robust results. The resulting models are then driven by a Late Pliocene climate model simulation with biogeochemical as well as temperature variables. Similarities and differences with previous model-proxy comparisons (e.g. PlioMIP) are discussed.

  19. Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials.

    Science.gov (United States)

    Lahuerta, Juan-Jose; Paiva, Bruno; Vidriales, Maria-Belen; Cordón, Lourdes; Cedena, Maria-Teresa; Puig, Noemi; Martinez-Lopez, Joaquin; Rosiñol, Laura; Gutierrez, Norma C; Martín-Ramos, María-Luisa; Oriol, Albert; Teruel, Ana-Isabel; Echeveste, María-Asunción; de Paz, Raquel; de Arriba, Felipe; Hernandez, Miguel T; Palomera, Luis; Martinez, Rafael; Martin, Alejandro; Alegre, Adrian; De la Rubia, Javier; Orfao, Alberto; Mateos, María-Victoria; Blade, Joan; San-Miguel, Jesus F

    2017-09-01

    Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with MM and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of "operational cure" was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients

  20. Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways.

    OpenAIRE

    Segars, J H; Marks, M S; Hirschfeld, S; Driggers, P H; Martinez, E; Grippo, J F; Brown, M; Wahli, W; Ozato, K

    1993-01-01

    The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene d...

  1. Analysis of the Multiple-Solution Response of a Flexible Rotor Supported on Non-Linear Squeeze Film Dampers

    Science.gov (United States)

    ZHU, C. S.; ROBB, D. A.; EWINS, D. J.

    2002-05-01

    The multiple-solution response of rotors supported on squeeze film dampers is a typical non-linear phenomenon. The behaviour of the multiple-solution response in a flexible rotor supported on two identical squeeze film dampers with centralizing springs is studied by three methods: synchronous circular centred-orbit motion solution, numerical integration method and slow acceleration method using the assumption of a short bearing and cavitated oil film; the differences of computational results obtained by the three different methods are compared in this paper. It is shown that there are three basic forms for the multiple-solution response in the flexible rotor system supported on the squeeze film dampers, which are the resonant, isolated bifurcation and swallowtail bifurcation multiple solutions. In the multiple-solution speed regions, the rotor motion may be subsynchronous, super-subsynchronous, almost-periodic and even chaotic, besides synchronous circular centred, even if the gravity effect is not considered. The assumption of synchronous circular centred-orbit motion for the journal and rotor around the static deflection line can be used only in some special cases; the steady state numerical integration method is very useful, but time consuming. Using the slow acceleration method, not only can the multiple-solution speed regions be detected, but also the non-synchronous response regions.

  2. 350 Year Cloud Reconstruction Deduced from Northeast Caribbean Coral Proxies

    Science.gov (United States)

    Winter, A.; Sammarco, P. W.; Mikolajewicz, U.; Jury, M.; Zanchettin, D.

    2014-12-01

    Clouds are a major factor influencing the global climate and its response to external forcing through their implications for the global hydrological cycle, and hence for the planetary radiative budget. Clouds also contribute to regional climates and their variability through, e.g., the changes they induce in regional precipitation patterns. There have been very few studies of decadal and longer-term changes in cloud cover in the tropics and sub-tropics, both over land and the ocean. In the tropics, there is great uncertainty regarding how global warming will affect cloud cover. Observational satellite data are too short to unambiguously discern any temporal trends in cloud cover. Corals generally live in well-mixed coastal regions and can often record environmental conditions of large areas of the upper ocean. This is particularly the case at low latitudes. Scleractinian corals are sessile, epibenthic fauna, and the type of environmental information recorded at the location where the coral has been living is dependent upon the species of coral considered and proxy index of interest. Skeletons of scleractinian corals are considered to provide among the best records of high-resolution (sub-annual) environmental variability in the tropical and sub-tropical oceans. Zooxanthellate hermatypic corals in tropical and sub-tropical seas precipitate CaCO3 skeletons as they grow. This growth is made possible through the manufacture of CaCO3crystals, facilitated by the zooxanthellae. During the process of crystallization, the holobiont binds carbon of different isotopes into the crystals. Stable carbon isotope concentrations vary with a variety of environmental conditions. In the Caribbean, d13C in corals of the species Montastraea faveolata can be used as a proxy for changes in cloud cover. In this contribution, we will demonstrate that the stable isotope 13C varies concomitantly with cloud cover for the northeastern Caribbean region. Using this proxy we have been able to

  3. USE OF MULTIPLE RESPONSE QUESTIONS (MRQS DURING LECTURE SESSIONS AS A TOOL TO ENHANCE LEARNING

    Directory of Open Access Journals (Sweden)

    Rosh

    2015-12-01

    Full Text Available INTRODUCTION Lecture classes are time tested solid method of teaching and have lot of advantages and few disadvantages. The main drawback is its unidirectional monotonous nature and many a time students fail to concentrate and understand especially when the sessions are long, and from the students’ point of view, many are boring too. Lecture sessions are still continued because of its various advantages. There are many methods tried to improve efficacy and effectiveness of lecture sessions including reinforcement, questions and discussions. There are many studies incorporating multiple choice questions (MCQs in lecture sessions for this purpose, with positive results. These sessions evoke creative thinking and enhance learning. For this purpose MCQs are to be prepared with care considering the areas to be covered. In order to make lecture classes more impressive, interesting and effective, we tried introducing a short multiple response session in between, along with some rewards for correct responses in terms of study materials. AIMS AND OBJECTIVES To study the impact of incorporation of MRQs during theory sessions to enhance the efficacy of teaching- learning process MATERIAL AND METHODS Study was conducted in a private medical college in Calicut. We surveyed 169 MBBS students initially with questionnaire covering various aspects of a lecture classes in general. For the next 6 months we incorporated MRQs in routine theory classes. Survey was then conducted again on the same group using same questionnaire and the results were compared. Scores were given according to performance, a maximum of 5 per question. RESULTS After 6 months the data showed substantial improvement in the understanding pattern of students. The average score regarding the usefulness increased from 3.57 to 3.91. After the intervention a substantial number agreed that the sessions have become more interesting, the score changed from 2.99 to 3.87. This also increased the

  4. Response of secondary production and its components to multiple stressors in nematode field populations.

    NARCIS (Netherlands)

    Doroszuk, A.; Brake, te E.; Crespo-Gonzalez, D.; Kammenga, J.E.

    2007-01-01

    Realistic measures of the impact of individual or multiple stressors are important for ecological risk assessment. Although multiple anthropogenic stressors are common in human-dominated environments, knowledge of their influence on functional population parameters such as secondary production (P)

  5. Simulation of Wake Vortex Radiometric Detection via Jet Exhaust Proxy

    Science.gov (United States)

    Daniels, Taumi S.

    2015-01-01

    This paper describes an analysis of the potential of an airborne hyperspectral imaging IR instrument to infer wake vortices via turbine jet exhaust as a proxy. The goal was to determine the requirements for an imaging spectrometer or radiometer to effectively detect the exhaust plume, and by inference, the location of the wake vortices. The effort examines the gas spectroscopy of the various major constituents of turbine jet exhaust and their contributions to the modeled detectable radiance. Initially, a theoretical analysis of wake vortex proxy detection by thermal radiation was realized in a series of simulations. The first stage used the SLAB plume model to simulate turbine jet exhaust plume characteristics, including exhaust gas transport dynamics and concentrations. The second stage used these plume characteristics as input to the Line By Line Radiative Transfer Model (LBLRTM) to simulate responses from both an imaging IR hyperspectral spectrometer or radiometer. These numerical simulations generated thermal imagery that was compared with previously reported wake vortex temperature data. This research is a continuation of an effort to specify the requirements for an imaging IR spectrometer or radiometer to make wake vortex measurements. Results of the two-stage simulation will be reported, including instrument specifications for wake vortex thermal detection. These results will be compared with previously reported results for IR imaging spectrometer performance.

  6. Proxy Graph: Visual Quality Metrics of Big Graph Sampling.

    Science.gov (United States)

    Nguyen, Quan Hoang; Hong, Seok-Hee; Eades, Peter; Meidiana, Amyra

    2017-06-01

    Data sampling has been extensively studied for large scale graph mining. Many analyses and tasks become more efficient when performed on graph samples of much smaller size. The use of proxy objects is common in software engineering for analysis and interaction with heavy objects or systems. In this paper, we coin the term 'proxy graph' and empirically investigate how well a proxy graph visualization can represent a big graph. Our investigation focuses on proxy graphs obtained by sampling; this is one of the most common proxy approaches. Despite the plethora of data sampling studies, this is the first evaluation of sampling in the context of graph visualization. For an objective evaluation, we propose a new family of quality metrics for visual quality of proxy graphs. Our experiments cover popular sampling techniques. Our experimental results lead to guidelines for using sampling-based proxy graphs in visualization.

  7. The role of proxy information in missing data analysis.

    Science.gov (United States)

    Huang, Rong; Liang, Yuanyuan; Carrière, K C

    2005-10-01

    This article investigates the role of proxy data in dealing with the common problem of missing data in clinical trials using repeated measures designs. In an effort to avoid the missing data situation, some proxy information can be gathered. The question is how to treat proxy information, that is, is it always better to utilize proxy information when there are missing data? A model for repeated measures data with missing values is considered and a strategy for utilizing proxy information is developed. Then, simulations are used to compare the power of a test using proxy to simply utilizing all available data. It is concluded that using proxy information can be a useful alternative when such information is available. The implications for various clinical designs are also considered and a data collection strategy for efficiently estimating parameters is suggested.

  8. Proxy decision making and dementia: Using Construal Level Theory to analyse the thoughts of decision makers.

    Science.gov (United States)

    Convey, Helen; Holt, Janet; Summers, Barbara

    2018-03-08

    This study explored the feasibility of using Construal Level Theory to analyse proxy decision maker thinking about a hypothetical ethical dilemma, relating to a person who has dementia. Proxy decision makers make decisions on behalf of individuals who are living with dementia when dementia affects that individual's decision making ability. Ethical dilemmas arise because there is a need to balance the individual's past and contemporary values and views. Understanding of how proxy decision makers respond is incomplete. Construal Level Theory contends that individuals imagine reactions and make predications about the future by crossing psychological distance. This involves abstract thinking, giving meaning to decisions. There is no empirical evidence of Construal Level Theory being used to analyse proxy decision maker thinking. Exploring the feasibility of using Construal Level Theory to understand dementia carer thinking regarding proxy decisions may provide insights which inform the support given. Descriptive qualitative research with semi-structured interviews. Seven participants were interviewed using a hypothetical dementia care scenario in February 2016. Interview transcripts were analysed for themes. Construal Level Theory was applied to analyse participant responses within themes using the Linguistic Category Model. Participants travelled across psychological distance, using abstract thinking to clarify goals and provide a basis for decisions. When thinking concretely participants established boundaries regarding the ethical dilemma. Construal Level Theory gives insight into proxy decision maker thinking and the levels of abstraction used. Understanding what dementia carers think about when making proxy decisions may help nurses to understand their perspectives and to provide appropriate support. © 2018 John Wiley & Sons Ltd.

  9. Coaching Ourselves to Perform Multiplicity and Advocacy: A Response to Stephens and Mills

    Science.gov (United States)

    Cahnmann-Taylor, Melisa

    2014-01-01

    Cahnmann-Taylor draws on Boalian Theatre of the Oppressed to offer a practice for literacy teachers and coaches that can open up multiple perspectives and multiple levels of intentions and motivations for a teacher's decision making. She challenges coaches and teachers to engage in artistic examinations of multiplicity to move toward performing…

  10. New camera-based microswitch technology to monitor small head and mouth responses of children with multiple disabilities.

    Science.gov (United States)

    Lancioni, Giulio E; Bellini, Domenico; Oliva, Doretta; Singh, Nirbhay N; O'Reilly, Mark F; Green, Vanessa A; Furniss, Fred

    2014-06-01

    Assessing a new camera-based microswitch technology, which did not require the use of color marks on the participants' face. Two children with extensive multiple disabilities participated. The responses selected for them consisted of small, lateral head movements and mouth closing or opening. The intervention was carried out according to a multiple probe design across responses. The technology involved a computer with a CPU using a 2-GHz clock, a USB video camera with a 16-mm lens, a USB cable connecting the camera and the computer, and a special software program written in ISO C++ language. The new technology was satisfactorily used with both children. Large increases in their responding were observed during the intervention periods (i.e. when the responses were followed by preferred stimulation). The new technology may be an important resource for persons with multiple disabilities and minimal motor behavior.

  11. The response of mouse skin to multiple small doses of radiation

    International Nuclear Information System (INIS)

    Denekamp, J.; Harris, S.R.

    1975-01-01

    The response of mouse skin has been tested by irradiating the foot of albino mice and scoring erythema and desquamation during the following month. Multiple small doses of 150, 250 and 350 rad have been given 'daily', and the test dose necessary to achieve a given reaction has been determined one day after the last small fraction. This test dose has been compared with the single dose necessary to produce the same reaction level in previously untreated mice, in order to determine the ratio of the slopes of the dose-response curve at low and high doses: Slope ratio = (single dose - test dose)/total fractionated priming dose. In three separate experiments the slope ratio decreased as the dose per fraction was reduced from 350 to 150 rad. This conflicts with the data of Dutreix et al, who found a constant slope ratio over this dose range. The present data are compared with those obtained by Denekamp using 4, 9 and 14 fractions of 300 rad and by Douglas et al, using the same experimental technique, over the dose range 45 to 200 rad/fraction. In addition, the results from multifraction experiments in which equal dose increments were administered until the requisite skin reaction was achieved are also analysed in terms of their slope ratio (Fowler et al. Douglas et al). When all these results are plotted it is impossible to be sure whether the slope ratio is decreasing over the range 300 to 45 rad per fraction, although it seems likely. Most of the values at low doses lie in the range 0.15 to 0.25, indicating that at low doses the radiation is only 15 to 25% as effective per rad in causing cell death as at higher doses. (author)

  12. Nonlinear dynamic response of whole pool multiple spent fuel racks subject to three-dimensional excitations

    International Nuclear Information System (INIS)

    Zhao, Y.; Wilson, P.R.; Stevenson, J.D.

    1995-01-01

    The seismic evaluation of submerged free standing spent fuel storage racks is more complicated than most other nuclear structural systems. When subjected to three dimensional (3-D) floor seismic excitations the dynamic responses of racks in a pool are hydro dynamically coupled with each other, with the fuel assemblies water in gaps. The motion behavior of the racks is significantly different from that observed using a 3D single rack mode. Few seismic analyses using 3-D whole pool multiple rack models are available in the literature. I this paper an analysis was performed for twelve racks using potential theory for the fluid-structure interaction, and using a 3-D whole pool multi-rack finite element model developed herein. The analysis includes the potential nonlinear dynamic behavior of the impact of fuel-rack, rack-rack and rack-pool wall, the tilting or uplift and the frictional sliding of rack supports, and the impact of the rack supports to the pool floor. (author). 12 refs., 7 figs., 1 tab

  13. mEBT: multiple-matching Evidence-based Translator of Murine Genomic Responses for Human Immunity Studies.

    Science.gov (United States)

    Tae, Donghyun; Seok, Junhee

    2018-05-29

    In this paper, we introduce multiple-matching Evidence-based Translator (mEBT) to discover genomic responses from murine expression data for human immune studies, which are significant in the given condition of mice and likely have similar responses in the corresponding condition of human. mEBT is evaluated over multiple data sets and shows improved inter-species agreement. mEBT is expected to be useful for research groups who use murine models to study human immunity. http://cdal.korea.ac.kr/mebt/. jseok14@korea.ac.kr. Supplementary data are available at Bioinformatics online.

  14. RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines

    International Nuclear Information System (INIS)

    Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M.; Pritzker, Laura B.; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

    2016-01-01

    Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced “RNA disruption” is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3’-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues

  15. Response to dexamethasone is glucose-sensitive in multiple myeloma cell lines

    Directory of Open Access Journals (Sweden)

    Turturro Francesco

    2011-09-01

    Full Text Available Abstract Background Hyperglycemia is among the major side effects of dexamethasone (DEX. Glucose or glucocorticoid (GC regulates the expression of thioredoxin-interacting protein (TXNIP that controls the production of reactive oxygen species (ROS through the modulation of thioredoxin (TRX activity. Methods Multiple myeloma (MM cells were grown in 5 or 20 mM/L glucose with or without 25 μM DEX. Semiquantitative reverse transcription-PCR (RT-PCR was used to assess TXNIP RNA expression in response to glucose and DEX. ROS were detected by 5-6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H2DCFDA. TRX activity was assayed by the insulin disulfide-reducing assay. Proliferation was evaluated using CellTiter96 reagent with 490-nm absorbtion and used to calculate the DEX IC50 in 20 mM/L glucose using the Chou's dose effect equation. Results TXNIP RNA level responded to glucose or DEX with the same order of magnitude ARH77 > NCIH929 > U266B1 in these cells. MC/CAR cells were resistant to the regulation. ROS level increased concurrently with reduced TRX activity. Surprisingly glucose increased TRX activity in MC/CAR cells keeping ROS level low. DEX and glucose were lacking the expected additive effect on TXNIP RNA regulation when used concurrently in sensitive cells. ROS level was significantly lower when DEX was used in conditions of hyperglycemia in ARH77/NCIH9292 cells but not in U266B1 cells. Dex-IC50 increased 10-fold when the dose response effect of DEX was evaluated with glucose in ARH && and MC/Car cells Conclusions Our study shows for the first time that glucose or DEX regulates important components of ROS production through TXNIP modulation or direct interference with TRX activity in MM cells. We show that glucose modulates the activity of DEX through ROS regualtion in MM cells. A better understanding of these pathways may help in improving the efficacy and reducing the toxicity of DEX, a drug still highly used in the treatment of

  16. RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines.

    Science.gov (United States)

    Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M; Pritzker, Laura B; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

    2016-02-24

    Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced "RNA disruption" is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3'-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is

  17. Community Response to Multiple Sound Sources: Integrating Acoustic and Contextual Approaches in the Analysis

    Directory of Open Access Journals (Sweden)

    Peter Lercher

    2017-06-01

    Full Text Available Sufficient data refer to the relevant prevalence of sound exposure by mixed traffic sources in many nations. Furthermore, consideration of the potential effects of combined sound exposure is required in legal procedures such as environmental health impact assessments. Nevertheless, current practice still uses single exposure response functions. It is silently assumed that those standard exposure-response curves accommodate also for mixed exposures—although some evidence from experimental and field studies casts doubt on this practice. The ALPNAP-study population (N = 1641 shows sufficient subgroups with combinations of rail-highway, highway-main road and rail-highway-main road sound exposure. In this paper we apply a few suggested approaches of the literature to investigate exposure-response curves and its major determinants in the case of exposure to multiple traffic sources. Highly/moderate annoyance and full scale mean annoyance served as outcome. The results show several limitations of the current approaches. Even facing the inherent methodological limitations (energy equivalent summation of sound, rating of overall annoyance the consideration of main contextual factors jointly occurring with the sources (such as vibration, air pollution or coping activities and judgments of the wider area soundscape increases the variance explanation from up to 8% (bivariate, up to 15% (base adjustments up to 55% (full contextual model. The added predictors vary significantly, depending on the source combination. (e.g., significant vibration effects with main road/railway, not highway. Although no significant interactions were found, the observed additive effects are of public health importance. Especially in the case of a three source exposure situation the overall annoyance is already high at lower levels and the contribution of the acoustic indicators is small compared with the non-acoustic and contextual predictors. Noise mapping needs to go down to

  18. Completeness and utility of interview data from proxy respondents in prenatal care research in rural China.

    Science.gov (United States)

    Nwaru, Bright I; Klemetti, Reija; Yuan, Shen; Kun, Huang; Wang, Yang; Hemminki, Elina

    2012-05-01

    In household surveys, the use of data provided by relatives can increase response rates and generalisability of research findings. This study assessed the quality of data from relatives and the impact of the data source on the association between the use of prenatal care and pregnancy outcomes. Data for 3,673 new mothers and 293 proxy respondents were available from a house-hold survey in 2008-2009 in rural China. Analyses were performed using chi-square test, ANOVA, Kruskal-Wallis test, and logistic regression models. Differences in the studied variables were small, but proxy respondents were slightly more likely to have missing data than the new mothers. Differences and missing data were more common for the use of prenatal care and outcome variables (mode of delivery, place of delivery, birth weight, use of postnatal care, and gestational age at birth) than for the background characteristics of the participants. Husbands' reports were closer to the index reports than that of the other proxies. The associations between the exposures and outcomes were mostly similar between the proxy and index respondents. Relatives can be interviewed instead of women to study prenatal care without a substantial negative impact on study results. Studies using proxy respondents should stratify the analysis by type of respondents.

  19. Multiscale combination of climate model simulations and proxy records over the last millennium

    Science.gov (United States)

    Chen, Xin; Xing, Pei; Luo, Yong; Nie, Suping; Zhao, Zongci; Huang, Jianbin; Tian, Qinhua

    2018-05-01

    To highlight the compatibility of climate model simulation and proxy reconstruction at different timescales, a timescale separation merging method combining proxy records and climate model simulations is presented. Annual mean surface temperature anomalies for the last millennium (851-2005 AD) at various scales over the land of the Northern Hemisphere were reconstructed with 2° × 2° spatial resolution, using an optimal interpolation (OI) algorithm. All target series were decomposed using an ensemble empirical mode decomposition method followed by power spectral analysis. Four typical components were obtained at inter-annual, decadal, multidecadal, and centennial timescales. A total of 323 temperature-sensitive proxy chronologies were incorporated after screening for each component. By scaling the proxy components using variance matching and applying a localized OI algorithm to all four components point by point, we obtained merged surface temperatures. Independent validation indicates that the most significant improvement was for components at the inter-annual scale, but this became less evident with increasing timescales. In mid-latitude land areas, 10-30% of grids were significantly corrected at the inter-annual scale. By assimilating the proxy records, the merged results reduced the gap in response to volcanic forcing between a pure reconstruction and simulation. Difficulty remained in verifying the centennial information and quantifying corresponding uncertainties, so additional effort should be devoted to this aspect in future research.

  20. Multiple linear B-cell epitopes of classical swine fever virus glycoprotein E2 expressed in E.coli as multiple epitope vaccine induces a protective immune response

    Directory of Open Access Journals (Sweden)

    Wei Jian-Chao

    2011-07-01

    Full Text Available Abstract Classical swine fever is a highly contagious disease of swine caused by classical swine fever virus, an OIE list A pathogen. Epitope-based vaccines is one of the current focuses in the development of new vaccines against classical swine fever virus (CSFV. Two B-cell linear epitopes rE2-ba from the E2 glycoprotein of CSFV, rE2-a (CFRREKPFPHRMDCVTTTVENED, aa844-865 and rE2-b (CKEDYRYAISSTNEIGLLGAGGLT, aa693-716, were constructed and heterologously expressed in Escherichia coli as multiple epitope vaccine. Fifteen 6-week-old specified-pathogen-free (SPF piglets were intramuscularly immunized with epitopes twice at 2-week intervals. All epitope-vaccinated pigs could mount an anamnestic response after booster vaccination with neutralizing antibody titers ranging from 1:16 to 1:256. At this time, the pigs were subjected to challenge infection with a dose of 1 × 106 TCID50 virulent CSFV strain. After challenge infection, all of the rE2-ba-immunized pigs were alive and without symptoms or signs of CSF. In contrast, the control pigs continuously exhibited signs of CSF and had to be euthanized because of severe clinical symptoms at 5 days post challenge infection. The data from in vivo experiments shown that the multiple epitope rE2-ba shown a greater protection (similar to that of HCLV vaccine than that of mono-epitope peptide(rE2-a or rE2-b. Therefore, The results demonstrated that this multiple epitope peptide expressed in a prokaryotic system can be used as a potential DIVA (differentiating infected from vaccinated animals vaccine. The E.coli-expressed E2 multiple B-cell linear epitopes retains correct immunogenicity and is able to induce a protective immune response against CSFV infection.

  1. Role of inflammation gene polymorphisms on pain and response to radiotherapy in multiple myeloma patients with painful bone destructions

    OpenAIRE

    Rudžianskienė, Milda; Inčiūra, Arturas; Gerbutavičius, Rolandas; Dambrauskienė, Rūta; Rudžianskas, Viktoras; Juozaitytė, Elona

    2016-01-01

    Background: Previous researches have demonstrated, that the severity of pain perception and it’s response to analgesia is highly dependent on gene polymorphism encoding for cytokines. We evaluated 12 single nucleotide polymorphisms (SNP) in 6 genes encoding for cytokines in multiple myeloma patients (n = 81) and assessed their influence on pain severity and response to palliative radiotherapy. Methods: Pain intensity was assessed by Visual Analogue Scale. The total dose of opioids was convert...

  2. Methodological Considerations in Couples' Fertility Intentions: Missing Men and the Viability of Women's Proxy Reports.

    Science.gov (United States)

    Stykes, J Bart

    2018-02-19

    Introduction Recent efforts show potential to advance research on unintended childbearing by taking a couple-level approach. However, this work has neither adequately addressed methodological concerns stemming from the challenges associated with male fertility data nor considered the viability of women's proxy reports of fathers intentions. Methods Data from the Early Childhood Longitudinal Study, Birth Cohort (ECLS-B) were used to assess the implications of low response rates among men on couples' unintended childbearing. Then, the accuracy of women's proxy reports of fathers intentions was assessed. Weighted logistic regression analyses were conducted to determine how women's characteristics were associated with men's survey participation whereas weighted multinomial logistic regression analyses were applied to determine how women's characteristics were linked with the accuracy of her proxy report. Results Almost half (46%) of women cannot be matched with data from the child's father, and this discrepancy is most problematic for women who are black, foreign-born, less educated, and unmarried at birth. Women's proxy reports appear viable as 75% of women's reports are consistent with men's responses. Yet, proxy reports underestimate disagreement in couples' intentions as mothers who intended the birth are at an increased risk of "inaccurately" reporting that fathers share their intentions. Discussion Direct approaches to couples' intentions yield privileged samples and systematically omit women at the greatest risk of an unintended birth. However, proxies underestimate disagreement in couples' intentions-a key contribution to the couple approach. Accordingly each approach has its own merits which must be considered in light of specified research questions.

  3. Proxy studies of energy transfer to the magnetosphere

    International Nuclear Information System (INIS)

    Scurry, L.; Russell, C.T.

    1991-01-01

    The transfer of energy into the magnetosphere is studied using as proxy the Am geomagnetic index and multilinear regressions and correlations with solar wind data. In particular, the response of Am to the reconnection mechanism is examined in relation to the orientation of the interplanetary magnetic field as well as the upstream plasma parameters. A functional dependence of Am on clock angle, the orientation of the IMF in the plane perpendicular to the flow, is derived after first correcting the index for nonreconnection effects due to dynamic pressure and velocity. An examination of the effect of upstream magnetosonic Mach number shows the reconnection mechanism to become less efficient at high Mach numbers. The reconnection mechanism is shown to be slightly enhanced by higher dynamic pressures

  4. Reducing the number of options on multiple-choice questions: response time, psychometrics and standard setting.

    Science.gov (United States)

    Schneid, Stephen D; Armour, Chris; Park, Yoon Soo; Yudkowsky, Rachel; Bordage, Georges

    2014-10-01

    Despite significant evidence supporting the use of three-option multiple-choice questions (MCQs), these are rarely used in written examinations for health professions students. The purpose of this study was to examine the effects of reducing four- and five-option MCQs to three-option MCQs on response times, psychometric characteristics, and absolute standard setting judgements in a pharmacology examination administered to health professions students. We administered two versions of a computerised examination containing 98 MCQs to 38 Year 2 medical students and 39 Year 3 pharmacy students. Four- and five-option MCQs were converted into three-option MCQs to create two versions of the examination. Differences in response time, item difficulty and discrimination, and reliability were evaluated. Medical and pharmacy faculty judges provided three-level Angoff (TLA) ratings for all MCQs for both versions of the examination to allow the assessment of differences in cut scores. Students answered three-option MCQs an average of 5 seconds faster than they answered four- and five-option MCQs (36 seconds versus 41 seconds; p = 0.008). There were no significant differences in item difficulty and discrimination, or test reliability. Overall, the cut scores generated for three-option MCQs using the TLA ratings were 8 percentage points higher (p = 0.04). The use of three-option MCQs in a health professions examination resulted in a time saving equivalent to the completion of 16% more MCQs per 1-hour testing period, which may increase content validity and test score reliability, and minimise construct under-representation. The higher cut scores may result in higher failure rates if an absolute standard setting method, such as the TLA method, is used. The results from this study provide a cautious indication to health professions educators that using three-option MCQs does not threaten validity and may strengthen it by allowing additional MCQs to be tested in a fixed amount

  5. Sympathetic skin response in multiple sclerosis: a meta-analysis of case-control studies.

    Science.gov (United States)

    Margaritella, Nicolò; Mendozzi, Laura; Garegnani, Massimo; Gilardi, Elisabetta; Nemni, Raffaello; Pugnetti, Luigi

    2018-01-01

    The usefulness of sympathetic skin responses (SSR) in multiple sclerosis (MS) has been advocated by several studies in the last 20 years; however, due to a great heterogeneity of findings, a comprehensive meta-analysis of case-control studies is in order to pinpoint consistencies and investigate the causes of discrepancies. We searched MEDLINE, EMBASE and Cochrane databases for case-control studies comparing SSR absence frequency and latency between patients with MS and healthy controls. Thirteen eligible studies including 415 MS patients and 331 healthy controls were identified. The pooled analysis showed that SSR can be always obtained in healthy controls while 34% of patients had absent SSRs in at least one limb (95% CI 22-47%; p studies (I 2  = 90.3%). Patients' age explained 22% of the overall variability and positive correlations were found with Expanded Disability Status Scale and disease duration. The pooled mean difference of SSR latency showed a significant increase in patients on both upper (193 ms; 95% CI 120-270 ms) and lower (350 ms; 95% CI 190-510 ms) extremities. We tested the discriminatory value of SSR latency thresholds defined as the 95% confidence interval (CI) upper bound of the healthy controls, and validated the results on a new dataset. The lower limb threshold of 1.964 s produces the best results in terms of sensitivity 0.86, specificity 0.67, positive predicted value 0.75 and negative predicted value 0.80. Despite a considerable heterogeneity of findings, there is evidence that SSR is a useful tool in MS.

  6. Application of Item Response Theory to Modeling of Expanded Disability Status Scale in Multiple Sclerosis.

    Science.gov (United States)

    Novakovic, A M; Krekels, E H J; Munafo, A; Ueckert, S; Karlsson, M O

    2017-01-01

    In this study, we report the development of the first item response theory (IRT) model within a pharmacometrics framework to characterize the disease progression in multiple sclerosis (MS), as measured by Expanded Disability Status Score (EDSS). Data were collected quarterly from a 96-week phase III clinical study by a blinder rater, involving 104,206 item-level observations from 1319 patients with relapsing-remitting MS (RRMS), treated with placebo or cladribine. Observed scores for each EDSS item were modeled describing the probability of a given score as a function of patients' (unobserved) disability using a logistic model. Longitudinal data from placebo arms were used to describe the disease progression over time, and the model was then extended to cladribine arms to characterize the drug effect. Sensitivity with respect to patient disability was calculated as Fisher information for each EDSS item, which were ranked according to the amount of information they contained. The IRT model was able to describe baseline and longitudinal EDSS data on item and total level. The final model suggested that cladribine treatment significantly slows disease-progression rate, with a 20% decrease in disease-progression rate compared to placebo, irrespective of exposure, and effects an additional exposure-dependent reduction in disability progression. Four out of eight items contained 80% of information for the given range of disabilities. This study has illustrated that IRT modeling is specifically suitable for accurate quantification of disease status and description and prediction of disease progression in phase 3 studies on RRMS, by integrating EDSS item-level data in a meaningful manner.

  7. Multiple sclerosis patients have a diminished serologic response to vitamin D supplementation compared to healthy controls.

    Science.gov (United States)

    Bhargava, Pavan; Steele, Sonya U; Waubant, Emmanuelle; Revirajan, Nisha R; Marcus, Jacqueline; Dembele, Marieme; Cassard, Sandra D; Hollis, Bruce W; Crainiceanu, Ciprian; Mowry, Ellen M

    2016-05-01

    Vitamin D insufficiency is a risk factor for multiple sclerosis (MS), and patients do not always show the expected response to vitamin D supplementation. We aimed to determine if vitamin D supplementation leads to a similar increase in serum 25-hydroxyvitamin-D (25(OH)D) levels in patients with MS and healthy controls (HCs). Participants in this open-label study were female, white, aged 18-60 years, had 25(OH)D levels ⩽ 75 nmol/l at screening, and had relapsing-remitting MS (RRMS) or were HCs. Participants received 5000 IU/day of vitamin D3 for 90 days. Utilizing generalized estimating equations we examined the relationship between the primary outcome (serum 25(OH)D level) and the primary (MS versus HC status) and secondary predictors. For this study 27 MS patients and 30 HCs were enrolled. There was no significant difference in baseline 25(OH)D level or demographics except for higher body mass index (BMI) in the MS group (25.3 vs. 23.6 kg/m(2), p=0.035). In total, 24 MS subjects and 29 HCs completed the study. In a multivariate model accounting for BMI, medication adherence, and oral contraceptive use, MS patients had a 16.7 nmol/l (95%CI: 4.2, 29.2, p=0.008) lower increase in 25(OH)D levels compared with HCs. Patients with MS had a lower increase in 25(OH)D levels with supplementation, even after accounting for putative confounders. © The Author(s), 2015.

  8. One thousand years of fires: Integrating proxy and model data

    Directory of Open Access Journals (Sweden)

    Natalie Marie Kehrwald

    2016-04-01

    Full Text Available The current fires raging across Indonesia are emitting more carbon than the annual fossil fuel emissions of Germany or Japan, and the fires are still consuming vast tracts of rainforest and peatlands. The National Interagency Fire Center (www.nifc.gov notes that 2015 is one worst fire years on record in the U.S., where more than 9 million acres burned -- equivalent to the combined size of Massachusetts and New Jersey. The U.S. and Indonesian fires have already displaced tens of thousands of people, and their impacts on ecosystems are still unclear. In the case of Indonesia, the burning peat is destroying much of the existing soil, with unknown implications for the type of vegetation regrowth. Such large fires result from a combination of fire management practices, increasing anthropogenic land use, and a changing climate. The expected increase in fire activity in the upcoming decades has led to a surge in research trying to understand their causes, the factors that may have influenced similar times of fire activity in the past, and the implications of such fire activity in the future. Multiple types of complementary data provide information on the impacts of current fires and the extent of past fires. The wide array of data encompasses different spatial and temporal resolutions (Figure 1 and includes fire proxy information such as charcoal and tree ring fire scars, observational records, satellite products, modern emissions data, fire models within global land cover and vegetation models, and sociodemographic data for modeling past human land use and ignition frequency. Any single data type is more powerful when combined with another source of information. Merging model and proxy data enables analyses of how fire activity modifies vegetation distribution, air and water quality, and proximity to cities; these analyses in turn support land management decisions relating to conservation and development.

  9. Camera-based microswitch technology to monitor mouth, eyebrow, and eyelid responses of children with profound multiple disabilities

    NARCIS (Netherlands)

    Lancioni, G.E.; Bellini, D.; Oliva, D.; Singh, N.N.; O'Reilly, M.F.; Sigafoos, J.; Lang, R.B.; Didden, H.C.M.

    2011-01-01

    A camera-based microswitch technology was recently used to successfully monitor small eyelid and mouth responses of two adults with profound multiple disabilities (Lancioni et al., Res Dev Disab 31:1509-1514, 2010a). This technology, in contrast with the traditional optic microswitches used for

  10. Using a Fine-Grained Multiple-Choice Response Format in Educational Drill-and-Practice Video Games

    Science.gov (United States)

    Beserra, Vagner; Nussbaum, Miguel; Grass, Antonio

    2017-01-01

    When using educational video games, particularly drill-and-practice video games, there are several ways of providing an answer to a quiz. The majority of paper-based options can be classified as being either multiple-choice or constructed-response. Therefore, in the process of creating an educational drill-and-practice video game, one fundamental…

  11. Modeling hydrologic responses to deforestation/forestation and climate change at multiple scales in the Southern US and China

    Science.gov (United States)

    Ge Sun; Steven McNulty; Jianbiao Lu; James Vose; Devendra Amayta; Guoyi Zhou; Zhiqiang Zhang

    2006-01-01

    Watershed management and restoration practices require a clear understanding of the basic eco-hydrologic processes and ecosystem responses to disturbances at multiple scales (Bruijnzeel, 2004; Scott et al., 2005). Worldwide century-long forest hydrologic research has documented that deforestation and forestation (i.e. reforestation and afforestation) can have variable...

  12. Using a Classroom Response System to Improve Multiple-Choice Performance in AP[R] Physics

    Science.gov (United States)

    Bertrand, Peggy

    2009-01-01

    Participation in rigorous high school courses such as Advanced Placement (AP[R]) Physics increases the likelihood of college success, especially for students who are traditionally underserved. Tackling difficult multiple-choice exams should be part of any AP program because well-constructed multiple-choice questions, such as those on AP exams and…

  13. Multiple stress response of lowland stream benthic macroinvertebrates is dependent on habitat type

    DEFF Research Database (Denmark)

    Graeber, Daniel; Jensen, Tinna M.; Rasmussen, Jes

    2017-01-01

    Worldwide, lowland stream ecosystems are exposed to multiple anthropogenic stress due to the combination of water scarcity, eutrophication and fine sedimentation. The understanding of the effects of such multiple stress on stream benthic macroinvertebrates has been growing in the recent years...

  14. Optimizing TCP Performance over UMTS with Split TCP Proxy

    DEFF Research Database (Denmark)

    Hu, Liang; Dittmann, Lars

    2009-01-01

    . To cope with large delay bandwidth product, we propose a novel concept of split TCP proxy which is placed at GGSN between UNITS network and Internet. The split proxy divides the bandwidth delay product into two parts, resulting in two TCP connections with smaller bandwidth delay products which can...... be pipelined and thus operating at higher speeds. Simulation results show, the split TCP proxy can significantly improve the TCP performance in terms of RLC throughput under high bit rate DCH channel scenario (e.g.256 kbps). On the other hand, it only brings small performance improvement under low bit rate DCH...... scenario (e.g.64 kbps). Besides, the split TCP proxy brings more performance gain for downloading large files than downloading small ones. To the end, for the configuration of the split proxy, an aggressive initial TCP congestion window size (e.g. 10 MSS) at proxy is particularly useful for radio links...

  15. Estimation of sedimentary proxy records together with associated uncertainty

    OpenAIRE

    Goswami, B.; Heitzig, J.; Rehfeld, K.; Marwan, N.; Anoop, A.; Prasad, S.; Kurths, J.

    2014-01-01

    Sedimentary proxy records constitute a significant portion of the recorded evidence that allows us to investigate paleoclimatic conditions and variability. However, uncertainties in the dating of proxy archives limit our ability to fix the timing of past events and interpret proxy record intercomparisons. While there are various age-modeling approaches to improve the estimation of the age–depth relations of archives, relatively little focus has been placed on the propagation...

  16. Time-and-ID-Based Proxy Reencryption Scheme

    OpenAIRE

    Mtonga, Kambombo; Paul, Anand; Rho, Seungmin

    2014-01-01

    Time- and ID-based proxy reencryption scheme is proposed in this paper in which a type-based proxy reencryption enables the delegator to implement fine-grained policies with one key pair without any additional trust on the proxy. However, in some applications, the time within which the data was sampled or collected is very critical. In such applications, for example, healthcare and criminal investigations, the delegatee may be interested in only some of the messages with some types sampled wi...

  17. Salmon: Robust Proxy Distribution for Censorship Circumvention

    Directory of Open Access Journals (Sweden)

    Douglas Frederick

    2016-10-01

    Full Text Available Many governments block their citizens’ access to much of the Internet. Simple workarounds are unreliable; censors quickly discover and patch them. Previously proposed robust approaches either have non-trivial obstacles to deployment, or rely on low-performance covert channels that cannot support typical Internet usage such as streaming video. We present Salmon, an incrementally deployable system designed to resist a censor with the resources of the “Great Firewall” of China. Salmon relies on a network of volunteers in uncensored countries to run proxy servers. Although any member of the public can become a user, Salmon protects the bulk of its servers from being discovered and blocked by the censor via an algorithm for quickly identifying malicious users. The algorithm entails identifying some users as especially trustworthy or suspicious, based on their actions. We impede Sybil attacks by requiring either an unobtrusive check of a social network account, or a referral from a trustworthy user.

  18. Development of six PROMIS pediatrics proxy-report item banks.

    Science.gov (United States)

    Irwin, Debra E; Gross, Heather E; Stucky, Brian D; Thissen, David; DeWitt, Esi Morgan; Lai, Jin Shei; Amtmann, Dagmar; Khastou, Leyla; Varni, James W; DeWalt, Darren A

    2012-02-22

    Pediatric self-report should be considered the standard for measuring patient reported outcomes (PRO) among children. However, circumstances exist when the child is too young, cognitively impaired, or too ill to complete a PRO instrument and a proxy-report is needed. This paper describes the development process including the proxy cognitive interviews and large-field-test survey methods and sample characteristics employed to produce item parameters for the Patient Reported Outcomes Measurement Information System (PROMIS) pediatric proxy-report item banks. The PROMIS pediatric self-report items were converted into proxy-report items before undergoing cognitive interviews. These items covered six domains (physical function, emotional distress, social peer relationships, fatigue, pain interference, and asthma impact). Caregivers (n = 25) of children ages of 5 and 17 years provided qualitative feedback on proxy-report items to assess any major issues with these items. From May 2008 to March 2009, the large-scale survey enrolled children ages 8-17 years to complete the self-report version and caregivers to complete the proxy-report version of the survey (n = 1548 dyads). Caregivers of children ages 5 to 7 years completed the proxy report survey (n = 432). In addition, caregivers completed other proxy instruments, PedsQL™ 4.0 Generic Core Scales Parent Proxy-Report version, PedsQL™ Asthma Module Parent Proxy-Report version, and KIDSCREEN Parent-Proxy-52. Item content was well understood by proxies and did not require item revisions but some proxies clearly noted that determining an answer on behalf of their child was difficult for some items. Dyads and caregivers of children ages 5-17 years old were enrolled in the large-scale testing. The majority were female (85%), married (70%), Caucasian (64%) and had at least a high school education (94%). Approximately 50% had children with a chronic health condition, primarily asthma, which was diagnosed or treated within 6

  19. Development of six PROMIS pediatrics proxy-report item banks

    Directory of Open Access Journals (Sweden)

    Irwin Debra E

    2012-02-01

    Full Text Available Abstract Background Pediatric self-report should be considered the standard for measuring patient reported outcomes (PRO among children. However, circumstances exist when the child is too young, cognitively impaired, or too ill to complete a PRO instrument and a proxy-report is needed. This paper describes the development process including the proxy cognitive interviews and large-field-test survey methods and sample characteristics employed to produce item parameters for the Patient Reported Outcomes Measurement Information System (PROMIS pediatric proxy-report item banks. Methods The PROMIS pediatric self-report items were converted into proxy-report items before undergoing cognitive interviews. These items covered six domains (physical function, emotional distress, social peer relationships, fatigue, pain interference, and asthma impact. Caregivers (n = 25 of children ages of 5 and 17 years provided qualitative feedback on proxy-report items to assess any major issues with these items. From May 2008 to March 2009, the large-scale survey enrolled children ages 8-17 years to complete the self-report version and caregivers to complete the proxy-report version of the survey (n = 1548 dyads. Caregivers of children ages 5 to 7 years completed the proxy report survey (n = 432. In addition, caregivers completed other proxy instruments, PedsQL™ 4.0 Generic Core Scales Parent Proxy-Report version, PedsQL™ Asthma Module Parent Proxy-Report version, and KIDSCREEN Parent-Proxy-52. Results Item content was well understood by proxies and did not require item revisions but some proxies clearly noted that determining an answer on behalf of their child was difficult for some items. Dyads and caregivers of children ages 5-17 years old were enrolled in the large-scale testing. The majority were female (85%, married (70%, Caucasian (64% and had at least a high school education (94%. Approximately 50% had children with a chronic health condition, primarily

  20. Důvěryhodná proxy v SSL/TLS spojení

    OpenAIRE

    Smolík, Jiří

    2017-01-01

    The problem of SSL/TLS interception ("trusted proxy in SSL/TLS connection") has been known for years and many implementations exist. However, all of them share a single technical solution which is based solely on the PKI authentication mechanism and suffers from multiple serious disadvantages. Most importantly, it is not compatible with several aspects or future trends of SSL/TLS and PKI, there's almost no space for improvement and its real use may spawn legal issues. After we analyze technic...

  1. Multiple linear regression to estimate time-frequency electrophysiological responses in single trials.

    Science.gov (United States)

    Hu, L; Zhang, Z G; Mouraux, A; Iannetti, G D

    2015-05-01

    Transient sensory, motor or cognitive event elicit not only phase-locked event-related potentials (ERPs) in the ongoing electroencephalogram (EEG), but also induce non-phase-locked modulations of ongoing EEG oscillations. These modulations can be detected when single-trial waveforms are analysed in the time-frequency domain, and consist in stimulus-induced decreases (event-related desynchronization, ERD) or increases (event-related synchronization, ERS) of synchrony in the activity of the underlying neuronal populations. ERD and ERS reflect changes in the parameters that control oscillations in neuronal networks and, depending on the frequency at which they occur, represent neuronal mechanisms involved in cortical activation, inhibition and binding. ERD and ERS are commonly estimated by averaging the time-frequency decomposition of single trials. However, their trial-to-trial variability that can reflect physiologically-important information is lost by across-trial averaging. Here, we aim to (1) develop novel approaches to explore single-trial parameters (including latency, frequency and magnitude) of ERP/ERD/ERS; (2) disclose the relationship between estimated single-trial parameters and other experimental factors (e.g., perceived intensity). We found that (1) stimulus-elicited ERP/ERD/ERS can be correctly separated using principal component analysis (PCA) decomposition with Varimax rotation on the single-trial time-frequency distributions; (2) time-frequency multiple linear regression with dispersion term (TF-MLRd) enhances the signal-to-noise ratio of ERP/ERD/ERS in single trials, and provides an unbiased estimation of their latency, frequency, and magnitude at single-trial level; (3) these estimates can be meaningfully correlated with each other and with other experimental factors at single-trial level (e.g., perceived stimulus intensity and ERP magnitude). The methods described in this article allow exploring fully non-phase-locked stimulus-induced cortical

  2. Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk.

    Science.gov (United States)

    Nolan, David; Castley, Alison; Tschochner, Monika; James, Ian; Qiu, Wei; Sayer, David; Christiansen, Frank T; Witt, Campbell; Mastaglia, Frank; Carroll, William; Kermode, Allan

    2012-08-07

    The identification of a vitamin D-responsive (VDRE) motif within the HLA-DRB1*15:01 promoter region provides an attractive explanation for the combined effects of HLA-DR inheritance and vitamin D exposure on multiple sclerosis (MS) risk. We therefore sought to incorporate HLA-DRB1 promoter variation, including the VDRE motif, in an assessment of HLA-DRB1-associated MS risk. We utilized 32 homozygous HLA cell lines (covering 17 DRB1 alleles) and 53 heterozygote MS samples (20 DRB1 alleles) for HLA-DRB1 promoter sequencing. The influence of HLA-DRB1 variation on MS risk was then assessed among 466 MS cases and 498 controls. The majority of HLA*DRB1 alleles (including HLA-DRB1*15:01) express the functional VDRE motif, apart from HLA-DRB1*04, *07, and *09 alleles that comprise the HLA-DR53 serologic group. Allele-specific variation within functional X-box and Y-box motifs was also associated with serologically defined HLA-DR haplotypes. Incorporating these results in an analysis of MS risk, we identified a strong protective effect of HLA-DRB1*04, *07, and *09 (DR53) alleles (p = 10(-12)) and elevated risk associated with DRB1*15 and *16 (DR51) and *08 (DR8) alleles (p < 10(-18)). HLA-DRB1 groups corresponding to serologic HLA-DR profiles as well as promoter polymorphism haplotypes effectively stratified MS risk over an 11-fold range, suggesting functional relationships between risk-modifying HLA-DRB1 alleles. An independent contribution of VDRE motif variation to increase MS risk was not discernible, although vitamin D-dependent regulation of HLA-DR expression may still play an important role given that HLA-DRB1*04/*07/*09 (DR53) alleles that express the "nonresponsive" VDRE motif were associated with significantly reduced risk of MS.

  3. Responsive Neurostimulation System (RNS in setting of cranioplasty and history of multiple craniotomies

    Directory of Open Access Journals (Sweden)

    Jason Ledesma

    2016-09-01

    Conclusion: The case illustrates a possible limitation of SEEG placement, particularly in patients with a history of cranioplasty and multiple prior craniotomies. We also describe the first placement of an RNS generator and system in the setting of prior cranioplasty.

  4. Proxy-produced ethnographic work: what are the problems, issues, and dilemmas arising from proxy ethnography?

    DEFF Research Database (Denmark)

    Martinussen, Marie Louise; Højbjerg, Karin; Tamborg, Andreas Lindenskov

    2018-01-01

    This article addresses the implications of research-student cooperation in the production of empirical material. For the student to replace the experienced researcher and work under the researcher’s supervision, we call such work proxy-produced ethnographic work. The specific relations...... and positions arising from such a setup between the teacher/researcher and the proxy ethnographer/student are found to have implications for the ethnographies produced. This article’s main focus is to show how these relations and positions have not distorted the ethnographic work and the ethnographies but......, rather, have oriented it in certain ways. It is shown how the participating researchers – both senior and junior - have distinctive, incorporated dispositions with which they pre-consciously participate in an implicit and subtle relation that can make it very easy to overlook distortions during...

  5. Atmospheric multidecadal variations in the North Atlantic realm: proxy data, observations, and atmospheric circulation model studies

    Directory of Open Access Journals (Sweden)

    K. Grosfeld

    2007-01-01

    Full Text Available We investigate the spatial and temporal characteristics of multidecadal climate variability in the North Atlantic realm, using observational data, proxy data and model results. The dominant pattern of multidecadal variability of SST depicts a monopolar structure in the North Atlantic during the instrumental period with cold (warm phases during 1900–1925 and 1970–1990 (1870–1890 and 1940–1960. Two atmospheric general circulation models of different complexity forced with global SST over the last century show SLP anomaly patterns from the warm and cold phases of the North Atlantic similar to the corresponding observed patterns. The analysis of a sediment core from Cariaco Basin, a coral record from the northern Red Sea, and a long-term sea level pressure (SLP reconstruction reveals that the multidecadal mode of the atmospheric circulation characterizes climate variability also in the pre-industrial era. The analyses of SLP reconstruction and proxy data depict a persistent atmospheric mode at least over the last 300 years, where SLP shows a dipolar structure in response to monopolar North Atlantic SST, in a similar way as the models' responses do. The combined analysis of observational and proxy data with model experiments provides an understanding of multidecadal climate modes during the late Holocene. The related patterns are useful for the interpretation of proxy data in the North Atlantic realm.

  6. Predicting multi-level drug response with gene expression profile in multiple myeloma using hierarchical ordinal regression.

    Science.gov (United States)

    Zhang, Xinyan; Li, Bingzong; Han, Huiying; Song, Sha; Xu, Hongxia; Hong, Yating; Yi, Nengjun; Zhuang, Wenzhuo

    2018-05-10

    Multiple myeloma (MM), like other cancers, is caused by the accumulation of genetic abnormalities. Heterogeneity exists in the patients' response to treatments, for example, bortezomib. This urges efforts to identify biomarkers from numerous molecular features and build predictive models for identifying patients that can benefit from a certain treatment scheme. However, previous studies treated the multi-level ordinal drug response as a binary response where only responsive and non-responsive groups are considered. It is desirable to directly analyze the multi-level drug response, rather than combining the response to two groups. In this study, we present a novel method to identify significantly associated biomarkers and then develop ordinal genomic classifier using the hierarchical ordinal logistic model. The proposed hierarchical ordinal logistic model employs the heavy-tailed Cauchy prior on the coefficients and is fitted by an efficient quasi-Newton algorithm. We apply our hierarchical ordinal regression approach to analyze two publicly available datasets for MM with five-level drug response and numerous gene expression measures. Our results show that our method is able to identify genes associated with the multi-level drug response and to generate powerful predictive models for predicting the multi-level response. The proposed method allows us to jointly fit numerous correlated predictors and thus build efficient models for predicting the multi-level drug response. The predictive model for the multi-level drug response can be more informative than the previous approaches. Thus, the proposed approach provides a powerful tool for predicting multi-level drug response and has important impact on cancer studies.

  7. Contracts, covenants and advance care planning: an empirical study of the moral obligations of patient and proxy.

    Science.gov (United States)

    Fins, Joseph J; Maltby, Barbara S; Friedmann, Erika; Greene, Michele G; Norris, Kaye; Adelman, Ronald; Byock, Ira

    2005-01-01

    Previously we had speculated that the patient-proxy relationship existed on a contractual to covenantal continuum. In order to assess this hypothesis, and to better understand the moral obligations of the patient-proxy relationship, we surveyed 50 patient-proxy pairs as well as 52 individuals who had acted as proxies for someone who had died. Using structured vignettes representative of three distinct disease trajectories (cancer, acute stroke, and congestive heart failure), we assessed whether respondents believed that proxies should follow explicit instructions regarding life-sustaining therapy and act contractually or whether more discretionary or covenantal judgments were ethically permissible. Additional variables included the valence of initial patient instructions--for example, "to do nothing" or "to do everything"--as well as the quality of information available to the proxy. Responses were graded on a contractual to covenantal continuum using a modified Likert scale employing a prospectively scored survey instrument. Our data indicate that the patient-proxy relationship exists on a contractual to covenantal continuum and that variables such as disease trajectory, the clarity of prognosis, instructional valence, and the quality of patient instructions result in statistically significant differences in response. The use of interpretative or covenantal judgment was desired by patients and proxies when the prognosis was grim, even if initial instructions were to pursue more aggressive care. Nonetheless, there was a valence effect: patients and proxies intended that negative instructions to be left alone be heeded. These data suggest that the delegation of patient self-determination is morally complex. Advance care planning should take into account both the exercise of autonomy and the interpretative burdens assumed by the proxy. Patients and proxies think inductively and contextually. Neither group viewed deviation from patient instructions as a violation of

  8. Proxy indicators as measure of local economic dispositions in South ...

    African Journals Online (AJOL)

    in international markets. The proxy is a coincidental and pro-cyclic indicator, with a correlation of 0.86. Key similarities exist between the economy and the profitability of hardware stores, although the proxy is not as accurate as the volume of sales in hardware stores. The correlation is measured at 0.85. The profitability of the ...

  9. Tellurium Stable Isotopes as a Paleoredox Proxy

    Science.gov (United States)

    Wasserman, N.; Johnson, T. M.

    2017-12-01

    Despite arguments for variably-oxygenated shallow waters and anoxic deep marine waters, which delayed animal development until the Neoproterozoic Oxidation Event, the magnitude of atmospheric oxygen during the Proterozoic is still uncertain [1]. The evidence for low pO2 (<0.1-1% PAL) is based on geochemical and isotopic proxies, which track the mobilization of Fe and Mn on the continents. For example, large chromium isotope shifts occur at the Neoproterozoic Oxidation Event due to the initiation of Cr redox cycling, but this proxy is insensitive to fluctuations in the lower-pO2 conditions at other times during the Proterozoic. Tellurium, a metalloid with a lower threshold to oxidation, may be sensitive to pO2 shifts in a lower range. In the reduced forms, Te(-II) and Te(0), the element is insoluble and immobile. However, in the more oxidized phases, Te(IV) and Te(VI), Te can form soluble oxyanions (though it tends to adsorb to Fe-oxyhydroxides and clays) [2]. Te stable isotopes have been shown to fractionate during abiotic or biologic reduction of Te(VI) or Te(IV) to elemental Te(0) [3, 4]. Utilizing hydride generation MC-ICP-MS, we are able to obtain high precision (2σ 0.04‰) measurements of δ128Te/125Te for natural samples containing < 10 ng of Te. A suite of Phanerozoic and Proterozoic ironstones show significant variation in δ128Te/125Te (<0.5‰), suggesting that the Te redox cycle was active during the Proterozoic. Future directions will include Te isotope measurements of Precambrian paleosols to determine natural isotope variation before the Great Oxidation Event and experiments to determine fractionation during adsorption to Fe-oxyhydroxides. [1] Planavsky et al. (2014) Science 346 (6209), pp. 635-638 [2] Qin et al. (2017) Environmental Science and Technology 51 (11), pp 6027-6035 [3] Baesman et al. (2007) Applied Environmental Microbiology 73 (7), pp 2135-2143 [4] Smithers and Krause (1968) Canadian Journal of Chemistry 46(4): pp 583-591

  10. Existence, Multiplicity, and Stability of Positive Solutions of a Predator-Prey Model with Dinosaur Functional Response

    Directory of Open Access Journals (Sweden)

    Xiaozhou Feng

    2017-01-01

    Full Text Available We investigate the property of positive solutions of a predator-prey model with Dinosaur functional response under Dirichlet boundary conditions. Firstly, using the comparison principle and fixed point index theory, the sufficient conditions and necessary conditions on coexistence of positive solutions of a predator-prey model with Dinosaur functional response are established. Secondly, by virtue of bifurcation theory, perturbation theory of eigenvalues, and the fixed point index theory, we establish the bifurcation of positive solutions of the model and obtain the stability and multiplicity of the positive solution under certain conditions. Furthermore, the local uniqueness result is studied when b and d are small enough. Finally, we investigate the multiplicity, uniqueness, and stability of positive solutions when k>0 is sufficiently large.

  11. Perbandingan proxy pada linux dan windows untuk mempercepat browsing website

    Directory of Open Access Journals (Sweden)

    Dafwen Toresa

    2017-05-01

    Full Text Available AbstrakPada saat ini sangat banyak organisasi, baik pendidikan, pemerintahan,  maupun perusahaan swasta berusaha membatasi akses para pengguna ke internet dengan alasan bandwidth yang dimiliki mulai terasa lambat ketika para penggunanya mulai banyak yang melakukan browsing ke internet. Mempercepat akses browsing menjadi perhatian utama dengan memanfaatkan teknologi Proxy server. Penggunaan proxy server perlu mempertimbangkan sistem operasi pada server dan tool yang digunakan belum diketahui performansi terbaiknya pada sistem operasi apa.  Untuk itu dirasa perlu untuk menganalisis performan Proxy server pada sistem operasi berbeda yaitu Sistem Operasi Linux dengan tools Squid  dan Sistem Operasi Windows dengan tool Winroute. Kajian ini dilakukan untuk mengetahui perbandingan kecepatan browsing dari komputer pengguna (client. Browser yang digunakan di komputer pengguna adalah Mozilla Firefox. Penelitian ini menggunakan 2 komputer klien dengan pengujian masing-masingnya 5 kali pengujian pengaksesan/browsing web yang dituju melalui proxy server. Dari hasil pengujian yang dilakukan, diperoleh kesimpulan bahwa penerapan proxy server di sistem operasi linux dengan tools squid lebih cepat browsing dari klien menggunakan web browser yang sama dan komputer klien yang berbeda dari pada proxy server sistem operasi windows dengan tools winroute.  Kata kunci: Proxy, Bandwidth, Browsing, Squid, Winroute AbstractAt this time very many organizations, both education, government, and private companies try to limit the access of users to the internet on the grounds that the bandwidth owned began to feel slow when the users began to do a lot of browsing to the internet. Speed up browsing access is a major concern by utilizing Proxy server technology. The use of proxy servers need to consider the operating system on the server and the tool used is not yet known the best performance on what operating system. For that it is necessary to analyze Performance Proxy

  12. Complex, non-monotonic dose-response curves with multiple maxima: Do we (ever) sample densely enough?

    Science.gov (United States)

    Cvrčková, Fatima; Luštinec, Jiří; Žárský, Viktor

    2015-01-01

    We usually expect the dose-response curves of biological responses to quantifiable stimuli to be simple, either monotonic or exhibiting a single maximum or minimum. Deviations are often viewed as experimental noise. However, detailed measurements in plant primary tissue cultures (stem pith explants of kale and tobacco) exposed to varying doses of sucrose, cytokinins (BA or kinetin) or auxins (IAA or NAA) revealed that growth and several biochemical parameters exhibit multiple reproducible, statistically significant maxima over a wide range of exogenous substance concentrations. This results in complex, non-monotonic dose-response curves, reminiscent of previous reports of analogous observations in both metazoan and plant systems responding to diverse pharmacological treatments. These findings suggest the existence of a hitherto neglected class of biological phenomena resulting in dose-response curves exhibiting periodic patterns of maxima and minima, whose causes remain so far uncharacterized, partly due to insufficient sampling frequency used in many studies.

  13. Evaluation of the serum free light chain (sFLC) analysis in prediction of response in symptomatic multiple myeloma patients

    DEFF Research Database (Denmark)

    Toftmann Hansen, Charlotte; Pedersen, Per T; Nielsen, Lars C

    2014-01-01

    BACKGROUND: Observational data from clinical studies indicate that the goal of first-line therapy in newly diagnosed patients with symptomatic multiple myeloma (MM) should be very good partial response (VGPR) or better, preferably before high-dose treatment. We evaluated the value of early...... patients with no response to treatment. The mean per cent reduction in iFLC 3 d after start of treatment was 52.3% and 23.6% (P = 0.021) in patients achieving ≥VGPR and PR, respectively. The mean per cent reduction in M-protein in patients achieving ≥VGPR and PR was not significantly different in the 6-wk...

  14. New hybrid multivariate analysis approach to optimize multiple response surfaces considering correlations in both inputs and outputs

    OpenAIRE

    Hejazi, Taha Hossein; Amirkabir University of Technology - Iran; Seyyed-Esfahani, Mirmehdi; Amirkabir University of Technology - Iran; Ramezani, Majid; Amirkabir University of Technology - Iran

    2014-01-01

    Quality control in industrial and service systems requires the correct setting of input factors by which the outputs result at minimum cost with desirable characteristics. There are often more than one input and output in such systems. Response surface methodology in its multiple variable forms is one of the most applied methods to estimate and improve the quality characteristics of products with respect to control factors. When there is some degree of correlation among the variables, the exi...

  15. Multiplicative Genotype-Environment Interaction as a Cause of Reversed Response to Directional Selection

    OpenAIRE

    Gimelfarb, A.

    1986-01-01

    In experiments with directional selection on a quantitative character a "reversed response" to selection is occasionally observed, when selection of individuals for a higher (lower) value of the character results in a lower (higher) value of the character among their offspring. A sudden change in environments or random drift is often assumed to be responsible for this. It is demonstrated in this paper that these two causes cannot account for the reversed response at least in some of the exper...

  16. Relationship between cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers: Exploring multiple mediation model.

    Science.gov (United States)

    Cai, Wen-Peng; Pan, Yu; Zhang, Shui-Miao; Wei, Cun; Dong, Wei; Deng, Guang-Hui

    2017-10-01

    The current study aimed to explore the association of cognitive emotion regulation, social support, resilience and acute stress responses in Chinese soldiers and to understand the multiple mediation effects of social support and resilience on the relationship between cognitive emotion regulation and acute stress responses. A total of 1477 male soldiers completed mental scales, including the cognitive emotion regulation questionnaire-Chinese version, the perceived social support scale, the Chinese version of the Connor-Davidson resilience scale, and the military acute stress scale. As hypothesized, physiological responses, psychological responses, and acute stress were associated with negative-focused cognitive emotion regulation, and negatively associated with positive-focused cognitive emotion regulation, social supports and resilience. Besides, positive-focused cognitive emotion regulation, social support, and resilience were significantly associated with one another, and negative-focused cognitive emotion regulation was negatively associated with social support. Regression analysis and bootstrap analysis showed that social support and resilience had partly mediating effects on negative strategies and acute stress, and fully mediating effects on positive strategies and acute stress. These results thus indicate that military acute stress is significantly associated with cognitive emotion regulation, social support, and resilience, and that social support and resilience have multiple mediation effects on the relationship between cognitive emotion regulation and acute stress responses. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Immune responses of B. malayi thioredoxin (TRX) and venom allergen homologue (VAH) chimeric multiple antigen for lymphatic filariasis.

    Science.gov (United States)

    Anugraha, Gandhirajan; Jeyaprita, Parasurama Jawaharlal; Madhumathi, Jayaprakasam; Sheeba, Tamilvanan; Kaliraj, Perumal

    2013-12-01

    Although multiple vaccine strategy for lymphatic filariasis has provided tremendous hope, the choice of antigens used in combination has determined its success in the previous studies. Multiple antigens comprising key vaccine candidates from different life cycle stages would provide a promising strategy if the antigenic combination is chosen by careful screening. In order to analyze one such combination, we have used a chimeric construct carrying the well studied B. malayi antigens thioredoxin (BmTRX) and venom allergen homologue (BmVAH) as a fusion protein (TV) and evaluated its immune responses in mice model. The efficacy of fusion protein vaccine was explored in comparison with the single antigen vaccines and their cocktail. In mice, TV induced significantly high antibody titer of 1,28,000 compared to cocktail vaccine TRX+VAH (50,000) and single antigen vaccine TRX (16,000) or VAH (50,000). Furthermore, TV elicited higher level of cellular proliferative response together with elevated levels of IFN-γ, IL-4 and IL-5 indicating a Th1/Th2 balanced response. The isotype antibody profile showed significantly high level of IgG1 and IgG2b confirming the balanced response elicited by TV. Immunization with TV antigen induced high levels of both humoral and cellular immune responses compared to either cocktail or antigen given alone. The result suggests that TV is highly immunogenic in mice and hence the combination needs to be evaluated for its prophylactic potential.

  18. Patient-reported questionnaires in MS rehabilitation: responsiveness and minimal important difference of the multiple sclerosis questionnaire for physiotherapists (MSQPT).

    Science.gov (United States)

    van der Maas, Nico Arie

    2017-03-16

    The Multiple Sclerosis Questionnaire for Physical Therapists (MSQPT) is a patient-rated outcome questionnaire for evaluating the rehabilitation of persons with multiple sclerosis (MS). Responsiveness was evaluated, and minimal important difference (MID) estimates were calculated to provide thresholds for clinical change for four items, three sections and the total score of the MSQPT. This multicentre study used a combined distribution- and anchor-based approach with multiple anchors and multiple rating of change questions. Responsiveness was evaluated using effect size, standardized response mean (SRM), modified SRM and relative efficiency. For distribution-based MID estimates, 0.2 and 0.33 standard deviations (SD), standard error of measurement (SEM) and minimal detectable change were used . Triangulation of anchor- and distribution-based MID estimates provided a range of MID values for each of the four items, the three sections and the total score of the MSQPT. The MID values were tested for their sensitivity and specificity for amelioration and deterioration for each of the four items, the three sections and the total score of the MSQPT. The MID values of each item and section and of the total score with the best sensitivity and specificity were selected as thresholds for clinical change. The outcome measures were the MSQPT, Hamburg Quality of Life Questionnaire for Multiple Sclerosis (HAQUAMS), rating of change questionnaires, Expanded Disability Status Scale, 6-metre timed walking test, Berg Balance Scale and 6-minute walking test. The effect size ranged from 0.46 to 1.49. The SRM data showed comparable results. The modified SRM ranged from 0.00 to 0.60. Anchor-based MID estimates were very low and were comparable with SD- and SEM-based estimates. The MSQPT was more responsive than the HAQUAMS in detecting improvement but less responsive in finding deterioration. The best MID estimates of the items, sections and total score, expressed in percentage of their

  19. Retrospektive evaluation of the response of montane forest ecosystem to multiple stress

    Czech Academy of Sciences Publication Activity Database

    Cudlín, Pavel; Novotný, Radek; Moravec, Ivo; Chmelíková, Ewa

    2001-01-01

    Roč. 20, č. 1 (2001), s. 108-124 ISSN 1335-342X R&D Projects: GA ČR GA526/98/1147 Institutional research plan: CEZ:AV0Z6087904 Keywords : norway spruce * multiple stress * crown structure Subject RIV: EH - Ecology, Behaviour Impact factor: 0.192, year: 2001

  20. Cellular response of pulp fibroblast to single or multiple photobiomodulation applications

    Science.gov (United States)

    Fernandes, Amanda; Lourenço Neto, Natalino; Teixeira Marques, Nadia Carolina; Lourenço Ribeiro Vitor, Luciana; Tavares Oliveira Prado, Mariel; Cardoso Oliveira, Rodrigo; Moreira Machado, Maria Aparecida Andrade; Marchini Oliveira, Thais

    2018-06-01

    This study aimed to evaluate in vitro the effects of single or multiple photobiomodulation (PBM) applications on the viability and proliferation of pulp fibroblasts. Pulp fibroblasts from human deciduous teeth were obtained from a biorepository, plated into 96-well plates, and irradiated according to the experimental groups. At 24 h, 48 h, and 72 h after irradiation, cell viability and proliferation were assessed through MTT and Crystal Violet assays, respectively. The intragroup comparison revealed statistically significant differences for 2.5 J cm‑2 (3×) with increasing viability at 72 h over 48 h (p  =  0.027). The intergroup analysis showed a greater viability of the multiple PBM applications 2.5 J cm‑2 (3×) over the single application 7.5 J cm‑2 (1×) at 72 h. The application of 5 J cm‑2 (1×) exhibited greater proliferation than the application of 7.5 J cm‑2 (1×), 2.5 J cm‑2 (2×) and 2.5 J cm‑2 (3×). Single or multiple PBM applications demonstration different stimulatory effects on pulp fibroblast. The results show that the group submitted to multiple irradiation presented significantly higher cell viability than the groups with single irradiation at 72 h. However, the photobiomodulation therapy with single irradiations was more effective on cell proliferation at 24 h.

  1. The biological clock modulates the human cortisol response in a multiplicative fashion

    NARCIS (Netherlands)

    van de Werken, Maan; Booij, Sanne H.; van der Zwan, J Esi; Simons, Mirre J. P.; Gordijn, Marijke C. M.; Beersma, Domien G. M.

    Human cortisol levels follow a clear circadian rhythm. We investigated the contribution of alternation of sleep and wakefulness and the circadian clock, using forced desynchrony. Cortisol levels were best described by a multiplication of a circadian and a wake-time component. The human cortisol

  2. Influence of Number Size, Problem Structure and Response Mode on Children's Solutions of Multiplication Word Problems.

    Science.gov (United States)

    De Corte, E.; And Others

    One important finding from recent research on multiplication word problems is that children's performances are strongly affected by the nature of the multiplier (whether it is an integer, decimal larger than 1 or a decimal smaller than 1). On the other hand, the size of the multiplicand has little or no effect on problem difficulty. The aim of the…

  3. Taking Teacher Responsibility into Account(ability): Explicating Its Multiple Components and Theoretical Status

    Science.gov (United States)

    Lauermann, Fani; Karabenick, Stuart A.

    2011-01-01

    Accountability systems have important implications for schooling. Missing from discussions about their implementation, however, are ways they affect teacher responsibility. Responsibility has been insufficiently explicated in the education literature, including its impact on teacher motivation, emotion, and behavior. We propose that a…

  4. Broadband Structural Dynamics: Understanding the Impulse-Response of Structures Across Multiple Length and Time Scales

    Science.gov (United States)

    2010-08-18

    Spectral domain response calculated • Time domain response obtained through inverse transform Approach 4: WASABI Wavelet Analysis of Structural Anomalies...differences at unity scale! Time Function Transform Apply Spectral Domain Transfer Function Time Function Inverse Transform Transform Transform  mtP

  5. Stochastic order in dichotomous item response models for fixed tests, research adaptive tests, or multiple abilities

    NARCIS (Netherlands)

    van der Linden, Willem J.

    1995-01-01

    Dichotomous item response theory (IRT) models can be viewed as families of stochastically ordered distributions of responses to test items. This paper explores several properties of such distributiom. The focus is on the conditions under which stochastic order in families of conditional

  6. Assessment of the Coral Temperature Proxies for Orbicella faveolata in the Southwestern Gulf of Mexico

    Science.gov (United States)

    Vara, M. A.; DeLong, K. L.; Herrmann, A. D.; Ouellette, G., Jr.; Richey, J. N.

    2017-12-01

    Coral Sr/Ca is a robust proxy of sea surface temperature (SST); however, discrepancies in the Sr/Ca-SST relationship among colonies of the same species may reduce confidence in absolute temperature reconstructions. Furthermore, terrestrial carbonate weathering can provide local sources of Sr and/or Ca to coastal waters that may disrupt the temperature-based coral Sr/Ca signal. Thus other trace metal SST proxies have been suggested to circumvent these issues (Li/Ca, Li/Mg, and Sr-U). Coral Ba/Ca has been used as a proxy for runoff and coastal upwelling, and therefore may be used to identify intervals when these processes overprint the Sr/Ca-SST signal. This study tests multiple coral SST proxies using reproducibility assessments to determine the best performing SST proxy. We conduct these assessments with cores recovered in 1991 by the U.S. Geological Survey from five Orbicella faveolata colonies from three reefs offshore of Veracruz, Mexico (19.06°N, 96.93°W) in water depths varying from 3 to 12 m. Previous studies found micromilling the complex skeletal structure of O. faveolata challenging and that monthly resolution may not recover full seasonal cycles. We use a laser ablation inductively coupled plasma mass spectrometer to simultaneously sample this coral's structure at weekly intervals spanning 8 years for Li/Ca, Li/Mg, Sr-U, Sr/Ca, and Ba/Ca. Here we found coral Li/Ca means and seasonal variations are similar among colonies thus this proxy may capture absolute temperature and SST variability. Similar to previous research with Porites corals, Li/Ca in these O. faveolata corals decreases with increases in SST with similar slopes and intercepts. During the last 10 years of these corals' lives, coral Sr/Ca analysis reveals a mean shift among colonies suggesting an external source could have disrupted the Sr/Ca signal, possibly seasonal runoff and/or winter upwelling common to Veracruz waters. Coral Ba/Ca analyses reveals elevated values in winters that coincide

  7. He said, she said: The gender wage gap according to self and proxy reports in the Current Population Survey.

    Science.gov (United States)

    Reynolds, Jeremy; Wenger, Jeffrey B

    2012-03-01

    Roughly half the labor force data in the Current Population Survey (CPS) are provided by proxy respondents, and since 1979, men's reliance on proxies has dropped dramatically while women's reliance on proxies has increased. Few authors, however, have examined how combining these first-hand and second-hand reports may influence our understanding of long-term economic trends. We exploit the outgoing rotation group structure of the CPS by matching individual records one year apart, and we find that self-reported wages are higher than proxy-reported wages even after controlling for all time invariant characteristics. Furthermore, we find that changes in the use of proxy respondents by men and women since 1979 have made current estimates of the gender wage gap larger than they would have been without changes in reporting status. This suggests that the gender wage gap has closed more than previously estimated. We recommend that researchers combine self and proxy responses with great care, especially when analyzing time trends or making gender comparisons. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy

    DEFF Research Database (Denmark)

    Toftmann Hansen, Charlotte; Pedersen, Per T.; Jensen, Bo Amdi

    Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy.......Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy....

  9. Validity of proxy data obtained by different psychological autopsy information reconstruction techniques.

    Science.gov (United States)

    Fang, L; Zhang, J

    2010-01-01

    Two informants were interviewed for each of 416 living controls (individuals sampled from the normal population) interviewed in a Chinese case-control psychological autopsy study. The validity of proxy data, obtained using seven psychological autopsy information reconstruction techniques (types 1, 2 and A - E), was evaluated, with living controls' self reports used as the gold-standard. Proxy data for reconstruction technique types 1, 2 and D on the Impulsivity Inventory Scale (total impulsivity score) were no different from the living controls' self report gold standard, whereas data for types A and E were smaller than data from living controls. On the 'acceptance or resignation' sub-scale of the avoidance coping dimension of the Moos Coping Response Inventory, information obtained by reconstruction technique types 1 and D was not significantly different from the living controls' self reports, whereas proxy data from types 2, A and E were smaller than those from the living controls. No statistically significant differences were identified for other proxy data obtained by reconstruction technique types 1, 2, A, D and E. These results indicate that using a second informant does not significantly enhance information reconstruction for the target.

  10. [Analysis of prevalence of self-reported hearing loss and associated factors: primary versus proxy informant].

    Science.gov (United States)

    Quevedo, André Luis Alves de; Leotti, Vanessa Bielefeldt; Goulart, Bárbara Niegia Garcia de

    2017-07-03

    The objective was to evaluate differences between prevalence rates for self-reported hearing loss and associated factors, obtained from responses by primary and proxy informants in a Population-Based Study on Human Communication Disorders (DCH-POP in Portuguese). This was a study on epidemiological methods using data from a cross-sectional household survey with a sample of 1,253 individuals from Southern Brazil. To verify differences between prevalence rates comparing primary informants and proxy informants, we used the chi-square or Fisher's exact test for categorical variables and Mann-Whitney for continuous variables. The log-binomial model was adjusted for hearing loss as the dependent variable, considering three datasets: the entire sample, only primary informants, and only proxy informants, estimating association by prevalence ratios. In the final models, only the independent variables age and dizziness were associated with hearing loss, independently of the dataset that was used. Proxy informants generally underestimated the prevalence rates for the target outcomes, when compared to primary informants.

  11. Pooling Data from Multiple Longitudinal Studies: The Role of Item Response Theory in Integrative Data Analysis

    Science.gov (United States)

    Curran, Patrick J.; Hussong, Andrea M.; Cai, Li; Huang, Wenjing; Chassin, Laurie; Sher, Kenneth J.; Zucker, Robert A.

    2010-01-01

    There are a number of significant challenges encountered when studying development over an extended period of time including subject attrition, changing measurement structures across group and developmental period, and the need to invest substantial time and money. Integrative data analysis is an emerging set of methodologies that overcomes many of the challenges of single sample designs through the pooling of data drawn from multiple existing developmental studies. This approach is characterized by a host of advantages, but this also introduces several new complexities that must be addressed prior to broad adoption by developmental researchers. In this paper we focus on methods for fitting measurement models and creating scale scores using data drawn from multiple longitudinal studies. We present findings from the analysis of repeated measures of internalizing symptomatology that were pooled from three existing developmental studies. We describe and demonstrate each step in the analysis and we conclude with a discussion of potential limitations and directions for future research. PMID:18331129

  12. Endoplasmic reticulum stress response as a potential therapeutic target in multiple sclerosis

    OpenAIRE

    Getts, Meghann Teague; Getts, Daniel R.; Kohm, Adam P.; Miller, Stephen D

    2008-01-01

    Multiple Sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system (CNS). Since current treatments are aimed at nonspecifically down-regulating inflammation and natural mechanisms of repair and remyelination within the CNS are inadequate for recovery of function, MS patients presently only have available treatments that delay symptom progression. The complex nature of this disease means that only multifaceted treatments hold the promise of a cure. Recent studies i...

  13. Hemodynamic responses during and after multiple sets of stretching exercises performed with and without the Valsalva maneuver.

    Science.gov (United States)

    Lima, Tainah P; Farinatti, Paulo T V; Rubini, Ercole C; Silva, Elirez B; Monteiro, Walace D

    2015-05-01

    This study investigated the acute hemodynamic responses to multiple sets of passive stretching exercises performed with and without the Valsalva maneuver. Fifteen healthy men aged 21 to 29 years with poor flexibility performed stretching protocols comprising 10 sets of maximal passive unilateral hip flexion, sustained for 30 seconds with equal intervals between sets. Protocols without and with the Valsalva maneuver were applied in a random counterbalanced order, separated by 48-hour intervals. Hemodynamic responses were measured by photoplethysmography pre-exercise, during the stretching sets, and post-exercise. The effects of stretching sets on systolic and diastolic blood pressure were cumulative until the fourth set in protocols performed with and without the Valsalva maneuver. The heart rate and rate pressure product increased in both protocols, but no additive effect was observed due to the number of sets. Hemodynamic responses were always higher when stretching was performed with the Valsalva maneuver, causing an additional elevation in the rate pressure product. Multiple sets of unilateral hip flexion stretching significantly increased blood pressure, heart rate, and rate pressure product values. A cumulative effect of the number of sets occurred only for systolic and diastolic blood pressure, at least in the initial sets of the stretching protocols. The performance of the Valsalva maneuver intensified all hemodynamic responses, which resulted in significant increases in cardiac work during stretching exercises.

  14. Human cortical responses to slow and fast binaural beats reveal multiple mechanisms of binaural hearing.

    Science.gov (United States)

    Ross, Bernhard; Miyazaki, Takahiro; Thompson, Jessica; Jamali, Shahab; Fujioka, Takako

    2014-10-15

    When two tones with slightly different frequencies are presented to both ears, they interact in the central auditory system and induce the sensation of a beating sound. At low difference frequencies, we perceive a single sound, which is moving across the head between the left and right ears. The percept changes to loudness fluctuation, roughness, and pitch with increasing beat rate. To examine the neural representations underlying these different perceptions, we recorded neuromagnetic cortical responses while participants listened to binaural beats at a continuously varying rate between 3 Hz and 60 Hz. Binaural beat responses were analyzed as neuromagnetic oscillations following the trajectory of the stimulus rate. Responses were largest in the 40-Hz gamma range and at low frequencies. Binaural beat responses at 3 Hz showed opposite polarity in the left and right auditory cortices. We suggest that this difference in polarity reflects the opponent neural population code for representing sound location. Binaural beats at any rate induced gamma oscillations. However, the responses were largest at 40-Hz stimulation. We propose that the neuromagnetic gamma oscillations reflect postsynaptic modulation that allows for precise timing of cortical neural firing. Systematic phase differences between bilateral responses suggest that separate sound representations of a sound object exist in the left and right auditory cortices. We conclude that binaural processing at the cortical level occurs with the same temporal acuity as monaural processing whereas the identification of sound location requires further interpretation and is limited by the rate of object representations. Copyright © 2014 the American Physiological Society.

  15. Secure Mobile Agent from Leakage-Resilient Proxy Signatures

    Directory of Open Access Journals (Sweden)

    Fei Tang

    2015-01-01

    Full Text Available A mobile agent can sign a message in a remote server on behalf of a customer without exposing its secret key; it can be used not only to search for special products or services, but also to make a contract with a remote server. Hence a mobile agent system can be used for electronic commerce as an important key technology. In order to realize such a system, Lee et al. showed that a secure mobile agent can be constructed using proxy signatures. Intuitively, a proxy signature permits an entity (delegator to delegate its signing right to another entity (proxy to sign some specified messages on behalf of the delegator. However, the proxy signatures are often used in scenarios where the signing is done in an insecure environment, for example, the remote server of a mobile agent system. In such setting, an adversary could launch side-channel attacks to exploit some leakage information about the proxy key or even other secret states. The proxy signatures which are secure in the traditional security models obviously cannot provide such security. Based on this consideration, in this paper, we design a leakage-resilient proxy signature scheme for the secure mobile agent systems.

  16. Multiple bony metastases of breast cancer. Role of CA 15.3 and response to hormone therapy

    International Nuclear Information System (INIS)

    Lopez C, Nayara; Ramon G, Natividad; Sanchez M, Jose Ignacio; De Santiago G, Javier

    2012-01-01

    Bone metastases are involved in a 65-75% of advanced metastatic breast cancer cases. Tumoral markers (CEA, CA 15.3) are useful in the follow-up and evaluation of response to treatment. Hormonal therapy is the optimal treatment option in low grade metastatic breast cancer due to low toxicity and general long term good response. We present a breast cancer case treated with surgery, chemotherapy and radiotherapy. The patient was asymptomatic during the follow-up and multiple bone metastases were diagnosed as a result of an increased CA 15.3 marker found. Hormone therapy was the recommended initial treatment with good response and tolerance. Bone lesions remained stabilized for 7 years but after treatment suspension new bone lesions appeared. CA 15.3 marker had increased again. Reintroduction of hormonal therapy achieved again the stabilization of the lesions

  17. Heterogeneity of response to antipsychotics from multiple disorders in the schizophrenia spectrum.

    Science.gov (United States)

    Garver, D L; Holcomb, J A; Christensen, J D

    2000-12-01

    Antipsychotic response after the initiation of neuroleptic treatment shows wide variation in schizophrenic patient populations. In this overview, the authors suggest that the variance in antipsychotic drug response within schizophrenia can be reduced by resolving the schizophrenias into several discrete "endophenotypes," each with different etiologic underpinnings. Studies relating differences in the relative speed or completeness of antipsychotic response to differences in distribution of 2 biological markers with possible etiologic significance are reviewed. Such studies had assessed recently hospitalized, neuroleptic-free patients undergoing exacerbation of nonaffective psychotic disorders. Prior to initiation of neuroleptic, the cohort of patients had been assessed for the quantity of the dopamine metabolite homovanillic acid in plasma (pHVA) and had undergone the first of 2 magnetic resonance imaging (MRI) studies for analyses of ventricle volumes. A second MRI was subsequently performed during a period of (partial) remission to determine within-patient stability of ventricular volumes. These selected studies assessed the distribution of pHVA and distribution of rates of ventricular change, with non-normal distributions resolved by K-means clustering. The speed and completeness of neuroleptic-induced antipsychotic response were related to 3 clusters of patients delineated by modal distributions of pHVA and of apparent rates of ventricular change. At least 3 unique "endophenotypes" of the "group of the schizophrenias" can be defined with respect to speed and completeness of antipsychotic response. Each endophenotype appears to show at least one unique biological feature that differentiates it from a normal comparison group. A rapidly responsive psychosis was associated with excessive production of dopamine, as identifiable by elevation of pHVA and a "good-prognosis" course. A delayed-response psychosis had low-to-normal pHVA, clinically demonstrated persistent

  18. Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.

    Directory of Open Access Journals (Sweden)

    Peter C Cook

    2011-03-01

    Full Text Available Infection of the mammalian host by schistosome larvae occurs via the skin, although nothing is known about the development of immune responses to multiple exposures of schistosome larvae, and/or their excretory/secretory (E/S products. Here, we show that multiple (4x exposures, prior to the onset of egg laying by adult worms, modulate the skin immune response and induce CD4(+ cell hypo-responsiveness in the draining lymph node, and even modulate the formation of hepatic egg-induced granulomas. Compared to mice exposed to a single infection (1x, dermal cells from multiply infected mice (4x, were less able to support lymph node cell proliferation. Analysis of dermal cells showed that the most abundant in 4x mice were eosinophils (F4/80(+MHC-II(-, but they did not impact the ability of antigen presenting cells (APC to support lymphocyte proliferation to parasite antigen in vitro. However, two other cell populations from the dermal site of infection appear to have a critical role. The first comprises arginase-1(+, Ym-1(+ alternatively activated macrophage-like cells, and the second are functionally compromised MHC-II(hi cells. Through the administration of exogenous IL-12 to multiply infected mice, we show that these suppressive myeloid cell phenotypes form as a consequence of events in the skin, most notably an enrichment of IL-4 and IL-13, likely resulting from an influx of RELMα-expressing eosinophils. We further illustrate that the development of these suppressive dermal cells is dependent upon IL-4Rα signalling. The development of immune hypo-responsiveness to schistosome larvae and their effect on the subsequent response to the immunopathogenic egg is important in appreciating how immune responses to helminth infections are modulated by repeated exposure to the infective early stages of development.

  19. L-Amino Acids Elicit Diverse Response Patterns in Taste Sensory Cells: A Role for Multiple Receptors

    Science.gov (United States)

    Pal Choudhuri, Shreoshi; Delay, Rona J.; Delay, Eugene R.

    2015-01-01

    Umami, the fifth basic taste, is elicited by the L-amino acid, glutamate. A unique characteristic of umami taste is the response potentiation by 5’ ribonucleotide monophosphates, which are also capable of eliciting an umami taste. Initial reports using human embryonic kidney (HEK) cells suggested that there is one broadly tuned receptor heterodimer, T1r1+T1r3, which detects L-glutamate and all other L-amino acids. However, there is growing evidence that multiple receptors detect glutamate in the oral cavity. While much is understood about glutamate transduction, the mechanisms for detecting the tastes of other L-amino acids are less well understood. We used calcium imaging of isolated taste sensory cells and taste cell clusters from the circumvallate and foliate papillae of C57BL/6J and T1r3 knockout mice to determine if other receptors might also be involved in detection of L-amino acids. Ratiometric imaging with Fura-2 was used to study calcium responses to monopotassium L-glutamate, L-serine, L-arginine, and L-glutamine, with and without inosine 5’ monophosphate (IMP). The results of these experiments showed that the response patterns elicited by L-amino acids varied significantly across taste sensory cells. L-amino acids other than glutamate also elicited synergistic responses in a subset of taste sensory cells. Along with its role in synergism, IMP alone elicited a response in a large number of taste sensory cells. Our data indicate that synergistic and non-synergistic responses to L-amino acids and IMP are mediated by multiple receptors or possibly a receptor complex. PMID:26110622

  20. Microstructural response and grain refinement mechanism of commercially pure titanium subjected to multiple laser shock peening impacts

    International Nuclear Information System (INIS)

    Lu, J.Z.; Wu, L.J.; Sun, G.F.; Luo, K.Y.; Zhang, Y.K.; Cai, J.; Cui, C.Y.; Luo, X.M.

    2017-01-01

    The microstructural response and grain subdivision process in commercially pure (CP) titanium subjected to multiple laser shock peening (LSP) impacts were investigated by means of optical microscopy (OM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations. The micro-hardness curves as a function of the impact time were also determined. The deformation-induced grain refinement mechanism of the close-packed hexagonal (hcp) material by laser shock wave was subsequently analyzed. Experimental results showed that uniform equiaxed grains with an average size of less than 50 nm were generated due to the ultra-high plastic strain induced by multiple LSP impacts. Special attention was paid to four types of novel deformation-induced microstructural features, including a layered slip band in the tension deformation zone, and inverse-transformation martensite, micro-twin grating and micro-twin collision in the compression deformation zone. Furthermore, the grain refinement mechanism in the near-surface layer of CP titanium subjected to multiple LSP impacts contains two types of simultaneous subdivision modes: multi-directional mechanical twin (MT)-MT intersections at (sub)micrometer scale, and the intersection between longitudinal secondary MTs and transverse dislocation walls at nanometer scale. In addition, both grain refinement (nanocrystallization) and the existence of a small amount of inverse-transformation martensite induced by multiple LSP impacts contribute to an increase in the micro-hardness of the near-surface layer.

  1. Acute Responses of a Physical Training Session with a Nintendo Wii on Hemodynamic Variables of an Individual with Multiple Sclerosis.

    Science.gov (United States)

    Monteiro Junior, Renato Sobral; Dantas, Aretha; de Souza, Cíntia Pereira; da Silva, Elirez Bezerra

    2012-12-01

    Multiple sclerosis is a neurological illness that decreases motor functions. This disease can cause weakness of cardiorespiratory muscles and impaired functional capacity and quality of life. Therefore it requires preventive treatments. This study investigated the acute responses of a virtual physical training session with the Nintendo(®) (Kyoto, Japan) Wii™ on hemodynamic variables of an individual with multiple sclerosis (relapsing-remitting). A 34-year-old man with multiple sclerosis with previous experience in aerobic, strength, and functional training (2 years) was tested. His Expanded Disability Status Scale was 2.5. We compared the heart rate, blood pressure, and double product obtained at rest and during (heart rate) and after the Nintendo Wii games "Boxing" and "Sword Play." In rest, the variables were measured in the supine position. Our results showed positive hemodynamic alterations after execution of both games. The peak of heart rate was 121 beats per minute (65% of maximal heart rate) and 104 beats per minute (56% of maximal heart rate) for "Boxing" and "Sword Play," respectively. The training session with "Boxing" was able to stimulate the heart rate to achieve the recommended values for the maintenance of physical fitness in accordance with the American College of Sports Medicine guidelines. We conclude that an exercise training program with the Nintendo Wii may improve physical fitness in people with multiple sclerosis. Moreover, these activities could improve affective status and perhaps maintain the individual engaged at treatment program.

  2. Cryptanalytic Performance Appraisal of Improved CCH2 Proxy Multisignature Scheme

    Directory of Open Access Journals (Sweden)

    Raman Kumar

    2014-01-01

    Full Text Available Many of the signature schemes are proposed in which the t out of n threshold schemes are deployed, but they still lack the property of security. In this paper, we have discussed implementation of improved CCH1 and improved CCH2 proxy multisignature scheme based on elliptic curve cryptosystem. We have represented time complexity, space complexity, and computational overhead of improved CCH1 and CCH2 proxy multisignature schemes. We have presented cryptanalysis of improved CCH2 proxy multisignature scheme and showed that improved CCH2 scheme suffered from various attacks, that is, forgery attack and framing attack.

  3. Web proxy cache replacement strategies simulation, implementation, and performance evaluation

    CERN Document Server

    ElAarag, Hala; Cobb, Jake

    2013-01-01

    This work presents a study of cache replacement strategies designed for static web content. Proxy servers can improve performance by caching static web content such as cascading style sheets, java script source files, and large files such as images. This topic is particularly important in wireless ad hoc networks, in which mobile devices act as proxy servers for a group of other mobile devices. Opening chapters present an introduction to web requests and the characteristics of web objects, web proxy servers and Squid, and artificial neural networks. This is followed by a comprehensive review o

  4. The B Cell Response to Foot-and-Mouth Disease Virus in Cattle following Sequential Vaccination with Multiple Serotypes.

    Science.gov (United States)

    Grant, Clare F J; Carr, B Veronica; Kotecha, Abhay; van den Born, Erwin; Stuart, David I; Hammond, John A; Charleston, Bryan

    2017-05-01

    Foot-and-mouth disease virus (FMDV) is a highly contagious viral disease. Antibodies are pivotal in providing protection against FMDV infection. Serological protection against one FMDV serotype does not confer interserotype protection. However, some historical data have shown that interserotype protection can be induced following sequential FMDV challenge with multiple FMDV serotypes. In this study, we have investigated the kinetics of the FMDV-specific antibody-secreting cell (ASC) response following homologous and heterologous inactivated FMDV vaccination regimes. We have demonstrated that the kinetics of the B cell response are similar for all four FMDV serotypes tested following a homologous FMDV vaccination regime. When a heterologous vaccination regime was used with the sequential inoculation of three different inactivated FMDV serotypes (O, A, and Asia1 serotypes) a B cell response to FMDV SAT1 and serotype C was induced. The studies also revealed that the local lymphoid tissue had detectable FMDV-specific ASCs in the absence of circulating FMDV-specific ASCs, indicating the presence of short-lived ASCs, a hallmark of a T-independent 2 (TI-2) antigenic response to inactivated FMDV capsid. IMPORTANCE We have demonstrated the development of intraserotype response following a sequential vaccination regime of four different FMDV serotypes. We have found indication of short-lived ASCs in the local lymphoid tissue, further evidence of a TI-2 response to FMDV. Copyright © 2017 American Society for Microbiology.

  5. Multiple Mechanisms are Responsible for Transactivation of the Epidermal Growth Factor Receptor in Mammary Epithelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Rodland, Karin D.; Bollinger, Nikki; Ippolito, Danielle L.; Opresko, Lee; Coffey, Robert J.; Zangar, Richard C.; Wiley, H. S.

    2008-11-14

    REVIEW ENTIRE DOCUMENT AT: https://pnlweb.pnl.gov/projects/bsd/ERICA%20Manuscripts%20for%20Review/KD%20Rodland%20D7E80/HMEC_transactivation_ms01_15+Figs.pdf ABSTRACT: Using a single nontransformed strain of human mammary epithelial cells, we found that the ability of multiple growth factors and cytokines to induce ERK phosphorylation was dependent on EGFR activity. These included lysophosphatidic acid (LPA), uridine triphosphate, growth hormone, vascular endothelial growth factor, insulin-like growth factor-1 (IGF-1), and tumor necrosis factoralpha. In contrast, hepatocyte growth factor could stimulate ERK phosphorylation independent of EGFR activity...

  6. Plastic responses of a sessile prey to multiple predators: a field and experimental study.

    Directory of Open Access Journals (Sweden)

    Philipp Emanuel Hirsch

    Full Text Available Theory predicts that prey facing a combination of predators with different feeding modes have two options: to express a response against the feeding mode of the most dangerous predator, or to express an intermediate response. Intermediate phenotypes protect equally well against several feeding modes, rather than providing specific protection against a single predator. Anti-predator traits that protect against a common feeding mode displayed by all predators should be expressed regardless of predator combination, as there is no need for trade-offs.We studied phenotypic anti-predator responses of zebra mussels to predation threat from a handling-time-limited (crayfish and a gape-size-limited (roach predator. Both predators dislodge mussels from the substrate but diverge in their further feeding modes. Mussels increased expression of a non-specific defense trait (attachment strength against all combinations of predators relative to a control. In response to roach alone, mussels showed a tendency to develop a weaker and more elongated shell. In response to crayfish, mussels developed a harder and rounder shell. When exposed to either a combination of predators or no predator, mussels developed an intermediate phenotype. Mussel growth rate was positively correlated with an elongated weaker shell and negatively correlated with a round strong shell, indicating a trade-off between anti-predator responses. Field observations of prey phenotypes revealed the presence of both anti-predator phenotypes and the trade-off with growth, but intra-specific population density and bottom substrate had a greater influence than predator density.Our results show that two different predators can exert both functionally equivalent and inverse selection pressures on a single prey. Our field study suggests that abiotic factors and prey population density should be considered when attempting to explain phenotypic diversity in the wild.

  7. Noncoding Subgenomic Flavivirus RNA: Multiple Functions in West Nile Virus Pathogenesis and Modulation of Host Responses

    Directory of Open Access Journals (Sweden)

    Justin A. Roby

    2014-01-01

    Full Text Available Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV, Japanese encephalitis virus (JEV, yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested so far are shown to produce a unique subgenomic flavivirus RNA (sfRNA derived from the 3' untranslated region (UTR. sfRNA is a product of incomplete degradation of genomic RNA by the cell 5'–3' exoribonuclease XRN1 which stalls at highly ordered secondary RNA structures at the beginning of the 3'UTR. Generation of sfRNA results in inhibition of XRN1 activity leading to an increase in stability of many cellular mRNAs. Mutant WNV deficient in sfRNA generation was highly attenuated displaying a marked decrease in cytopathicity in cells and pathogenicity in mice. sfRNA has also been shown to inhibit the antiviral activity of IFN-α/β by yet unknown mechanism and of the RNAi pathway by likely serving as a decoy substrate for Dicer. Thus, sfRNA is involved in modulating multiple cellular pathways to facilitate viral pathogenicity; however the overlying mechanism linking all these multiple functions of sfRNA remains to be elucidated.

  8. Middle school science teachers' reaction and pedagogical response to high stakes accountability: A multiple case study

    Science.gov (United States)

    Tse, Kenneth

    The purpose of this study was to understand how science teachers reacted to the high stakes accountability and standardized testing in California. In a multiple case study of middle and intermediate schools in Southern California, four research questions focused on the perceptions of secondary science teachers and how they responded to the changes in the accountability specifically geared towards science as a content area, the pedagogical skills teachers were using both outside and inside of the classroom that impact instruction, the pedagogical training received that related specifically to the content standards, the tools or impediments that existed for teachers to successfully utilize these pedagogical methods and types of support and assistance the school site administration and/or school district offered in learning about the California Science Standards and the STAR test. Interviews were conducted with multiple middle/intermediate school teachers, science department chairpersons and school site administrators to gather information about what the classroom teachers were doing pedagogically to improve student performance on the STAR tests. Moreover, the study described the issues that supported the professional development of the teacher and what schools and districts were doing to support them.

  9. Simplified response monitoring criteria for multiple myeloma in patients undergoing therapy with novel agents using computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Schabel, Christoph; Horger, Marius; Kum, Sara [Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Weisel, Katja [Department of Internal Medicine II – Hematology & Oncology, Eberhard-Karls-University Tuebingen, Otfried-Müller-Str. 5, 72076 Tuebingen (Germany); Fritz, Jan [Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 600 N Wolfe St., Baltimore, MD 21287 (United States); Ioanoviciu, Sorin D. [Department of Internal Medicine, Clinical Municipal Hospital Timisoara, Gheorghe Dima Str. 5, 300079 Timisoara (Romania); Bier, Georg, E-mail: georg.bier@med.uni-tuebingen.de [Department of Neuroradiology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)

    2016-12-15

    Highlights: • A simplified method for response monitoring of multiple myeloma is proposed. • Medullary bone lesions of all limbs were included and analysed. • Diameters of ≥2 medullary bone lesions are sufficient for therapy monitoring. - Abstract: Introduction: Multiple myeloma is a malignant hematological disorder of the mature B-cell lymphocytes originating in the bone marrow. While therapy monitoring is still mainly based on laboratory biomarkers, the additional use of imaging has been advocated due to inaccuracies of serological biomarkers or in a-secretory myelomas. Non-enhanced CT and MRI have similar sensitivities for lesions in yellow marrow-rich bone marrow cavities with a favourable risk and cost-effectiveness profile of CT. Nevertheless, these methods are still limited by frequently high numbers of medullary lesions and its time consumption for proper evaluation. Objective: To establish simplified response criteria by correlating size and CT attenuation changes of medullary multiple myeloma lesions in the appendicular skeleton with the course of lytic bone lesions in the entire skeleton. Furthermore to evaluate these criteria with respect to established hematological myeloma-specific parameters for the prediction of treatment response to bortezomib or lenalidomide. Materials and methods: Non-enhanced reduced-dose whole-body CT examinations of 78 consecutive patients (43 male, 35 female, mean age 63.69 ± 9.2 years) with stage III multiple myeloma were retrospectively re-evaluated. On per patient basis, size and mean CT attenuation of 2–4 representative lesions in the limbs were measured at baseline and at a follow-up after a mean of 8 months. Results were compared with the course of lytical bone lesions as well with that of specific hematological biomarkers. Myeloma response was assessed according to the International Myeloma Working Group (IMWG) uniform response criteria. Testing for correlation between response of medullary lesions (Resp

  10. Multiple stressor effects on marine infauna: responses of estuarine taxa and functional traits to sedimentation, nutrient and metal loading

    KAUST Repository

    Ellis, Joanne

    2017-09-14

    Sedimentation, nutrients and metal loading to coastal environments are increasing, associated with urbanization and global warming, hence there is a growing need to predict ecological responses to such change. Using a regression technique we predicted how maximum abundance of 20 macrobenthic taxa and 22 functional traits separately and interactively responded to these key stressors. The abundance of most taxa declined in response to sedimentation and metal loading while a unimodal response was often associated with nutrient loading. Optimum abundances for both taxa and traits occurred at relatively low stressor levels, highlighting the vulnerability of estuaries to increasing stressor loads. Individual taxa were more susceptible to stress than traits, suggesting that functional traits may be less sensitive for detecting changes in ecosystem health. Multiplicative effects were more common than additive interactions. The observed sensitivity of most taxa to increasing sedimentation and metal loading and the documented interaction effects between multiple stressors have important implications for understanding and managing the ecological consequences of eutrophication, sedimentation and contaminants on coastal ecosystems.

  11. Development of a proxy-reported pulmonary outcome scale for preterm infants with bronchopulmonary dysplasia

    Directory of Open Access Journals (Sweden)

    Laughon Matthew M

    2011-07-01

    Full Text Available Abstract Background To develop an accurate, proxy-reported bedside measurement tool for assessment of the severity of bronchopulmonary dysplasia (also called chronic lung disease in preterm infants to supplement providers' current biometric measurements of the disease. Methods We adapted Patient-Reported Outcomes Measurement Information System (PROMIS methodology to develop the Proxy-Reported Pulmonary Outcomes Scale (PRPOS. A multidisciplinary group of registered nurses, nurse practitioners, neonatologists, developmental specialists, and feeding specialists at five academic medical centers participated in the PRPOS development, which included five phases: (1 identification of domains, items, and responses; (2 item classification and selection using a modified Delphi process; (3 focus group exploration of items and response options; (4 cognitive interviews on a preliminary scale; and (5 final revision before field testing. Results Each phase of the process helped us to identify, classify, review, and revise possible domains, questions, and response options. The final items for field testing include 26 questions or observations that a nurse assesses before, during, and after routine care time and feeding. Conclusions We successfully created a prototype scale using modified PROMIS methodology. This process can serve as a model for the development of proxy-reported outcomes scales in other pediatric populations.

  12. Single Parents and the Work Setting: The Impact of Multiple Job and Homelife Responsibilities.

    Science.gov (United States)

    Burden, Dianne S.

    1986-01-01

    Examines the impact of combined work/family responsibilities on single-parent employees. Results indicated that parent employees, but particularly single female parents, were at risk for high job-family role strain and reduced levels of well-being. In spite of increased strain, however, single parents exhibited high levels of job satisfaction and…

  13. Multiple bottlenecks in hierarchical control of action sequences: what does "response selection" select in skilled typewriting?

    Science.gov (United States)

    Yamaguchi, Motonori; Logan, Gordon D; Li, Vanessa

    2013-08-01

    Does response selection select words or letters in skilled typewriting? Typing performance involves hierarchically organized control processes: an outer loop that controls word level processing, and an inner loop that controls letter (or keystroke) level processing. The present study addressed whether response selection occurs in the outer loop or the inner loop by using the psychological refractory period (PRP) paradigm in which Task1 required typing single words and Task2 required vocal responses to tones. The number of letters (string length) in the words was manipulated to discriminate selection of words from selection of keystrokes. In Experiment 1, the PRP effect depended on string length of words in Task1, suggesting that response selection occurs in the inner loop. To assess contributions of the outer loop, the influence of string length was examined in a lexical-decision task that also involves word encoding and lexical access (Experiment 2), or to-be-typed words were preexposed so outer-loop processing could finish before typing started (Experiment 3). Response time for Task2 (RT2) did not depend on string length with lexical decision, and RT2 still depended on string length with typing preexposed strings. These results support the inner-loop locus of the PRP effect. In Experiment 4, typing was performed as Task2, and the effect of string length on typing RT interacted with stimulus onset asynchrony superadditively, implying that another bottleneck also exists in the outer loop. We conclude that there are at least two bottleneck processes in skilled typewriting. 2013 APA, all rights reserved

  14. Assessment of a mussel as a metal bioindicator of coastal contamination: Relationships between metal bioaccumulation and multiple biomarker responses

    International Nuclear Information System (INIS)

    Chandurvelan, Rathishri; Marsden, Islay D.; Glover, Chris N.; Gaw, Sally

    2015-01-01

    This is the first study to use a multiple biomarker approach on the green-lipped mussel, Perna canaliculus to test its feasibility as a bioindicator of coastal metal contamination in New Zealand (NZ). Mussels were collected from six low intertidal sites varying in terms of anthropogenic impacts, within two regions (West Coast and Nelson) of the South Island of NZ. Trace elements, including arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), nickel (Ni), and zinc (Zn), were measured in the gills, digestive gland, foot and mantle, and in the surface sediments from where mussels were collected. Metal levels in the sediment were relatively low and there was only one site (Mapua, Nelson) where a metal (Ni) exceeded the Australian and New Zealand Interim Sediment Quality Guideline values. Metal levels in the digestive gland were generally higher than those from the other tissues. A variety of biomarkers were assessed to ascertain mussel health. Clearance rate, a physiological endpoint, correlated with metal level in the tissues, and along with scope for growth, was reduced in the most contaminated site. Metallothionein-like protein content and catalase activity in the digestive gland, and catalase activity and lipid peroxidation in the gill, were also correlated to metal accumulation. Although there were few regional differences, the sampling sites were clearly distinguishable based on the metal contamination profiles and biomarker responses. P. canaliculus appears to be a useful bioindicator species for coastal habitats subject to metal contamination. In this study tissue and whole organism responses provided insight into the biological stress responses of mussels to metal contaminants, indicating that such measurements could be a useful addition to biomonitoring programmes in NZ. - Highlights: • Multiple biomarker responses were measured in mussels from 6 sites. • Metal content of mussel tissues correlated with specific biomarker responses. • Clearance rate

  15. Assessment of a mussel as a metal bioindicator of coastal contamination: Relationships between metal bioaccumulation and multiple biomarker responses

    Energy Technology Data Exchange (ETDEWEB)

    Chandurvelan, Rathishri, E-mail: rch118@uclive.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Marsden, Islay D., E-mail: islay.marsden@canterbury.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Glover, Chris N., E-mail: chris.glover@canterbury.ac.nz [School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand); Gaw, Sally, E-mail: sally.gaw@canterbury.ac.nz [Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch 8140 (New Zealand)

    2015-04-01

    This is the first study to use a multiple biomarker approach on the green-lipped mussel, Perna canaliculus to test its feasibility as a bioindicator of coastal metal contamination in New Zealand (NZ). Mussels were collected from six low intertidal sites varying in terms of anthropogenic impacts, within two regions (West Coast and Nelson) of the South Island of NZ. Trace elements, including arsenic (As), cadmium (Cd), copper (Cu), lead (Pb), nickel (Ni), and zinc (Zn), were measured in the gills, digestive gland, foot and mantle, and in the surface sediments from where mussels were collected. Metal levels in the sediment were relatively low and there was only one site (Mapua, Nelson) where a metal (Ni) exceeded the Australian and New Zealand Interim Sediment Quality Guideline values. Metal levels in the digestive gland were generally higher than those from the other tissues. A variety of biomarkers were assessed to ascertain mussel health. Clearance rate, a physiological endpoint, correlated with metal level in the tissues, and along with scope for growth, was reduced in the most contaminated site. Metallothionein-like protein content and catalase activity in the digestive gland, and catalase activity and lipid peroxidation in the gill, were also correlated to metal accumulation. Although there were few regional differences, the sampling sites were clearly distinguishable based on the metal contamination profiles and biomarker responses. P. canaliculus appears to be a useful bioindicator species for coastal habitats subject to metal contamination. In this study tissue and whole organism responses provided insight into the biological stress responses of mussels to metal contaminants, indicating that such measurements could be a useful addition to biomonitoring programmes in NZ. - Highlights: • Multiple biomarker responses were measured in mussels from 6 sites. • Metal content of mussel tissues correlated with specific biomarker responses. • Clearance rate

  16. Cellular immune responses against CT7 (MAGE-C1) and humoral responses against other cancer-testis antigens in multiple myeloma patients.

    Science.gov (United States)

    Lendvai, Nikoletta; Gnjatic, Sacha; Ritter, Erika; Mangone, Michael; Austin, Wayne; Reyner, Karina; Jayabalan, David; Niesvizky, Ruben; Jagannath, Sundar; Bhardwaj, Nina; Chen-Kiang, Selina; Old, Lloyd J; Cho, Hearn Jay

    2010-01-29

    The type I melanoma antigen gene (MAGE) proteins CT7 (MAGE-C1) and MAGE-A3 are commonly expressed in multiple myeloma (MM), and their expression correlates with increased plasma cell proliferation and poor clinical outcome. They belong to the cancer-testis antigen (CTAg) group of tumor-associated proteins, some of which elicit spontaneous immune responses in cancer patients. CT7 and MAGE-A3 are promising antigenic targets for therapeutic tumor vaccines in myeloma; therefore, it is critical to determine if they are immunogenic in MM patients. We analyzed cellular and humoral immune responses against CTAgs in patients with plasma cell dyscrasias: MM, monoclonal gammopathy of undetermined significance (MGUS), and Waldenström's macroglobulinemia (WM). Bone marrow lymphocytes from two of four untreated MM patients exhibited CT7-specific cellular immune responses as measured by an autologous cellular immunity assay, the first such immune response to CT7 to be reported in cancer patients. Sera from 24 patients were screened by ELISA for humoral immune responses to CTAgs. Two patients with MM demonstrated positive titers, one for MAGE-A1 and the other for SSX1. These data demonstrate that CTAgs, particularly CT7, are immunogenic in MM patients and merit further exploration as targets of immunological therapy in MM.

  17. Changes in the potential multiple cropping system in response to climate change in China from 1960-2010.

    Science.gov (United States)

    Liu, Luo; Xu, Xinliang; Zhuang, Dafang; Chen, Xi; Li, Shuang

    2013-01-01

    The multiple cropping practice is essential to agriculture because it has been shown to significantly increase the grain yield and promote agricultural economic development. In this study, potential multiple cropping systems in China are calculated based on meteorological observation data by using the Agricultural Ecology Zone (AEZ) model. Following this, the changes in the potential cropping systems in response to climate change between the 1960s and the 2010s were subsequently analyzed. The results indicate that the changes of potential multiple cropping systems show tremendous heterogeneity in respect to the spatial pattern in China. A key finding is that the magnitude of change of the potential cropping systems showed a pattern of increase both from northern China to southern China and from western China to eastern China. Furthermore, the area found to be suitable only for single cropping decreased, while the area suitable for triple cropping increased significantly from the 1960s to the 2000s. During the studied period, the potential multiple cropping index (PMCI) gap between rain-fed and irrigated scenarios increased from 18% to 24%, which indicated noticeable growth of water supply limitations under the rain-fed scenario. The most significant finding of this research was that from the 1960s to the 2000s climate change had led to a significant increase of PMCI by 13% under irrigated scenario and 7% under rain-fed scenario across the whole of China. Furthermore, the growth of the annual mean temperature is identified as the main reason underlying the increase of PMCI. It has also been noticed that across China the changes of potential multiple cropping systems under climate change were different from region to region.

  18. Munchausen Syndrome by Proxy: Unusual Manifestations and Disturbing Sequelae.

    Science.gov (United States)

    Porter, Gerald E.; And Others

    1994-01-01

    This study documents previously unreported findings in cases of Munchausen Syndrome by Proxy (in which a mother fabricates an illness in her child). In the reported case, esophageal perforation, retrograde intussusception, tooth loss, and bradycardia were found. (Author/DB)

  19. Ocean currents generate large footprints in marine palaeoclimate proxies

    NARCIS (Netherlands)

    van Sebille, E.; Scussolini, P.; Durgadoo, J.V.; Peeters, F.J.C.; Biastoch, A.; Weijer, W.; Turney, C.; Paris, C.B.; Zahn, R.

    2015-01-01

    Fossils of marine microorganisms such as planktic foraminifera are among the cornerstones of palaeoclimatological studies. It is often assumed that the proxies derived from their shells represent ocean conditions above the location where they were deposited. Planktic foraminifera, however, are

  20. Chemosensory perception, symptoms and autonomic responses during chemical exposure in multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Andersson, Linus; Claeson, Anna Sara; Dantoft, Thomas Meinertz

    2016-01-01

    Purpose: Multiple chemical sensitivity (MCS) is a prevalent medically unexplained symptom characterized by symptom reactions to everyday chemical exposure below hygienic thresholds. The aim of this study was to investigate the expressions of hyper-reactivity in MCS during whole-body exposure to low...... concentrations of the odorant n-butanol. Methods: We exposed 18 participants with MCS and 18 non-ill controls to a low concentration of the odorant n-butanol using an exposure chamber. The first 10 min constituted blank exposure, after which the n-butanol concentration increased and reached a plateau at 11.5 mg....../m3. Results: MCS participants, compared with controls, reported greater perceived odor intensities, more unpleasantness to the exposure and increasing symptoms over time. MCS participants also expressed higher pulse rate and lower pulse rate variability than controls did. No group differences were...

  1. Music Therapy by Proxy: Using Humanised Images in Song

    Directory of Open Access Journals (Sweden)

    Carol Chambers

    2013-07-01

    Full Text Available Developing awareness, exploration and expression of emotionally sensitive issues can be difficult for some clients in music therapy. They may find it hard to express emotion through improvised music and may turn instead to the perceived security of the repetition of known songs.This paper presents the results from a completed research PhD, a qualitative case study based on naturalistic clinical practice, which examined the song choices of one woman in a medium-secure forensic unit over the three-year course of her music therapy. A descriptive narrative account was subjected to analysis according to a modified form of therapeutic narrative analysis (Aldridge and Aldridge 2002, resulting in the abstraction of a series of generative metaphoric images, framed within a chronological series of events. Crucially, these images were found to be humanised figures, yet they were also emotionally decentred or depersonalised. When approached from the philosophical and methodological perspective of behaviourism, which views these as conditioned responses associating music with life experiences as part of a process of developing self-identity, such images can be seen to provide an unspoken voice for the client’s feelings to be expressed in a manner that is personally revealing, socially acceptable, culturally accessible and therapeutically constructive.I assert that using these third-person characters as a form of proxy facilitates mutual reference and experimentation, and places music firmly at the heart of a socially constructed process of music therapy.

  2. Immunomodulatory effects and adaptive immune response to daratumumab in multiple myeloma

    DEFF Research Database (Denmark)

    Krejcik, Jakub; Casneuf, T.; Nijhof, I.

    2015-01-01

    (range) was 64 (31-84) years and median time from diagnosis was 5.12 (0.77-23.77) years. Seventy-six percent of patients had received >3 prior therapies and 91% were refractory to their last treatment. Clinical response was evaluated using IMWG consensus recommendations. Peripheral blood (PB) samples...... assays. T-cell subpopulation counts were modelled over time with linear mixed modelling. Two group comparisons were performed using non-parametric Wilcoxon rank sum tests. Results: Data from 148 patients receiving 16 mg/kg DARA in GEN501 (n = 42) and Sirius (n = 106) were analyzed for changes in immune...... response. In PB, robust mean increases in CD3+ (44%), CD4+ (32%) and CD8+ (62%) T-cell counts per 100 days were seen with DARA treatment. However, responding evaluable patients (n = 45) showed significantly greater increases from baseline than nonresponders (n = 93) in CD3+ (P = 0.00012), CD4+ (P = 0...

  3. Plant eco-physiological responses to multiple environmental and climate changes

    Energy Technology Data Exchange (ETDEWEB)

    Rost Albert, K.

    2009-03-15

    The current global changes of temperature, precipitation, atmospheric CO{sub 2} and UV-B radiation impact in concert ecosystems and processes in an unpredictable way. Therefore multifactor experimentation is needed to unravel the variability in strength of these drivers, whether the factors act additively or synergistically and to establish cause-effect relations between ecosystem processes. This thesis deals with heath plant responses to global change factors (the CLIMAITE project). In a Danish temperate heath ecosystem elevated CO{sub 2}, experimental summer drought, and passive nighttime warming was applied in all combinations (based on the scenario for Denmark anno 2075) and the responses after one year of treatment were investigated through a growing season in Hairgrass (Deschampsia flexousa) and Heather (Calluna vulgaris). In a high arctic heath ecosystem situated in NE-Greenland UV-B exclusion experiments were conducted on Salix arctica and Vaccinium uliginosum during six years. Responses of photosynthesis performance were characterized on the leaf scale by means of leaf gas-exchange (A/Ci curves), chlorophyll-a fluorescence, leaf nitrogen, carbon and delta13C and secondary compounds. The main findings were 1) The different growth strategies of the evergreen Calluna versus the opportunistic bi-phasic Deschampsia affects the photosynthesis response to drought and autumn warming; 2) Elevated CO{sub 2} and warming synergistically increase photosynthesis in spring and autumn; 3) Summer drought decreased photosynthesis in both species, but where Calluna maintained photosynthetic metabolism then major proportion of grass leaves wilted down; 4) Elevated CO{sub 2} did not decrease stomatal conductance, but the treatments affected soil water content positively, pointing to the complex water relations when plants of contrasting growth strategy co-occur; 5) Water availability affected the magnitude of photosynthesis to a higher degree than warming and elevated CO{sub 2

  4. Item difficulty of multiple choice tests dependant on different item response formats – An experiment in fundamental research on psychological assessment

    Directory of Open Access Journals (Sweden)

    KLAUS D. KUBINGER

    2007-12-01

    Full Text Available Multiple choice response formats are problematical as an item is often scored as solved simply because the test-taker is a lucky guesser. Instead of applying pertinent IRT models which take guessing effects into account, a pragmatic approach of re-conceptualizing multiple choice response formats to reduce the chance of lucky guessing is considered. This paper compares the free response format with two different multiple choice formats. A common multiple choice format with a single correct response option and five distractors (“1 of 6” is used, as well as a multiple choice format with five response options, of which any number of the five is correct and the item is only scored as mastered if all the correct response options and none of the wrong ones are marked (“x of 5”. An experiment was designed, using pairs of items with exactly the same content but different response formats. 173 test-takers were randomly assigned to two test booklets of 150 items altogether. Rasch model analyses adduced a fitting item pool, after the deletion of 39 items. The resulting item difficulty parameters were used for the comparison of the different formats. The multiple choice format “1 of 6” differs significantly from “x of 5”, with a relative effect of 1.63, while the multiple choice format “x of 5” does not significantly differ from the free response format. Therefore, the lower degree of difficulty of items with the “1 of 6” multiple choice format is an indicator of relevant guessing effects. In contrast the “x of 5” multiple choice format can be seen as an appropriate substitute for free response format.

  5. DNA methylation–based immune response signature improves patient diagnosis in multiple cancers

    Science.gov (United States)

    Jeschke, Jana; Bizet, Martin; Calonne, Emilie; Dedeurwaerder, Sarah; Garaud, Soizic; Koch, Alexander; Larsimont, Denis; Salgado, Roberto; Van den Eynden, Gert; Willard Gallo, Karen; Defrance, Matthieu; Sotiriou, Christos

    2017-01-01

    BACKGROUND. The tumor immune response is increasingly associated with better clinical outcomes in breast and other cancers. However, the evaluation of tumor-infiltrating lymphocytes (TILs) relies on histopathological measurements with limited accuracy and reproducibility. Here, we profiled DNA methylation markers to identify a methylation of TIL (MeTIL) signature that recapitulates TIL evaluations and their prognostic value for long-term outcomes in breast cancer (BC). METHODS. MeTIL signature scores were correlated with clinical endpoints reflecting overall or disease-free survival and a pathologic complete response to preoperative anthracycline therapy in 3 BC cohorts from the Jules Bordet Institute in Brussels and in other cancer types from The Cancer Genome Atlas. RESULTS. The MeTIL signature measured TIL distributions in a sensitive manner and predicted survival and response to chemotherapy in BC better than did histopathological assessment of TILs or gene expression–based immune markers, respectively. The MeTIL signature also improved the prediction of survival in other malignancies, including melanoma and lung cancer. Furthermore, the MeTIL signature predicted differences in survival for malignancies in which TILs were not known to have a prognostic value. Finally, we showed that MeTIL markers can be determined by bisulfite pyrosequencing of small amounts of DNA from formalin-fixed, paraffin-embedded tumor tissue, supporting clinical applications for this methodology. CONCLUSIONS. This study highlights the power of DNA methylation to evaluate tumor immune responses and the potential of this approach to improve the diagnosis and treatment of breast and other cancers. FUNDING. This work was funded by the Fonds National de la Recherche Scientifique (FNRS) and Télévie, the INNOVIRIS Brussels Region BRUBREAST Project, the IUAP P7/03 program, the Belgian “Foundation against Cancer,” the Breast Cancer Research Foundation (BCRF), and the Fonds Gaston Ithier

  6. Proxy-rated quality of life in Alzheimer's disease

    DEFF Research Database (Denmark)

    Vogel, Asmus; Bhattacharya, Suvosree; Waldorff, Frans Boch

    2012-01-01

    The study investigated the change in proxy rated quality of life (QoL) of a large cohort of home living patients with Alzheimer's disease (AD) over a period of 36 months.......The study investigated the change in proxy rated quality of life (QoL) of a large cohort of home living patients with Alzheimer's disease (AD) over a period of 36 months....

  7. The Difference Between Using Proxy Server and VPN

    Directory of Open Access Journals (Sweden)

    David Dwiputra Kurniadi

    2015-11-01

    For example, looking for software, game through internet. But sometimes, there are some websites that cannot be opened as they have Internet Positive notificatio. To solve that problem, hacker found the solution by creating Proxy Server or VPN. In this time internet is very modern and very easy to access and there are a lot of Proxy Server and VPN that can be easly used.

  8. The Multiple Functions of the Nucleolus in Plant Development, Disease and Stress Responses

    Directory of Open Access Journals (Sweden)

    Natalia O. Kalinina

    2018-02-01

    Full Text Available The nucleolus is the most conspicuous domain in the eukaryotic cell nucleus, whose main function is ribosomal RNA (rRNA synthesis and ribosome biogenesis. However, there is growing evidence that the nucleolus is also implicated in many other aspects of cell biology, such as regulation of cell cycle, growth and development, senescence, telomerase activity, gene silencing, responses to biotic and abiotic stresses. In the first part of the review, we briefly assess the traditional roles of the plant nucleolus in rRNA synthesis and ribosome biogenesis as well as possible functions in other RNA regulatory pathways such as splicing, nonsense-mediated mRNA decay and RNA silencing. In the second part of the review we summarize recent progress and discuss already known and new hypothetical roles of the nucleolus in plant growth and development. In addition, this part will highlight studies showing new nucleolar functions involved in responses to pathogen attack and abiotic stress. Cross-talk between the nucleolus and Cajal bodies is also discussed in the context of their association with poly(ADP ribosepolymerase (PARP, which is known to play a crucial role in various physiological processes including growth, development and responses to biotic and abiotic stresses.

  9. The Multiple Functions of the Nucleolus in Plant Development, Disease and Stress Responses

    Science.gov (United States)

    Kalinina, Natalia O.; Makarova, Svetlana; Makhotenko, Antonida; Love, Andrew J.; Taliansky, Michael

    2018-01-01

    The nucleolus is the most conspicuous domain in the eukaryotic cell nucleus, whose main function is ribosomal RNA (rRNA) synthesis and ribosome biogenesis. However, there is growing evidence that the nucleolus is also implicated in many other aspects of cell biology, such as regulation of cell cycle, growth and development, senescence, telomerase activity, gene silencing, responses to biotic and abiotic stresses. In the first part of the review, we briefly assess the traditional roles of the plant nucleolus in rRNA synthesis and ribosome biogenesis as well as possible functions in other RNA regulatory pathways such as splicing, nonsense-mediated mRNA decay and RNA silencing. In the second part of the review we summarize recent progress and discuss already known and new hypothetical roles of the nucleolus in plant growth and development. In addition, this part will highlight studies showing new nucleolar functions involved in responses to pathogen attack and abiotic stress. Cross-talk between the nucleolus and Cajal bodies is also discussed in the context of their association with poly(ADP ribose)polymerase (PARP), which is known to play a crucial role in various physiological processes including growth, development and responses to biotic and abiotic stresses. PMID:29479362

  10. Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene Dosing and Drug Affinity Responsive Target Stability Screening

    Directory of Open Access Journals (Sweden)

    Yoon-Dong Park

    2016-08-01

    Full Text Available Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development.

  11. Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2012-05-01

    Full Text Available Brendon J Coventry, Martin L AshdownDiscipline of Surgery, University of Adelaide, Royal Adelaide Hospital and Faculty of Medicine, University of Melbourne, AustraliaAbstract: Over 50 years of cancer therapy history reveals complete clinical responses (CRs from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies for advanced solid malignancies occur with an approximately similar frequency of 5%–10%. This has remained frustratingly almost static. However, CRs usually underpin strong durable 5-year patient survival. How can this apparent paradox be explained?Over some 20 years, realization that (1 chronic inflammation is intricately associated with cancer, and (2 the immune system is delicately balanced between responsiveness and tolerance of cancer, provides a greatly significant insight into ways cancer might be more effectively treated. In this review, divergent aspects from the largely segmented literature and recent conferences are drawn together to provide observations revealing some emerging reasoning, in terms of "final common pathways" of cancer cell damage, immune stimulation, and auto-vaccination events, ultimately leading to cancer cell destruction. Created from this is a unifying overarching concept to explain why multiple approaches to cancer therapy can provide complete responses at almost equivalent rates. This "missing" aspect provides a reasoned explanation for what has, and is being, increasingly reported in the mainstream literature – that inflammatory and immune responses appear intricately associated with, if not causative of, complete responses induced by divergent forms of cancer therapy. Curiously, whether by chemotherapy, radiation, surgery, or other means, therapy-induced cell injury results, leaving inflammation and immune system stimulation as a final common denominator across all of these mechanisms of cancer

  12. The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part I: cellular response.

    Science.gov (United States)

    Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

    2015-02-01

    Osteoarthritis (OA) is a complex disease of the joint for which current treatments are unsatisfactory, thus motivating development of tissue engineering (TE)-based therapies. To date, TE strategies have had some success, developing replacement tissue constructs with biochemical properties approaching that of native cartilage. However, poor biomechanical properties and limited postimplantation integration with surrounding tissue are major shortcomings that need to be addressed. Functional tissue engineering strategies that apply physiologically relevant biophysical cues provide a platform to improve TE constructs before implantation. In the previous decade, new experimental and theoretical findings in cartilage biomechanics and electromechanics have emerged, resulting in an increased understanding of the complex interplay of multiple biophysical cues in the extracellular matrix of the tissue. The effect of biophysical stimulation on cartilage, and the resulting chondrocyte-mediated biosynthesis, remodeling, degradation, and repair, has, therefore, been extensively explored by the TE community. This article compares and contrasts the cellular response of chondrocytes to multiple biophysical stimuli, and may be read in conjunction with its companion paper that compares and contrasts the subsequent intracellular signal transduction cascades. Mechanical, magnetic, and electrical stimuli promote proliferation, differentiation, and maturation of chondrocytes within established dose parameters or "biological windows." This knowledge will provide a framework for ongoing studies incorporating multiple biophysical cues in TE functional neocartilage for treatment of OA.

  13. Dendrimer-magnetic nanoparticles as multiple stimuli responsive and enzymatic drug delivery vehicle

    International Nuclear Information System (INIS)

    Chandra, Sudeshna; Noronha, Glen; Dietrich, Sascha; Lang, Heinrich; Bahadur, Dhirendra

    2015-01-01

    Two different chain lengths of (poly)ethylene glycol-PAMAM dendrimers namely, L6-PEG-PAMAM and S6-PEG-PAMAM with six end-grafted ethylene glycol ether-tentacles of type CH 2 CH 2 C(O)O(CH 2 CH 2 O) 9 CH 3 and CH 2 CH 2 C(O)O(CH 2 CH 2 O) 2 C 2 H 5 , respectively, were synthesized. These dendrimers have multiple σ-donor capabilities and therefore, were used for stabilizing the magnetite (Fe 3 O 4 ) nanoparticles. Both the dendrimer-magnetic nanoparticles (L6-PEG-PAMAM-MNPs and S6-PEG-PAMAM-MNPs) were characterized by different spectroscopic and microstructural techniques. The nanoparticles were mesoporous and superparamagnetic and therefore, explored for their possible use in delivery of cancer drug, doxorubicin (DOX). In the developed drug delivery system, achieving high drug-loading efficiency with controllable release were the main challenges. The change in zeta potential and quenching of fluorescence intensity suggests chemical interaction between DOX and the nanoparticles. The loading efficiency was calculated to be over 95% with a sustained pH and temperature sensitive release. Further, enzyme cathepsin B has also been used to degrade the dendritic shell to trigger sustained drug release in the vicinity of tumor cells

  14. Dendrimer-magnetic nanoparticles as multiple stimuli responsive and enzymatic drug delivery vehicle

    Energy Technology Data Exchange (ETDEWEB)

    Chandra, Sudeshna; Noronha, Glen [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India); Dietrich, Sascha; Lang, Heinrich [Technische Universität Chemnitz, Institute of Chemistry, Straße der Nationen 62, d-09111 Chemnitz (Germany); Bahadur, Dhirendra, E-mail: dhirenb@iitb.ac.in [Metallurgical and Materials Science Department, Indian Institute of Technology Bombay, Powai, Mumbai, 400076 (India)

    2015-04-15

    Two different chain lengths of (poly)ethylene glycol-PAMAM dendrimers namely, L6-PEG-PAMAM and S6-PEG-PAMAM with six end-grafted ethylene glycol ether-tentacles of type CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 9}CH{sub 3} and CH{sub 2}CH{sub 2}C(O)O(CH{sub 2}CH{sub 2}O){sub 2}C{sub 2}H{sub 5}, respectively, were synthesized. These dendrimers have multiple σ-donor capabilities and therefore, were used for stabilizing the magnetite (Fe{sub 3}O{sub 4}) nanoparticles. Both the dendrimer-magnetic nanoparticles (L6-PEG-PAMAM-MNPs and S6-PEG-PAMAM-MNPs) were characterized by different spectroscopic and microstructural techniques. The nanoparticles were mesoporous and superparamagnetic and therefore, explored for their possible use in delivery of cancer drug, doxorubicin (DOX). In the developed drug delivery system, achieving high drug-loading efficiency with controllable release were the main challenges. The change in zeta potential and quenching of fluorescence intensity suggests chemical interaction between DOX and the nanoparticles. The loading efficiency was calculated to be over 95% with a sustained pH and temperature sensitive release. Further, enzyme cathepsin B has also been used to degrade the dendritic shell to trigger sustained drug release in the vicinity of tumor cells.

  15. Efficacy of multiple anticancer therapies may depend on host immune response

    Directory of Open Access Journals (Sweden)

    Kritika Karri

    2017-06-01

    Full Text Available The host immune system is a key player in anticancer therapy response and resistance. Although the impact of host immune response in the ‘war against cancer’ has been studied and it has been the basis for immunotherapy, understanding of its role in attenuating the action of conventional anticancer therapies is an area that has not been fully explored. In spite of advances in systemic therapy, the 5-year survival rate for adenocarcinoma is still a mere 13% and the primary reason for treatment failure is believed to be due to acquired resistance to therapy. Hence, there is a need for identifying reliable biomarkers for guided treatment of lung and colon adenocarcinoma and to better predict the outcomes of specific anticancer therapies. In this work, gene expression data were analyzed using public resources and this study shows how host immune competence underscores the efficacy of various anticancer therapies. Additionally, the result provides insight on the regulation of certain biochemical pathways relating to the immune system, and suggests that smart chemotherapeutic intervention strategies could be based on a patient’s immune profile.

  16. Combining item response theory with multiple imputation to equate health assessment questionnaires.

    Science.gov (United States)

    Gu, Chenyang; Gutman, Roee

    2017-09-01

    The assessment of patients' functional status across the continuum of care requires a common patient assessment tool. However, assessment tools that are used in various health care settings differ and cannot be easily contrasted. For example, the Functional Independence Measure (FIM) is used to evaluate the functional status of patients who stay in inpatient rehabilitation facilities, the Minimum Data Set (MDS) is collected for all patients who stay in skilled nursing facilities, and the Outcome and Assessment Information Set (OASIS) is collected if they choose home health care provided by home health agencies. All three instruments or questionnaires include functional status items, but the specific items, rating scales, and instructions for scoring different activities vary between the different settings. We consider equating different health assessment questionnaires as a missing data problem, and propose a variant of predictive mean matching method that relies on Item Response Theory (IRT) models to impute unmeasured item responses. Using real data sets, we simulated missing measurements and compared our proposed approach to existing methods for missing data imputation. We show that, for all of the estimands considered, and in most of the experimental conditions that were examined, the proposed approach provides valid inferences, and generally has better coverages, relatively smaller biases, and shorter interval estimates. The proposed method is further illustrated using a real data set. © 2016, The International Biometric Society.

  17. Cuttlefish dynamic camouflage: responses to substrate choice and integration of multiple visual cues.

    Science.gov (United States)

    Allen, Justine J; Mäthger, Lydia M; Barbosa, Alexandra; Buresch, Kendra C; Sogin, Emilia; Schwartz, Jillian; Chubb, Charles; Hanlon, Roger T

    2010-04-07

    Prey camouflage is an evolutionary response to predation pressure. Cephalopods have extensive camouflage capabilities and studying them can offer insight into effective camouflage design. Here, we examine whether cuttlefish, Sepia officinalis, show substrate or camouflage pattern preferences. In the first two experiments, cuttlefish were presented with a choice between different artificial substrates or between different natural substrates. First, the ability of cuttlefish to show substrate preference on artificial and natural substrates was established. Next, cuttlefish were offered substrates known to evoke three main camouflage body pattern types these animals show: Uniform or Mottle (function by background matching); or Disruptive. In a third experiment, cuttlefish were presented with conflicting visual cues on their left and right sides to assess their camouflage response. Given a choice between substrates they might encounter in nature, we found no strong substrate preference except when cuttlefish could bury themselves. Additionally, cuttlefish responded to conflicting visual cues with mixed body patterns in both the substrate preference and split substrate experiments. These results suggest that differences in energy costs for different camouflage body patterns may be minor and that pattern mixing and symmetry may play important roles in camouflage.

  18. Evaluation of the Multiple Sclerosis Walking Scale-12 (MSWS-12) in a Dutch sample: Application of item response theory.

    Science.gov (United States)

    Mokkink, Lidwine Brigitta; Galindo-Garre, Francisca; Uitdehaag, Bernard Mj

    2016-12-01

    The Multiple Sclerosis Walking Scale-12 (MSWS-12) measures walking ability from the patients' perspective. We examined the quality of the MSWS-12 using an item response theory model, the graded response model (GRM). A total of 625 unique Dutch multiple sclerosis (MS) patients were included. After testing for unidimensionality, monotonicity, and absence of local dependence, a GRM was fit and item characteristics were assessed. Differential item functioning (DIF) for the variables gender, age, duration of MS, type of MS and severity of MS, reliability, total test information, and standard error of the trait level (θ) were investigated. Confirmatory factor analysis showed a unidimensional structure of the 12 items of the scale, explaining 88% of the variance. Item 2 did not fit into the GRM model. Reliability was 0.93. Items 8 and 9 (of the 11 and 12 item version respectively) showed DIF on the variable severity, based on the Expanded Disability Status Scale (EDSS). However, the EDSS is strongly related to the content of both items. Our results confirm the good quality of the MSWS-12. The trait level (θ) scores and item parameters of both the 12- and 11-item versions were highly comparable, although we do not suggest to change the content of the MSWS-12. © The Author(s), 2016.

  19. CSF inflammatory biomarkers responsive to treatment in progressive multiple sclerosis capture residual inflammation associated with axonal damage.

    Science.gov (United States)

    Romme Christensen, Jeppe; Komori, Mika; von Essen, Marina Rode; Ratzer, Rikke; Börnsen, Lars; Bielekova, Bibi; Sellebjerg, Finn

    2018-05-01

    Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation. To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers. CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS. CSF concentrations of 20 inflammatory biomarkers and CSF biomarkers of axonal damage (neurofilament light chain (NFL)) and demyelination were analysed using electrochemiluminescent assay and enzyme-linked immunosorbent assay (ELISA). In all, 17 natalizumab- and 23 methylprednisolone-treated patients had paired CSF samples. CSF sCD27 displayed superior standardised response means and highly significant decreases during both natalizumab and methylprednisolone treatment; however, post-treatment levels remained above healthy donor reference levels. Correlation analyses of CSF inflammatory biomarkers and NFL before, during and after treatment demonstrated that CSF sCD27 consistently correlates with NFL. These findings validate CSF sCD27 as a responsive and sensitive biomarker of intrathecal inflammation in progressive MS, capturing residual inflammation after treatment. Importantly, CSF sCD27 correlates with NFL, consistent with residual inflammation after anti-inflammatory treatment being associated with axonal damage.

  20. Quantitative assessment of the multiple processes responsible for bilirubin homeostasis in health and disease

    Directory of Open Access Journals (Sweden)

    Levitt DG

    2014-09-01

    Full Text Available David G Levitt,1 Michael D Levitt2 1Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis, MN, USA; 2Research Service, Veterans Affairs Medical Center, Minneapolis, MN, USAAbstract: Serum bilirubin measurements are commonly obtained for the evaluation of ill patients and to screen for liver disease in routine physical exams. An enormous research effort has identified the multiple mechanisms involved in the production and metabolism of conjugated (CB and unconjugated bilirubin (UB. While the qualitative effects of these mechanisms are well understood, their expected quantitative influence on serum bilirubin homeostasis has received less attention. In this review, each of the steps involved in bilirubin production, metabolism, hepatic cell uptake, and excretion is quantitatively examined. We then attempt to predict the expected effect of normal and defective function on serum UB and CB levels in health and disease states including hemolysis, extra- and intrahepatic cholestasis, hepatocellular diseases (eg, cirrhosis, hepatitis, and various congenital defects in bilirubin conjugation and secretion (eg, Gilbert's, Dubin–Johnson, Crigler–Najjar, Rotor syndromes. Novel aspects of this review include: 1 quantitative estimates of the free and total UB and CB in the plasma, hepatocyte, and bile; 2 detailed discussion of the important implications of the recently recognized role of the hepatic OATP transporters in the maintenance of CB homeostasis; 3 discussion of the differences between the standard diazo assay versus chromatographic measurement of CB and UB; 4 pharmacokinetic implications of the extremely high-affinity albumin binding of UB; 5 role of the enterohepatic circulation in physiologic jaundice of newborn and fasting hyperbilirubinemia; and 6 insights concerning the clinical interpretation of bilirubin measurements.Keywords: liver, conjugation, diazo, albumin, Rotor

  1. Dynamics of habitat selection in birds: adaptive response to nest predation depends on multiple factors.

    Science.gov (United States)

    Devries, J H; Clark, R G; Armstrong, L M

    2018-05-01

    According to theory, habitat selection by organisms should reflect underlying habitat-specific fitness consequences and, in birds, reproductive success has a strong impact on population growth in many species. Understanding processes affecting habitat selection also is critically important for guiding conservation initiatives. Northern pintails (Anas acuta) are migratory, temperate-nesting birds that breed in greatest concentrations in the prairies of North America and their population remains below conservation goals. Habitat loss and changing land use practices may have decoupled formerly reliable fitness cues with respect to nest habitat choices. We used data from 62 waterfowl nesting study sites across prairie Canada (1997-2009) to examine nest survival, a primary fitness metric, at multiple scales, in combination with estimates of habitat selection (i.e., nests versus random points), to test for evidence of adaptive habitat choices. We used the same habitat covariates in both analyses. Pintail nest survival varied with nest initiation date, nest habitat, pintail breeding pair density, landscape composition and annual moisture. Selection of nesting habitat reflected patterns in nest survival in some cases, indicating adaptive selection, but strength of habitat selection varied seasonally and depended on population density and landscape composition. Adaptive selection was most evident late in the breeding season, at low breeding densities and in cropland-dominated landscapes. Strikingly, at high breeding density, habitat choice appears to become maladaptive relative to nest predation. At larger spatial scales, the relative availability of habitats with low versus high nest survival, and changing land use practices, may limit the reproductive potential of pintails.

  2. Serological response to influenza vaccination among children vaccinated for multiple influenza seasons.

    Directory of Open Access Journals (Sweden)

    Sajjad Rafiq

    Full Text Available To evaluate if, among children aged 3 to 15 years, influenza vaccination for multiple seasons affects the proportion sero-protected.Participants were 131 healthy children aged 3-15 years. Participants were vaccinated with trivalent inactivated seasonal influenza vaccine (TIV over the 2005-06, 2006-07 and 2007-8 seasons. Number of seasons vaccinated were categorized as one (2007-08; two (2007-08 and 2006-07 or 2007-08 and 2005-06 or three (2005-06, 2006-07, and 2007-08. Pre- and post-vaccination sera were collected four weeks apart. Antibody titres were determined by hemagglutination inhibition (HAI assay using antigens to A/Solomon Islands/03/06 (H1N1, A/Wisconsin/67/05 (H3N2 and B/Malaysia/2506/04. The proportions sero-protected were compared by number of seasons vaccinated using cut-points for seroprotection of 1:40 vs. 1:320. The proportions of children sero-protected against H1N1 and H3N2 was high (>85% regardless of number of seasons vaccinated and regardless of cut-point for seroprotection. For B Malaysia there was no change in proportions sero-protected by number of seasons vaccinated; however the proportions protected were lower than for H1N1 and H3N2, and there was a lower proportion sero-protected when the higher, compared to lower, cut-point was used for sero-protection.The proportion of children sero-protected is not affected by number of seasons vaccinated.

  3. Family factors in end-of-life decision-making: family conflict and proxy relationship.

    Science.gov (United States)

    Parks, Susan Mockus; Winter, Laraine; Santana, Abbie J; Parker, Barbara; Diamond, James J; Rose, Molly; Myers, Ronald E

    2011-02-01

    Few studies have examined proxy decision-making regarding end-of-life treatment decisions. Proxy accuracy is defined as whether proxy treatment choices are consistent with the expressed wishes of their index elder. The purpose of this study was to examine proxy accuracy in relation to two family factors that may influence proxy accuracy: perceived family conflict and type of elder-proxy relationship. Telephone interviews with 202 community-dwelling elders and their proxy decision makers were conducted including the Life-Support Preferences Questionnaire (LSPQ), and a measure of family conflict, and sociodemographic characteristics, including type of relationship. Elder-proxy accuracy was associated with the type of elder-proxy relationship. Adult children demonstrated the lowest elder-proxy accuracy and spousal proxies the highest elder-proxy accuracy. Elder-proxy accuracy was associated with family conflict. Proxies reporting higher family conflict had lower elder-proxy accuracy. No interaction between family conflict and relationship type was revealed. Spousal proxies were more accurate in their substituted judgment than adult children, and proxies who perceive higher degree of family conflict tended to be less accurate than those with lower family conflict. Health care providers should be aware of these family factors when discussing advance care planning.

  4. Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T.

    Science.gov (United States)

    Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; van der Zwaag, Wietske

    2018-02-20

    External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and negative BOLD responses (NBRs) to visual checkerboard stimulation, occurring in various brain regions within and beyond the visual cortex. Recently-proposed accelerated fMRI techniques were employed for data acquisition, and procedures for exclusion of large draining vein contributions, together with ICA-assisted denoising, were included in the analysis to improve response estimation. Besides the visual cortex, significant PBRs were found in the lateral geniculate nucleus and superior colliculus, as well as the pre-central sulcus; in these regions, response durations increased monotonically with stimulus duration, in tight covariation with the visual PBR duration. Significant NBRs were found in the visual cortex, auditory cortex, default-mode network (DMN) and superior parietal lobule; NBR durations also tended to increase with stimulus duration, but were significantly less sustained than the visual PBR, especially for the DMN and superior parietal lobule. Responses in visual and auditory cortex were further studied for checkerboard contrast dependence, and their amplitudes were found to increase monotonically with contrast, linearly correlated with the visual PBR amplitude. Overall, these findings suggest the presence of dynamic neuronal interactions across multiple brain regions, sensitive to stimulus intensity and duration, and demonstrate the richness of information obtainable when jointly mapping positive and negative BOLD responses at a whole-brain scale, with ultra-high field fMRI. © 2018 Wiley Periodicals, Inc.

  5. Seismic response analysis of a piping system subjected to multiple support excitations in a base isolated NPP building

    International Nuclear Information System (INIS)

    Surh, Han-Bum; Ryu, Tae-Young; Park, Jin-Sung; Ahn, Eun-Woo; Choi, Chul-Sun; Koo, Ja Choon; Choi, Jae-Boong; Kim, Moon Ki

    2015-01-01

    Highlights: • Piping system in the APR 1400 NPP with a base isolation design is studied. • Seismic response of piping system in base isolated building are investigated. • Stress classification method is examined for piping subjected to seismic loading. • Primary stress of piping is reduced due to base isolation design. • Substantial secondary stress is observed in the main steam piping. - Abstract: In this study, the stress response of the piping system in the advanced power reactor 1400 (APR 1400) with a base isolation design subjected to seismic loading is addressed. The piping system located between the auxiliary building with base isolation and the turbine building with a fixed base is considered since it can be subjected to substantial relative support movement during seismic events. First, the support responses with respect to the base characteristic are investigated to perform seismic analysis for multiple support excitations. Finite element analyses are performed to predict the piping stress response through various analysis methods such as the response spectrum, seismic support movement and time history method. To separately evaluate the inertial effect and support movement effect on the piping stress, the stress is decomposed into a primary and secondary stress using the proposed method. Finally, influences of the base isolation design on the piping system in the APR 1400 are addressed. The primary stress based on the inertial loading is effectively reduced in a base isolation design, whereas a considerable amount of secondary stress is generated in the piping system connecting a base isolated building with a fixed base building. It is also confirmed that both the response spectrum analysis and seismic support movement analysis provide more conservative estimations of the piping stress compared to the time history analysis

  6. Plant eco-physiological responses to multiple environmental and climate changes

    DEFF Research Database (Denmark)

    Albert, Kristian Rost

    2009-01-01

    arctic plants in both short and long term (Paper V, VII, VIII); 9) Ambient UV-B decreased net photosynthesis via effects on PSII performance in combination with effects on Calvin Cycle (Paper V, VII); 10) Current UV-B level is a important factor affecting high arctic plants, particularly in years......The current global changes of temperature, precipitation, atmospheric CO2 and UV-B radiation impact in concert ecosystems and processes in an unpredictable way. Therefore multifactor experimentation is needed to unravel the variability in strength of these drivers, whether the factors act...... additively or synergistically and to establish cause-effect relations between ecosystem processes. This thesis deals with heath plant responses to global change factors (the CLIMAITE project). In a Danish temperate heath ecosystem elevated CO2, experimental summer drought, and passive nighttime warming...

  7. Multiple redox states of multiheme cytochromes may enable bacterial response to changing redox environments

    Science.gov (United States)

    Arbour, T.; Wrighton, K. C.; Mullin, S. W.; Castelle, C.; Luef, B.; Gilbert, B.; Banfield, J. F.

    2013-12-01

    Multiheme c-type cytochromes (MHCs) are key components in electron-transport pathways that enable some microorganisms to transfer electron byproducts of metabolism to a variety of minerals. As a response to changes in mineral redox potential, microbial communities may shift their membership, or individual organisms may adjust protein expression. Alternatively, the ability to respond may be conferred by the innate characteristics of certain electron-transport-chain components. Here, we used potentiostat-controlled microbial fuel cells (MFCs) to measure the timescale of response to imposed changes in redox conditions, thus placing constraints on the importance of these different mechanisms. In the experiments, a solid electrode acts as an electron-accepting mineral whose redox potential can be precisely controlled. We inoculated duplicate MFCs with a sediment/groundwater mixture from an aquifer at Rifle, Colorado, supplied acetate as an electron donor, and obtained stable, mixed-species biofilms dominated by Geobacter and a novel Geobacter-related family. We poised the anode at potentials spanning the range of natural Fe(III)-reduction, then performed cyclic voltammetry (CV) to characterize the overall biofilm redox signature. The apparent biofilm midpoint potential shifted directly with anode set potential when the latter was changed within the range from about -250 to -50 mV vs. SHE. Following a jump in set potential by 200 mV, the CV-midpoint shift by ~100 mV over a timescale of ~30 minutes to a few hours, depending on the direction of the potential change. The extracellular electron transfer molecules, whose overall CV signature is very similar to those of purified MHCs, appear to span a broad redox range (~200 mV), supporting the hypothesis that MHCs confer substantial redox flexibility. This flexibility may be a principle reason for the abundance of MHCs expressed by microorganisms capable of extracellular electron transfer to minerals.

  8. Testing For The Linearity of Responses To Multiple Anthropogenic Climate Forcings

    Science.gov (United States)

    Forest, C. E.; Stone, P. H.; Sokolov, A. P.

    To test whether climate forcings are additive, we compare climate model simulations in which anthropogenic forcings are applied individually and in combination. Tests are performed with different values for climate system properties (climate sensitivity and rate of heat uptake by the deep ocean) as well as for different strengths of the net aerosol forcing, thereby testing for the dependence of linearity on these properties. The MIT 2D Land-Ocean Climate Model used in this study consists of a zonally aver- aged statistical-dynamical atmospheric model coupled to a mixed-layer Q-flux ocean model, with heat anomalies diffused into the deep ocean. Following our previous stud- ies, the anthropogenic forcings are the changes in concentrations of greenhouse gases (1860-1995), sulfate aerosol (1860-1995), and stratospheric and tropospheric ozone (1979-1995). The sulfate aerosol forcing is applied as a surface albedo change. For an aerosol forcing of -1.0 W/m2 and an effective ocean diffusitivity of 2.5 cm2/s, the nonlinearity of the response of global-mean surface temperatures to the combined forcing shows a strong dependence on climate sensitivity. The fractional change in decadal averages ([(TG + TS + TO) - TGSO]/TGSO) for the 1986-1995 period compared to pre-industrial times are 0.43, 0.90, and 1.08 with climate sensitiv- ities of 3.0, 4.5, and 6.2 C, respectively. The values of TGSO for these three cases o are 0.52, 0.62, and 0.76 C. The dependence of linearity on climate system properties, o the role of climate system feedbacks, and the implications for the detection of climate system's response to individual forcings will be presented. Details of the model and forcings can be found at http://web.mit.edu/globalchange/www/.

  9. Comparing Apples to Apples: Paleoclimate Model-Data comparison via Proxy System Modeling

    Science.gov (United States)

    Dee, Sylvia; Emile-Geay, Julien; Evans, Michael; Noone, David

    2014-05-01

    The wealth of paleodata spanning the last millennium (hereinafter LM) provides an invaluable testbed for CMIP5-class GCMs. However, comparing GCM output to paleodata is non-trivial. High-resolution paleoclimate proxies generally contain a multivariate and non-linear response to regional climate forcing. Disentangling the multivariate environmental influences on proxies like corals, speleothems, and trees can be complex due to spatiotemporal climate variability, non-stationarity, and threshold dependence. Given these and other complications, many paleodata-GCM comparisons take a leap of faith, relating climate fields (e.g. precipitation, temperature) to geochemical signals in proxy data (e.g. δ18O in coral aragonite or ice cores) (e.g. Braconnot et al., 2012). Isotope-enabled GCMs are a step in the right direction, with water isotopes providing a connector point between GCMs and paleodata. However, such studies are still rare, and isotope fields are not archived as part of LM PMIP3 simulations. More importantly, much of the complexity in how proxy systems record and transduce environmental signals remains unaccounted for. In this study we use proxy system models (PSMs, Evans et al., 2013) to bridge this conceptual gap. A PSM mathematically encodes the mechanistic understanding of the physical, geochemical and, sometimes biological influences on each proxy. To translate GCM output to proxy space, we have synthesized a comprehensive, consistently formatted package of published PSMs, including δ18O in corals, tree ring cellulose, speleothems, and ice cores. Each PSM is comprised of three sub-models: sensor, archive, and observation. For the first time, these different components are coupled together for four major proxy types, allowing uncertainties due to both dating and signal interpretation to be treated within a self-consistent framework. The output of this process is an ensemble of many (say N = 1,000) realizations of the proxy network, all equally plausible

  10. Multiple-endpoint assay provides a detailed mechanistic view of responses to herbicide exposure in Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    Nestler, Holger; Groh, Ksenia J.; Schönenberger, René; Behra, Renata; Schirmer, Kristin; Eggen, Rik I.L.; Suter, Marc J.-F.

    2012-01-01

    The release of herbicides into the aquatic environment raises concerns about potential detrimental effects on ecologically important non-target species, such as unicellular algae, necessitating ecotoxicological risk assessment. Algal toxicity tests based on growth, a commonly assessed endpoint, are integrative, and hence do not provide information about underlying toxic mechanisms and effects. This limitation may be overcome by measuring more specific biochemical and physiological endpoints. In the present work, we developed and applied a novel multiple-endpoint assay, and analyzed the effects of the herbicides paraquat, diuron and norflurazon, each representing a specific mechanism of toxic action, on the single celled green alga Chlamydomonas reinhardtii. The endpoints added to assessment of growth were pigment content, maximum and effective photosystem II quantum yield, ATP content, esterase and oxidative activity. All parameters were measured at 2, 6 and 24 h of exposure, except for growth and pigment content, which were determined after 6 and 24 h only. Effective concentrations causing 50% of response (EC50s) and lowest observable effect concentrations (LOECs) were determined for all endpoints and exposure durations where possible. The assay provided a detailed picture of the concentration- and time-dependent development of effects elicited by the analyzed herbicides, thus improving the understanding of the underlying toxic mechanisms. Furthermore, the response patterns were unique to the respective herbicide and reflected the different mechanisms of toxicity. The comparison of the endpoint responses and sensitivities revealed that several physiological and biochemical parameters reacted earlier or stronger to disturbances than growth. Overall, the presented multiple-endpoint assay constitutes a promising basis for investigating stressor and toxicant effects in green algae.

  11. The interactive effects of multiple stressors on physiological stress responses and club cell investment in fathead minnows

    International Nuclear Information System (INIS)

    Manek, Aditya K.; Ferrari, Maud C.O.; Niyogi, Som; Chivers, Douglas P.

    2014-01-01

    Anthropogenic activities have dramatically increased over the past decades, with the consequence that many organisms are simultaneously exposed to multiple stressors. Understanding how organisms respond to these stressors is a key focus for scientists from many disciplines. Here we investigated the interactive effects of two stressors, UV radiation (UVR) and cadmium (Cd) exposure on a common freshwater fish, fathead minnow (Pimephales promelas). UVR is known to influence the density of epidermal club cells (ECCs), which are not only a key component of the innate immune system of fishes, but are also the source of chemical alarm cues that serve to warn other fishes of nearby predators. In contrast, Cd impairs the physiological stress response and ability of fish to respond to alarm cues. We used an integrative approach to examine physiological stress response as well as investment in ECCs. Fish exposed to UVR had higher levels of cortisol than non-exposed controls, but Cd reduced cortisol levels substantially for fish exposed to UVR. Fish exposed to UVR, either in the presence or absence of Cd, showed consistent decreases in ECC investment compared to non-exposed controls. Despite differences in ECC number, there was no difference in the potency of alarm cues prepared from the skin of UVR and Cd exposed or non-exposed fish indicating that UVR and Cd exposure combined may have little influence on chemically-mediated predator–prey interactions. - Highlights: • UV radiation caused a physiological stress response (cortisol release) in fish. • Cd reduced cortisol levels substantially for fish exposed to UV. • Fish exposed to UV, with or without Cd, showed decreases in club cell investment. • There was no difference in alarm cues potency from UV and Cd exposed fish. • Our work highlights the difficulty of untangling effects of multiple stressors

  12. The interactive effects of multiple stressors on physiological stress responses and club cell investment in fathead minnows

    Energy Technology Data Exchange (ETDEWEB)

    Manek, Aditya K., E-mail: aditya.manek@usask.ca [Department of Biology, University of Saskatchewan, Saskatoon, S7N 5E2 SK (Canada); Ferrari, Maud C.O. [Department of Biomedical Sciences, WCVM, University of Saskatchewan, Saskatoon, SK S7N 5B4 (Canada); Niyogi, Som; Chivers, Douglas P. [Department of Biology, University of Saskatchewan, Saskatoon, S7N 5E2 SK (Canada)

    2014-04-01

    Anthropogenic activities have dramatically increased over the past decades, with the consequence that many organisms are simultaneously exposed to multiple stressors. Understanding how organisms respond to these stressors is a key focus for scientists from many disciplines. Here we investigated the interactive effects of two stressors, UV radiation (UVR) and cadmium (Cd) exposure on a common freshwater fish, fathead minnow (Pimephales promelas). UVR is known to influence the density of epidermal club cells (ECCs), which are not only a key component of the innate immune system of fishes, but are also the source of chemical alarm cues that serve to warn other fishes of nearby predators. In contrast, Cd impairs the physiological stress response and ability of fish to respond to alarm cues. We used an integrative approach to examine physiological stress response as well as investment in ECCs. Fish exposed to UVR had higher levels of cortisol than non-exposed controls, but Cd reduced cortisol levels substantially for fish exposed to UVR. Fish exposed to UVR, either in the presence or absence of Cd, showed consistent decreases in ECC investment compared to non-exposed controls. Despite differences in ECC number, there was no difference in the potency of alarm cues prepared from the skin of UVR and Cd exposed or non-exposed fish indicating that UVR and Cd exposure combined may have little influence on chemically-mediated predator–prey interactions. - Highlights: • UV radiation caused a physiological stress response (cortisol release) in fish. • Cd reduced cortisol levels substantially for fish exposed to UV. • Fish exposed to UV, with or without Cd, showed decreases in club cell investment. • There was no difference in alarm cues potency from UV and Cd exposed fish. • Our work highlights the difficulty of untangling effects of multiple stressors.

  13. Multiple-endpoint assay provides a detailed mechanistic view of responses to herbicide exposure in Chlamydomonas reinhardtii

    Energy Technology Data Exchange (ETDEWEB)

    Nestler, Holger [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland); Groh, Ksenia J.; Schoenenberger, Rene; Behra, Renata [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); Schirmer, Kristin [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland); EPF Lausanne, School of Architecture, Civil and Environmental Engineering, 1015 Lausanne (Switzerland); Eggen, Rik I.L. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland); Suter, Marc J.-F., E-mail: suter@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Ueberlandstrasse 133, 8600 Duebendorf (Switzerland); ETH Zurich, Swiss Federal Institute of Technology, Institute of Biogeochemistry and Pollutant Dynamics, Universitaetstrasse 16, 8092 Zurich (Switzerland)

    2012-04-15

    The release of herbicides into the aquatic environment raises concerns about potential detrimental effects on ecologically important non-target species, such as unicellular algae, necessitating ecotoxicological risk assessment. Algal toxicity tests based on growth, a commonly assessed endpoint, are integrative, and hence do not provide information about underlying toxic mechanisms and effects. This limitation may be overcome by measuring more specific biochemical and physiological endpoints. In the present work, we developed and applied a novel multiple-endpoint assay, and analyzed the effects of the herbicides paraquat, diuron and norflurazon, each representing a specific mechanism of toxic action, on the single celled green alga Chlamydomonas reinhardtii. The endpoints added to assessment of growth were pigment content, maximum and effective photosystem II quantum yield, ATP content, esterase and oxidative activity. All parameters were measured at 2, 6 and 24 h of exposure, except for growth and pigment content, which were determined after 6 and 24 h only. Effective concentrations causing 50% of response (EC50s) and lowest observable effect concentrations (LOECs) were determined for all endpoints and exposure durations where possible. The assay provided a detailed picture of the concentration- and time-dependent development of effects elicited by the analyzed herbicides, thus improving the understanding of the underlying toxic mechanisms. Furthermore, the response patterns were unique to the respective herbicide and reflected the different mechanisms of toxicity. The comparison of the endpoint responses and sensitivities revealed that several physiological and biochemical parameters reacted earlier or stronger to disturbances than growth. Overall, the presented multiple-endpoint assay constitutes a promising basis for investigating stressor and toxicant effects in green algae.

  14. Humoral Responses to Diverse Autoimmune Disease-Associated Antigens in Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Kishore Malyavantham

    Full Text Available To compare frequencies of autoreactive antibody responses to endogenous disease-associated antigens in healthy controls (HC, relapsing and progressive MS and to assess their associations with clinical and MRI measures of MS disease progression.The study analyzed 969 serum samples from 315 HC, 411 relapsing remitting MS (RR-MS, 128 secondary progressive MS (SP-MS, 33 primary progressive MS (PP-MS and 82 patients with other neurological diseases for autoantibodies against two putative MS antigens CSF114(Glc and KIR4.1a and KIR4.1b and against 24 key endogenous antigens linked to diseases such as vasculitis, systemic sclerosis, rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, polymyositis, scleroderma, polymyositis, dermatomyositis, mixed connective tissue disease and primary biliary cirrhosis. Associations with disability and MRI measures of lesional injury and neurodegeneration were assessed.The frequencies of anti-KIR4.1a and anti-KIR4.1b peptide IgG positivity were 9.8% and 11.4% in HC compared to 4.9% and 7.5% in RR-MS, 8.6% for both peptides in SP-MS and 6.1% for both peptides in PP-MS (p = 0.13 for KIR4.1a and p = 0.34 for KIR4.1b, respectively. Antibodies against CSF114(Glc, KIR4.1a and KIR4.1b peptides were not associated with MS compared to HC, or with MS disease progression. HLA DRB1*15:01 positivity and anti-Epstein Barr virus antibodies, which are MS risk factors, were not associated with these putative MS antibodies.Antibody responses to KIR4.1a and KIR4.1b peptides are not increased in MS compared to HC nor associated with MS disease progression. The frequencies of the diverse autoreactive antibodies investigated are similar in MS and HC.

  15. Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding.

    Directory of Open Access Journals (Sweden)

    Janet Chamberlain

    Full Text Available Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1 signaling in the vessel wall would raise arterial blood pressure and promote atheroma.Apoe(-/- and Apoe(-/-/IL-1R1(-/- mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe(-/-/IL-R1(-/- mice had a reduced blood pressure and significantly less atheroma than Apoe(-/- mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p < 0.05. This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress.The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man.

  16. Multiple phenological responses to climate change among 42 plant species in Xi'an, China.

    Science.gov (United States)

    Dai, Junhu; Wang, Huanjiong; Ge, Quansheng

    2013-09-01

    Phenological data of 42 woody plants in a temperate deciduous forest from the Chinese Phenological Observation Network (CPON) and the corresponding meteorological data from 1963 to 2011 in Xi'an, Shaanxi Province, China were collected and analyzed. The first leaf date (FLD), leaf coloring date (LCD) and first flower date (FFD) are revealed as strong biological signals of climatic change. The FLD, LCD and FFD of most species are sensitive to average temperature during a certain period before phenophase onset. Regional precipitation also has a significant impact on phenophases of about half of the species investigated. Affected by climate change, the FLD and FFD of these species have advanced by 5.54 days and 10.20 days on average during 2003-2011 compared with the period 1963-1996, respectively. Meanwhile, the LCD has delayed by 10.59 days, and growing season length has extended 16.13 days. Diverse responses of phenology commonly exist among different species and functional groups during the study period. Especially for FFD, the deviations between the above two periods ranged from -20.68 to -2.79 days; biotic pollination species showed a significantly greater advance than abiotic pollination species. These results were conducive to the understanding of possible changes in both the structure of plant communities and interspecific relationships in the context of climate change.

  17. Response function of NaI(Tl) detectors and multiple backscattering of gamma rays in aluminium

    International Nuclear Information System (INIS)

    Sabharwal, Arvind D.; Singh, Manpreet; Singh, Bhajan; Sandhu, B.S.

    2008-01-01

    The response function, converting the observed pulse-height distribution of a NaI(Tl) detector to a true photon spectrum, is obtained experimentally with the help of an inverse matrix approach. The energy of gamma-ray photons continuously decreases as the number of scatterings increases in a sample having finite dimensions when one deals with the depth of the sample. The present experiments are undertaken to study the effect of target thickness on intensity distribution of gamma photons multiply backscattered from an aluminium target. A NaI(Tl) gamma-ray detector detects the photons backscattered from the aluminium target. The subtraction of analytically estimated singly scattered distribution from the observed intensity distribution (originating from interactions of primary gamma-ray photons with the target) results in multiply backscattered events. We observe that for each incident gamma photon energy, the number of multiply backscattered photons increases with increase in target thickness and then saturates at a particular target thickness called the saturation thickness (depth). Saturation thickness for multiply backscattering of gamma photons is found to decrease with increase in energy of incident gamma-ray photons

  18. Environmental emergency response plans (EERPs): A single plan approach to satisfy multiple regulations

    International Nuclear Information System (INIS)

    Muzyka, L.

    1995-01-01

    Conrail is a freight railroad operating in twelve northeast and midwestern states transporting goods and materials over 11,700 miles of railroad. To repair, maintain, rebuild, and manufacture locomotives and rail cars, and to maintain the track, right of way, bridges, tunnels and other structures, Conrail uses petroleum products, solvents and cleaners. These products are stored in hundreds of storage tanks in and around the yards and right of way. To power the trains, locomotives are fueled with diesel fuel. With large volumes of fuel, lubricants, solvents and cleaners, safe and efficient handling of petroleum and chemicals is crucial to avoid negative impacts on the environment. Conrail recently revisited the issue of environmental emergency response planning. In an attempt to assure full compliance with a myriad of federal, state, and local regulation, a ''single plan approach'' was chosen. Single plans for each facility, coined EERPs, were decided on after careful review of the regulations, and evaluation of the company's operational and organizational needs

  19. Complete clinical responses to cancer therapy caused by multiple divergent approaches: a repeating theme lost in translation

    International Nuclear Information System (INIS)

    Coventry, Brendon J; Ashdown, Martin L

    2012-01-01

    Over 50 years of cancer therapy history reveals complete clinical responses (CRs) from remarkably divergent forms of therapies (eg, chemotherapy, radiotherapy, surgery, vaccines, autologous cell transfers, cytokines, monoclonal antibodies) for advanced solid malignancies occur with an approximately similar frequency of 5%–10%. This has remained frustratingly almost static. However, CRs usually underpin strong durable 5-year patient survival. How can this apparent paradox be explained? Over some 20 years, realization that (1) chronic inflammation is intricately associated with cancer, and (2) the immune system is delicately balanced between responsiveness and tolerance of cancer, provides a greatly significant insight into ways cancer might be more effectively treated. In this review, divergent aspects from the largely segmented literature and recent conferences are drawn together to provide observations revealing some emerging reasoning, in terms of “final common pathways” of cancer cell damage, immune stimulation, and auto-vaccination events, ultimately leading to cancer cell destruction. Created from this is a unifying overarching concept to explain why multiple approaches to cancer therapy can provide complete responses at almost equivalent rates. This “missing” aspect provides a reasoned explanation for what has, and is being, increasingly reported in the mainstream literature – that inflammatory and immune responses appear intricately associated with, if not causative of, complete responses induced by divergent forms of cancer therapy. Curiously, whether by chemotherapy, radiation, surgery, or other means, therapy-induced cell injury results, leaving inflammation and immune system stimulation as a final common denominator across all of these mechanisms of cancer therapy. This aspect has been somewhat obscured and has been “lost in translation” to date

  20. [The value of serum heavy/light chain immunoassay to assess therapeutic response in patients with multiple myeloma].

    Science.gov (United States)

    Yu, X C; Su, W; Zhuang, J L

    2018-04-14

    Objective: To assess the value of immunoglobulin heavy/light chain (HLC) immunoassay on therapeutic response in patients with multiple myeloma(MM). Methods: A total of 45 newly diagnosed MM patients were retrospectively enrolled in Peking Union Medical College Hospital from 2013 to 2016, whose 115 serum samples were consecutively collected. HLC was tested to evaluate response and compare with other methods for M protein detection. Results: ①There were 30 males and 15 females in total of whom the monoclonal immunoglobulin was IgG in 27 (IgGκ∶IgGλ 12∶15) and IgA (IgAκ∶IgAλ 9∶9) in 18. The arerage age of the studied population was 59 (range 43-80) . ② In 34 patients with serum sample at diagnosis, 32 (94.1%) had abnormal HLC ratio (rHLC) while 2 patients with IgG had normal rHLC. The percentages of abnormal rHLC was 81.8% (18/22) at partial response、50.0%(9/18) at very good complete response and 16.0%(4/25) at complete response. ③In 25 patients reaching CR, there were 13 with IgG and 12 with IgA. 4 patients equally split of IgG and IgA had abnormal rHLC at complete response. ④By monitoring the rHLC of some patients consecutively, we found that the remission of rHLC was to some extent behind the remission of SPE and IEF, or even rFLC. Conclusion: Immunoglobulin HLC detection is one feasible method for minimal residual disease detection.

  1. Metabolic stress responses in Drosophila are modulated by brain neurosecretory cells that produce multiple neuropeptides.

    Directory of Open Access Journals (Sweden)

    Lily Kahsai

    Full Text Available In Drosophila, neurosecretory cells that release peptide hormones play a prominent role in the regulation of development, growth, metabolism, and reproduction. Several types of peptidergic neurosecretory cells have been identified in the brain of Drosophila with release sites in the corpora cardiaca and anterior aorta. We show here that in adult flies the products of three neuropeptide precursors are colocalized in five pairs of large protocerebral neurosecretory cells in two clusters (designated ipc-1 and ipc-2a: Drosophila tachykinin (DTK, short neuropeptide F (sNPF and ion transport peptide (ITP. These peptides were detected by immunocytochemistry in combination with GFP expression driven by the enhancer trap Gal4 lines c929 and Kurs-6, both of which are expressed in ipc-1 and 2a cells. This mix of colocalized peptides with seemingly unrelated functions is intriguing and prompted us to initiate analysis of the function of the ten neurosecretory cells. We investigated the role of peptide signaling from large ipc-1 and 2a cells in stress responses by monitoring the effect of starvation and desiccation in flies with levels of DTK or sNPF diminished by RNA interference. Using the Gal4-UAS system we targeted the peptide knockdown specifically to ipc-1 and 2a cells with the c929 and Kurs-6 drivers. Flies with reduced DTK or sNPF levels in these cells displayed decreased survival time at desiccation and starvation, as well as increased water loss at desiccation. Our data suggest that homeostasis during metabolic stress requires intact peptide signaling by ipc-1 and 2a neurosecretory cells.

  2. Recent research and applications of numerical simulation for dynamic response of long-span bridges subjected to multiple loads.

    Science.gov (United States)

    Chen, Zhiwei; Chen, Bo

    2014-01-01

    Many long-span bridges have been built throughout the world in recent years but they are often subject to multiple types of dynamic loads, especially those located in wind-prone regions and carrying both trains and road vehicles. To ensure the safety and functionality of these bridges, dynamic responses of long-span bridges are often required for bridge assessment. Given that there are several limitations for the assessment based on field measurement of dynamic responses, a promising approach is based on numerical simulation technologies. This paper provides a detailed review of key issues involved in dynamic response analysis of long-span multiload bridges based on numerical simulation technologies, including dynamic interactions between running trains and bridge, between running road vehicles and bridge, and between wind and bridge, and in the wind-vehicle-bridge coupled system. Then a comprehensive review is conducted for engineering applications of newly developed numerical simulation technologies to safety assessment of long-span bridges, such as assessment of fatigue damage and assessment under extreme events. Finally, the existing problems and promising research efforts for the numerical simulation technologies and their applications to assessment of long-span multiload bridges are explored.

  3. Gradient-based model calibration with proxy-model assistance

    Science.gov (United States)

    Burrows, Wesley; Doherty, John

    2016-02-01

    Use of a proxy model in gradient-based calibration and uncertainty analysis of a complex groundwater model with large run times and problematic numerical behaviour is described. The methodology is general, and can be used with models of all types. The proxy model is based on a series of analytical functions that link all model outputs used in the calibration process to all parameters requiring estimation. In enforcing history-matching constraints during the calibration and post-calibration uncertainty analysis processes, the proxy model is run for the purposes of populating the Jacobian matrix, while the original model is run when testing parameter upgrades; the latter process is readily parallelized. Use of a proxy model in this fashion dramatically reduces the computational burden of complex model calibration and uncertainty analysis. At the same time, the effect of model numerical misbehaviour on calculation of local gradients is mitigated, this allowing access to the benefits of gradient-based analysis where lack of integrity in finite-difference derivatives calculation would otherwise have impeded such access. Construction of a proxy model, and its subsequent use in calibration of a complex model, and in analysing the uncertainties of predictions made by that model, is implemented in the PEST suite.

  4. Time-and-ID-Based Proxy Reencryption Scheme

    Directory of Open Access Journals (Sweden)

    Kambombo Mtonga

    2014-01-01

    Full Text Available Time- and ID-based proxy reencryption scheme is proposed in this paper in which a type-based proxy reencryption enables the delegator to implement fine-grained policies with one key pair without any additional trust on the proxy. However, in some applications, the time within which the data was sampled or collected is very critical. In such applications, for example, healthcare and criminal investigations, the delegatee may be interested in only some of the messages with some types sampled within some time bound instead of the entire subset. Hence, in order to carter for such situations, in this paper, we propose a time-and-identity-based proxy reencryption scheme that takes into account the time within which the data was collected as a factor to consider when categorizing data in addition to its type. Our scheme is based on Boneh and Boyen identity-based scheme (BB-IBE and Matsuo’s proxy reencryption scheme for identity-based encryption (IBE to IBE. We prove that our scheme is semantically secure in the standard model.

  5. Multiple biomarkers responses in Prochilodus lineatus allowed assessing changes in the water quality of Salado River basin (Santa Fe, Argentina)

    Energy Technology Data Exchange (ETDEWEB)

    Cazenave, Jimena, E-mail: jcazenave@inali.unl.edu.a [Laboratorio de Ictiologia, Instituto Nacional de Limnologia (INALI-CONICET-UNL), Paraje El Pozo, Ciudad Universitaria UNL, 3000 Santa Fe (Argentina); Bacchetta, Carla; Parma, Maria J.; Scarabotti, Pablo A. [Laboratorio de Ictiologia, Instituto Nacional de Limnologia (INALI-CONICET-UNL), Paraje El Pozo, Ciudad Universitaria UNL, 3000 Santa Fe (Argentina); Wunderlin, Daniel A. [Dto. Bioquimica Clinica-CIBICI-CONICET, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre esq Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina)

    2009-11-15

    This field study assessed water quality of Salado River basin by using a set of biomarkers in the fish Prochilodus lineatus. Multiple biomarkers were measured, including morphological indexes (condition factor, liver somatic index), hematological (red and white blood cells) and biochemical (glucose, total protein and cholinesterase activity) parameters. Besides, detoxication and oxidative stress markers (antioxidant enzymes, lipid peroxidation) were measured in liver, gills and kidney. Despite water quality assessment did not show marked differences among sites, biomarkers responses indicate that fish are living under stressful environmental conditions. According to multivariate analysis glucose, glutathione S-transferase activity, lipid peroxidation levels and the count of white blood cells are key biomarkers to contribute to discrimination of sites. So, we suggest use those biomarkers in future monitoring of freshwater aquatic systems. - A battery of biomarkers was successfully applied to assess the health of the fish Prochilodus lineatus from Salado River basin.

  6. Improvement of fatigue in multiple sclerosis by physical exercise is associated to modulation of systemic interferon response.

    Science.gov (United States)

    Mulero, Patricia; Almansa, Raquel; Neri, María José; Bermejo-Martin, Jesús Francisco; Archanco, Miguel; Arenillas, Juan Francisco; Téllez, Nieves

    2015-03-15

    Mechanisms underlying multiple sclerosis (MS) fatigue and the causes of the beneficial effect of exercise on this symptom are not clarified. Our aim was to evaluate gene expression profiles in MS patients who improved their fatigue status after an exercise program and to compare them with healthy controls (HC). Gene expression in whole blood was profiled at baseline in 7 HC and also in 7 fatigued-MS patients. Patients underwent an exercise program for 6 months, and their fatigue status and gene expression profiles were again analyzed. MS patients showed a significant activation of genes participating in the systemic interferon response in comparison with HC that disappeared at the end of the program. Our results provide a biological basis for the observed benefit of exercise in MS. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. A Complete Response Case in a Patient with Multiple Lung Metastases of Rectal Cancer Treated with Bevacizumab plus XELIRI Therapy

    Directory of Open Access Journals (Sweden)

    Hiroki Hashida

    2017-01-01

    Full Text Available It has been reported that many patients with lung metastasis of colorectal cancer (CRC underwent chemotherapy with fluorouracil, folinic acid, oxaliplatin, irinotecan, or capecitabine. There is a small number of reports about the capecitabine and irinotecan (XELIRI plus bevacizumab (BV therapy for patients with metastatic CRC in Japan. We report a case of successful BV+XELIRI therapy for rectal cancer with multiple lung metastases as first-line chemotherapy. A 53-year-old female presented with advanced rectal cancer and metastatic lung tumors. Following surgery, the patient was treated with XELIRI+BV. After 6 courses, a computed tomography scan showed complete response of the lung metastases. No recurrence has occurred for 3 years after chemotherapy was stopped.

  8. Histopathological analysis of the therapeutic response to cryotherapy with liquid nitrogen in patients with multiple actinic keratosis.

    Science.gov (United States)

    Oliveira, Marina Câmara de; Trevisan, Flávia; Pinto, Clovis Antônio Lopes; Xavier, Célia Antônia; Pinto, Jaqueline Campoi Calvo Lopes

    2015-01-01

    Actinic keratoses are premalignant lesions of the skin caused by excessive sun exposure. Lesions may become mainly squamous cell carcinoma. Cryotherapy with liquid nitrogen is one of the main treatments. In order to evaluate the response of actinic keratosis to cryotherapy by histopathology, two lesions were selected in each of 14 patients with multiple actinic keratoses. In one lesion a biopsy was performed and in the other lesion a biopsy was performed after cryotherapy. Subsequently, both biopsies were compared histologically. Of the thirteen patients who completed the study, the best results were obtained in lesions undergoing cryotherapy concerning the atypia of keratinocytes, epithelial thickness and corneal layer and lymphocytic infiltrate. Despite the small number of patients, it was concluded that, if performed correctly, cryotherapy has high efficacy in the treatment of actinic keratoses.

  9. Multiple biomarkers responses in Prochilodus lineatus allowed assessing changes in the water quality of Salado River basin (Santa Fe, Argentina)

    International Nuclear Information System (INIS)

    Cazenave, Jimena; Bacchetta, Carla; Parma, Maria J.; Scarabotti, Pablo A.; Wunderlin, Daniel A.

    2009-01-01

    This field study assessed water quality of Salado River basin by using a set of biomarkers in the fish Prochilodus lineatus. Multiple biomarkers were measured, including morphological indexes (condition factor, liver somatic index), hematological (red and white blood cells) and biochemical (glucose, total protein and cholinesterase activity) parameters. Besides, detoxication and oxidative stress markers (antioxidant enzymes, lipid peroxidation) were measured in liver, gills and kidney. Despite water quality assessment did not show marked differences among sites, biomarkers responses indicate that fish are living under stressful environmental conditions. According to multivariate analysis glucose, glutathione S-transferase activity, lipid peroxidation levels and the count of white blood cells are key biomarkers to contribute to discrimination of sites. So, we suggest use those biomarkers in future monitoring of freshwater aquatic systems. - A battery of biomarkers was successfully applied to assess the health of the fish Prochilodus lineatus from Salado River basin.

  10. Comparison of lipid peroxidation and catalase response in invasive dreissenid mussels exposed to single and multiple stressors.

    Science.gov (United States)

    Nowicki, Carly J; Kashian, Donna R

    2018-02-14

    Dreissenid mussels Dreissena bugensis (quagga mussel) and Dreissena polymorpha (zebra mussel) are prolific invasive species to the freshwaters of the United States and Western Europe. In the Great Lakes, D. polymorpha has initially dominated the system since its invasion in the mid-1980s; however, recently D. bugensis has displaced D. polymorpha as the dominant species. Dreissena bugensis has several competitive advantages over D. polymorpha, including greater tolerances to deeper and colder waters and lower respiration rates. Nevertheless, physiological differences between the species remain largely unknown. The oxidative stress response is a mechanism used by all organisms to mitigate environmental stress by reducing oxygen radicals in the body, and comparing this mechanism between similar species can be useful for understanding how different species compete in aquatic environments. We compared oxidative stress biomarkers (lipid peroxidation [LPO] and catalase [CAT] activity) in mussels after exposure to 4 stressors (i.e., high densities, temperature, hypoxia, and polychlorinated biphenyls [PCBs]) independently and in combinations of 2 stressors. Overall, D. bugensis had lower LPO and CAT activity than D. polymorpha when exposed to single stressors; however, in multiple stressor treatments D. bugensis had increased LPO, especially with high temperatures and PCBs. The lower lipid damage in D. bugensis compared with D. polymorpha under single stressor conditions may come at the cost of the ability to respond to multiple stressors. Environ Toxicol Chem 2018;9999:1-12. © 2018 SETAC. © 2018 SETAC.

  11. High Agreement was Obtained Across Scores from Multiple Equated Scales for Social Anxiety Disorder using Item Response Theory.

    Science.gov (United States)

    Sunderland, Matthew; Batterham, Philip; Calear, Alison; Carragher, Natacha; Baillie, Andrew; Slade, Tim

    2018-04-10

    There is no standardized approach to the measurement of social anxiety. Researchers and clinicians are faced with numerous self-report scales with varying strengths, weaknesses, and psychometric properties. The lack of standardization makes it difficult to compare scores across populations that utilise different scales. Item response theory offers one solution to this problem via equating different scales using an anchor scale to set a standardized metric. This study is the first to equate several scales for social anxiety disorder. Data from two samples (n=3,175 and n=1,052), recruited from the Australian community using online advertisements, were utilised to equate a network of 11 self-report social anxiety scales via a fixed parameter item calibration method. Comparisons between actual and equated scores for most of the scales indicted a high level of agreement with mean differences <0.10 (equivalent to a mean difference of less than one point on the standardized metric). This study demonstrates that scores from multiple scales that measure social anxiety can be converted to a common scale. Re-scoring observed scores to a common scale provides opportunities to combine research from multiple studies and ultimately better assess social anxiety in treatment and research settings. Copyright © 2018. Published by Elsevier Inc.

  12. Objective spatiotemporal proxy-model comparisons of the Asian monsoon for the last millennium

    Science.gov (United States)

    Anchukaitis, K. J.; Cook, E. R.; Ammann, C. M.; Buckley, B. M.; D'Arrigo, R. D.; Jacoby, G.; Wright, W. E.; Davi, N.; Li, J.

    2008-12-01

    The Asian monsoon system can be studied using a complementary proxy/simulation approach which evaluates climate models using estimates of past precipitation and temperature, and which subsequently applies the best understanding of the physics of the climate system as captured in general circulation models to evaluate the broad-scale dynamics behind regional paleoclimate reconstructions. Here, we use a millennial-length climate field reconstruction of monsoon season summer (JJA) drought, developed from tree- ring proxies, with coupled climate simulations from NCAR CSM1.4 and CCSM3 to evaluate the cause of large- scale persistent droughts over the last one thousand years. Direct comparisons are made between the external forced response within the climate model and the spatiotemporal field reconstruction. In order to identify patterns of drought associated with internal variability in the climate system, we use a model/proxy analog technique which objectively selects epochs in the model that most closely reproduce those observed in the reconstructions. The concomitant ocean-atmosphere dynamics are then interpreted in order to identify and understand the internal climate system forcing of low frequency monsoon variability. We examine specific periods of extensive or intensive regional drought in the 15th, 17th, and 18th centuries, many of which are coincident with major cultural changes in the region.

  13. Can a physician predict the clinical response to first-line immunomodulatory treatment in relapsing–remitting multiple sclerosis?

    Directory of Open Access Journals (Sweden)

    Mezei Z

    2012-10-01

    Full Text Available Zsolt Mezei,1 Daniel Bereczki,1,2 Lilla Racz,1 Laszlo Csiba,1 Tunde Csepany11Department of Neurology, University of Debrecen, Debrecen, Hungary; 2Department of Neurology, Semmelweis University, Budapest, HungaryBackground: Decreased relapse rate and slower disease progression have been reported with long-term use of immunomodulatory treatments (IMTs, interferon beta or glatiramer acetate in relapsing–remitting multiple sclerosis. There are, however, patients who do not respond to such treatments, and they can be potential candidates for alternative therapeutic approaches.Objective: To identify clinical factors as possible predictors of poor long-term response.Methods: A 9-year prospective, continuous follow-up at a single center in Hungary to assess clinical efficacy of IMT.Results: In a patient group of 81 subjects with mean IMT duration of 54 ± 33 months, treatment efficacy expressed as annual relapse rate and change in clinical severity from baseline did not depend on the specific IMT (any of the interferon betas or glatiramer acetate, and on mono- or multifocal features of the initial appearance of the disease. Responders had shorter disease duration and milder clinical signs at the initiation of treatment. Relapse-rate reduction in the initial 2 years of treatment predicted clinical efficacy in subsequent years.Conclusion: Based on these observations, we suggest that a 2-year trial period is sufficient to decide on the efficacy of a specific IMT. For those with insufficient relapse reduction in the first 2 years of treatment, a different IMT or other therapeutic approaches should be recommended.Keywords: multiple sclerosis, immunomodulatory, EDSS, relapse, response

  14. Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency.

    Science.gov (United States)

    Cornelius, Nanna; Frerman, Frank E; Corydon, Thomas J; Palmfeldt, Johan; Bross, Peter; Gregersen, Niels; Olsen, Rikke K J

    2012-08-01

    Riboflavin-responsive forms of multiple acyl-CoA dehydrogenation deficiency (RR-MADD) have been known for years, but with presumed defects in the formation of the flavin adenine dinucleotide (FAD) co-factor rather than genetic defects of electron transfer flavoprotein (ETF) or electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO). It was only recently established that a number of RR-MADD patients carry genetic defects in ETF-QO and that the well-documented clinical efficacy of riboflavin treatment may be based on a chaperone effect that can compensate for inherited folding defects of ETF-QO. In the present study, we investigate the molecular mechanisms and the genotype-phenotype relationships for the riboflavin responsiveness in MADD, using a human HEK-293 cell expression system. We studied the influence of riboflavin and temperature on the steady-state level and the activity of variant ETF-QO proteins identified in patients with RR-MADD, or non- and partially responsive MADD. Our results showed that variant ETF-QO proteins associated with non- and partially responsive MADD caused severe misfolding of ETF-QO variant proteins when cultured in media with supplemented concentrations of riboflavin. In contrast, variant ETF-QO proteins associated with RR-MADD caused milder folding defects when cultured at the same conditions. Decreased thermal stability of the variants showed that FAD does not completely correct the structural defects induced by the variation. This may cause leakage of electrons and increased reactive oxygen species, as reflected by increased amounts of cellular peroxide production in HEK-293 cells expressing the variant ETF-QO proteins. Finally, we found indications of prolonged association of variant ETF-QO protein with the Hsp60 chaperonin in the mitochondrial matrix, supporting indications of folding defects in the variant ETF-QO proteins.

  15. Candidate Gene Study of TRAIL and TRAIL Receptors: Association with Response to Interferon Beta Therapy in Multiple Sclerosis Patients

    Science.gov (United States)

    Órpez-Zafra, Teresa; Pinto-Medel, María Jesús; Oliver-Martos, Begoña; Ortega-Pinazo, Jesús; Arnáiz, Carlos; Guijarro-Castro, Cristina; Varadé, Jezabel; Álvarez-Lafuente, Roberto; Urcelay, Elena; Sánchez-Jiménez, Francisca

    2013-01-01

    TRAIL and TRAIL Receptor genes have been implicated in Multiple Sclerosis pathology as well as in the response to IFN beta therapy. The objective of our study was to evaluate the association of these genes in relation to the age at disease onset (AAO) and to the clinical response upon IFN beta treatment in Spanish MS patients. We carried out a candidate gene study of TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 genes. A total of 54 SNPs were analysed in 509 MS patients under IFN beta treatment, and an additional cohort of 226 MS patients was used to validate the results. Associations of rs1047275 in TRAILR-2 and rs7011559 in TRAILR-4 genes with AAO under an additive model did not withstand Bonferroni correction. In contrast, patients with the TRAILR-1 rs20576-CC genotype showed a better clinical response to IFN beta therapy compared with patients carrying the A-allele (recessive model: p = 8.88×10−4, pc = 0.048, OR = 0.30). This SNP resulted in a non synonymous substitution of Glutamic acid to Alanine in position 228 (E228A), a change previously associated with susceptibility to different cancer types and risk of metastases, suggesting a lack of functionality of TRAILR-1. In order to unravel how this amino acid change in TRAILR-1 would affect to death signal, we performed a molecular modelling with both alleles. Neither TRAIL binding sites in the receptor nor the expression levels of TRAILR-1 in peripheral blood mononuclear cell subsets (monocytes, CD4+ and CD8+ T cells) were modified, suggesting that this SNP may be altering the death signal by some other mechanism. These findings show a role for TRAILR-1 gene variations in the clinical outcome of IFN beta therapy that might have relevance as a biomarker to predict the response to IFN beta in MS. PMID:23658636

  16. Inhibition of estrogen-responsive gene activation by the retinoid X receptor beta: evidence for multiple inhibitory pathways.

    Science.gov (United States)

    Segars, J H; Marks, M S; Hirschfeld, S; Driggers, P H; Martinez, E; Grippo, J F; Brown, M; Wahli, W; Ozato, K

    1993-04-01

    The retinoid X receptor beta (RXR beta; H-2RIIBP) forms heterodimers with various nuclear hormone receptors and binds multiple hormone response elements, including the estrogen response element (ERE). In this report, we show that endogenous RXR beta contributes to ERE binding activity in nuclear extracts of the human breast cancer cell line MCF-7. To define a possible regulatory role of RXR beta regarding estrogen-responsive transcription in breast cancer cells, RXR beta and a reporter gene driven by the vitellogenin A2 ERE were transfected into estrogen-treated MCF-7 cells. RXR beta inhibited ERE-driven reporter activity in a dose-dependent and element-specific fashion. This inhibition occurred in the absence of the RXR ligand 9-cis retinoic acid. The RXR beta-induced inhibition was specific for estrogen receptor (ER)-mediated ERE activation because inhibition was observed in ER-negative MDA-MB-231 cells only following transfection of the estrogen-activated ER. No inhibition of the basal reporter activity was observed. The inhibition was not caused by simple competition of RXR beta with the ER for ERE binding, since deletion mutants retaining DNA binding activity but lacking the N-terminal or C-terminal domain failed to inhibit reporter activity. In addition, cross-linking studies indicated the presence of an auxiliary nuclear factor present in MCF-7 cells that contributed to RXR beta binding of the ERE. Studies using known heterodimerization partners of RXR beta confirmed that RXR beta/triiodothyronine receptor alpha heterodimers avidly bind the ERE but revealed the existence of another triiodothyronine-independent pathway of ERE inhibition. These results indicate that estrogen-responsive genes may be negatively regulated by RXR beta through two distinct pathways.

  17. Candidate gene study of TRAIL and TRAIL receptors: association with response to interferon beta therapy in multiple sclerosis patients.

    Directory of Open Access Journals (Sweden)

    Carlos López-Gómez

    Full Text Available TRAIL and TRAIL Receptor genes have been implicated in Multiple Sclerosis pathology as well as in the response to IFN beta therapy. The objective of our study was to evaluate the association of these genes in relation to the age at disease onset (AAO and to the clinical response upon IFN beta treatment in Spanish MS patients. We carried out a candidate gene study of TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 genes. A total of 54 SNPs were analysed in 509 MS patients under IFN beta treatment, and an additional cohort of 226 MS patients was used to validate the results. Associations of rs1047275 in TRAILR-2 and rs7011559 in TRAILR-4 genes with AAO under an additive model did not withstand Bonferroni correction. In contrast, patients with the TRAILR-1 rs20576-CC genotype showed a better clinical response to IFN beta therapy compared with patients carrying the A-allele (recessive model: p = 8.88×10(-4, pc = 0.048, OR = 0.30. This SNP resulted in a non synonymous substitution of Glutamic acid to Alanine in position 228 (E228A, a change previously associated with susceptibility to different cancer types and risk of metastases, suggesting a lack of functionality of TRAILR-1. In order to unravel how this amino acid change in TRAILR-1 would affect to death signal, we performed a molecular modelling with both alleles. Neither TRAIL binding sites in the receptor nor the expression levels of TRAILR-1 in peripheral blood mononuclear cell subsets (monocytes, CD4+ and CD8+ T cells were modified, suggesting that this SNP may be altering the death signal by some other mechanism. These findings show a role for TRAILR-1 gene variations in the clinical outcome of IFN beta therapy that might have relevance as a biomarker to predict the response to IFN beta in MS.

  18. Satellite Altimeters and Gravimeters as Proxy of the Indonesian Throughflow

    Science.gov (United States)

    Susanto, R. D.; Song, Y. T.

    2014-12-01

    The Indonesian Throughflow (ITF), the only pathway for interocean exchange between the Pacific to the Indian Ocean, plays an important role in global ocean circulation and climate. Yet, continuous ITF measurement is difficult and expensive. We demonstrate a plausible approach to derive the ITF transport proxy using satellite altimetry sea surface height (SSH), gravimetry ocean bottom pressure (OBP) data, in situ measurements from the Makassar Strait from 1996-1998 and 2004-2009, and a theoretical formulation. We first identified the optimal locations in the Pacific and Indian Ocean based on the optimal correlation between the ITF transport through the Makassar Strait and the pressure gradients, represented by the SSH and OBP differences between the Pacific and Indian Oceans at a 1° x 1° horizontal resolution. These geographical locations (centred at off-equatorial in the western Pacific Ocean and centred at along the equator in the eastern Indian Ocean) that control the strength and variability of the ITF transport in the Makassar Strait differ from early studies. The proxy time series follow the observation time series quite well, resolving the intraseasonal, monsoonal, and interannual signals with the 1993-2011 annual mean proxy transport of 11.6 ± 3.2 Sv. Our formulation provides a continuous approach to derive the ITF proxy as long as the satellite data are available. Such a continuous record would be difficult to achieve by in situ measurements alone due to logistical and financial challenges. Ideally, the proxy can be used to complement or fill in the gaps of the observations for a continuous ITF proxy for better understanding the ocean climate and validating ocean circulation models.

  19. The Intra-Industry Effects of Proxy Contests

    OpenAIRE

    Fang Chen; Jian Huang; Han Yu

    2018-01-01

    This paper is the first study on the intra-industry effects of proxy contests. Using a sample of proxy contests from January 1988 through December 2008, we identify a striking cross-sectional difference in market reaction to the target companies. As much as 61% of the target firms have a significant positive cumulative abnormal return (CARs) in the period (‒10, +10) around the announcement day, while 39% of the target firms have the negative CARs in the same event window. Moreover, we find th...

  20. Health anxiety by proxy in women with severe health anxiety

    DEFF Research Database (Denmark)

    Thorgaard, Mette Viller; Frostholm, Lisbeth; Walker, Lynn

    2017-01-01

    Health anxiety (HA) refers to excessive worries and anxiety about harbouring serious illness based on misinterpretation of bodily sensations or changes as signs of serious illness. Severe HA is associated with disability and high health care costs. However, the impact of parental HA on excessive...... concern with their children's health (health anxiety by proxy) is scantly investigated. The aim of this study is to investigate HA by proxy in mothers with severe HA. Fifty mothers with severe HA and two control groups were included, i.e. mothers with rheumatoid arthritis (N = 49) and healthy mothers (N...

  1. Efficient sparse matrix-matrix multiplication for computing periodic responses by shooting method on Intel Xeon Phi

    Science.gov (United States)

    Stoykov, S.; Atanassov, E.; Margenov, S.

    2016-10-01

    Many of the scientific applications involve sparse or dense matrix operations, such as solving linear systems, matrix-matrix products, eigensolvers, etc. In what concerns structural nonlinear dynamics, the computations of periodic responses and the determination of stability of the solution are of primary interest. Shooting method iswidely used for obtaining periodic responses of nonlinear systems. The method involves simultaneously operations with sparse and dense matrices. One of the computationally expensive operations in the method is multiplication of sparse by dense matrices. In the current work, a new algorithm for sparse matrix by dense matrix products is presented. The algorithm takes into account the structure of the sparse matrix, which is obtained by space discretization of the nonlinear Mindlin's plate equation of motion by the finite element method. The algorithm is developed to use the vector engine of Intel Xeon Phi coprocessors. It is compared with the standard sparse matrix by dense matrix algorithm and the one developed by Intel MKL and it is shown that by considering the properties of the sparse matrix better algorithms can be developed.

  2. MULTIPLE BIOMARKER RESPONSE IN THE MUSSEL, PERNA PERNA TO ASSESS THE MARINE QUALITY IN THE BIG CASABLANCA AREA

    Directory of Open Access Journals (Sweden)

    LAILA EL JOURMI

    2014-03-01

    Full Text Available The aim of this study is to assess the marine environment quality in the Big Casablanca area. A number of biochemical markers were measured in the brown mussel, Perna perna, sampled from four sampling sites characterized by a different degree of contamination and human impacts. As biochemical indices; Catalase (CAT, Glutathione S-transferase (GST, Acetylcholinesterase (AChE, as well as Malondialdehyde (MDA and Metallothioneine (MT were evaluated in whole soft tissues of mussels collected from the selected sites. The biomarkers showed statistically significant differences at the polluted sites when compared to the control ones. Our data indicated that CAT and GST activity, MDA and MT concentration in whole mussel bodies, are a higher and significant (p < 0.05 in mussels collected at polluted sites when compared to specimen sampled from control ones. In contrary the response of AChE activity was significantly (p<0.05 inhibited in mussels from polluted sites when compared to control values. The multiple biomarker responses obtained for October 2010 and 2011, clearly demonstrate the potential presence of different contaminants in Site1 and Site2 reflecting the intensity of pollution in these areas.

  3. Critical analysis of the stringent complete response in multiple myeloma: contribution of sFLC and bone marrow clonality.

    Science.gov (United States)

    Martínez-López, Joaquín; Paiva, Bruno; López-Anglada, Lucía; Mateos, María-Victoria; Cedena, Teresa; Vidríales, María-Belén; Sáez-Gómez, María Auxiliadora; Contreras, Teresa; Oriol, Albert; Rapado, Inmaculada; Teruel, Ana-Isabel; Cordón, Lourdes; Blanchard, María Jesús; Bengoechea, Enrique; Palomera, Luis; de Arriba, Felipe; Cueto-Felgueroso, Cecilia; Orfao, Alberto; Bladé, Joan; San Miguel, Jesús F; Lahuerta, Juan José

    2015-08-13

    Stringent complete response (sCR) criteria are used in multiple myeloma as a deeper response category compared with CR, but prospective validation is lacking, it is not always clear how evaluation of clonality is performed, and is it not known what the relative clinical influence is of the serum free light chain ratio (sFLCr) and bone marrow (BM) clonality to define more sCR. To clarify this controversy, we focused on 94 patients that reached CR, of which 69 (73%) also fulfilled the sCR criteria. Patients with sCR displayed slightly longer time to progression (median, 62 vs 53 months, respectively; P = .31). On analyzing this contribution to the prognosis of sFLCr or clonality, it was found that the sFLCr does not identify patients in CR at distinct risk; by contrast, low-sensitive multiparametric flow cytometry (MFC) immunophenotyping (2 colors), which is equivalent to immunohistochemistry, identifies a small number of patients (5 cases) with high residual tumor burden and dismal outcome; nevertheless, using traditional 4-color MFC, persistent clonal BM disease was detectable in 36% of patients, who, compared with minimal residual disease-negative cases, had a significantly inferior outcome. These results show that the current definition of sCR should be revised. © 2015 by The American Society of Hematology.

  4. A small graphene oxide sheet/polyvinylidene fluoride bilayer actuator with large and rapid responses to multiple stimuli.

    Science.gov (United States)

    Xu, Guochuang; Zhang, Miao; Zhou, Qinqin; Chen, Hongwu; Gao, Tiantian; Li, Chun; Shi, Gaoquan

    2017-11-16

    A high-performance actuator should be able to deliver large-shape deformations, fast actuations and sensitive responses to multiple stimuli. Here, we report such an actuator constructed from one layer of polyvinylidene fluoride (PVDF) with a high coefficient of thermal expansion (CTE), and another layer of small sheets of graphene oxide (SGO) with a negative CTE. The opposite deformations of both actuation layers make the SGO/PVDF bilayer actuator highly sensitive to the temperature stimulus with a large bending sensitivity of 1.5 cm -1 °C -1 . Upon irradiation with 60 mW cm -2 infrared light, this SGO/PVDF bilayer actuator displayed an extremely rapid tip displacement rate of 140 mm s -1 . Furthermore, this actuator can also sensitively respond to moisture because of its SGO layer, showing a curvature change from -22 to 13 cm -1 upon changing the relative humidity (RH) from 11% to 86%. This actuator can generate a contractile or relaxed stress 18 times that of mammalian skeletal muscle, under light irradiation or moisture with a response time as short as 1 s, being capable of lifting an object with a weight 80 times that of itself. Furthermore, it also showed excellent stability and repeatability.

  5. The interplay of multiple feedback loops with post-translational kinetics results in bistability of mycobacterial stress response

    International Nuclear Information System (INIS)

    Tiwari, Abhinav; Igoshin, Oleg A; Balázsi, Gábor; Gennaro, Maria Laura

    2010-01-01

    Bacterial persistence is the phenomenon in which a genetically identical fraction of a bacterial population can survive exposure to stress by reduction or cessation of growth. Persistence in mycobacteria has been recently linked to a stress-response network, consisting of the MprA/MprB two-component system and alternative sigma factor σ E . This network contains multiple positive transcriptional feedback loops which may give rise to bistability, making it a good candidate for controlling the mycobacterial persistence switch. To analyze the possibility of bistability, we develop a method that involves decoupling of the network into transcriptional and post-translational interaction modules. As a result we reduce the dimensionality of the dynamical system and independently analyze input–output relations in the two modules to formulate a necessary condition for bistability in terms of their logarithmic gains. We show that neither the positive autoregulation in the MprA/MprB network nor the σ E -mediated transcriptional feedback is sufficient to induce bistability in a biochemically realistic parameter range. Nonetheless, inclusion of the post-translational regulation of σ E by RseA increases the effective cooperativity of the system, resulting in bistability that is robust to parameter variation. We predict that overexpression or deletion of RseA, the key element controlling the ultrasensitive response, can eliminate bistability

  6. The conceptualization and measurement of cognitive reserve using common proxy indicators: Testing some tenable reflective and formative models.

    Science.gov (United States)

    Ikanga, Jean; Hill, Elizabeth M; MacDonald, Douglas A

    2017-02-01

    The examination of cognitive reserve (CR) literature reveals a lack of consensus regarding conceptualization and pervasive problems with its measurement. This study aimed at examining the conceptual nature of CR through the analysis of reflective and formative models using eight proxies commonly employed in the CR literature. We hypothesized that all CR proxies would significantly contribute to a one-factor reflective model and that educational and occupational attainment would produce the strongest loadings on a single CR factor. The sample consisted of 149 participants (82 male/67 female), with 18.1 average years of education and ages of 45-99 years. Participants were assessed for eight proxies of CR (parent socioeconomic status, intellectual functioning, level of education, health literacy, occupational prestige, life leisure activities, physical activities, and spiritual and religious activities). Primary statistical analyses consisted of confirmatory factor analysis (CFA) to test reflective models and structural equation modeling (SEM) to evaluate multiple indicators multiple causes (MIMIC) models. CFA did not produce compelling support for a unitary CR construct when using all eight of our CR proxy variables in a reflective model but fairly cogent evidence for a one-factor model with four variable proxies. A second three-factor reflective model based upon an exploratory principal components analysis of the eight proxies was tested using CFA. Though all eight indicators significantly loaded on their assigned factors, evidence in support of overall model fit was mixed. Based upon the results involving the three-factor reflective model, two alternative formative models were developed and evaluated. While some support was obtained for both, the model in which the formative influences were specified as latent variables appeared to best account for the contributions of all eight proxies to the CR construct. While the findings provide partial support for our

  7. Multi-proxy reconstructions and the power of integration across marine, terrestrial, and freshwater ecosystems. (Invited)

    Science.gov (United States)

    Black, B.

    2013-12-01

    Over the past decade, dendrochronology (tree-ring analysis) techniques have been increasingly applied to growth increments of various bivalve, fish, and coral species. In particular, the use of crossdating ensures that all increments in a dataset have assigned the correct calendar year of formation and that the resulting chronology is exactly placed in time. Such temporal alignment facilitates direct comparisons among chronologies that span diverse taxa and ecosystems, illustrating the pervasive, synchronizing influence of climate from alpine forests to the continental slope. Such an approach can be particularly beneficial to reconstructions in that each species captures climate signals from its unique 'perspective' of life history and habitat. For example, combinations of tree-ring data and chronologies for the long-lived bivalve Pacific geoduck (Panopea generosa) capture substantially more variance in regional sea surface temperatures than either proxy could explain alone. Just as importantly, networks of chronologies spanning multiple trophic levels can help identify climate variables critical to ecosystem functioning, which can then be targeted to generate most biologically relevant reconstructions possible. Along the west coast of North America, fish and bivalve chronologies in combination with records of seabird reproductive success indicate that winter sea-level pressure is closely associated with California Current productivity, which can be hind-cast over the past six centuries using coastal tree-ring chronologies. Thus, multiple proxies not only increase reconstruction skill, but also help isolate climate variables most closely linked to ecosystem structure and functioning.

  8. Application of PET/CT in treatment response evaluation and recurrence prediction in patients with newly-diagnosed multiple myeloma.

    Science.gov (United States)

    Li, Ying; Liu, Junru; Huang, Beihui; Chen, Meilan; Diao, Xiangwen; Li, Juan

    2017-04-11

    Multiple myeloma (MM) causes osteolytic lesions which can be detected by 18F-fluorodeoxyglucose positron emission tomography/Computed tomography (18F-FDG PET/CT). We prospectively involve 96 Newly diagnosed MM to take PET/CT scan at scheduled treatment time (figure 1), and 18F-FDG uptake of lesion was measured by SUVmax and T/Mmax. All MM patients took bortezomib based chemotherapy as induction and received ASCT and maintenance. All clinical features were analyzed with the PET/CT image changes, and some relationships between treatment response and FDG uptakes changes were found: Osteolytic lesions of MM uptakes higher FDG than healthy volunteers, and this trend is more obvious in extramedullary lesions. Compared to X-ray, PET/CT was more sensitive both in discoering bone as well as extramedullary lesions. In newly diagnosed MM, several adverse clinical factors were related to high FDG uptakes of bone lesions. Bone lesion FDG uptakes of MM with P53 mutation or with hypodiploidy and complex karyotype were also higher than those without such changes. In treatment response, PET/CT showed higher sensitivity in detecting tumor residual disease than immunofixation electrophoresis. But in relapse prediction, it might show false positive disease recurrences and the imaging changes might be influenced by infections and hemoglobulin levels. PET/CT is sensitive in discovering meduallary and extrameduallary lesions of MM, and the 18F-FDG uptake of lesions are related with clinical indictors and biological features of plasma cells. In evaluating treatment response and survival, PET/CT showed its superiority. But in predicting relapse or refractory, it may show false positive results.

  9. Gene Cluster Responsible for Secretion of and Immunity to Multiple Bacteriocins, the NKR-5-3 Enterocins

    Science.gov (United States)

    Ishibashi, Naoki; Himeno, Kohei; Masuda, Yoshimitsu; Perez, Rodney Honrada; Iwatani, Shun; Wilaipun, Pongtep; Leelawatcharamas, Vichien; Nakayama, Jiro; Sonomoto, Kenji

    2014-01-01

    Enterococcus faecium NKR-5-3, isolated from Thai fermented fish, is characterized by the unique ability to produce five bacteriocins, namely, enterocins NKR-5-3A, -B, -C, -D, and -Z (Ent53A, Ent53B, Ent53C, Ent53D, and Ent53Z). Genetic analysis with a genome library revealed that the bacteriocin structural genes (enkA [ent53A], enkC [ent53C], enkD [ent53D], and enkZ [ent53Z]) that encode these peptides (except for Ent53B) are located in close proximity to each other. This NKR-5-3ACDZ (Ent53ACDZ) enterocin gene cluster (approximately 13 kb long) includes certain bacteriocin biosynthetic genes such as an ABC transporter gene (enkT), two immunity genes (enkIaz and enkIc), a response regulator (enkR), and a histidine protein kinase (enkK). Heterologous-expression studies of enkT and ΔenkT mutant strains showed that enkT is responsible for the secretion of Ent53A, Ent53C, Ent53D, and Ent53Z, suggesting that EnkT is a wide-range ABC transporter that contributes to the effective production of these bacteriocins. In addition, EnkIaz and EnkIc were found to confer self-immunity to the respective bacteriocins. Furthermore, bacteriocin induction assays performed with the ΔenkRK mutant strain showed that EnkR and EnkK are regulatory proteins responsible for bacteriocin production and that, together with Ent53D, they constitute a three-component regulatory system. Thus, the Ent53ACDZ gene cluster is essential for the biosynthesis and regulation of NKR-5-3 enterocins, and this is, to our knowledge, the first report that demonstrates the secretion of multiple bacteriocins by an ABC transporter. PMID:25149515

  10. Increased CD8+ T cell response to Epstein-Barr virus lytic antigens in the active phase of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Daniela F Angelini

    Full Text Available It has long been known that multiple sclerosis (MS is associated with an increased Epstein-Barr virus (EBV seroprevalence and high immune reactivity to EBV and that infectious mononucleosis increases MS risk. This evidence led to postulate that EBV infection plays a role in MS etiopathogenesis, although the mechanisms are debated. This study was designed to assess the prevalence and magnitude of CD8+ T-cell responses to EBV latent (EBNA-3A, LMP-2A and lytic (BZLF-1, BMLF-1 antigens in relapsing-remitting MS patients (n = 113 and healthy donors (HD (n = 43 and to investigate whether the EBV-specific CD8+ T cell response correlates with disease activity, as defined by clinical evaluation and gadolinium-enhanced magnetic resonance imaging. Using HLA class I pentamers, lytic antigen-specific CD8+ T cell responses were detected in fewer untreated inactive MS patients than in active MS patients and HD while the frequency of CD8+ T cells specific for EBV lytic and latent antigens was higher in active and inactive MS patients, respectively. In contrast, the CD8+ T cell response to cytomegalovirus did not differ between HD and MS patients, irrespective of the disease phase. Marked differences in the prevalence of EBV-specific CD8+ T cell responses were observed in patients treated with interferon-β and natalizumab, two licensed drugs for relapsing-remitting MS. Longitudinal studies revealed expansion of CD8+ T cells specific for EBV lytic antigens during active disease in untreated MS patients but not in relapse-free, natalizumab-treated patients. Analysis of post-mortem MS brain samples showed expression of the EBV lytic protein BZLF-1 and interactions between cytotoxic CD8+ T cells and EBV lytically infected plasma cells in inflammatory white matter lesions and meninges. We therefore propose that inability to control EBV infection during inactive MS could set the stage for intracerebral viral reactivation and disease relapse.

  11. Registered nurse buddies: Educators by proxy?

    Science.gov (United States)

    Rebeiro, Geraldine; Evans, Alicia; Edward, Karen-Leigh; Chapman, Rose

    2017-08-01

    The informal clinical teaching role of the buddy nurse seems to be a uniquely Australian title, with little consistency in terminology for informal nurse educator roles internationally. Not all registered nurses are professionally developed for the informal role of facilitating the clinical learning of students in clinical settings, yet these roles are expected by nursing professional bodies. In Australia the registered nurses (RN) experience of being a buddy nurse has been reported as lacking clarity, being unsupported and structureless. Whist there is a plethora of literature published about formal RN educator roles, little is available on the informal buddy nurse role. A view of the buddy nurse role in reference to the limited but available literature in the Australian context is offered in this paper. International perspectives are also gathered describing informal clinical education RN's roles with similar responsibilities to the Australian buddy nurse. The significance of this dialogue is to ignite debate about the role, potentially informing policy for the improved support of the role within the Australian nursing landscape. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Data Cleaning Methods for Client and Proxy Logs

    NARCIS (Netherlands)

    Weinreich, H.; Obendorf, H.; Herder, E.; Edmonds, A.; Hawkey, K.; Kellar, M.; Turnbull, D.

    2006-01-01

    In this paper we present our experiences with the cleaning of Web client and proxy usage logs, based on a long-term browsing study with 25 participants. A detailed clickstream log, recorded using a Web intermediary, was combined with a second log of user interface actions, which was captured by a

  13. Comparison of independent proxies in the reconstruction of deep ...

    African Journals Online (AJOL)

    Independent proxies were assessed in two Late Quaternary sediment cores from the eastern South Atlantic to compare deep-water changes during the last 400 kyr. ... is exclusively observed during interglacials, with maximum factor loadings in ... only slightly without a significant glacial-interglacial pattern, as measured in a ...

  14. TEX86 paleothermometry : proxy validation and application in marine sediments

    NARCIS (Netherlands)

    Huguet, C.

    2007-01-01

    Determination of past sea surface temperature (SST) is of primary importance for the reconstruction of natural climatic changes, modelling of climate and reconstruction of ocean circulation. Recently, a new SST proxy was introduced, the TetraEther indeX of lipids with 86 carbons (TEX86), which is

  15. Shareholder Activism through Proxy Proposals : The European Perspective

    NARCIS (Netherlands)

    Cziraki, P.; Renneboog, L.D.R.; Szilagyi, P.G.

    2009-01-01

    This paper is the first to investigate the corporate governance role of shareholderinitiated proxy proposals in European firms. While proposals in the US are nonbinding even if they pass the shareholder vote, they are legally binding in the UK and most of Continental Europe. Nonetheless, submissions

  16. Munchausen Syndrome by Proxy: A Study of Psychopathology.

    Science.gov (United States)

    Bools, Christopher; And Others

    1994-01-01

    This study evaluated 100 mothers with Munchausen Syndrome by Proxy (the fabrication of illness by a mother in her child). Approximately half of the mothers had either smothered or poisoned their child as part of their fabrications. Lifetime psychiatric histories were reported for 47 of the mothers. The most notable psychopathology was personality…

  17. Climate proxy data as groundwater tracers in regional flow systems

    Science.gov (United States)

    Clark, J. F.; Morrissey, S. K.; Stute, M.

    2008-05-01

    The isotopic and chemical signatures of groundwater reflect local climate conditions. By systematically analyzing groundwater and determining their hydrologic setting, records of past climates can be constructed. Because of their chemistries and relatively uncomplicated source functions, dissolved noble gases have yielded reliable records of continental temperatures for the last 30,000 to 50,000 years. Variations in the stable isotope compositions of groundwater due to long term climate changes have also been documented over these time scales. Because glacial - interglacial climate changes are relatively well known, these climate proxies can be used as "stratigraphic" markers within flow systems and used to distinguish groundwaters that have recharged during the Holocene from those recharged during the last glacial period, important time scales for distinguishing regional and local flow systems in many aquifers. In southern Georgia, the climate proxy tracers were able to identify leakage from surface aquifers into the Upper Floridan aquifer in areas previously thought to be confined. In south Florida, the transition between Holocene and glacial signatures in the Upper Floridan aquifer occurs mid-way between the recharge area and Lake Okeechobee. Down gradient of the lake, the proxies are uniform, indicating recharge during the last glacial period. Furthermore, there is no evidence for leakage from the shallow aquifers into the Upper Floridan. In the Lower Floridan, the climate proxies indicate that the saline water entered the aquifer after sea level rose to its present level.

  18. Slices: A shape-proxy based on planar sections

    KAUST Repository

    McCrae, James

    2011-12-01

    Minimalist object representations or shape-proxies that spark and inspire human perception of shape remain an incompletely understood, yet powerful aspect of visual communication. We explore the use of planar sections, i.e., the contours of intersection of planes with a 3D object, for creating shape abstractions, motivated by their popularity in art and engineering. We first perform a user study to show that humans do define consistent and similar planar section proxies for common objects. Interestingly, we observe a strong correlation between user-defined planes and geometric features of objects. Further we show that the problem of finding the minimum set of planes that capture a set of 3D geometric shape features is both NP-hard and not always the proxy a user would pick. Guided by the principles inferred from our user study, we present an algorithm that progressively selects planes to maximize feature coverage, which in turn influence the selection of subsequent planes. The algorithmic framework easily incorporates various shape features, while their relative importance values are computed and validated from the user study data. We use our algorithm to compute planar slices for various objects, validate their utility towards object abstraction using a second user study, and conclude showing the potential applications of the extracted planar slice shape proxies.

  19. Munchausen Syndrome by Proxy (MSBP): An Intergenerational Perspective.

    Science.gov (United States)

    Rappaport, Sol R.; Hochstadt, Neil J.

    1993-01-01

    Presents new information about Munchausen Syndrome by Proxy (MSBP), factitious disorder in which caretaker may induce or exaggerate medical illness in his or her child that may lead to illness and even death. Provides psychosocial history of caregiver using intergenerational model. Presents case of MSBP involving three siblings and information…

  20. Slices: A shape-proxy based on planar sections

    KAUST Repository

    McCrae, James; Singh, Karan S.; Mitra, Niloy J.

    2011-01-01

    of intersection of planes with a 3D object, for creating shape abstractions, motivated by their popularity in art and engineering. We first perform a user study to show that humans do define consistent and similar planar section proxies for common objects

  1. Multiple Signaling Pathways Coordinately Regulate Forgetting of Olfactory Adaptation through Control of Sensory Responses in Caenorhabditis elegans.

    Science.gov (United States)

    Kitazono, Tomohiro; Hara-Kuge, Sayuri; Matsuda, Osamu; Inoue, Akitoshi; Fujiwara, Manabi; Ishihara, Takeshi

    2017-10-18

    invertebrates. We found that in Caenorhabditis elegans hermaphrodite, the noncell autonomous regulations of forgetting of olfactory adaptation is regulated by three conserved proteins: a membrane protein, MACO-1; a receptor tyrosine kinase, SCD-2: and its ligand, HEN-1. MACO-1 and SCD-2/HEN-1, working in coordination, accelerate forgetting by controlling sensory responses in parallel. Furthermore, temporal regulation of neuronal activity is important for proper forgetting. We suggest that multiple pathways may coordinately and temporally regulate forgetting through control of sensory responses. This study should lead to a better understanding of forgetting in higher organisms. Copyright © 2017 the authors 0270-6474/17/3710240-12$15.00/0.

  2. On the Use of Human Mobility Proxies for Modeling Epidemics

    Science.gov (United States)

    Tizzoni, Michele; Bajardi, Paolo; Decuyper, Adeline; Kon Kam King, Guillaume; Schneider, Christian M.; Blondel, Vincent; Smoreda, Zbigniew; González, Marta C.; Colizza, Vittoria

    2014-01-01

    Human mobility is a key component of large-scale spatial-transmission models of infectious diseases. Correctly modeling and quantifying human mobility is critical for improving epidemic control, but may be hindered by data incompleteness or unavailability. Here we explore the opportunity of using proxies for individual mobility to describe commuting flows and predict the diffusion of an influenza-like-illness epidemic. We consider three European countries and the corresponding commuting networks at different resolution scales, obtained from (i) official census surveys, (ii) proxy mobility data extracted from mobile phone call records, and (iii) the radiation model calibrated with census data. Metapopulation models defined on these countries and integrating the different mobility layers are compared in terms of epidemic observables. We show that commuting networks from mobile phone data capture the empirical commuting patterns well, accounting for more than 87% of the total fluxes. The distributions of commuting fluxes per link from mobile phones and census sources are similar and highly correlated, however a systematic overestimation of commuting traffic in the mobile phone data is observed. This leads to epidemics that spread faster than on census commuting networks, once the mobile phone commuting network is considered in the epidemic model, however preserving to a high degree the order of infection of newly affected locations. Proxies' calibration affects the arrival times' agreement across different models, and the observed topological and traffic discrepancies among mobility sources alter the resulting epidemic invasion patterns. Results also suggest that proxies perform differently in approximating commuting patterns for disease spread at different resolution scales, with the radiation model showing higher accuracy than mobile phone data when the seed is central in the network, the opposite being observed for peripheral locations. Proxies should therefore be

  3. Characteristics influencing therapy switch behavior after suboptimal response to first-line treatment in patients with multiple sclerosis.

    Science.gov (United States)

    Teter, Barbara; Agashivala, Neetu; Kavak, Katelyn; Chouhfeh, Lynn; Hashmonay, Ron; Weinstock-Guttman, Bianca

    2014-06-01

    Factors driving disease-modifying therapy (DMT) switch behavior are not well understood. The objective of this paper is to identify patient characteristics and clinical events predictive of therapy switching in patients with suboptimal response to DMT. This retrospective study analyzed patients with relapsing-remitting multiple sclerosis (MS) and a suboptimal response to initial therapy with either interferon β or glatiramer acetate. Suboptimal responders were defined as patients with ≥1 MS event (clinical relapse, worsening disability, or MRI worsening) while on DMT. Switchers were defined as those who changed DMT within six to 12 months after the MS event. Of 606 suboptimal responders, 214 (35.3%) switched therapy. Switchers were younger at symptom onset (p = 0.012), MS diagnosis (p = 0.004), DMT initiation (p < 0.001), and first MS event (p = 0.011) compared with nonswitchers. Compared with one relapse alone, MRI worsening alone most strongly predicted switch behavior (odds ratio 6.3; 95% CI, 3.1-12.9; p < 0.001), followed by ≥2 relapses (2.8; 95% CI, 1.1-7.3; p = 0.040), EDSS plus MRI worsening (2.5; 95% CI, 1.1-5.9; p = 0.031) and EDSS worsening alone (2.2; 95% CI, 1.2-4.1; p = 0.009). Younger patients with disease activity, especially MRI changes, are more likely to have their therapy switched sooner than patients who are older at the time of MS diagnosis and DMT initiation. © The Author(s) 2013.

  4. The integration of multiple independent data reveals an unusual response to Pleistocene climatic changes in the hard tick Ixodes ricinus.

    Science.gov (United States)

    Porretta, Daniele; Mastrantonio, Valentina; Mona, Stefano; Epis, Sara; Montagna, Matteo; Sassera, Davide; Bandi, Claudio; Urbanelli, Sandra

    2013-03-01

    In the last few years, improved analytical tools and the integration of genetic data with multiple sources of information have shown that temperate species exhibited more complex responses to ice ages than previously thought. In this study, we investigated how Pleistocene climatic changes affected the current distribution and genetic diversity of European populations of the tick Ixodes ricinus, an ectoparasite with high ecological plasticity. We first used mitochondrial and nuclear genetic markers to investigate the phylogeographic structure of the species and its Pleistocene history using coalescent-based methods; then we used species distribution modelling to infer the climatic niche of the species at last glacial maximum; finally, we reviewed the literature on the I. ricinus hosts to identify the locations of their glacial refugia. Our results support the scenario that during the last glacial phase, I. ricinus never experienced a prolonged allopatric divergence in separate glacial refugia, but persisted with interconnected populations across Southern and Central Europe. The generalist behaviour in host choice of I. ricinus would have played a major role in maintaining connections between its populations. Although most of the hosts persisted in separate refugia, from the point of view of I. ricinus, they represented a continuity of 'bridges' among populations. Our study highlights the importance of species-specific ecology in affecting responses to Pleistocene glacial-interglacial cycles. Together with other cases in Europe and elsewhere, it contributes to setting new hypotheses on how species with wide ecological plasticity coped with Pleistocene climatic changes. © 2013 Blackwell Publishing Ltd.

  5. Proxy-Produced Ethnographic Work: What Are the Problems, Issues, and Dilemmas Arising from Proxy-Ethnography?

    Science.gov (United States)

    Martinussen, Marie; Højbjerg, Karin; Tamborg, Andreas Lindenskov

    2018-01-01

    This article addresses the implications of researcher-student cooperation in the production of empirical material. For the student to replace the experienced researcher and work under the researcher's supervision, we call such work proxy-produced ethnographic work. Although there are clear advantages, the specific relations and positions arising…

  6. Evaluation of the sea ice proxy IP against observational and diatom proxy data in the SW Labrador Sea

    DEFF Research Database (Denmark)

    Weckström, K.; Andersen, M.L.; Kuijpers, A.

    2013-01-01

    The recent rapid decline in Arctic sea ice cover has increased the need to improve the accuracy of the sea ice component in climate models and to provide detailed long-term sea ice concentration records, which are only available via proxy data. Recently, the highly branched isoprenoid IP25...

  7. Is serum neopterin level a marker of responsiveness to interferon beta-1a therapy in multiple sclerosis?

    Science.gov (United States)

    Casoni, F; Merelli, E; Bedin, R; Sola, P; Bertolotto, A; Faglioni, P

    2004-01-01

    Interferon beta (INFbeta) may induce the expression of several proteins, including neopterin, considered a biological marker of INFbeta activity. The aim of this study was to determine the serum neopterin concentration at the beginning of, and during, IFNbeta-1a therapy in relapsing-remitting multiple sclerosis (r-r MS) patients, and to look for a possible correlation between protein synthesis and the clinical course of the disease. Thirteen r-r MS patients were treated with INFbeta-1a (i.m. 6 MIU/week) for 2 years. Blood samples for neopterin determinations were taken daily over a period of 1 week at the end of each 6 months of therapy, and tested for neutralizing antibodies (NABs). Neopterin levels peaked 24-48 h post-injection and returned to baseline after 120 h. After 1 year of therapy, four patients dropped out of the study because of progression of the disease: in these subjects a significant decrement of neopterin was observed. Neopterin baseline values were not found to decrease over the 2 years of therapy, and neopterin may be considered to be a useful marker of responsiveness to IFNbeta.

  8. Optimization and modeling of spot welding parameters with simultaneous multiple response consideration using multi objective Taguchi method and RSM

    Energy Technology Data Exchange (ETDEWEB)

    Muhammad, Nora Siah; Manurung Yupiter HP; Hafidzi, Moham Mad; Abas, Sun Haji Kiyai; Tham, Ghalib; Haru Man, Esa [Universiti Teknologi MARA (UiTM), Selangor (Malaysia)

    2012-08-15

    This paper presents an alternative method to optimize process parameters of resistance spot welding (RSW) towards weld zone development. The optimization approach attempts to consider simultaneously the multiple quality characteristics, namely weld nugget and heat affected zone (HAZ), using multi objective Taguchi method (MTM). The experimental study was conducted for plate thickness of 1.5mm under different welding current, weld time and hold time. The optimum welding parameters were investigated using the Taguchi method with L9 orthogonal array. The optimum value was analyzed by means of MTM, which involved the calculation of total normalized quality loss (TNQL) and multi signal to noise ratio (MSNR). A significant level of the welding parameters was further obtained by using analysis of variance (ANOVA). Furthermore, the first order model for predicting the weld zone development is derived by using response surface methodology (RSM). Based on the experimental confirmation test, the proposed method can be effectively applied to estimate the size of weld zone, which can be used to enhance and optimized the welding performance in RSW or other application.

  9. Adaptive Immune Responses in a Multiple Sclerosis Patient with Acute Varicella-Zoster Virus Reactivation during Treatment with Fingolimod

    Directory of Open Access Journals (Sweden)

    Andrea Harrer

    2015-09-01

    Full Text Available Fingolimod, an oral sphingosine 1-phosphate (S1P receptor modulator, is approved for the treatment of relapsing forms of multiple sclerosis (MS. The interference with S1P signaling leads to retention particularly of chemokine receptor-7 (CCR7 expressing T cells in lymph nodes. The immunological basis of varicella zoster virus (VZV infections during fingolimod treatment is unclear. Here, we studied the dynamics of systemic and intrathecal immune responses associated with symptomatic VZV reactivation including cessation of fingolimod and initiation of antiviral therapy. Key features in peripheral blood were an about two-fold increase of VZV-specific IgG at diagnosis of VZV reactivation as compared to the previous months, a relative enrichment of effector CD4+ T cells (36% versus mean 12% in controls, and an accelerated reconstitution of absolute lymphocytes counts including a normalized CD4+/CD8+ ratio and reappearance of CCR7+ T cells. In cerebrospinal fluid (CSF the lymphocytic pleocytosis and CD4+/CD8+ ratios at diagnosis of reactivation and after nine days of fingolimod discontinuation remained unchanged. During this time CCR7+ T cells were not observed in CSF. Further research into fingolimod-associated VZV reactivation and immune reconstitution is mandatory to prevent morbidity and mortality associated with this potentially life-threatening condition.

  10. Optimization and modeling of spot welding parameters with simultaneous multiple response consideration using multi objective Taguchi method and RSM

    International Nuclear Information System (INIS)

    Muhammad, Nora Siah; Manurung Yupiter HP; Hafidzi, Moham Mad; Abas, Sun Haji Kiyai; Tham, Ghalib; Haru Man, Esa

    2012-01-01

    This paper presents an alternative method to optimize process parameters of resistance spot welding (RSW) towards weld zone development. The optimization approach attempts to consider simultaneously the multiple quality characteristics, namely weld nugget and heat affected zone (HAZ), using multi objective Taguchi method (MTM). The experimental study was conducted for plate thickness of 1.5mm under different welding current, weld time and hold time. The optimum welding parameters were investigated using the Taguchi method with L9 orthogonal array. The optimum value was analyzed by means of MTM, which involved the calculation of total normalized quality loss (TNQL) and multi signal to noise ratio (MSNR). A significant level of the welding parameters was further obtained by using analysis of variance (ANOVA). Furthermore, the first order model for predicting the weld zone development is derived by using response surface methodology (RSM). Based on the experimental confirmation test, the proposed method can be effectively applied to estimate the size of weld zone, which can be used to enhance and optimized the welding performance in RSW or other application

  11. Organic molecules in the polar ice: from chemical analysis to environmental proxies

    Science.gov (United States)

    Barbante, Carlo; Zennaro, Piero; Giorio, Chiara; Kehrwald, Natalie; Benton, Alisa K.; Wolff, Eric W.; Kalberer, Markus; Kirchgeorg, Torben; Zangrando, Roberta; Barbaro, Elena; Gambaro, Andrea

    2015-04-01

    The molecular and isotopic compositions of organic matter buried in ice contains information that helps reconstruct past environmental conditions, evaluate histories of climate change, and assess impacts of humans on ecosystems. In recent years novel analytical techniques were developed to quantify molecular compounds in ice cores. As an example, biomass burning markers, including monosaccharide anhydrides, lightweight carboxylic acids, lignin and resin pyrolysis products, black carbon, and charcoal records help in reconstructing past fire activity across seasonal to millennial time scales. Terrestrial biomarkers, such as plant waxes (e.g. long-chain n-alkanes) are also a promising paleo vegetation proxy in ice core studies. Polycyclic aromatic hydrocarbons are ubiquitous pollutants recently detected in ice cores. These hydrocarbons primarily originate from incomplete combustion of organic matter and fossil fuels (e.g. diesel engines, domestic heating, industrial combustion) and therefore can be tracers of past combustion activities. In order to be suitable for paloeclimate purposes, organic molecular markers detected in ice cores should include the following important features. Markers have to be stable under oxidizing atmospheric conditions, and ideally should not react with hydroxyl radicals, during their transport to polar regions. Organic markers must be released in large amounts in order to be detected at remote distances from the sources. Proxies must be specific, in order to differentiate them from other markers with multiple sources. The extraction of glaciochemical information from ice cores is challenging due to the low concentrations of some impurities, thereby demanding rigorous control of external contamination sources and sensitive analytical techniques. Here, we review the analysis and use of organic molecules in ice as proxies of important environmental and climatic processes.

  12. Tropical Hydroclimate Change during Heinrich Stadial 1: An Integrative Proxy-Model Synthesis

    Science.gov (United States)

    Lawman, A. E.; Sun, T.; Shanahan, T. M.; Di Nezio, P. N.; Gomez, K.; Piatrunia, N.; Sun, C.; Wu, X.; Kageyama, M.; Merkel, U.; Otto-Bliesner, B. L.; Abe-Ouchi, A.; Lohmann, G.; Singarayer, J. S.

    2017-12-01

    We explore the response of tropical climate to abrupt cooling of the North Atlantic (NA) during Heinrich Stadial 1 (HS1) combining paleoclimate proxies with model simulations. A total of 146 published paleoclimate records from tropical locations are used to categorize whether HS1 was wetter, drier, or unchanged relative to a deglacial baseline state. Only records with sufficient resolution to resolve HS1 and sufficient length to characterize the deglacial trend are considered. This synthesis reveals large-scale patterns of hydroclimate change relative to glacial conditions, confirming previously reported weaker Indian summer monsoon, a wetter southern Africa, and drying over the Caribbean. Our synthesis also reveals large-scale drying over the Maritime continent as well as wetter conditions in northern Australia and southern tropical South America. Our reinterpretation of the available proxy data reveals far more complexity and uncertainties for equatorial East Africa, a region that appears to straddle a pattern of dryer conditions to the north and wetter conditions to the south. Overall, these patterns of hydroclimate change depart from a southward shift of the Inter Tropical Convergence Zone (ITCZ), particularly outside the tropical Atlantic. We explore mechanisms driving these changes using a multi-model ensemble of "hosing" simulations performed relative to glacial conditions. The models show robust weakening of the Afro-Asian Monsoon, which we attribute to ventilation of colder mid-latitude air. Not all models simulate the remaining patterns inferred from the proxy data. The best-agreeing models indicate that cooling over the tropical NA and the Caribbean may be essential to communicate the response to the global tropics. This response can induce warming over the tropical South Atlantic via the wind-evaporation-SST feedback, driving wetter conditions in South Africa and tropical South America. Cooling over the Caribbean is communicated to the Pacific over the

  13. Proxy assessment of patients before and after radiotherapy for brain metastases. Results of a prospective study using the DEGRO brain module

    International Nuclear Information System (INIS)

    Steinmann, D.; Vordermark, D.; Geinitz, H.; Aschoff, R.; Bayerl, A.; Gerstein, J.; Hipp, M.; Schaefer, C.; Oorschot, B. van; Wypior, H.J.

    2013-01-01

    Purpose: Proxies of patients with poor performance status could give useful information about the patients' quality of life (QoL). We applied a newly developed questionnaire in a prospective QoL study of patients undergoing radiotherapy for brain metastases in order to make the first move to validate this instrument, and we compared the results with scores obtained using validated patient-completed instruments. Materials and methods: From January 2007 to June 2010, 166 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. The EORTC-QLQ-C15-PAL and the brain module BN20 were used to assess QoL in patients at the start of treatment and 3 months later. At the same time points, 141 of their proxies estimated the QoL with the new DEGRO brain module (DBM), a ten-item questionnaire rating the general condition as well as functions and impairment by symptoms in areas relevant to patients with brain metastases. Results: At 3 months, 85 of 141 patients (60%) with initial response by a proxy were alive. Sixty-seven of these patients (79% of 3-month survivors) and 65 proxies completed the second set of questionnaires. After 3 months, QoL significantly deteriorated in all items of proxy-assessed QoL except headache. Correlations between self-assessed and proxy-assessed QoL were high in single items such as nausea, headache, and fatigue. Conclusions: The high correlation between self-assessment and proxy ratings as well as a similar change over time for both approaches suggest that in patients with brain metastases, proxy assessment using the DBM questionnaire can be an alternative approach to obtaining QoL data when patients are unable to complete questionnaires themselves. Our self-constructed and first applied DBM is the only highly specific instrument for patients with brain metastases, but further tests are needed for its final validation. (orig.)

  14. Synergistic immune responses induced by endogenous retrovirus and herpesvirus antigens result in increased production of inflammatory cytokines in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Brudek, T; Christensen, T; Hansen, H J

    2008-01-01

    Human endogenous retroviruses (HERV) and herpesviruses are increasingly associated with the pathogenesis of the neurological inflammatory disease multiple sclerosis (MS). Herpesviruses are capable of HERV activation and simultaneous presence of HERV and herpesvirus antigens have a synergistic...... effect on cell-mediated immune responses, which tend to be higher in MS patients in comparison with healthy individuals. Here, we investigate whether these synergistic immune responses are reflected in changes in the production of proinflammatory cytokines. Using enzyme-linked immunosorbent assays...

  15. SOLAR CYCLE PROPAGATION, MEMORY, AND PREDICTION: INSIGHTS FROM A CENTURY OF MAGNETIC PROXIES

    International Nuclear Information System (INIS)

    Muñoz-Jaramillo, Andrés; DeLuca, Edward E.; Dasi-Espuig, María; Balmaceda, Laura A.

    2013-01-01

    The solar cycle and its associated magnetic activity are the main drivers behind changes in the interplanetary environment and Earth's upper atmosphere (commonly referred to as space weather). These changes have a direct impact on the lifetime of space-based assets and can create hazards to astronauts in space. In recent years there has been an effort to develop accurate solar cycle predictions (with aims at predicting the long-term evolution of space weather), leading to nearly a hundred widely spread predictions for the amplitude of solar cycle 24. A major contributor to the disagreement is the lack of direct long-term databases covering different components of the solar magnetic field (toroidal versus poloidal). Here, we use sunspot area and polar faculae measurements spanning a full century (as our toroidal and poloidal field proxies) to study solar cycle propagation, memory, and prediction. Our results substantiate predictions based on the polar magnetic fields, whereas we find sunspot area to be uncorrelated with cycle amplitude unless multiplied by area-weighted average tilt. This suggests that the joint assimilation of tilt and sunspot area is a better choice (with aims to cycle prediction) than sunspot area alone, and adds to the evidence in favor of active region emergence and decay as the main mechanism of poloidal field generation (i.e., the Babcock-Leighton mechanism). Finally, by looking at the correlation between our poloidal and toroidal proxies across multiple cycles, we find solar cycle memory to be limited to only one cycle.

  16. A Multi-Proxy Paradigm in the Pursuit of Ocean Paleoredox

    Science.gov (United States)

    Anbar, A. D.; Duan, Y.; Kendall, B.; Reinhard, C.; Severmann, S.; Lyons, T. W.

    2011-12-01

    The geologic record provides abundant evidence for variations in ocean oxygenation throughout Earth history. Expansion of ocean anoxic zones is expected in the future as a consequence of global climate change, with attendant effects on global nutrient inventories, carbon cycling and fluxes of trace greenhouse gases to the atmosphere. Therefore, studying ancient ocean redox variations not only teaches us about the history of the Earth system, but also provides insights into how the system may respond to analogous human perturbations. However, the extent, duration, causes, and consequences of most past variations are poorly understood. This problem motivates the development of paleoredox proxies, including novel stable isotope systems such as Mo, Fe, U and Tl. Experience with these emerging isotope systems demonstrates great promise but also many challenges. The Mo isotope system is illustrative. To first order, the geochemical cycling and isotope systematics of this element are straightforward, making it a useful proxy. However, critical unresolved issues include: (a) uncertainties in the ocean inputs through time; (b) ambiguities about fractionation mechanisms; (c) inadequate understanding of how modern analogs map to ancient systems. Similar challenges confront all the novel isotope systems. The way forward requires integration of multiple isotopic proxies, as well as information gleaned from careful analyses of element concentrations. For example, an episode of Mo enrichment in the 2.5 Ga Mt. McRae Shale is generally interpreted as resulting from buildup of Mo in seawater due to oxidative weathering. This enrichment is therefore thought to indicate a "whiff" of O2 in the environment prior to the Great Oxidation Event that began at 2.4 Ga. Molybdenum isotopes are consistent with this interpretation. However, Mo enrichment due to enhanced input from low-T hydrothermal sources in an anoxic regime cannot be completely excluded given the current state of knowledge of

  17. Adaptive proxy map server for efficient vector spatial data rendering

    Science.gov (United States)

    Sayar, Ahmet

    2013-01-01

    The rapid transmission of vector map data over the Internet is becoming a bottleneck of spatial data delivery and visualization in web-based environment because of increasing data amount and limited network bandwidth. In order to improve both the transmission and rendering performances of vector spatial data over the Internet, we propose a proxy map server enabling parallel vector data fetching as well as caching to improve the performance of web-based map servers in a dynamic environment. Proxy map server is placed seamlessly anywhere between the client and the final services, intercepting users' requests. It employs an efficient parallelization technique based on spatial proximity and data density in case distributed replica exists for the same spatial data. The effectiveness of the proposed technique is proved at the end of the article by the application of creating map images enriched with earthquake seismic data records.

  18. Munchausen syndrome and Munchausen syndrome by proxy in dermatology.

    Science.gov (United States)

    Boyd, Alan S; Ritchie, Coleman; Likhari, Sunaina

    2014-08-01

    Patients with Munchausen syndrome purposefully injure themselves, often with the injection of foreign materials, to gain hospital admission and the attention associated with having a difficult-to-identify condition. Munchausen syndrome by proxy occurs when a child's caregiver, typically the mother, injures the child for the same reasons. Cases of Munchausen syndrome and Munchausen syndrome by proxy with primary cutaneous involvement appear to be rarely described in the literature suggesting either that diagnosis is not made readily or that it is, in fact, an uncommon disorder. At the center of both conditions is significant psychological pathology and treatment is difficult as many patients with Munchausen syndrome when confronted with these diagnostic possibilities simply leave the hospital. Little is known about the long-term outcome or prognosis of these patients. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  19. Mobile Multicast in Hierarchical Proxy Mobile IPV6

    Science.gov (United States)

    Hafizah Mohd Aman, Azana; Hashim, Aisha Hassan A.; Mustafa, Amin; Abdullah, Khaizuran

    2013-12-01

    Mobile Internet Protocol Version 6 (MIPv6) environments have been developing very rapidly. Many challenges arise with the fast progress of MIPv6 technologies and its environment. Therefore the importance of improving the existing architecture and operations increases. One of the many challenges which need to be addressed is the need for performance improvement to support mobile multicast. Numerous approaches have been proposed to improve mobile multicast performance. This includes Context Transfer Protocol (CXTP), Hierarchical Mobile IPv6 (HMIPv6), Fast Mobile IPv6 (FMIPv6) and Proxy Mobile IPv6 (PMIPv6). This document describes multicast context transfer in hierarchical proxy mobile IPv6 (H-PMIPv6) to provide better multicasting performance in PMIPv6 domain.

  20. Accuracy of Caregiver Proxy Reports of Home Care Service Use.

    Science.gov (United States)

    Chappell, Neena L; Kadlec, Helena

    2016-12-01

    Although much of the research on service use by older adults with dementia relies on proxy reports by informal caregivers, little research assesses the accuracy of these reports, and that which does exist, does not focus on home care services. This brief report compares proxy reports by family caregivers to those with dementia with provincial Ministry of Health records collected for payment and monitoring. The four home care services examined include home nursing care, adult day care, home support, and respite care. Data come from a province-wide study of caregivers in British Columbia, Canada. Caregiver reports are largely consistent with Ministry records, ranging from 81.0% agreement for home support to 96.6% for respite care. Spouses living with the care recipient (the vast majority of the sample) are the most accurate. Others, whether living with the care recipient or not, have only a 50-50 chance of being correct.

  1. A comparison of proxy performance in coral biodiversity monitoring

    Science.gov (United States)

    Richards, Zoe T.

    2013-03-01

    The productivity and health of coral reef habitat is diminishing worldwide; however, the effect that habitat declines have on coral reef biodiversity is not known. Logistical and financial constraints mean that surveys of hard coral communities rarely collect data at the species level; hence it is important to know if there are proxy metrics that can reliably predict biodiversity. Here, the performances of six proxy metrics are compared using regression analyses on survey data from a location in the northern Great Barrier Reef. Results suggest generic richness is a strong explanatory variable for spatial patterns in species richness (explaining 82 % of the variation when measured on a belt transect). The most commonly used metric of reef health, percentage live coral cover, is not positively or linearly related to hard coral species richness. This result raises doubt as to whether management actions based on such reefscape information will be effective for the conservation of coral biodiversity.

  2. Multiple stressor effects on marine infauna: responses of estuarine taxa and functional traits to sedimentation, nutrient and metal loading

    KAUST Repository

    Ellis, Joanne; Clark, D.; Atalah, J.; Jiang, W.; Taiapa, C.; Patterson, M.; Sinner, J.; Hewitt, J.

    2017-01-01

    loading and the documented interaction effects between multiple stressors have important implications for understanding and managing the ecological consequences of eutrophication, sedimentation and contaminants on coastal ecosystems.

  3. Geo-Proxy-Based Site Classification for Regional Zonation of Seismic Site Effects in South Korea

    Directory of Open Access Journals (Sweden)

    Chang-Guk Sun

    2018-02-01

    Full Text Available Seismic site effects and topographic effects related to ground motion occur during an earthquake due to site-specific geotechnical or geological characteristics, including the geological or geographical structure and the characteristics of near-surface sub-soil layers. Site-specific site effects due to geological conditions have been confirmed in recent earthquake events. Earthquake-induced damage has mainly occurred at accumulated soft soil layers under basins or along coasts and rivers. An alternative method has recently been proposed for evaluating regional seismic site effects and amplification factors using digital elevation models (DEM. High-quality DEMs at high resolutions may be employed to resolve finer-scale variations in topographic gradients and consequently, correlated site response parameters. Because there are many regions in South Korea lacking borehole datasets, which are insufficient for site classification only using borehole datasets, a DEM-based proxy for seismic zonation can be effective. Thus, in this study, geo-proxy-based site classification was proposed based on empirical correlations with site response parameters and conducted for regional zonation of seismic site effects to identify the amplification of characteristics in the western metropolitan areas of South Korea, depending on the site-specific geo-spatial conditions.

  4. Testing New Proxies for Photosymbiosis in the Fossil Record

    Science.gov (United States)

    Tornabene, C.; Martindale, R. C.; Schaller, M. F.

    2015-12-01

    Photosymbiosis is a mutualistic relationship that many corals have developed with dinoflagellates called zooxanthellae. The dinoflagellates, of the genus Symbiodinium, photosynthesize and provide corals with most of their energy, while in turn coral hosts live in waters where zooxanthellae have optimal exposure to sunlight. Thanks to this relationship, symbiotic corals calcify faster than non-symbiotic corals. Photosymbiosis is therefore considered the evolutionary innovation that allowed corals to become major reef-builders through geological time.This relationship is extremely difficult to study. Zooxanthellae, which are housed in the coral tissue, are not preserved in fossil coral skeletons, thus determining whether corals had symbionts requires a robust proxy. In order to address this critical question, the goal of this research is to test new proxies for ancient photosymbiosis. Currently the project is focused on assessing the nitrogen (δ15N) isotopes of corals' organic matrices, sensu Muscatine et al. (2005), as well as carbon and oxygen (δ13C, δ18O) isotopes of fossil coral skeletons. Samples from Modern, Pleistocene, Oligocene and Triassic coral skeletons were analyzed to test the validity of these proxies. Coral samples comprise both (interpreted) symbiotic and non-symbiotic fossil corals from the Oligocene and Triassic as well as symbiotic fossil corals from the Modern and Pleistocene to corroborate our findings with the results of Muscatine et al. (2005). Samples were tested for diagenesis through petrographic and scanning electron microscope (SEM) analyses to avoid contamination. Additionally, a novel technique that has not yet been applied to the fossil record was tested. The technique aims to recognize dinosterol, a dinoflagellate biomarker, in both modern and fossil coral samples. The premise of this proxy is that symbiotic corals should contain the dinoflagellate biomarker, whereas those lacking symbionts should lack dinosterol. Results from this

  5. Evaluation of Organic Proxies for Quantifying Past Primary Productivity

    Science.gov (United States)

    Raja, M.; Rosell-Melé, A.; Galbraith, E.

    2017-12-01

    Ocean primary productivity is a key element of the marine carbon cycle. However, its quantitative reconstruction in the past relies on the use of biogeochemical models as the available proxy approaches are qualitative at best. Here, we present an approach that evaluates the use of phytoplanktonic biomarkers (i.e. chlorins and alkenones) as quantitative proxies to reconstruct past changes in marine productivity. We compare biomarkers contents in a global suite of core-top sediments to sea-surface chlorophyll-a abundance estimated by satellites over the last 20 years, and the results are compared to total organic carbon (TOC). We also assess satellite data and detect satellite limitations and biases due to the complexity of optical properties and the actual defined algorithms. Our findings show that sedimentary chlorins can be used to track total sea-surface chlorophyll-a abundance as an indicator for past primary productivity. However, degradation processes restrict the application of this proxy to concentrations below a threshold value (1µg/g). Below this threshold, chlorins are a useful tool to identify reducing conditions when used as part of a multiproxy approach to assess redox sedimentary conditions (e.g. using Re, U). This is based on the link between anoxic/disoxic conditions and the flux of organic matter from the sea-surface to the sediments. We also show that TOC is less accurate than chlorins for estimating sea-surface chlorophyll-a due to the contribution of terrigenous organic matter, and the different degradation pathways of all organic compounds that TOC includes. Alkenones concentration also relates to primary productivity, but they are constrained by different processes in different regions. In conclusion, as lons as specific constraints are taken into account, our study evaluates the use of chlorins and alkenones as quantitative proxies of past primary productivity, with more accuracy than by using TOC.

  6. FADDEEV: A fortran code for the calculation of the frequency response matrix of multiple-input, multiple-output dynamic systems

    International Nuclear Information System (INIS)

    Owens, D.H.

    1972-06-01

    The KDF9/EGDON programme FADDEEV has been written to investigate a technique for the calculation of the matrix of frequency responses G(jw) describing the response of the output vector y from the multivariable differential/algebraic system S to the drive of the system input vector u. S: Ex = Ax + Bu, y = Cx, G(jw) = C(jw E - A ) -1 B. The programme uses an algorithm due to Faddeev and has been written with emphasis upon: (a) simplicity of programme structure and computational technique which should enable a user to find his way through the programme fairly easily, and hence facilitate its manipulation as a subroutine in a larger code; (b) rapid computational ability, particularly in systems with fairly large number of inputs and outputs and requiring the evaluation of the frequency responses at a large number of frequencies. Transport or time delays must be converted by the user to Pade or Bode approximations prior to input. Conditions under which the algorithm fails to give accurate results are identified, and methods for increasing the accuracy of the calculations are discussed. The conditions for accurate results using FADDEEV indicate that its application is specialized. (author)

  7. PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma.

    Science.gov (United States)

    Zamagni, Elena; Nanni, Cristina; Mancuso, Katia; Tacchetti, Paola; Pezzi, Annalisa; Pantani, Lucia; Zannetti, Beatrice; Rambaldi, Ilaria; Brioli, Annamaria; Rocchi, Serena; Terragna, Carolina; Martello, Marina; Marzocchi, Giulia; Borsi, Enrica; Rizzello, Ilaria; Fanti, Stefano; Cavo, Michele

    2015-10-01

    To evaluate the role of 18F-FDG PET/CT in 282 symptomatic multiple myeloma patients treated up-front between 2002 and 2012. All patients were studied by PET/CT at baseline, during posttreatment follow-up, and at the time of relapse. Their median duration of follow-up was 67 months. Forty-two percent of the patients at diagnosis had >3 focal lesions, and in 50% SUVmax was >4.2; extramedullary disease was present in 5%. On multivariate analysis, ISS stage 3, SUVmax >4.2, and failure to achieve best complete response (CR) were the leading factors independently associated with shorter progression-free survival (PFS) and overall survival (OS). These 3 variables were used to construct a prognostic scoring system based on the number of risk factors. After treatment, PET/CT negativity (PET-neg) was observed in 70% of patients, whereas conventionally defined CR was achieved in 53%. Attainment of PET-neg favorably influenced PFS and OS. PET-neg was an independent predictor of prolonged PFS and OS for patients with conventionally defined CR. Sixty-three percent of patients experienced relapse or progression; in 12%, skeletal progression was exclusively detected by systematic PET/CT performed during follow-up. A multivariate analysis revealed that persistence of SUVmax >4.2 following first-line treatment was independently associated with exclusive PET/CT progression. PET/CT combined with ISS stage and achievement or not of CR on first-line therapy sorted patients into different prognostic groups. PET/CT led to a more careful evaluation of CR. Finally, in patients with persistent high glucose metabolism after first-line treatment, PET/CT can be recommended during follow-up, to screen for otherwise unidentifiable progression. ©2015 American Association for Cancer Research.

  8. Thermal management of a multiple mini-channel heat sink by the integration of a thermal responsive shape memory material

    International Nuclear Information System (INIS)

    Di Maio, E.; Mastrullo, R.; Mauro, A.W.; Toto, D.

    2014-01-01

    In this paper, a novel application of a thermo-responsive shape memory polymer (SMP) is proposed to smart-control the forced flow of water in a multi mini-channel heat sink. In particular, it is reported that millimeter-sized cylinders made of SMP could be used to smartly obstruct the fluid flow by adapting the flow cross section to the heat load to be removed. By integrating the sensing, the control and the actuation functions within a unique, millimeter-sized device, these micro-valves, unlike the traditional actuators normally used for flow control, could be easily embedded into small heat sinks, with significant space and energy saving, useful, in particular, in systems where several miniaturized components have to be cooled concurrently, such as the modern mainframes or the concentrated photovoltaic solar cells. Two possible configurations for the SMP were considered in this study: an “open” configuration, without any obstruction of the water flow free and an “obstructed” configuration, with the millimeter-sized cylinder partially occupying the mini-channel. A numerical, steady state analysis was carried out with water in single-phase forced convection, to determine the effect of these two states on the internal fluid flow characteristics under different conditions of heat flux and pressure drop and to evaluate the overall thermal behavior of the smart-controlled multiple mini-channel heat sink in terms of ability to control the temperature of the system and to reduce the energy consumption. -- Highlights: • A novel application of a SMP material is investigated for the thermal management of a heat sink. • Numerical simulations to find the matching of the heat sink and material system after regulation were carried out. • The investigated system is able to control the heat sink temperature. • Further analysis for system stability are required

  9. Circulating CD4+CXCR5+ T cells contribute to proinflammatory responses in multiple ways in coronary artery disease.

    Science.gov (United States)

    Ding, Ru; Gao, Wenwu; He, Zhiqing; Wu, Feng; Chu, Yang; Wu, Jie; Ma, Lan; Liang, Chun

    2017-11-01

    Coronary artery disease (CAD) is a common subtype of cardiovascular disease. The major contributing event is atherosclerosis, which is a progressive inflammatory condition resulting in the thickening of the arterial wall and the formation of atheromatous plaques. Recent evidence suggests that circulating CD4 + CXCR5 + T cells can contribute to inflammatory reactions. In this study, the frequency, phenotype, and function of circulating CD4 + CXCR5 + T cells in CAD patients were examined. Data showed that circulating CD4 + CXCR5 + T cells in CAD patients were enriched with a PD-1 + CCR7 - subset, which was previously identified as the most potent in B cell help. The CD4 + CXCR5 + T cells in CAD patients also secreted significantly higher levels of IFN-γ, IL-17A, and IL-21 than those from healthy controls. Depleting the PD-1 + population significantly reduced the cytokine secretion. Interestingly, the CD4 + CXCR5 + PD-1 - T cells significantly upregulated PD-1 following anti-CD3/CD28 or SEB stimulation. CD4 + CXCR5 + T cells from CAD patients also demonstrated more potent capacity to stimulate B cell inflammation than those from healthy individuals. The phosphorylation of STAT1 and STAT3 were significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD than controls. The IL-6 and IFN-γ expression were also significantly higher in B cells incubated with CD4 + CXCR5 + T cells from CAD. Together, this study demonstrated that CAD patients presented a highly activated CD4 + CXCR5 + T cell subset that could contribute to proinflammatory responses in multiple ways. The possibility of using CD4 + CXCR5 + T cells as a therapeutic target should therefore be examined in CAD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Intensified Sampling in Response to a Salmonella Heidelberg Outbreak Associated with Multiple Establishments Within a Single Poultry Corporation.

    Science.gov (United States)

    Green, Alice; Defibaugh-Chavez, Stephanie; Douris, Aphrodite; Vetter, Danah; Atkinson, Richard; Kissler, Bonnie; Khroustalev, Allison; Robertson, Kis; Sharma, Yudhbir; Becker, Karen; Dessai, Uday; Antoine, Nisha; Allen, Latasha; Holt, Kristin; Gieraltowski, Laura; Wise, Matthew; Schwensohn, Colin

    2018-03-01

    On June 28, 2013, the Food Safety and Inspection Service (FSIS) was notified by the Centers for Disease Control and Prevention (CDC) of an investigation of a multistate cluster of illnesses of Salmonella enterica serovar Heidelberg. Since case-patients in the cluster reported consumption of a variety of chicken products, FSIS used a simple likelihood-based approach using traceback information to focus on intensified sampling efforts. This article describes the multiphased product sampling approach taken by FSIS when epidemiologic evidence implicated chicken products from multiple establishments operating under one corporation. The objectives of sampling were to (1) assess process control of chicken slaughter and further processing and (2) determine whether outbreak strains were present in products from these implicated establishments. As part of the sample collection process, data collected by FSIS personnel to characterize product included category (whole chicken and type of chicken parts), brand, organic or conventional product, injection with salt solutions or flavorings, and whether product was skinless or skin-on. From the period September 9, 2013, through October 31, 2014, 3164 samples were taken as part of this effort. Salmonella percent positive declined from 19.7% to 5.3% during this timeframe as a result of regulatory and company efforts. The results of intensified sampling for this outbreak investigation informed an FSIS regulatory response and corrective actions taken by the implicated establishments. The company noted that a multihurdle approach to reduce Salmonella in products was taken, including on-farm efforts such as environmental testing, depopulation of affected flocks, disinfection of affected houses, vaccination, and use of various interventions within the establishments over the course of several months.

  11. Analisis Algoritma Pergantian Cache Pada Proxy Web Server Internet Dengan Simulasi

    OpenAIRE

    Nurwarsito, Heru

    2007-01-01

    Pertumbuhan jumlah client internet dari waktu ke waktu terus bertambah, maka respon akses internet menjadi semakin lambat. Untuk membantu kecepatan akses tersebut maka diperlukan cache pada Proxy Server. Penelitian ini bertujuan untuk menganalisis performansi Proxy Server pada Jaringan Internet terhadap penggunaan algoritma pergantian cache-nya.Analisis Algoritma Pergantian Cache Pada Proxy Server didesain dengan metoda pemodelan simulasi jaringan internet yang terdiri dari Web server, Proxy ...

  12. Error characterization for asynchronous computations: Proxy equation approach

    Science.gov (United States)

    Sallai, Gabriella; Mittal, Ankita; Girimaji, Sharath

    2017-11-01

    Numerical techniques for asynchronous fluid flow simulations are currently under development to enable efficient utilization of massively parallel computers. These numerical approaches attempt to accurately solve time evolution of transport equations using spatial information at different time levels. The truncation error of asynchronous methods can be divided into two parts: delay dependent (EA) or asynchronous error and delay independent (ES) or synchronous error. The focus of this study is a specific asynchronous error mitigation technique called proxy-equation approach. The aim of this study is to examine these errors as a function of the characteristic wavelength of the solution. Mitigation of asynchronous effects requires that the asynchronous error be smaller than synchronous truncation error. For a simple convection-diffusion equation, proxy-equation error analysis identifies critical initial wave-number, λc. At smaller wave numbers, synchronous error are larger than asynchronous errors. We examine various approaches to increase the value of λc in order to improve the range of applicability of proxy-equation approach.

  13. Marine proxy evidence linking decadal North Pacific and Atlantic climate

    Energy Technology Data Exchange (ETDEWEB)

    Hetzinger, S. [University of Toronto Mississauga, CPS-Department, Mississauga, ON (Canada); Leibniz Institute of Marine Sciences, IFM-GEOMAR, Kiel (Germany); Halfar, J. [University of Toronto Mississauga, CPS-Department, Mississauga, ON (Canada); Mecking, J.V.; Keenlyside, N.S. [Leibniz Institute of Marine Sciences, IFM-GEOMAR, Kiel (Germany); University of Bergen, Geophysical Institute and Bjerknes Centre for Climate Research, Bergen (Norway); Kronz, A. [University of Goettingen, Geowissenschaftliches Zentrum, Goettingen (Germany); Steneck, R.S. [University of Maine, Darling Marine Center, Walpole, ME (United States); Adey, W.H. [Smithsonian Institution, Department of Botany, Washington, DC (United States); Lebednik, P.A. [ARCADIS U.S. Inc., Walnut Creek, CA (United States)

    2012-09-15

    Decadal- to multidecadal variability in the extra-tropical North Pacific is evident in 20th century instrumental records and has significant impacts on Northern Hemisphere climate and marine ecosystems. Several studies have discussed a potential linkage between North Pacific and Atlantic climate on various time scales. On decadal time scales no relationship could be confirmed, potentially due to sparse instrumental observations before 1950. Proxy data are limited and no multi-centennial high-resolution marine geochemical proxy records are available from the subarctic North Pacific. Here we present an annually-resolved record (1818-1967) of Mg/Ca variations from a North Pacific/Bering Sea coralline alga that extends our knowledge in this region beyond available data. It shows for the first time a statistically significant link between decadal fluctuations in sea-level pressure in the North Pacific and North Atlantic. The record is a lagged proxy for decadal-scale variations of the Aleutian Low. It is significantly related to regional sea surface temperature and the North Atlantic Oscillation (NAO) index in late boreal winter on these time scales. Our data show that on decadal time scales a weaker Aleutian Low precedes a negative NAO by several years. This atmospheric link can explain the coherence of decadal North Pacific and Atlantic Multidecadal Variability, as suggested by earlier studies using climate models and limited instrumental data. (orig.)

  14. Short-term indicators. Intensities as a proxy for savings

    Energy Technology Data Exchange (ETDEWEB)

    Boonekamp, P.G.M.; Gerdes, J. [ECN Policy Studies, Petten (Netherlands); Faberi, S. [Institute of Studies for the Integration of Systems ISIS, Rome (Italy)

    2013-12-15

    The ODYSSEE database on energy efficiency indicators (www.odyssee-indicators.org) has been set up to enable the monitoring and evaluation of realised energy efficiency improvements and related energy savings. The database covers the 27 EU countries as well as Norway and Croatia and data are available from 1990 on. This work contributes to the growing need for quantitative monitoring and evaluation of the impacts of energy policies and measures, both at the EU and national level, e.g. due to the Energy Services Directive and the proposed Energy Efficiency Directive. Because the underlying data become available only after some time, the savings figures are not always timely available. This is especially true for the ODEX efficiency indices per sector that rely on a number of indicators. Therefore, there is a need for so-called short-term indicators that become available shortly after the year has passed for which data are needed. The short term indicators do not replace the savings indicators but function as a proxy for the savings in the most recent year. This proxy value is faster available, but will be less accurate than the saving indicators themselves. The short term indicators have to be checked regularly with the ODEX indicators in order to see whether they can function still as a proxy.

  15. New Literacies, Multiple Literacies, Unlimited Literacies: What Now, What Next, Where to? A Response to "Blue Listerine, Parochialism and ASL Literacy"

    Science.gov (United States)

    Paul, Peter V.

    2006-01-01

    This article is a response to "Blue Listerine, Parochialism, and ASL Literacy" (Czubek, 2006). The author presents his views on the concepts of literacy and the new and multiple literacies. In addition, the merits of print literacy and other types of literacies are discussed. Although the author agrees that there is an American Sign…

  16. Dynamic Testing of Analogical Reasoning in 5- to 6-Year-Olds : Multiple-Choice Versus Constructed-Response Training Items

    NARCIS (Netherlands)

    Stevenson, C.E.; Heiser, W.J.; Resing, W.C.M.

    2016-01-01

    Multiple-choice (MC) analogy items are often used in cognitive assessment. However, in dynamic testing, where the aim is to provide insight into potential for learning and the learning process, constructed-response (CR) items may be of benefit. This study investigated whether training with CR or MC

  17. Performance of Men and Women on Multiple-Choice and Constructed-Response Tests for Beginning Teachers. Research Report. ETS RR-04-48

    Science.gov (United States)

    Livingston, Samuel A.; Rupp, Stacie L.

    2004-01-01

    Some previous research results imply that women tend to perform better, relative to men, on constructed-response (CR) tests than on multiple-choice (MC) tests in the same subjects. An analysis of data from several tests used in the licensing of beginning teachers supported this hypothesis, to varying degrees, in most of the tests investigated. The…

  18. Dynamic Testing of Analogical Reasoning in 5- to 6-Year-Olds: Multiple-Choice versus Constructed-Response Training Items

    Science.gov (United States)

    Stevenson, Claire E.; Heiser, Willem J.; Resing, Wilma C. M.

    2016-01-01

    Multiple-choice (MC) analogy items are often used in cognitive assessment. However, in dynamic testing, where the aim is to provide insight into potential for learning and the learning process, constructed-response (CR) items may be of benefit. This study investigated whether training with CR or MC items leads to differences in the strategy…

  19. Co-loading and intestine-specific delivery of multiple antioxidants in pH-responsive microspheres based on TEMPO-oxidized polysaccharides

    NARCIS (Netherlands)

    Shi, Mengxuan; Bai, Jie; Zhao, Liyun; Yu, Xinrui; Liang, Jingjing; Liu, Ying; Norde, Willem; Li, Yuan

    2017-01-01

    In this study, pH-responsive microspheres loaded with multiple antioxidants were developed for intestine-specific delivery and exhibited synergistic activity. They consist of chitosan (CS)-coated microspheres made of TEMPO-oxidized Konjac glucomannan (OKGM) polymers, of which the carboxyl (COO−)

  20. Efficient Conditional Proxy Re-encryption with Chosen-Ciphertext Security

    NARCIS (Netherlands)

    Weng, Jiang; Yang, Yanjiang; Tang, Qiang; Deng, Robert H.; Bao, Feng

    Recently, a variant of proxy re-encryption, named conditional proxy re-encryption (C-PRE), has been introduced. Compared with traditional proxy re-encryption, C-PRE enables the delegator to implement fine-grained delegation of decryption rights, and thus is more useful in many applications. In this

  1. Analysis of Quality of Proxy Questions in Health Surveys by Behavior Coding

    NARCIS (Netherlands)

    Benitez, I.; Padilla, J.L.; Ongena, Yfke

    2012-01-01

    The aim of this study is to show how to analyze the quality of questions for proxy informants by means of behavior coding. Proxy questions can undermine survey data quality because of the fact that proxies respond to questions on behalf of other people. Behavior coding can improve questions by

  2. The design and implementation about the project of optimizing proxy servers

    International Nuclear Information System (INIS)

    Wu Ling; Liu Baoxu

    2006-01-01

    Proxy server is an important facility in the network of an organization, which play an important role in security and access control and accelerating access of Internet. This article introduces the action of proxy servers, and expounds the resolutions to optimize proxy servers at IHEP: integration, dynamic domain name resolves and data synchronization. (authors)

  3. Some Proxy Signature and Designated verifier Signature Schemes over Braid Groups

    OpenAIRE

    Lal, Sunder; Verma, Vandani

    2009-01-01

    Braids groups provide an alternative to number theoretic public cryptography and can be implemented quite efficiently. The paper proposes five signature schemes: Proxy Signature, Designated Verifier, Bi-Designated Verifier, Designated Verifier Proxy Signature And Bi-Designated Verifier Proxy Signature scheme based on braid groups. We also discuss the security aspects of each of the proposed schemes.

  4. Effect of response format on cognitive reflection: Validating a two- and four-option multiple choice question version of the Cognitive Reflection Test.

    Science.gov (United States)

    Sirota, Miroslav; Juanchich, Marie

    2018-03-27

    The Cognitive Reflection Test, measuring intuition inhibition and cognitive reflection, has become extremely popular because it reliably predicts reasoning performance, decision-making, and beliefs. Across studies, the response format of CRT items sometimes differs, based on the assumed construct equivalence of tests with open-ended versus multiple-choice items (the equivalence hypothesis). Evidence and theoretical reasons, however, suggest that the cognitive processes measured by these response formats and their associated performances might differ (the nonequivalence hypothesis). We tested the two hypotheses experimentally by assessing the performance in tests with different response formats and by comparing their predictive and construct validity. In a between-subjects experiment (n = 452), participants answered stem-equivalent CRT items in an open-ended, a two-option, or a four-option response format and then completed tasks on belief bias, denominator neglect, and paranormal beliefs (benchmark indicators of predictive validity), as well as on actively open-minded thinking and numeracy (benchmark indicators of construct validity). We found no significant differences between the three response formats in the numbers of correct responses, the numbers of intuitive responses (with the exception of the two-option version, which had a higher number than the other tests), and the correlational patterns of the indicators of predictive and construct validity. All three test versions were similarly reliable, but the multiple-choice formats were completed more quickly. We speculate that the specific nature of the CRT items helps build construct equivalence among the different response formats. We recommend using the validated multiple-choice version of the CRT presented here, particularly the four-option CRT, for practical and methodological reasons. Supplementary materials and data are available at https://osf.io/mzhyc/ .

  5. A Quantitative Proxy for Sea-Ice Based on Diatoms: A Cautionary Tale.

    Science.gov (United States)

    Nesterovich, A.; Caissie, B.

    2016-12-01

    Sea ice in the Polar Regions supports unique and productive ecosystems, but the current decline in the Arctic sea ice extent prompts questions about previous sea ice declines and the response of ice related ecosystems. Since satellite data only extend back to 1978, the study of sea ice before this time requires a proxy. Being one of the most productive, diatom-dominated regions in the world and having a wide range of sea ice concentrations, the Bering and Chukchi seas are a perfect place to find a relationship between the presence of sea ice and diatom community composition. The aim of this work is to develop a diatom-based proxy for the sea ice extent. A total of 473 species have been identified in 104 sediment samples, most of which were collected on board the US Coast Guard Cutter Healy ice breaker (2006, 2007) and the Norseman II (2008). The study also included some of the archived diatom smear slides made from sediments collected in 1969. The assemblages were compared to satellite-derived sea ice extent data averaged over the 10 years preceding the sampling. Previous studies in the Arctic and Antarctic regions demonstrated that the Generalized Additive Model (GAM) is one of the best choices for proxy construction. It has the advantage of using only several species instead of the whole assemblage, thus including only sea ice-associated species and minimizing the noise created by species responding to other environmental factors. Our GAM on three species (Connia compita, Fragilariopsis reginae-jahniae, and Neodenticula seminae) has low standard deviation, high level of explained variation, and holds under the ten-fold cross-validation; the standard residual analysis is acceptable. However, a spatial residual analysis revealed that the model consistently over predicts in the Chukchi Sea and under predicts in the Bering Sea. Including a spatial model into the GAM didn't improve the situation. This has led us to test other methods, including a non-parametric model

  6. New Proxies for Climate change parameters: Foram Culturing and Pteropod Potentials

    Science.gov (United States)

    Keul, N.; Schneider, R. R.; Langer, G.; Bijma, J.; Peijnenburg, K. T.

    2017-12-01

    Global climate change is one of the most pressing challenges our society is currently facing and strong efforts are made to simulate future climate conditions. To better validate models that aim at predicting global temperature rise as a consequence of anthropogenic CO2 emissions, accurate atmospheric paleo-CO2 estimates in combination with temperature reconstructions are necessary. Consequently there is a strong need for reliable proxies, allowing reconstruction of climate change. With respect to foraminifera a combination of laboratory experiments and modeling is presented, to show the isolated impact of the different parameters of the carbonate system on trace element composition of their shells. We focus on U/Ca and Sr/Ca ratios, which have recently been established as new proxies reflecting changes in the carbonate system of seawater. While U/Ca correlates with carbonate ion concentration, Sr/Ca is primarily influenced by DIC. The latter is particularly promising since the impact of additional parameters is relatively well constrained and hence, Sr/Ca ratios may allow higher accuracy in carbonate system parameter reconstructions. Furthermore, our results will be discussed on how to advance our knowledge about foraminiferal biomineralization. Pteropods, among the first responders to ocean acidification and warming, are explored as carriers of marine paleoenvironmental signals. In order to characterize the stable isotopic composition of aragonitic pteropod shells and their variation in response to climate change parameters, pteropod shells were collected along a latitudinal transect in the Atlantic Ocean. By comparing shell oxygen isotopic composition to depth changes of the calculated aragonite equilibrium oxygen isotope values, we infer shallow calcification depths for Heliconoides inflatus (75 m), rendering this species a good potential proxy carrier for past variations in surface ocean properties. Furthermore, we demonstrate that indeed, pteropod shells are

  7. Motor and sensory responses after percutaneous tibial nerve stimulation in multiple sclerosis patients with lower urinary tract symptoms treated in daily practice.

    Science.gov (United States)

    Zecca, C; Digesu, G A; Robshaw, P; Puccini, F; Khullar, V; Tubaro, A; Gobbi, C

    2014-03-01

    Posterior tibial nerve stimulation (PTNS) is an effective treatment option for lower urinary tract symptoms (LUTS) in multiple sclerosis (MS) patients. Patients with MS and LUTS unresponsive to medical treatment received PTNS for 12 weeks after saline urodynamics to evaluate the prevalence of motor, sensory and combined responses during PTNS and to determine whether the type of response can predict treatment outcome. LUTS were also assessed using a 3-day bladder diary, patient perception of bladder condition (PPBC) questionnaire, patient perception of intensity of urgency scale (PPIUS), Kings Health QOL questionnaire (KHQ) and Overactive Bladder Questionnaire (OAB-q) before and after treatment. Patients were considered as "responders" if they reported an improvement >50% in their LUTS according to the PPBC. Sensory, motor and combined sensory/motor responses were compared between responders and non-responders. Eighty-three patients were included. 61% (51/83) of patients were responders. Sensory, motor and combined sensory/motor responses were found in 64% (53/83), 6% (5/83) and 30% (25/83) of patients respectively. A sensory response alone, or in combination with a motor response, was better associated with a successful outcome than the presence of a motor response alone (P = 0.001). A sensory response, either alone or in combination with a motor response, is more frequent and seems to be better associated with a successful outcome of PTNS than motor response alone. © 2014 The Author(s) European Journal of Neurology © 2014 EFNS.

  8. Prompt Proxy Mapping of Flood Damaged Rice Fields Using MODIS-Derived Indices

    Directory of Open Access Journals (Sweden)

    Youngjoo Kwak

    2015-11-01

    Full Text Available Flood mapping, particularly hazard and risk mapping, is an imperative process and a fundamental part of emergency response and risk management. This paper aims to produce a flood risk proxy map of damaged rice fields over the whole of Bangladesh, where monsoon river floods are dominant and frequent, affecting over 80% of the total population. This proxy risk map was developed to meet the request of the government on a national level. This study represents a rapid, straightforward methodology for estimating rice-crop damage in flood areas of Bangladesh during the large flood from July to September 2007, despite the lack of primary data. We improved a water detection algorithm to achieve a better discrimination capacity to discern flood areas by using a modified land surface water index (MLSWI. Then, rice fields were estimated utilizing a hybrid rice field map from land-cover classification and MODIS-derived indices, such as the normalized difference vegetation index (NDVI and enhanced vegetation index (EVI. The results showed that the developed method is capable of providing instant, comprehensive, nationwide mapping of flood risks, such as rice field damage. The detected flood areas and damaged rice fields during the 2007 flood were verified by comparing them with the Advanced Land Observing Satellite (ALOS AVNIR-2 images (a 10 m spatial resolution and in situ field survey data with moderate agreement (K = 0.57.

  9. Programming Algorithms of load balancing with HA-Proxy in HTTP services

    Directory of Open Access Journals (Sweden)

    José Teodoro Mejía Viteri

    2018-02-01

    Full Text Available The access to the public and private services through the web gains daily protagonism, and sometimes they must support amounts of requests that a team can not process, so there are solutions that use algorithms that allow to distribute the load of requests of a web application in several equipment; the objective of this work is to perform an analysis of load balancing scheduling algorithms through the HA-Proxy tool, and deliver an instrument that identifies the load distribution algorithm to be used and the technological infrastructure, to largely cover implementation. The information used for this work is based on a bibliographic analysis, eld study and implementation of the different load balancing algorithms in equipment, where the distribution and its performance will be analyzed. The incorporation of this technology to the management of services on the web, improves availability, helps business continuity and through the different forms of distribution of the requests of the algorithms that can be implemented in HA-Proxy to provide those responsible for information technology systems with a view of their advantages and disadvantages.

  10. Tracking variable sedimentation rates in orbitally forced paleoclimate proxy series

    Science.gov (United States)

    Li, M.; Kump, L. R.; Hinnov, L.

    2017-12-01

    This study addresses two fundamental issues in cyclostratigraphy: quantitative testing of orbital forcing in cyclic sedimentary sequences and tracking variable sedimentation rates. The methodology proposed here addresses these issues as an inverse problem, and estimates the product-moment correlation coefficient between the frequency spectra of orbital solutions and paleoclimate proxy series over a range of "test" sedimentation rates. It is inspired by the ASM method (1). The number of orbital parameters involved in the estimation is also considered. The method relies on the hypothesis that orbital forcing had a significant impact on the paleoclimate proxy variations, and thus is also tested. The null hypothesis of no astronomical forcing is evaluated using the Beta distribution, for which the shape parameters are estimated using a Monte Carlo simulation approach. We introduce a metric to estimate the most likely sedimentation rate using the product-moment correlation coefficient, H0 significance level, and the number of contributing orbital parameters, i.e., the CHO value. The CHO metric is applied with a sliding window to track variable sedimentation rates along the paleoclimate proxy series. Two forward models with uniform and variable sedimentation rates are evaluated to demonstrate the robustness of the method. The CHO method is applied to the classical Late Triassic Newark depth rank series; the estimated sedimentation rates match closely with previously published sedimentation rates and provide a more highly time-resolved estimate (2,3). References: (1) Meyers, S.R., Sageman, B.B., Amer. J. Sci., 307, 773-792, 2007; (2) Kent, D.V., Olsen, P.E., Muttoni, G., Earth-Sci. Rev.166, 153-180, 2017; (3) Li, M., Zhang, Y., Huang, C., Ogg, J., Hinnov, L., Wang, Y., Zou, Z., Li, L., 2017. Earth Plant. Sc. Lett. doi:10.1016/j.epsl.2017.07.015

  11. Polar cap index as a proxy for hemispheric Joule heating

    DEFF Research Database (Denmark)

    Chun, F.K.; Knipp, D.J.; McHarg, M.G.

    1999-01-01

    The polar cap (PC) index measures the level of geomagnetic activity in the polar cap based on magnetic perturbations from overhead ionospheric currents and distant field-aligned currents on the poleward edge of the nightside auroral oval. Because PC essentially measures the main sources of energy...... input into the polar cap, we propose to use PC as a proxy for the hemispheric Joule heat production rate (JH). In this study, JH is estimated from the Assimilative Mapping of Ionospheric Electrodynamics (AMIE) procedure. We fit hourly PC values to hourly averages of JH. Using a data base approximately...

  12. Improvement of a Quantum Proxy Blind Signature Scheme

    Science.gov (United States)

    Zhang, Jia-Lei; Zhang, Jian-Zhong; Xie, Shu-Cui

    2018-06-01

    Improvement of a quantum proxy blind signature scheme is proposed in this paper. Six-qubit entangled state functions as quantum channel. In our scheme, a trust party Trent is introduced so as to avoid David's dishonest behavior. The receiver David verifies the signature with the help of Trent in our scheme. The scheme uses the physical characteristics of quantum mechanics to implement message blinding, delegation, signature and verification. Security analysis proves that our scheme has the properties of undeniability, unforgeability, anonymity and can resist some common attacks.

  13. Use of modified electroconvulsive therapy in a case of polymyositis presenting with delusion of nihilism of proxy (Odysseus syndrome).

    Science.gov (United States)

    Shah, Ruchita; Grover, Sandeep; Krishna, Kodakandla; Singh, Dharminder

    2011-03-01

    We present a case of psychotic depression with polymyositis presenting with the distinct phenomenon of nihilism by proxy, which was treated with electroconvulsive therapy (ECT). A female patient with polymyositis was initially treated with pharmacotherapy. After initial response, there was deterioration in her mental state and hence, after careful consideration, neurological, and anaesthetic consultations, modified ECT was given with close monitoring. The mental state of the patient improved with a course of ECT, which proceeded without any complications. Her depressive symptoms including the delusion of nihilism by proxy responded to ECT. To the best of our knowledge, the use of ECT has not been reported in a case of polymyositis before, and this case shows that modified ECT can be given successfully in patients with polymyositis.

  14. Development of Virtual Resource Based IoT Proxy for Bridging Heterogeneous Web Services in IoT Networks.

    Science.gov (United States)

    Jin, Wenquan; Kim, DoHyeun

    2018-05-26

    The Internet of Things is comprised of heterogeneous devices, applications, and platforms using multiple communication technologies to connect the Internet for providing seamless services ubiquitously. With the requirement of developing Internet of Things products, many protocols, program libraries, frameworks, and standard specifications have been proposed. Therefore, providing a consistent interface to access services from those environments is difficult. Moreover, bridging the existing web services to sensor and actuator networks is also important for providing Internet of Things services in various industry domains. In this paper, an Internet of Things proxy is proposed that is based on virtual resources to bridge heterogeneous web services from the Internet to the Internet of Things network. The proxy enables clients to have transparent access to Internet of Things devices and web services in the network. The proxy is comprised of server and client to forward messages for different communication environments using the virtual resources which include the server for the message sender and the client for the message receiver. We design the proxy for the Open Connectivity Foundation network where the virtual resources are discovered by the clients as Open Connectivity Foundation resources. The virtual resources represent the resources which expose services in the Internet by web service providers. Although the services are provided by web service providers from the Internet, the client can access services using the consistent communication protocol in the Open Connectivity Foundation network. For discovering the resources to access services, the client also uses the consistent discovery interface to discover the Open Connectivity Foundation devices and virtual resources.

  15. Development of Virtual Resource Based IoT Proxy for Bridging Heterogeneous Web Services in IoT Networks

    Directory of Open Access Journals (Sweden)

    Wenquan Jin

    2018-05-01

    Full Text Available The Internet of Things is comprised of heterogeneous devices, applications, and platforms using multiple communication technologies to connect the Internet for providing seamless services ubiquitously. With the requirement of developing Internet of Things products, many protocols, program libraries, frameworks, and standard specifications have been proposed. Therefore, providing a consistent interface to access services from those environments is difficult. Moreover, bridging the existing web services to sensor and actuator networks is also important for providing Internet of Things services in various industry domains. In this paper, an Internet of Things proxy is proposed that is based on virtual resources to bridge heterogeneous web services from the Internet to the Internet of Things network. The proxy enables clients to have transparent access to Internet of Things devices and web services in the network. The proxy is comprised of server and client to forward messages for different communication environments using the virtual resources which include the server for the message sender and the client for the message receiver. We design the proxy for the Open Connectivity Foundation network where the virtual resources are discovered by the clients as Open Connectivity Foundation resources. The virtual resources represent the resources which expose services in the Internet by web service providers. Although the services are provided by web service providers from the Internet, the client can access services using the consistent communication protocol in the Open Connectivity Foundation network. For discovering the resources to access services, the client also uses the consistent discovery interface to discover the Open Connectivity Foundation devices and virtual resources.

  16. Statistical analysis with missing exposure data measured by proxy respondents: a misclassification problem within a missing-data problem.

    Science.gov (United States)

    Shardell, Michelle; Hicks, Gregory E

    2014-11-10

    In studies of older adults, researchers often recruit proxy respondents, such as relatives or caregivers, when study participants cannot provide self-reports (e.g., because of illness). Proxies are usually only sought to report on behalf of participants with missing self-reports; thus, either a participant self-report or proxy report, but not both, is available for each participant. Furthermore, the missing-data mechanism for participant self-reports is not identifiable and may be nonignorable. When exposures are binary and participant self-reports are conceptualized as the gold standard, substituting error-prone proxy reports for missing participant self-reports may produce biased estimates of outcome means. Researchers can handle this data structure by treating the problem as one of misclassification within the stratum of participants with missing self-reports. Most methods for addressing exposure misclassification require validation data, replicate data, or an assumption of nondifferential misclassification; other methods may result in an exposure misclassification model that is incompatible with the analysis model. We propose a model that makes none of the aforementioned requirements and still preserves model compatibility. Two user-specified tuning parameters encode the exposure misclassification model. Two proposed approaches estimate outcome means standardized for (potentially) high-dimensional covariates using multiple imputation followed by propensity score methods. The first method is parametric and uses maximum likelihood to estimate the exposure misclassification model (i.e., the imputation model) and the propensity score model (i.e., the analysis model); the second method is nonparametric and uses boosted classification and regression trees to estimate both models. We apply both methods to a study of elderly hip fracture patients. Copyright © 2014 John Wiley & Sons, Ltd.

  17. Simulating the Incorporation of Geochemical Proxies into Scleractinian Coral Skeletons: Effects of Different Environmental and Biological Factors and Implications for Paleo-reconstruction

    Science.gov (United States)

    Guo, W.

    2017-12-01

    Chemical and isotopic compositions of scleractinian coral skeletons reflect the physicochemical condition of the seawater in which corals grow. This makes coral skeleton one of the best archives of ocean climate and biogeochemical changes. A number of coral-based geochemical proxies have been developed and applied to reconstruct past seawater conditions, such as temperature, pH, carbonate chemistry and nutrient concentrations. Detailed laboratory and field-based studies of these proxies, however, indicate interpretation of the geochemistry of coral skeletons is not straightforward, due to the presence of `vital effects' and the variations of empirical proxy calibrations among and within different species. This poses challenges for the broad application of many geochemical proxies in corals, and highlights the need to better understand the fundamental processes governing the incorporation of different proxies. Here I present a numerical model that simulates the incorporation of a suite of geochemical proxies into coral skeletons, including δ11B, Mg/Ca, Sr/Ca, U/Ca, B/Ca and Ba/Ca. This model, building on previous theoretical studies of coral calcification, combines our current understanding of coral calcification mechanism with experimental constraints on the isotope and element partition during carbonate precipitation. It enables quantitative evaluation of the effects of different environmental and biological factors on each proxy. Specifically, this model shows that (1) the incorporation of every proxy is affected by multiple seawater parameters (e.g. temperature, pH, DIC) as opposed to one single parameter, and (2) biological factors, particularly the interplay between enzymatic alkalinity pumping and the exchange of coral calcifying fluid with external seawater, also exert significant controls. Based on these findings, I propose an inverse method for simultaneously reconstructing multiple seawater physicochemical parameters, and compare the performance of this

  18. A vaccine encoding conserved promiscuous HIV CD4 epitopes induces broad T cell responses in mice transgenic to multiple common HLA class II molecules.

    Directory of Open Access Journals (Sweden)

    Susan Pereira Ribeiro

    Full Text Available Current HIV vaccine approaches are focused on immunogens encoding whole HIV antigenic proteins that mainly elicit cytotoxic CD8+ responses. Mounting evidence points toward a critical role for CD4+ T cells in the control of immunodeficiency virus replication, probably due to cognate help. Vaccine-induced CD4+ T cell responses might, therefore, have a protective effect in HIV replication. In addition, successful vaccines may have to elicit responses to multiple epitopes in a high proportion of vaccinees, to match the highly variable circulating strains of HIV. Using rational vaccine design, we developed a DNA vaccine encoding 18 algorithm-selected conserved, "promiscuous" (multiple HLA-DR-binding B-subtype HIV CD4 epitopes - previously found to be frequently recognized by HIV-infected patients. We assessed the ability of the vaccine to induce broad T cell responses in the context of multiple HLA class II molecules using different strains of HLA class II- transgenic mice (-DR2, -DR4, -DQ6 and -DQ8. Mice displayed CD4+ and CD8+ T cell responses of significant breadth and magnitude, and 16 out of the 18 encoded epitopes were recognized. By virtue of inducing broad responses against conserved CD4+ T cell epitopes that can be recognized in the context of widely diverse, common HLA class II alleles, this vaccine concept may cope both with HIV genetic variability and increased population coverage. The vaccine may thus be a source of cognate help for HIV-specific CD8+ T cells elicited by conventional immunogens, in a wide proportion of vaccinees.

  19. Multi-proxy evidence of millennial climate variability from multiple Bahamian speleothems

    Science.gov (United States)

    Arienzo, Monica M.; Swart, Peter K.; Broad, Kenneth; Clement, Amy C.; Pourmand, Ali; Kakuk, Brian

    2017-04-01

    Northern Hemisphere tropical paleoclimate records support significant changes associated with Dansgaard Oeschger (D/O) events and Heinrich stadials 1 to 6 during the last 64,000 years. However, few absolutely dated terrestrial records from the western Atlantic span the last six Heinrich stadials. Here we present geochemical results from three new stalagmites collected from a cave in the Bahamas which encompass Heinrich stadials 1 to 6. We build on a previous study of the δ13C and δ18O values of the calcite and δ18O value of fluid inclusions from a single stalagmite from the same cave spanning the last three Heinrich stadials. Absolute geochronometry using U-Th equilibrium series demonstrates that the stalagmites formed between 63.8 and 13.8 kyr BP. The δ13C and δ18O values of the calcite show higher values associated with Heinrich stadials 1-6, and lower values during the D/O interstadial events. The Sr/Ca ratios of the calcite are shown to be relatively invariant, while in two of the samples the Mg/Ca ratios track the δ13C values. Increases in the δ18O values across Heinrich stadials 1-6 are interpreted as being driven by lower temperatures. The two deeper occurring stalagmites demonstrate increased Mg/Ca ratios and δ13C values during Heinrich stadials 1 and 2 which are interpreted as a signal of reduced flow rates in the epikarst and increased water/rock interactions as a result of increased aridity which potentially occurred across all six Heinrich stadials. The observed reductions in mean annual temperature and amount of precipitation across Heinrich stadials are proposed to be driven by a reduction in sea surface temperatures in the North Atlantic and an expanded Bermuda High. During D/O interstadials, the Bahamas cave records likely indicate warmer and/or wetter climate; however the isotopic shifts are not as significant as the isotopic excursions associated with Heinrich stadials.

  20. Multiple intravenous injections of allogeneic equine mesenchymal stem cells do not induce a systemic inflammatory response but do alter lymphocyte subsets in healthy horses.

    Science.gov (United States)

    Kol, Amir; Wood, Joshua A; Carrade Holt, Danielle D; Gillette, Jessica A; Bohannon-Worsley, Laurie K; Puchalski, Sarah M; Walker, Naomi J; Clark, Kaitlin C; Watson, Johanna L; Borjesson, Dori L

    2015-04-15

    Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses. We injected three doses of 25 × 10(6) allogeneic MSCs from either AT or BM (a total of 75 × 10(6) MSCs per horse) into five and five, respectively, healthy horses. Horses were followed up for 35 days after the first MSC infusion. We evaluated host inflammatory and immune response, including total leukocyte numbers, serum cytokine concentration, and splenic lymphocyte subsets. Repeated injection of allogeneic AT-MSCs or BM-MSCs did not elicit any clinical adverse effects. Repeated BM-MSC injection resulted in increased blood CD8(+) T-cell numbers. Multiple BM-MSC injections also increased splenic regulatory T cell numbers compared with AT-MSC-injected horses but not controls. These data demonstrate that multiple IV injections of allogeneic MSCs are well tolerated by healthy horses. No clinical signs or clinico-pathologic measurements of organ toxicity or systemic inflammatory response were recorded. Increased numbers of circulating CD8(+) T cells after multiple IV injections of allogeneic BM-MSCs may indicate a mild allo-antigen-directed cytotoxic response. Safety and efficacy of allogeneic MSC IV infusions in sick horses remain to be determined.

  1. Use of proxy models in the selection of production strategy in petroleum fields; Uso de metamodelos na selecao de estrategias de producao em campos de petroleo

    Energy Technology Data Exchange (ETDEWEB)

    Avansi, Guilherme D.; Schiozer, Denis J.; Risso, Fernanda V.A. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Engenharia Mecanica. Dept. de Engenharia de Petroleo; Suslick, Saul B. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Inst. de Geociencias

    2008-07-01

    The traditional process of production strategy demands many simulations due to the high number of variables and possibilities. Sub-optimal results can be obtained from manual processes; Automatic processes can mitigate this problem but the computational effort increases as a result of the number of simulations generated in the process. Thus, the objective of this work is an attempt of application of proxy models in the production strategy optimization and in the economic evaluation in petroleum fields, allowing the selection of production strategy evaluating a higher number of alternatives and increasing the chances to find better solutions. Proxies have been used in important applications such as risk analysis, history matching etc. The applied proxy models combine the following components: statistics methods, experimental planning, the response surface methodology and consistency checking. We have shown that proxy models can be used in a definition of production strategy, bringing an additional option in the process. The advantage is to find solutions that are not investigated by the traditional methods; proxy models create new possibilities to change a decision used in an economic evaluation process in a wider solution space. (author)

  2. BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma.

    Science.gov (United States)

    Niesvizky, Ruben; Jayabalan, David S; Christos, Paul J; Furst, Jessica R; Naib, Tara; Ely, Scott; Jalbrzikowski, Jessica; Pearse, Roger N; Zafar, Faiza; Pekle, Karen; Larow, April; Lent, Richard; Mark, Tomer; Cho, Hearn J; Shore, Tsiporah; Tepler, Jeffrey; Harpel, John; Schuster, Michael W; Mathew, Susan; Leonard, John P; Mazumdar, Madhu; Chen-Kiang, Selina; Coleman, Morton

    2008-02-01

    This trial determined the safety and efficacy of the combination regimen clarithromycin (Biaxin), lenalidomide (Revlimid), and dexamethasone (BiRD) as first-line therapy for multiple myeloma. Patients received BiRD in 28-day cycles. Dexamethasone (40 mg) was given orally once weekly, clarithromycin (500 mg) was given orally twice daily, and lenalidomide (25 mg) was given orally daily on days 1 to 21. Objective response was defined by standard criteria (ie, decrease in serum monoclonal protein [M-protein] by at least 50%, and a decrease in urine M-protein by at least 90%). Of the 72 patients enrolled, 65 had an objective response (90.3%). A combined stringent and conventional complete response rate of 38.9% was achieved, and 73.6% of the patients achieved at least a 90% decrease in M-protein levels. This regimen did not interfere with hematopoietic stem-cell harvest. Fifty-two patients who did not go on to receive transplants received continued therapy (complete response, 37%; very good partial response, 33%). The major adverse events were thromboembolic events, corticosteroid-related morbidity, and cytopenias. BiRD is an effective regimen with manageable side effects in the treatment of symptomatic, newly diagnosed multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT00151203.

  3. Comprehensive Analysis of CD8+-T-Cell Responses against Hepatitis C Virus Reveals Multiple Unpredicted Specificities

    OpenAIRE

    Lauer, Georg M.; Ouchi, Kei; Chung, Raymond T.; Nguyen, Tam N.; Day, Cheryl L.; Purkis, Deborah R.; Reiser, Markus; Kim, Arthur Y.; Lucas, Michaela; Klenerman, Paul; Walker, Bruce D.

    2002-01-01

    The hepatitis C virus (HCV)-specific CD8+-T-cell response is thought to play a critical role in HCV infection. Studies of these responses have largely relied on the analysis of a small number of previously described or predicted HCV epitopes, mostly restricted by HLA A2. In order to determine the actual breadth and magnitude of CD8+-T-cell responses in the context of diverse HLA class I alleles, we performed a comprehensive analysis of responses to all expressed HCV proteins. By using a panel...

  4. Triangulated Proxy Reporting: a technique for improving how communication partners come to know people with severe cognitive impairment.

    Science.gov (United States)

    Lyons, Gordon; De Bortoli, Tania; Arthur-Kelly, Michael

    2017-09-01

    This paper explains and demonstrates the pilot application of Triangulated Proxy Reporting (TPR); a practical technique for enhancing communication around people who have severe cognitive impairment (SCI). An introduction explains SCI and how this impacts on communication; and consequently on quality of care and quality of life. This is followed by an explanation of TPR and its origins in triangulation research techniques. An illustrative vignette explicates its utility and value in a group home for a resident with profound multiple disabilities. The Discussion and Conclusion sections propose the wider application of TPR for different cohorts of people with SCIs, their communication partners and service providers. TPR presents as a practical technique for enhancing communication interactions with people who have SCI. The paper demonstrates the potential of the technique for improving engagement amongst those with profound multiple disabilities, severe acquired brain injury and advanced dementia and their partners in and across different care settings. Implications for Rehabilitation Triangulated Proxy Reporting (TPR) shows potential to improve communications between people with severe cognitive impairments and their communication partners. TPR can lead to improved quality of care and quality of life for people with profound multiple disabilities, very advanced dementia and severe acquired brain injury, who otherwise are very difficult to support. TPR is a relatively simple and inexpensive technique that service providers can incorporate into practice to improving communications between clients with severe cognitive impairments, their carers and other support professionals.

  5. Starspot variability as an X-ray radiation proxy

    Science.gov (United States)

    Arkhypov, Oleksiy V.; Khodachenko, Maxim L.; Lammer, Helmut; Güdel, Manuel; Lüftinger, Teresa; Johnstone, Colin P.

    2018-05-01

    Stellar X-ray emission plays an important role in the study of exoplanets as a proxy for stellar winds and as a basis for the prediction of extreme ultraviolet (EUV) flux, unavailable for direct measurements, which in their turn are important factors for the mass-loss of planetary atmospheres. Unfortunately, the detection thresholds limit the number of stars with the directly measured X-ray fluxes. At the same time, the known connection between the sunspots and X-ray sources allows using of the starspot variability as an accessible proxy for the stellar X-ray emission. To realize this approach, we analysed the light curves of 1729 main-sequence stars with rotation periods 0.5 X-ray to bolometric luminosity ratio Rx. As a result, the regressions for stellar X-ray luminosity Lx(P, Teff) and its related EUV analogue LEUV were obtained for the main-sequence stars. It was shown that these regressions allow prediction of average (over the considered stars) values of log (Lx) and log (LEUV) with typical errors of 0.26 and 0.22 dex, respectively. This, however, does not include the activity variations in particular stars related to their individual magnetic activity cycles.

  6. Attribute-Based Proxy Re-Encryption with Keyword Search

    Science.gov (United States)

    Shi, Yanfeng; Liu, Jiqiang; Han, Zhen; Zheng, Qingji; Zhang, Rui; Qiu, Shuo

    2014-01-01

    Keyword search on encrypted data allows one to issue the search token and conduct search operations on encrypted data while still preserving keyword privacy. In the present paper, we consider the keyword search problem further and introduce a novel notion called attribute-based proxy re-encryption with keyword search (), which introduces a promising feature: In addition to supporting keyword search on encrypted data, it enables data owners to delegate the keyword search capability to some other data users complying with the specific access control policy. To be specific, allows (i) the data owner to outsource his encrypted data to the cloud and then ask the cloud to conduct keyword search on outsourced encrypted data with the given search token, and (ii) the data owner to delegate other data users keyword search capability in the fine-grained access control manner through allowing the cloud to re-encrypted stored encrypted data with a re-encrypted data (embedding with some form of access control policy). We formalize the syntax and security definitions for , and propose two concrete constructions for : key-policy and ciphertext-policy . In the nutshell, our constructions can be treated as the integration of technologies in the fields of attribute-based cryptography and proxy re-encryption cryptography. PMID:25549257

  7. Attribute-based proxy re-encryption with keyword search.

    Science.gov (United States)

    Shi, Yanfeng; Liu, Jiqiang; Han, Zhen; Zheng, Qingji; Zhang, Rui; Qiu, Shuo

    2014-01-01

    Keyword search on encrypted data allows one to issue the search token and conduct search operations on encrypted data while still preserving keyword privacy. In the present paper, we consider the keyword search problem further and introduce a novel notion called attribute-based proxy re-encryption with keyword search (ABRKS), which introduces a promising feature: In addition to supporting keyword search on encrypted data, it enables data owners to delegate the keyword search capability to some other data users complying with the specific access control policy. To be specific, ABRKS allows (i) the data owner to outsource his encrypted data to the cloud and then ask the cloud to conduct keyword search on outsourced encrypted data with the given search token, and (ii) the data owner to delegate other data users keyword search capability in the fine-grained access control manner through allowing the cloud to re-encrypted stored encrypted data with a re-encrypted data (embedding with some form of access control policy). We formalize the syntax and security definitions for ABRKS, and propose two concrete constructions for ABRKS: key-policy ABRKS and ciphertext-policy ABRKS. In the nutshell, our constructions can be treated as the integration of technologies in the fields of attribute-based cryptography and proxy re-encryption cryptography.

  8. 76 FR 33155 - Safety Zones; Multiple Firework Displays in Captain of the Port, Puget Sound Area of Responsibility

    Science.gov (United States)

    2011-06-08

    ... Environmental Health Risks and Safety Risks. This rule is not an economically significant rule and does not create an environmental risk to health or risk to safety that may disproportionately affect children...-AA00 Safety Zones; Multiple Firework Displays in Captain of the Port, Puget Sound Area of...

  9. The Multiple-Choice Model: Some Solutions for Estimation of Parameters in the Presence of Omitted Responses

    Science.gov (United States)

    Abad, Francisco J.; Olea, Julio; Ponsoda, Vicente

    2009-01-01

    This article deals with some of the problems that have hindered the application of Samejima's and Thissen and Steinberg's multiple-choice models: (a) parameter estimation difficulties owing to the large number of parameters involved, (b) parameter identifiability problems in the Thissen and Steinberg model, and (c) their treatment of omitted…

  10. A new method for synthesizing radiation dose-response data from multiple trials applied to prostate cancer

    DEFF Research Database (Denmark)

    Diez, Patricia; Vogelius, Ivan S; Bentzen, Søren M

    2010-01-01

    A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high).......A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high)....

  11. Mercury as a proxy for volcanic activity during extreme environmental turnover

    DEFF Research Database (Denmark)

    Sial, A.N.; Lacerda, L.D.; Ferreira, V.P.

    2013-01-01

    (KTB) and was, perhaps, responsible for dramatic climatic changes and decrease in biodiversity and mass extinction. We have used Hg concentrations as a proxy for volcanic activity and atmospheric Hg and CO2 buildup across the KTB at three localities. In the Salta Basin, Argentina, Hg contents display...... close to) this transition. At Stevns Klint, Denmark, Hg contents reached almost 250 ng·g− 1 within a 5 cm thick-clay layer, the Fiskeler Member (‘Fish Clay’) that comprises the KTB. Some co-variation between Hg and Al2O3 contents has been observed in all of the studied sections across the KTB......, suggesting that Hg is probably adsorbed onto clays. Thermo-desorption experiments in selected samples from the Yacoraite Formation showed Hg+ 2 as the major species present, which is in agreement with a volcanic origin. Combined Hg and C-isotope chemostratigraphy may become a powerful tool for the eventual...

  12. A DNA vaccine encoding multiple HIV CD4 epitopes elicits vigorous polyfunctional, long-lived CD4+ and CD8+ T cell responses.

    Directory of Open Access Journals (Sweden)

    Daniela Santoro Rosa

    Full Text Available T-cell based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4(+ T cells are important for the generation and maintenance of functional CD8(+ cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18, capable of eliciting broad CD4(+ T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4(+/CD8(+ T cell responses, and 8/18 vaccine-encoded peptides were recognized. In addition, HIVBr18 immunization was able to induce polyfunctional CD4(+ and CD8(+ T cells that proliferate and produce any two cytokines (IFNγ/TNFα, IFNγ/IL-2 or TNFα/IL-2 simultaneously in response to HIV-1 peptides. For CD4(+ T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFNγ/TNFα/IL-2. The vaccine also generated long-lived central and effector memory CD4(+ T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4(+ T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8(+ T cells and antibody responses- elicited by other HIV immunogens.

  13. Diatoms as Proxies for Abrupt Events in the Hudson River Estuary

    Science.gov (United States)

    Skorski, W.; Abbott, D. H.; Recasens, C.; Breger, D. L.

    2014-12-01

    The Hudson River estuary has been subject to many abrupt events throughout its history including hurricanes, droughts and pluvials. Hurricanes in particular are rare, discrete events that if fingerprinted can be used to develop better age models for Hudson River sediments. Proxies use observed physical characteristics or biological assemblages (e.g. diatom and foraminiferal assemblages) as tools to reconstruct past conditions prior to the modern instrumental record. Using a sediment core taken from the Hudson River (CDO2-29A), in New York City, drought and pluvial layers were selected based on Cs-137 dating while hurricane layers were determined from occurrences of tropical to subtropical foraminifera. Contrary to previous studies (Weaver, 1970, Weiss et al, 1978), more than sixty different diatom species have been identified using a scanning electron microscope (SEM). Cosmopolitan, hurricane and drought assemblages have begun to be identified after observing multiple layers (Table 1). Tropical foraminifera dominated by Globigerinoides ruber pink were also found in a hurricane layer that we infer was deposited during Hurricane Belle in 1976. More diatom abundance analyses and cataloged SEM pictures will provide further insight into these proxies. Table 1 Diatom Genera and Species Environment Clarification Cyclotella caspia Planktonic, marine-brackish Cosmopolitan Karayevia clevei Freshwater Cosmopolitan Melosira sp Planktonic, marine Cosmopolitan Thalassiosira sp Marine, brackish Cosmopolitan Staurosirella leptostauron Benthic, freshwater Cosmopolitan Actinoptychus senarius Planktonic or benthic, freshwater to brackish Hurricane and pluvial layers Amphora aff. sp Benthic, marine or freshwater Hurricane layers only Nitzschia sp Benthic, marine or freshwater Hurricane layers only Gomphonema sp Freshwater Hurricane layers only Surirella sp Marine-brackish Drought layer only Triceratium sp Marine Drought layer only Other Genera and species Environment Clarification

  14. SOLAR CYCLE PROPAGATION, MEMORY, AND PREDICTION: INSIGHTS FROM A CENTURY OF MAGNETIC PROXIES

    Energy Technology Data Exchange (ETDEWEB)

    Munoz-Jaramillo, Andres; DeLuca, Edward E. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Dasi-Espuig, Maria [Max-Planck-Institut fuer Sonnensystemforschung, D-37191 Katlenburg-Lindau (Germany); Balmaceda, Laura A., E-mail: amunoz@cfa.harvard.edu, E-mail: edeluca@cfa.harvard.edu, E-mail: dasi@mps.mpg.de, E-mail: lbalmaceda@icate-conicet.gob.ar [Institute for Astronomical, Terrestrial and Space Sciences (ICATE-CONICET), San Juan (Argentina)

    2013-04-20

    The solar cycle and its associated magnetic activity are the main drivers behind changes in the interplanetary environment and Earth's upper atmosphere (commonly referred to as space weather). These changes have a direct impact on the lifetime of space-based assets and can create hazards to astronauts in space. In recent years there has been an effort to develop accurate solar cycle predictions (with aims at predicting the long-term evolution of space weather), leading to nearly a hundred widely spread predictions for the amplitude of solar cycle 24. A major contributor to the disagreement is the lack of direct long-term databases covering different components of the solar magnetic field (toroidal versus poloidal). Here, we use sunspot area and polar faculae measurements spanning a full century (as our toroidal and poloidal field proxies) to study solar cycle propagation, memory, and prediction. Our results substantiate predictions based on the polar magnetic fields, whereas we find sunspot area to be uncorrelated with cycle amplitude unless multiplied by area-weighted average tilt. This suggests that the joint assimilation of tilt and sunspot area is a better choice (with aims to cycle prediction) than sunspot area alone, and adds to the evidence in favor of active region emergence and decay as the main mechanism of poloidal field generation (i.e., the Babcock-Leighton mechanism). Finally, by looking at the correlation between our poloidal and toroidal proxies across multiple cycles, we find solar cycle memory to be limited to only one cycle.

  15. Evaluation of Magnetic Resonance Imaging Responsiveness in Active Psoriatic Arthritis at Multiple Timepoints during the First 12 Weeks of Antitumor Necrosis Factor Therapy.

    Science.gov (United States)

    Feletar, Marie; Hall, Stephen; Bird, Paul

    2016-01-01

    To assess the responsiveness of high- and low-field extremity magnetic resonance imaging (MRI) variables at multiple timepoints in the first 12 weeks post-antitumor necrosis factor (anti-TNF) therapy initiation in patients with psoriatic arthritis (PsA) and active dactylitis. Twelve patients with active PsA and clinical evidence of dactylitis involving at least 1 digit were recruited. Patients underwent sequential high-field conventional (1.5 Tesla) and extremity low-field MRI (0.2 Tesla) of the affected hand or foot, pre- and postgadolinium at baseline (pre-TNF), 2 weeks (post-TNF), 6 weeks, and 12 weeks. A blinded observer scored all images on 2 occasions using the PsA MRI scoring system. Eleven patients completed the study, but only 6 patients completed all high-field and low-field MRI assessments. MRI scores demonstrated rapid response to TNF inhibition with score reduction in tenosynovitis, synovitis, and osteitis at 2 weeks. Intraobserver reliability was good to excellent for all variables. High-field MRI demonstrated greater sensitivity to tenosynovitis, synovitis, and osteitis and greater responsiveness to change posttreatment. Treatment responses were maintained to 12 weeks. This study demonstrates the use of MRI in detecting early response to biologic therapy. MRI variables of tenosynovitis, synovitis, and osteitis demonstrated responsiveness posttherapy with high-field scores more responsive to change than low-field scores.

  16. Is response to fire influenced by dietary specialization and mobility? A comparative study with multiple animal assemblages.

    Directory of Open Access Journals (Sweden)

    Xavier Santos

    Full Text Available Fire is a major agent involved in landscape transformation and an indirect cause of changes in species composition. Responses to fire may vary greatly depending on life histories and functional traits of species. We have examined the taxonomic and functional responses to fire of eight taxonomic animal groups displaying a gradient of dietary and mobility patterns: Gastropoda, Heteroptera, Formicidae, Coleoptera, Araneae, Orthoptera, Reptilia and Aves. The fieldwork was conducted in a Mediterranean protected area on 3 sites (one unburnt and two burnt with different postfire management practices with five replicates per site. We collected information from 4606 specimens from 274 animal species. Similarity in species composition and abundance between areas was measured by the Bray-Curtis index and ANOSIM, and comparisons between animal and plant responses by Mantel tests. We analyze whether groups with the highest percentage of omnivorous species, these species being more generalist in their dietary habits, show weak responses to fire (i.e. more similarity between burnt and unburnt areas, and independent responses to changes in vegetation. We also explore how mobility, i.e. dispersal ability, influences responses to fire. Our results demonstrate that differences in species composition and abundance between burnt and unburnt areas differed among groups. We found a tendency towards presenting lower differences between areas for groups with higher percentages of omnivorous species. Moreover, taxa with a higher percentage of omnivorous species had significantly more independent responses of changes in vegetation. High- (e.g. Aves and low-mobility (e.g. Gastropoda groups had the strongest responses to fire (higher R scores of the ANOSIM; however, we failed to find a significant general pattern with all the groups according to their mobility. Our results partially support the idea that functional traits underlie the response of organisms to environmental

  17. Is response to fire influenced by dietary specialization and mobility? A comparative study with multiple animal assemblages.

    Science.gov (United States)

    Santos, Xavier; Mateos, Eduardo; Bros, Vicenç; Brotons, Lluís; De Mas, Eva; Herraiz, Joan A; Herrando, Sergi; Miño, Àngel; Olmo-Vidal, Josep M; Quesada, Javier; Ribes, Jordi; Sabaté, Santiago; Sauras-Yera, Teresa; Serra, Antoni; Vallejo, V Ramón; Viñolas, Amador

    2014-01-01

    Fire is a major agent involved in landscape transformation and an indirect cause of changes in species composition. Responses to fire may vary greatly depending on life histories and functional traits of species. We have examined the taxonomic and functional responses to fire of eight taxonomic animal groups displaying a gradient of dietary and mobility patterns: Gastropoda, Heteroptera, Formicidae, Coleoptera, Araneae, Orthoptera, Reptilia and Aves. The fieldwork was conducted in a Mediterranean protected area on 3 sites (one unburnt and two burnt with different postfire management practices) with five replicates per site. We collected information from 4606 specimens from 274 animal species. Similarity in species composition and abundance between areas was measured by the Bray-Curtis index and ANOSIM, and comparisons between animal and plant responses by Mantel tests. We analyze whether groups with the highest percentage of omnivorous species, these species being more generalist in their dietary habits, show weak responses to fire (i.e. more similarity between burnt and unburnt areas), and independent responses to changes in vegetation. We also explore how mobility, i.e. dispersal ability, influences responses to fire. Our results demonstrate that differences in species composition and abundance between burnt and unburnt areas differed among groups. We found a tendency towards presenting lower differences between areas for groups with higher percentages of omnivorous species. Moreover, taxa with a higher percentage of omnivorous species had significantly more independent responses of changes in vegetation. High- (e.g. Aves) and low-mobility (e.g. Gastropoda) groups had the strongest responses to fire (higher R scores of the ANOSIM); however, we failed to find a significant general pattern with all the groups according to their mobility. Our results partially support the idea that functional traits underlie the response of organisms to environmental changes caused

  18. A Strategy for a Parametric Flood Insurance Using Proxies

    Science.gov (United States)

    Haraguchi, M.; Lall, U.

    2017-12-01

    Traditionally, the design of flood control infrastructure and flood plain zoning require the estimation of return periods, which have been calculated by river hydraulic models with rainfall-runoff models. However, this multi-step modeling process leads to significant uncertainty to assess inundation. In addition, land use change and changing climate alter the potential losses, as well as make the modeling results obsolete. For these reasons, there is a strong need to create parametric indexes for the financial risk transfer for large flood events, to enable rapid response and recovery. Hence, this study examines the possibility of developing a parametric flood index at the national or regional level in Asia, which can be quickly mobilized after catastrophic floods. Specifically, we compare a single trigger based on rainfall index with multiple triggers using rainfall and streamflow indices by conducting case studies in Bangladesh and Thailand. The proposed methodology is 1) selecting suitable indices of rainfall and streamflow (if available), 2) identifying trigger levels for specified return periods for losses using stepwise and logistic regressions, 3) measuring the performance of indices, and 4) deriving return periods of selected windows and trigger levels. Based on the methodology, actual trigger levels were identified for Bangladesh and Thailand. Models based on multiple triggers reduced basis risks, an inherent problem in an index insurance. The proposed parametric flood index can be applied to countries with similar geographic and meteorological characteristics, and serve as a promising method for ex-ante risk financing for developing countries. This work is intended to be a preliminary work supporting future work on pricing risk transfer mechanisms in ex-ante risk finance.

  19. Impact of the demand for 'proxy assent' on recruitment to a randomised controlled trial of vaccination testing in care homes.

    Science.gov (United States)

    Whelan, Paul James; Walwyn, Rebecca; Gaughran, Fiona; Macdonald, Alastair

    2013-01-01

    Legal frameworks are in place to protect those who lack the capacity to consent to research, such as the Mental Capacity Act in the UK. Assent is sought instead from a proxy, usually a relative. However, the same legislation may, perversely, affect the welfare of those who lack capacity and of others by hindering the process of recruitment into otherwise potentially beneficial research. In addition, the onus of responsibility is moved from those who know most about the study (ie, the scientific community) to those who know less (the proxies). In this paper, we describe the characteristics of a sample at different stages of the recruitment process of an influenza vaccine-based randomised control trial in elderly care home residents (the FEVER study). 62% (602/968) of potential subjects lacked capacity but only 29% (80/277) of those actually randomised. Older age, being female and living in an Elderly Mentally Ill care home were the only variables associated with lacking capacity. Considering this was a study based in a care home setting where the prevalence of dementia approximates 80%, the trial, like many others, was thus significantly biased. We believe that difficulties seeking proxy assent contributed significantly to this problem. Further thought should be given to how assent to enter research for those who lack capacity should be provided, and we suggest avenues for further discussion such as independent risk/benefit expert panels.

  20. Carbohydrates and phenols as quantitative molecular vegetation proxies in peats

    Science.gov (United States)

    Kaiser, K.; Benner, R. H.

    2012-12-01

    Vegetation in peatlands is intricately linked to local environmental conditions and climate. Here we use chemical analyses of carbohydrates and phenols to reconstruct paleovegetation in peat cores collected from 56.8°N (SIB04), 58.4°N (SIB06), 63.8°N (G137) and 66.5°N (E113) in the Western Siberian Lowland. Lignin phenols (vanillyl and syringyl phenols) were sensitive biomarkers for vascular plant contributions and provided additional information on the relative contributions of angiosperm and gymnosperm plants. Specific neutral sugar compositions allowed identification of sphagnum mosses, sedges (Cyperaceae) and lichens. Hydroxyphenols released by CuO oxidation were useful tracers of sphagnum moss contributions. The three independent molecular proxies were calibrated with a diverse group of peat-forming plants to yield quantitative estimates (%C) of vascular plant, sphagnum moss and lichen contributions in peat core samples. Correlation analysis indicated the three molecular proxies produced fairly similar results for paleovegetation compositions, generally within the error interval of each approach (≤26%). The lignin-based method generally lead to higher estimates of vascular plant vegetation. Several significant deviations were also observed due to different reactivities of carbohydrate and phenolic polymers during peat decomposition. Rapid vegetation changes on timescales of 50-200 years were observed in the southern cores SIB04 and SIB06 over the last 2000 years. Vanillyl and syringyl phenol ratios indicated these vegetation changes were largely due to varying inputs of angiosperm and gymnosperm plants. The northern permafrost cores G137 and E113 showed a more stable development. Lichens briefly replaced sphagnum mosses and vascular plants in both of these cores. Shifts in vegetation did not correlate well with Northern hemisphere climate variability over the last 2000 years. This suggested that direct climate forcing of peatland dynamics was overridden

  1. The response of amino acid cycling to global change across multiple biomes: Feedbacks on soil nitrogen availability

    Science.gov (United States)

    Brzostek, E. R.; Finzi, A. C.

    2010-12-01

    The cycling of organic nitrogen (N) in soil links soil organic matter decomposition to ecosystem productivity. Amino acids are a key pool of organic N in the soil, whose cycling is sensitive to alterations in microbial demand for carbon and N. Further, the amino acids released from the breakdown of protein by proteolytic enzymes are an important source of N that supports terrestrial productivity. The objective of this study was to measure changes in amino acid cycling in response to experimental alterations of precipitation and temperature in twelve global change experiments during the 2009 growing season. The study sites ranged from arctic tundra to xeric grasslands. The treatments experimentally increased temperature, increased or decreased precipitation, or some combination of both factors. The response of amino acid cycling to temperature and precipitation manipulations tended to be site specific, but the responses could be placed into a common framework. Changes in soil moisture drove a large response in amino acid cycling. Precipitation augmentation in xeric and mesic sites increased both amino acid pool sizes and production. However, treatments that decreased precipitation drove decreases in amino acid cycling in xeric sites, but led to increases in amino acid cycling in more mesic sites. Across sites, the response to soil warming was horizon specific. Amino acid cycling in organic rich horizons responded positively to warming, while negative responses were exhibited in lower mineral soil horizons. The variable response likely reflects a higher availability of protein substrate to sustain high rates of proteolytic enzyme activity in organic rich horizons. Overall, these results suggest that soil moisture and the availability of protein substrate may be important factors that mediate the response of amino acid cycling to predicted increases in soil temperatures.

  2. The combination of energy-dependent internal adaptation mechanisms and external factors enables Listeria monocytogenes to express a strong starvation survival response during multiple-nutrient starvation.

    Science.gov (United States)

    Lungu, Bwalya; Saldivar, Joshua C; Story, Robert; Ricke, Steven C; Johnson, Michael G

    2010-05-01

    The goal of this study was to characterize the starvation survival response (SSR) of a wild-type Listeria monocytogenes 10403S and an isogenic DeltasigB mutant strain during multiple-nutrient starvation conditions over 28 days. This study examined the effects of inhibitors of protein synthesis, the proton motive force, substrate level phosphorylation, and oxidative phosphorylation on the SSR of L. monocytogenes 10403S and a DeltasigB mutant during multiple-nutrient starvation. The effects of starvation buffer changes on viability were also examined. During multiple-nutrient starvation, both strains expressed a strong SSR, suggesting that L. monocytogenes possesses SigB-independent mechanism(s) for survival during multiple-nutrient starvation. Neither strain was able to express an SSR following starvation buffer changes, indicating that the nutrients/factors present in the starvation buffer could be a source of energy for cell maintenance and survival. Neither the wild-type nor the DeltasigB mutant strain was able to elicit an SSR when exposed to the protein synthesis inhibitor chloramphenicol within the first 4 h of starvation. However, both strains expressed an SSR when exposed to chloramphenicol after 6 h or more of starvation, suggesting that the majority of proteins required to elicit an effective SSR in L. monocytogenes are likely produced somewhere between 4 and 6 h of starvation. The varying SSRs of both strains to the different metabolic inhibitors under aerobic or anaerobic conditions suggested that (1) energy derived from the proton motive force is important for an effective SSR, (2) L. monocytogenes utilizes an anaerobic electron transport during multiple-nutrient starvation conditions, and (3) the glycolytic pathway is an important energy source during multiple-nutrient starvation when oxygen is available, and less important under anaerobic conditions. Collectively, the data suggest that the combination of energy-dependent internal adaptation mechanisms

  3. Stable carbon isotope fractionation in pollen of Atlas cedar: first steps towards a new palaeoecological proxy for Northwest Africa

    Science.gov (United States)

    Bell, Benjamin; Fletcher, William; Ryan, Peter; Grant, Helen; Ilmen, Rachid

    2016-04-01

    Analysis of stable carbon isotopes can provide information on climate and the environmental conditions at different growth stages of the plant, both past and present. Carbon isotope discrimination in plant tissue is already well understood, and can be used as a drought stress indicator for semi-arid regions. Stable carbon isotope ratios measured directly on pollen provides the potential for the development of long-term environmental proxies (spanning thousands of years), as pollen is well preserved in the environment. Atlas Cedar (Cedrus atlantica Endl. Manetti ex Carrière), is an ideal test case to develop a pollen stable carbon isotope proxy. The tree grows across a wide altitudinal and climatic range and is extremely sensitive to moisture availability. The pollen is abundant, and easily identifiable to the species level in pollen analysis because different cedar species are geographically confined to different regions of the world. In 2015 we sampled 76 individual cedar trees across latitudinal, altitudinal and environmental gradients, highly focused on the Middle Atlas region of Morocco, with 25 additional samples from botanical gardens across Europe and the US to extend these gradients. Here, we report new stable carbon isotope data from pollen, leaf and stem wood from these samples with a view to assessing and quantifying species-specific fractionation effects associated with pollen production. The isotopic response of individual trees at local and wider geographical scales to altitude and climatic conditions is presented. This research forms part of an ongoing PhD project working to develop and calibrate a modern carbon isotope proxy in Atlas cedar pollen, which can ultimately be applied to fossil sequences and complement existing multi-proxy records (e.g. pollen analysis in lake sediments, tree-rings).

  4. Dynamics of anti-MSP3 and Pfs230 antibody responses and multiplicity of infection in asymptomatic children from southern Ghana

    DEFF Research Database (Denmark)

    Amoah, Linda E; Acquah, Festus K; Ayanful-Torgby, Ruth

    2018-01-01

    BACKGROUND: During a Plasmodium infection, exposure of human host immune cells to both the asexual and the sexual stages of the parasite elicit immune responses. These responses may be protective and prevent the development of high parasitaemia and its associated clinical symptoms, or block...... the transmission of malaria to an uninfected person. This study aimed at examining the dynamics of naturally acquired immune responses against the asexual and sexual forms of Plasmodium falciparum as well as assessing differences in the multiplicity of infection (MOI) in asymptomatic Ghanaian children living...... 2015. Filter paper blood blots (DBS) as well as thick and thin blood smears were made from finger-pricked blood at each visit. Plasmodium falciparum parasite prevalence was determined by microscopy and PCR. Serum eluted from the DBS were used to assess anti-Pfs230 (sexual stage) and anti-MSP3 (asexual...

  5. Response to Therapeutic Plasma Exchange as a Rescue Treatment in Clinically Isolated Syndromes and Acute Worsening of Multiple Sclerosis: A Retrospective Analysis of 90 Patients.

    Directory of Open Access Journals (Sweden)

    Johannes Ehler

    Full Text Available Experience with therapeutic plasma exchange (TPE for acute relapses in clinically isolated syndrome (CIS or multiple sclerosis (MS patients has been derived from small and inhomogeneous patient populations so far. In the present study, we retrospectively evaluated features associated with TPE response in a larger cohort of CIS and MS patients with acute worsening of disease.Ninety CIS and MS patients with acute relapses or acute worsening of symptoms were firstly treated with TPE. The population consisted of 62 women and 28 men with a median age of 38 years (range 18-69 years.Primary endpoint was the clinical response to TPE, focused on the functional improvement of the target neurologic deficit. Secondary endpoint was an improvement in expanded disability status scale (EDSS scoring.A clinical response to TPE was observed in 65 out of 90 patients (72.2%, with marked improvement in 18 (20.0% and moderate improvement in 47 out of 90 patients (52.2%. The median EDSS was reduced from 3.75 before to 3.0 after TPE (p = 0.001. Response to TPE was significantly more frequent in patients with relapsing courses of disease (CIS, RR-MS, p = 0.001, no disease modifying drugs (p = 0.017, gadolinium-positive (Gd+ MRI lesions (p = 0.001 and EDSS ≤ 5.0 before TPE (p = 0.014. In the multiple logistic regression analysis only the detection of Gd+ MRI lesions was significantly altered (p = 0.004.Clinical response to TPE was achieved in the majority of our patients. We identified clinical and diagnostic features in CIS and MS relapses that might be helpful to identify patients responding to TPE. Gd+ MRI lesions before treatment were the best predictor of the response to TPE in our cohort.

  6. STRONTIUM DISTRIBUTION IN UPPER DEVONIAN CONODONT ELEMENTS: A PALAEOBIOLOGICAL PROXY

    Directory of Open Access Journals (Sweden)

    ANDREY V. ZHURAVLEV

    2017-04-01

    Full Text Available Conodonts are an extinct group of marine animals possessing debated affinities. The conodont elements are composed of calcium phosphate [apatite (CaF] and collagen-like proteins. Distribution of Sr in the bioapatite of albid, lamellar and paralamellar tissues of some Upper Devonian conodont element crowns from NW Russia was studied by microprobe. The calcium phosphate of the lamellar and paralamellar tissues demonstrates periodical oscillation of Sr contents across the lamellae (0.4-0.5 wt% in the outer part of lamella, and 0.2 wt% in the inner part. The albid tissue contains Sr of less than 0.4 wt%. It is suggested that oscillations of Sr concentrations reflect the periodic growth of the lamellae, and the average Ca/Sr ratio can be a proxy of the growth rate.

  7. Interactive images: Cuboid proxies for smart image manipulation

    KAUST Repository

    Zheng, Youyi

    2012-07-01

    Images are static and lack important depth information about the underlying 3D scenes. We introduce interactive images in the context of man-made environments wherein objects are simple and regular, share various non-local relations (e.g., coplanarity, parallelism, etc.), and are often repeated. Our interactive framework creates partial scene reconstructions based on cuboid-proxies with minimal user interaction. It subsequently allows a range of intuitive image edits mimicking real-world behavior, which are otherwise difficult to achieve. Effectively, the user simply provides high-level semantic hints, while our system ensures plausible operations by conforming to the extracted non-local relations. We demonstrate our system on a range of real-world images and validate the plausibility of the results using a user study. © 2012 ACM 0730-0301/2012/08-ART99.

  8. Towards a new paleotemperature proxy from reef coral occurrences.

    Science.gov (United States)

    Lauchstedt, Andreas; Pandolfi, John M; Kiessling, Wolfgang

    2017-09-05

    Global mean temperature is thought to have exceeded that of today during the last interglacial episode (LIG, ~ 125,000 yrs b.p.) but robust paleoclimate data are still rare in low latitudes. Occurrence data of tropical reef corals may provide new proxies of low latitude sea-surface temperatures. Using modern reef coral distributions we developed a geographically explicit model of sea surface temperatures. Applying this model to coral occurrence data of the LIG provides a latitudinal U-shaped pattern of temperature anomalies with cooler than modern temperatures around the equator and warmer subtropical climes. Our results agree with previously published estimates of LIG temperatures and suggest a poleward broadening of the habitable zone for reef corals during the LIG.

  9. The development of a fully-integrated immune response model (FIRM) simulator of the immune response through integration of multiple subset models.

    Science.gov (United States)

    Palsson, Sirus; Hickling, Timothy P; Bradshaw-Pierce, Erica L; Zager, Michael; Jooss, Karin; O'Brien, Peter J; Spilker, Mary E; Palsson, Bernhard O; Vicini, Paolo

    2013-09-28

    The complexity and multiscale nature of the mammalian immune response provides an excellent test bed for the potential of mathematical modeling and simulation to facilitate mechanistic understanding. Historically, mathematical models of the immune response focused on subsets of the immune system and/or specific aspects of the response. Mathematical models have been developed for the humoral side of the immune response, or for the cellular side, or for cytokine kinetics, but rarely have they been proposed to encompass the overall system complexity. We propose here a framework for integration of subset models, based on a system biology approach. A dynamic simulator, the Fully-integrated Immune Response Model (FIRM), was built in a stepwise fashion by integrating published subset models and adding novel features. The approach used to build the model includes the formulation of the network of interacting species and the subsequent introduction of rate laws to describe each biological process. The resulting model represents a multi-organ structure, comprised of the target organ where the immune response takes place, circulating blood, lymphoid T, and lymphoid B tissue. The cell types accounted for include macrophages, a few T-cell lineages (cytotoxic, regulatory, helper 1, and helper 2), and B-cell activation to plasma cells. Four different cytokines were accounted for: IFN-γ, IL-4, IL-10 and IL-12. In addition, generic inflammatory signals are used to represent the kinetics of IL-1, IL-2, and TGF-β. Cell recruitment, differentiation, replication, apoptosis and migration are described as appropriate for the different cell types. The model is a hybrid structure containing information from several mammalian species. The structure of the network was built to be physiologically and biochemically consistent. Rate laws for all the cellular fate processes, growth factor production rates and half-lives, together with antibody production rates and half-lives, are provided. The

  10. Step responses of a torsional system with multiple clearances: Study of vibro-impact phenomenon using experimental and computational methods

    Science.gov (United States)

    Oruganti, Pradeep Sharma; Krak, Michael D.; Singh, Rajendra

    2018-01-01

    Recently Krak and Singh (2017) proposed a scientific experiment that examined vibro-impacts in a torsional system under a step down excitation and provided preliminary measurements and limited non-linear model studies. A major goal of this article is to extend the prior work with a focus on the examination of vibro-impact phenomena observed under step responses in a torsional system with one, two or three controlled clearances. First, new measurements are made at several locations with a higher sampling frequency. Measured angular accelerations are examined in both time and time-frequency domains. Minimal order non-linear models of the experiment are successfully constructed, using piecewise linear stiffness and Coulomb friction elements; eight cases of the generic system are examined though only three are experimentally studied. Measured and predicted responses for single and dual clearance configurations exhibit double sided impacts and time varying periods suggest softening trends under the step down torque. Non-linear models are experimentally validated by comparing results with new measurements and with those previously reported. Several metrics are utilized to quantify and compare the measured and predicted responses (including peak to peak accelerations). Eigensolutions and step responses of the corresponding linearized models are utilized to better understand the nature of the non-linear dynamic system. Finally, the effect of step amplitude on the non-linear responses is examined for several configurations, and hardening trends are observed in the torsional system with three clearances.

  11. Association between response rates and survival outcomes in patients with newly diagnosed multiple myeloma. A systematic review and meta-regression analysis.

    Science.gov (United States)

    Mainou, Maria; Madenidou, Anastasia-Vasiliki; Liakos, Aris; Paschos, Paschalis; Karagiannis, Thomas; Bekiari, Eleni; Vlachaki, Efthymia; Wang, Zhen; Murad, Mohammad Hassan; Kumar, Shaji; Tsapas, Apostolos

    2017-06-01

    We performed a systematic review and meta-regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM). Response outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression-free survival (PFS). We used random-effect meta-regression models and conducted sensitivity analyses based on definition of CR and study quality. Seventy-two trials were included in the systematic review, 63 of which contributed data in meta-regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] -0.06, 0.10), in patients undergoing ASCT (-.11, 95% CI -0.44, 0.22) and in trials comparing ASCT with non-ASCT patients (.04, 95% CI -0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results. This meta-regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Neutralizing antibodies explain the poor clinical response to Interferon beta in a small proportion of patients with Multiple Sclerosis: a retrospective study

    Directory of Open Access Journals (Sweden)

    Cefaro Luca

    2009-10-01

    Full Text Available Abstract Background Neutralizing antibodies (NAbs against Interferon beta (IFNβ are reported to be associated with poor clinical response to therapy in multiple sclerosis (MS patients. We aimed to quantify the contribution of NAbs to the sub-optimal response of IFNβ treatment. Methods We studied the prevalence of NAbs in MS patients grouped according to their clinical response to IFNβ during the treatment period. Patients were classified as: group A, developing ≥ 1 relapse after the first 6 months of therapy; group B, exhibiting confirmed disability progression after the first 6 months of therapy, with or without superimposed relapses; group C, presenting a stable disease course during therapy. A cytopathic effect assay tested the presence of NAbs in a cohort of ambulatory MS patients treated with one of the available IFNβ formulations for at least one year. NAbs positivity was defined as NAbs titre ≥ 20 TRU. Results Seventeen patients (12.1% were NAbs positive. NAbs positivity correlated with poorer clinical response (p Conclusion The majority of patients with poor clinical response are NAbs negative suggesting that NAbs explains only partially the sub-optimal response to IFNβ.

  13. Pervasive gene expression responses to a fluctuating diet in Drosophila melanogaster: The importance of measuring multiple traits to decouple potential mediators of life span and reproduction.

    Science.gov (United States)

    Zandveld, Jelle; van den Heuvel, Joost; Mulder, Maarten; Brakefield, Paul M; Kirkwood, Thomas B L; Shanley, Daryl P; Zwaan, Bas J

    2017-11-01

    Phenotypic plasticity is an important concept in life-history evolution, and most organisms, including Drosophila melanogaster, show a plastic life-history response to diet. However, little is known about how these life-history responses are mediated. In this study, we compared adult female flies fed an alternating diet (yoyo flies) with flies fed a constant low (CL) or high (CH) diet and tested how whole genome expression was affected by these diet regimes and how the transcriptional responses related to different life-history traits. We showed that flies were able to respond quickly to diet fluctuations throughout life span by drastically changing their transcription. Importantly, by measuring the response of multiple life-history traits we were able to decouple groups of genes associated with life span or reproduction, life-history traits that often covary with a diet change. A coexpression network analysis uncovered which genes underpin the separate and shared regulation of these life-history traits. Our study provides essential insights to help unravel the genetic architecture mediating life-history responses to diet, and it shows that the flies' whole genome transcription response is highly plastic. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  14. Endoplasmic reticulum stress-responsive transcription factor ATF6α directs recruitment of the Mediator of RNA polymerase II transcription and multiple histone acetyltransferase complexes.

    Science.gov (United States)

    Sela, Dotan; Chen, Lu; Martin-Brown, Skylar; Washburn, Michael P; Florens, Laurence; Conaway, Joan Weliky; Conaway, Ronald C

    2012-06-29

    The basic leucine zipper transcription factor ATF6α functions as a master regulator of endoplasmic reticulum (ER) stress response genes. Previous studies have established that, in response to ER stress, ATF6α translocates to the nucleus and activates transcription of ER stress response genes upon binding sequence specifically to ER stress response enhancer elements in their promoters. In this study, we investigate the biochemical mechanism by which ATF6α activates transcription. By exploiting a combination of biochemical and multidimensional protein identification technology-based mass spectrometry approaches, we have obtained evidence that ATF6α functions at least in part by recruiting to the ER stress response enhancer elements of ER stress response genes a collection of RNA polymerase II coregulatory complexes, including the Mediator and multiple histone acetyltransferase complexes, among which are the Spt-Ada-Gcn5 acetyltransferase (SAGA) and Ada-Two-A-containing (ATAC) complexes. Our findings shed new light on the mechanism of action of ATF6α, and they outline a straightforward strategy for applying multidimensional protein identification technology mass spectrometry to determine which RNA polymerase II transcription factors and coregulators are recruited to promoters and other regulatory elements to control transcription.

  15. Soluble serum VCAM-1, whole blood mRNA expression and treatment response in natalizumab-treated multiple sclerosis

    DEFF Research Database (Denmark)

    Petersen, E R; Søndergaard, H B; Oturai, A B

    2016-01-01

    Background Natalizumab reduces disease activity in multiple sclerosis (MS). Natalizumab binds to the very late antigen-4 and inhibits vascular cell adhesion molecule-1 (VCAM-1)-mediated transmigration of immune cells across the blood-brain-barrier. This is associated with decreased serum...... levels of a panel of immunomarkers, associated with natalizumab-treatment, are not sensitive markers of MS disease activity. However, decreased expression of pro-inflammatory HLX1 and IL1B and increased expression of immunoregulatory EBI3 may indicate a less pathogenic immune activation status...

  16. The renal protective effect of angiotensin receptor blockers depends on intra-individual response variation in multiple risk markers

    DEFF Research Database (Denmark)

    Schievink, Bauke; de Zeeuw, Dick; Parving, Hans-Henrik

    2015-01-01

    , haemoglobin, cholesterol and uric acid after 6 months of losartan treatment were assessed in the RENAAL database. Improvement in predictive performance of renal outcomes (ESRD or doubling serum creatinine) for each individual using ARB-induced changes in all risk markers was assessed by the relative...... integrative discrimination index (RIDI). RESULTS: SBP response showed high variability (mean -5.7 mmHg, 5(th) to 95(th) percentile -36.5 to +24.0 mmHg) between individuals. Changes in off-target parameters also showed high variability between individuals. No congruency was observed between responses...

  17. Autoantigen La promotes efficient RNAi, antiviral response, and transposon silencing by facilitating multiple-turnover RISC catalysis.

    Science.gov (United States)

    Liu, Ying; Tan, Huiling; Tian, Hui; Liang, Chunyang; Chen, She; Liu, Qinghua

    2011-11-04

    The effector of RNA interference (RNAi) is the RNA-induced silencing complex (RISC). C3PO promotes the activation of RISC by degrading the Argonaute2 (Ago2)-nicked passenger strand of duplex siRNA. Active RISC is a multiple-turnover enzyme that uses the guide strand of siRNA to direct the Ago2-mediated sequence-specific cleavage of complementary mRNA. How this effector step of RNAi is regulated is currently unknown. Here, we used the human Ago2 minimal RISC system to purify Sjögren's syndrome antigen B (SSB)/autoantigen La as an activator of the RISC-mediated mRNA cleavage activity. Our reconstitution studies showed that La could promote multiple-turnover RISC catalysis by facilitating the release of cleaved mRNA from RISC. Moreover, we demonstrated that La was required for efficient RNAi, antiviral defense, and transposon silencing in vivo. Taken together, the findings of C3PO and La reveal a general concept that regulatory factors are required to remove Ago2-cleaved products to assemble or restore active RISC. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Development of the complex general linear model in the Fourier domain: application to fMRI multiple input-output evoked responses for single subjects.

    Science.gov (United States)

    Rio, Daniel E; Rawlings, Robert R; Woltz, Lawrence A; Gilman, Jodi; Hommer, Daniel W

    2013-01-01

    A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function.

  19. How entorhinal grid cells may learn multiple spatial scales from a dorsoventral gradient of cell response rates in a self-organizing map.

    Directory of Open Access Journals (Sweden)

    Stephen Grossberg

    Full Text Available Place cells in the hippocampus of higher mammals are critical for spatial navigation. Recent modeling clarifies how this may be achieved by how grid cells in the medial entorhinal cortex (MEC input to place cells. Grid cells exhibit hexagonal grid firing patterns across space in multiple spatial scales along the MEC dorsoventral axis. Signals from grid cells of multiple scales combine adaptively to activate place cells that represent much larger spaces than grid cells. But how do grid cells learn to fire at multiple positions that form a hexagonal grid, and with spatial scales that increase along the dorsoventral axis? In vitro recordings of medial entorhinal layer II stellate cells have revealed subthreshold membrane potential oscillations (MPOs whose temporal periods, and time constants of excitatory postsynaptic potentials (EPSPs, both increase along this axis. Slower (faster subthreshold MPOs and slower (faster EPSPs correlate with larger (smaller grid spacings and field widths. A self-organizing map neural model explains how the anatomical gradient of grid spatial scales can be learned by cells that respond more slowly along the gradient to their inputs from stripe cells of multiple scales, which perform linear velocity path integration. The model cells also exhibit MPO frequencies that covary with their response rates. The gradient in intrinsic rhythmicity is thus not compelling evidence for oscillatory interference as a mechanism of grid cell firing. A response rate gradient combined with input stripe cells that have normalized receptive fields can reproduce all known spatial and temporal properties of grid cells along the MEC dorsoventral axis. This spatial gradient mechanism is homologous to a gradient mechanism for temporal learning in the lateral entorhinal cortex and its hippocampal projections. Spatial and temporal representations may hereby arise from homologous mechanisms, thereby embodying a mechanistic "neural relativity" that

  20. P2X7 receptors regulate multiple types of membrane trafficking responses and non-classical secretion pathways.

    Science.gov (United States)

    Qu, Yan; Dubyak, George R

    2009-06-01

    Activation of the P2X7 receptor (P2X7R) triggers a remarkably diverse array of membrane trafficking responses in leukocytes and epithelial cells. These responses result in altered profiles of cell surface lipid and protein composition that can modulate the direct interactions of P2X7R-expressing cells with other cell types in the circulation, in blood vessels, at epithelial barriers, or within sites of immune and inflammatory activation. Additionally, these responses can result in the release of bioactive proteins, lipids, and large membrane complexes into extracellular compartments for remote communication between P2X7R-expressing cells and other cells that amplify or modulate inflammation, immunity, and responses to tissue damages. This review will discuss P2X7R-mediated effects on membrane composition and trafficking in the plasma membrane (PM) and intracellular organelles, as well as actions of P2X7R in controlling various modes of non-classical secretion. It will review P2X7R regulation of: (1) phosphatidylserine distribution in the PM outer leaflet; (2) shedding of PM surface proteins; (3) release of PM-derived microvesicles or microparticles; (4) PM blebbing; (5) cell-cell fusion resulting in formation of multinucleate cells; (6) phagosome maturation and fusion with lysosomes; (7) permeability of endosomes with internalized pathogen-associated molecular patterns; (8) permeability/integrity of mitochondria; (9) exocytosis of secretory lysosomes; and (10) release of exosomes from multivesicular bodies.

  1. catcher: A Software Program to Detect Answer Copying in Multiple-Choice Tests Based on Nominal Response Model

    Science.gov (United States)

    Kalender, Ilker

    2012-01-01

    catcher is a software program designed to compute the [omega] index, a common statistical index for the identification of collusions (cheating) among examinees taking an educational or psychological test. It requires (a) responses and (b) ability estimations of individuals, and (c) item parameters to make computations and outputs the results of…

  2. Mapping and characterization of positive and negative BOLD responses to visual stimulation in multiple brain regions at 7T

    NARCIS (Netherlands)

    Jorge, João; Figueiredo, Patrícia; Gruetter, Rolf; Van der Zwaag, W.

    External stimuli and tasks often elicit negative BOLD responses in various brain regions, and growing experimental evidence supports that these phenomena are functionally meaningful. In this work, the high sensitivity available at 7T was explored to map and characterize both positive (PBRs) and

  3. Responses of Spartina alterniflora to Multiple Stressors: Changing Precipitation Patterns, Accelerated Sea Level Rise, and Nutrient Enrichment

    Science.gov (United States)

    Coastal wetlands, well recognized for their ecosystem services, have faced many threats throughout the United States and elsewhere. Managers require good information on responses of wetlands to the combined stressors that these habitats experience, or may in the future as a resul...

  4. Noninvasive pulse pressure variation and stroke volume variation to predict fluid responsiveness at multiple thresholds : a prospective observational study

    NARCIS (Netherlands)

    Vos, Jaap Jan; Poterman, Marieke; Papineau Salm, Pieternel; Van Amsterdam, Kai; Struys, Michel M. R. F.; Scheeren, Thomas W. L.; Kalmar, Alain F.

    2015-01-01

    Pulse pressure variation (PPV) and stroke volume variation (SVV) are dynamic preload variables that can be measured noninvasively to assess fluid responsiveness (FR) in anesthetized patients with mechanical ventilation. Few studies have examined the effectiveness of predicting FR according to the

  5. Pooled Analysis of Multiple Crossover Trials To Optimize Individual Therapy Response to Renin-Angiotensin-Aldosterone System Intervention

    DEFF Research Database (Denmark)

    Petrykiv, Sergei I; Laverman, Gozewijn Dirk; Persson, Frederik

    2017-01-01

    to angiotensin receptor blockers; n=5) or NSAIDs (n=1), changing from RAASi to NSAIDs (n=2), and changing from high to low sodium intake (n=5). A two-stage meta-analysis was conducted: Deming regression was conducted in each study to assess correlations in response, and individual study results were then meta...

  6. ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency

    DEFF Research Database (Denmark)

    Olsen, Rikke K J; Olpin, Simon E; Andresen, Brage S

    2007-01-01

    Multiple acyl-CoA dehydrogenation deficiency (MADD) is a disorder of fatty acid, amino acid and choline metabolism that can result from defects in two flavoproteins, electron transfer flavoprotein (ETF) or ETF: ubiquinone oxidoreductase (ETF:QO). Some patients respond to pharmacological doses......; several had previously suffered cyclical vomiting. Urine organic acid and plasma acyl-carnitine profiles indicated MADD. Clinical and biochemical parameters were either totally or partly corrected after riboflavin treatment. All patients had mutations in the gene for ETF:QO. In one patient, we show...... that the ETF:QO mutations are associated with a riboflavin-sensitive impairment of ETF:QO activity. This patient also had partial deficiencies of flavin-dependent acyl-CoA dehydrogenases and respiratory chain complexes, most of which were restored to control levels after riboflavin treatment. Low activities...

  7. An Annual Plant Growth Proxy in the Mojave Desert Using MODIS-EVI Data

    Directory of Open Access Journals (Sweden)

    Kathryn A. Thomas

    2008-12-01

    Full Text Available In the arid Mojave Desert, the phenological response of vegetation is largely dependent upon the timing and amount of rainfall, and maps of annual plant cover at any one point in time can vary widely. Our study developed relative annual plant growth models as proxies for annual plant cover using metrics that captured phenological variability in Moderate-Resolution Imaging Spectroradiometer (MODIS Enhanced Vegetation Index (EVI satellite images. We used landscape phenologies revealed in MODIS data together with ecological knowledge of annual plant seasonality to develop a suite of metrics to describe annual growth on a yearly basis. Each of these metrics was applied to temporally-composited MODIS-EVI images to develop a relative model of annual growth. Each model was evaluated by testing how well it predicted field estimates of annual cover collected during 2003 and 2005 at the Mojave National Preserve. The best performing metric was the spring difference metric, which compared the average of three spring MODIS-EVI composites of a given year to that of 2002, a year of record drought. The spring difference metric showed correlations with annual plant cover of R2 = 0.61 for 2005 and R2 = 0.47 for 2003. Although the correlation is moderate, we consider it supportive given the characteristics of the field data, which were collected for a different study in a localized area and are not ideal for calibration to MODIS pixels. A proxy for annual growth potential was developed from the spring difference metric of 2005 for use as an environmental data layer in desert tortoise habitat modeling. The application of the spring difference metric to other imagery years presents potential for other applications such as fuels, invasive species, and dust-emission monitoring in the Mojave Desert.

  8. An Annual Plant Growth Proxy in the Mojave Desert Using MODIS-EVI Data.

    Science.gov (United States)

    Wallace, Cynthia S A; Thomas, Kathryn A

    2008-12-03

    In the arid Mojave Desert, the phenological response of vegetation is largely dependent upon the timing and amount of rainfall, and maps of annual plant cover at any one point in time can vary widely. Our study developed relative annual plant growth models as proxies for annual plant cover usi