Sample records for selfconsistent ssc model

  1. Three dimensional δf simulations of beams in the SSC

    NASA Astrophysics Data System (ADS)

    Koga, J.; Tajima, T.; Machida, S.

    1993-12-01

    A three dimensional δf strong-strong algorithm has been developed to apply to the study of such effects as space charge and beam-beam interaction phenomena in the Superconducting Super Collider (SSC). The algorithm is obtained from the merging of the particle tracking code Simpsons used for 3 dimensional space charge effects and a δf code. The δf method is used to follow the evolution of the non-gaussian part of the beam distribution. The advantages of this method are twofold. First, the Simpsons code utilizes a realistic accelerator model including synchrotron oscillations and energy ramping in 6 dimensional phase space with electromagnetic fields of the beams calculated using a realistic 3 dimensional field solver. Second, the beams are evolving in the fully self-consistent strong-strong sense with finite particle fluctuation noise is greatly reduced as opposed to the weak-strong models where one beam is fixed.

  2. A publicly available SSC+EC code.

    NASA Astrophysics Data System (ADS)

    Georganopoulos, M.; Perlman, E. S.; Kazanas, D.; Wingert, B.; Castro, R.

    2004-08-01

    We present a time-dependent one zone SSC+EC code that takes into account the KN-cross section, and calculates self-consistently all orders of Compton scattering. In particular, it produces separate results for the first order Compton component, and for the total Compton emission. The kinetic equation is solved using a stable implicit scheme, and the user can select from a range of physically motivated temporal electron injection profile. The code is written in C, is fully documented and will soon be publicly available through the Internet, along with a set of IDL visualization routines.

  3. Regional estimation of extreme suspended sediment concentrations using watershed characteristics

    NASA Astrophysics Data System (ADS)

    Tramblay, Yves; Ouarda, Taha B. M. J.; St-Hilaire, André; Poulin, Jimmy

    2010-01-01

    SummaryThe number of stations monitoring daily suspended sediment concentration (SSC) has been decreasing since the 1980s in North America while suspended sediment is considered as a key variable for water quality. The objective of this study is to test the feasibility of regionalising extreme SSC, i.e. estimating SSC extremes values for ungauged basins. Annual maximum SSC for 72 rivers in Canada and USA were modelled with probability distributions in order to estimate quantiles corresponding to different return periods. Regionalisation techniques, originally developed for flood prediction in ungauged basins, were tested using the climatic, topographic, land cover and soils attributes of the watersheds. Two approaches were compared, using either physiographic characteristics or seasonality of extreme SSC to delineate the regions. Multiple regression models to estimate SSC quantiles as a function of watershed characteristics were built in each region, and compared to a global model including all sites. Regional estimates of SSC quantiles were compared with the local values. Results show that regional estimation of extreme SSC is more efficient than a global regression model including all sites. Groups/regions of stations have been identified, using either the watershed characteristics or the seasonality of occurrence for extreme SSC values providing a method to better describe the extreme events of SSC. The most important variables for predicting extreme SSC are the percentage of clay in the soils, precipitation intensity and forest cover.

  4. Stennis Space Center Environmental Geographic Information System

    NASA Technical Reports Server (NTRS)

    Lovely, Janette; Cohan, Tyrus

    2000-01-01

    As NASA's lead center for rocket propulsion testing, the John C. Stennis Space Center (SSC) monitors and assesses the off-site impacts of such testing through its Environmental Office (SSC-EO) using acoustical models and ancillary data. The SSC-EO has developed a geographical database, called the SSC Environmental Geographic Information System (SSC-EGIS), that covers an eight-county area bordering the NASA facility. Through the SSC-EGIS, the Enivronmental Office inventories, assesses, and manages the nearly 139,000 acres that comprise Stennis Space Center and its surrounding acoustical buffer zone. The SSC-EGIS contains in-house data as well as a wide range of data obtained from outside sources, including private agencies and local, county, state, and U.S. government agencies. The database comprises cadastral/geodetic, hydrology, infrastructure, geo-political, physical geography, and socio-economic vector and raster layers. The imagery contained in the database is varied, including low-resolution imagery, such as Landsat TM and SPOT; high-resolution imagery, such as IKONOS and AVIRIS; and aerial photographs. The SSC-EGIS has been an integral part of several major projects and the model upon which similar EGIS's will be developed for other NASA facilities. The Corps of Engineers utilized the SSC-EGIS in a plan to establish wetland mitigation sites within the SSC buffer zone. Mississippi State University employed the SSC-EGIS in a preliminary study to evaluate public access points within the buffer zone. The SSC-EO has also expressly used the SSC-EGIS to assess noise pollution modeling, land management/wetland mitigation assessment, environmental hazards mapping, and protected areas mapping for archaeological sites and for threatened and endangered species habitats. The SSC-EO has several active and planned projects that will also make use of the SSC-EGIS during this and the coming fiscal year.

  5. Sediment-hosted stratabound copper deposit model: Chapter M in Mineral deposit model for resource assessment

    USGS Publications Warehouse

    Hayes, Timothy S.; Cox, Dennis P.; Bliss, James D.; Piatak, Nadine M.; Seal, Robert R.

    2015-01-01

    This report contains a descriptive model of sediment-hosted stratabound copper (SSC) deposits that supersedes the model of Cox and others (2003). This model is for use in assessments of mineral resource potential. SSC deposits are the second most important sources of copper in the world behind porphyry copper deposits. Around 20 percent of the copper in the world is produced from this class of deposits. They are also the most important sources of cobalt in the world, and they are fourth among classes of ore deposits in production of silver. SSC deposits are the basis of the economies of three countries: Democratic Republic of Congo, Poland, and Zambia. This report provides a description of the key features of SSC deposits; it identifies their tectonic-sedimentary environments; it illustrates geochemical, geophysical, and geoenvironmental characteristics of SSC deposits; it reviews and evaluates hypotheses on how these deposits formed; it presents exploration and assessment guides; and it lists some gaps in our knowledge about the SSC deposits. A summary follows that provides overviews of many subjects concerning SSC deposits.

  6. A Comparison of Turbidity-Based and Streamflow-Based Estimates of Suspended-Sediment Concentrations in Three Chesapeake Bay Tributaries

    USGS Publications Warehouse

    Jastram, John D.; Moyer, Douglas; Hyer, Kenneth

    2009-01-01

    Fluvial transport of sediment into the Chesapeake Bay estuary is a persistent water-quality issue with major implications for the overall health of the bay ecosystem. Accurately and precisely estimating the suspended-sediment concentrations (SSC) and loads that are delivered to the bay, however, remains challenging. Although manual sampling of SSC produces an accurate series of point-in-time measurements, robust extrapolation to unmeasured periods (especially highflow periods) has proven to be difficult. Sediment concentrations typically have been estimated using regression relations between individual SSC values and associated streamflow values; however, suspended-sediment transport during storm events is extremely variable, and it is often difficult to relate a unique SSC to a given streamflow. With this limitation for estimating SSC, innovative approaches for generating detailed records of suspended-sediment transport are needed. One effective method for improved suspended-sediment determination involves the continuous monitoring of turbidity as a surrogate for SSC. Turbidity measurements are theoretically well correlated to SSC because turbidity represents a measure of water clarity that is directly influenced by suspended sediments; thus, turbidity-based estimation models typically are effective tools for generating SSC data. The U.S. Geological Survey, in cooperation with the U.S. Environmental Protection Agency Chesapeake Bay Program and Virginia Department of Environmental Quality, initiated continuous turbidity monitoring on three major tributaries of the bay - the James, Rappahannock, and North Fork Shenandoah Rivers - to evaluate the use of turbidity as a sediment surrogate in rivers that deliver sediment to the bay. Results of this surrogate approach were compared to the traditionally applied streamflow-based approach for estimating SSC. Additionally, evaluation and comparison of these two approaches were conducted for nutrient estimations. Results demonstrate that the application of turbidity-based estimation models provides an improved method for generating a continuous record of SSC, relative to the classical approach that uses streamflow as a surrogate for SSC. Turbidity-based estimates of SSC were found to be more accurate and precise than SSC estimates from streamflow-based approaches. The turbidity-based SSC estimation models explained 92 to 98 percent of the variability in SSC, while streamflow-based models explained 74 to 88 percent of the variability in SSC. Furthermore, the mean absolute error of turbidity-based SSC estimates was 50 to 87 percent less than the corresponding values from the streamflow-based models. Statistically significant differences were detected between the distributions of residual errors and estimates from the two approaches, indicating that the turbidity-based approach yields estimates of SSC with greater precision than the streamflow-based approach. Similar improvements were identified for turbidity-based estimates of total phosphorus, which is strongly related to turbidity because total phosphorus occurs predominantly in particulate form. Total nitrogen estimation models based on turbidity and streamflow generated estimates of similar quality, with the turbidity-based models providing slight improvements in the quality of estimations. This result is attributed to the understanding that nitrogen transport is dominated by dissolved forms that relate less directly to streamflow and turbidity. Improvements in concentration estimation resulted in improved estimates of load. Turbidity-based suspended-sediment loads estimated for the James River at Cartersville, VA, monitoring station exhibited tighter confidence interval bounds and a coefficient of variation of 12 percent, compared with a coefficient of variation of 38 percent for the streamflow-based load.

  7. Increasing precision of turbidity-based suspended sediment concentration and load estimates.

    PubMed

    Jastram, John D; Zipper, Carl E; Zelazny, Lucian W; Hyer, Kenneth E

    2010-01-01

    Turbidity is an effective tool for estimating and monitoring suspended sediments in aquatic systems. Turbidity can be measured in situ remotely and at fine temporal scales as a surrogate for suspended sediment concentration (SSC), providing opportunity for a more complete record of SSC than is possible with physical sampling approaches. However, there is variability in turbidity-based SSC estimates and in sediment loadings calculated from those estimates. This study investigated the potential to improve turbidity-based SSC, and by extension the resulting sediment loading estimates, by incorporating hydrologic variables that can be monitored remotely and continuously (typically 15-min intervals) into the SSC estimation procedure. On the Roanoke River in southwestern Virginia, hydrologic stage, turbidity, and other water-quality parameters were monitored with in situ instrumentation; suspended sediments were sampled manually during elevated turbidity events; samples were analyzed for SSC and physical properties including particle-size distribution and organic C content; and rainfall was quantified by geologic source area. The study identified physical properties of the suspended-sediment samples that contribute to SSC estimation variance and hydrologic variables that explained variability of those physical properties. Results indicated that the inclusion of any of the measured physical properties in turbidity-based SSC estimation models reduces unexplained variance. Further, the use of hydrologic variables to represent these physical properties, along with turbidity, resulted in a model, relying solely on data collected remotely and continuously, that estimated SSC with less variance than a conventional turbidity-based univariate model, allowing a more precise estimate of sediment loading, Modeling results are consistent with known mechanisms governing sediment transport in hydrologic systems.

  8. X-Ray Spectral Variability Signatures of Flares in BL Lac Objects

    NASA Technical Reports Server (NTRS)

    Boettcher, Markus; Chiang, James; White, Nicholas E. (Technical Monitor)

    2002-01-01

    We are presenting a detailed parameter study of the time-dependent electron injection and kinematics and the self-consistent radiation transport in jets of intermediate and low-frequency peaked BL Lac objects. Using a time-dependent, combined synchrotron-self-Compton and external-Compton jet model, we study the influence of variations of several essential model parameters, such as the electron injection compactness, the relative contribution of synchrotron to external soft photons to the soft photon compactness, the electron- injection spectral index, and the details of the time profiles of the electron injection episodes giving rise to flaring activity. In the analysis of our results, we focus on the expected X-ray spectral variability signatures in a region of parameter space particularly well suited to reproduce the broadband spectral energy distributions of intermediate and low-frequency peaked BL Lac objects. We demonstrate that SSC- and external-Compton dominated models for the gamma-ray emission from blazars are producing significantly different signatures in the X-ray variability, in particular in the soft X-ray light curves and the spectral hysteresis at soft X-ray energies, which can be used as a powerful diagnostic to unveil the nature of the high-energy emission from BL Lac objects.

  9. New non-randomised model to assess the prevalence of discriminating behaviour: a pilot study on mephedrone

    PubMed Central

    2011-01-01

    Background An advantage of randomised response and non-randomised models investigating sensitive issues arises from the characteristic that individual answers about discriminating behaviour cannot be linked to the individuals. This study proposed a new fuzzy response model coined 'Single Sample Count' (SSC) to estimate prevalence of discriminating or embarrassing behaviour in epidemiologic studies. Methods The SSC was tested and compared to the established Forced Response (FR) model estimating Mephedrone use. Estimations from both SSC and FR were then corroborated with qualitative hair screening data. Volunteers (n = 318, mean age = 22.69 ± 5.87, 59.1% male) in a rural area in north Wales and a metropolitan area in England completed a questionnaire containing the SSC and FR in alternating order, and four questions canvassing opinions and beliefs regarding Mephedrone. Hair samples were screened for Mephedrone using a qualitative Liquid Chromatography-Mass Spectrometry method. Results The SSC algorithm improves upon the existing item count techniques by utilizing known population distributions and embeds the sensitive question among four unrelated innocuous questions with binomial distribution. Respondents are only asked to indicate how many without revealing which ones are true. The two probability models yielded similar estimates with the FR being between 2.6% - 15.0%; whereas the new SSC ranged between 0% - 10%. The six positive hair samples indicated that the prevalence rate in the sample was at least 4%. The close proximity of these estimates provides evidence to support the validity of the new SSC model. Using simulations, the recommended sample sizes as the function of the statistical power and expected prevalence rate were calculated. Conclusion The main advantages of the SSC over other indirect methods are: simple administration, completion and calculation, maximum use of the data and good face validity for all respondents. Owing to the key feature that respondents are not required to answer the sensitive question directly, coupled with the absence of forced response or obvious self-protective response strategy, the SSC has the potential to cut across self-protective barriers more effectively than other estimation models. This elegantly simple, quick and effective method can be successfully employed in public health research investigating compromising behaviours. PMID:21812979

  10. Space Science Cloud: a Virtual Space Science Research Platform Based on Cloud Model

    NASA Astrophysics Data System (ADS)

    Hu, Xiaoyan; Tong, Jizhou; Zou, Ziming

    Through independent and co-operational science missions, Strategic Pioneer Program (SPP) on Space Science, the new initiative of space science program in China which was approved by CAS and implemented by National Space Science Center (NSSC), dedicates to seek new discoveries and new breakthroughs in space science, thus deepen the understanding of universe and planet earth. In the framework of this program, in order to support the operations of space science missions and satisfy the demand of related research activities for e-Science, NSSC is developing a virtual space science research platform based on cloud model, namely the Space Science Cloud (SSC). In order to support mission demonstration, SSC integrates interactive satellite orbit design tool, satellite structure and payloads layout design tool, payload observation coverage analysis tool, etc., to help scientists analyze and verify space science mission designs. Another important function of SSC is supporting the mission operations, which runs through the space satellite data pipelines. Mission operators can acquire and process observation data, then distribute the data products to other systems or issue the data and archives with the services of SSC. In addition, SSC provides useful data, tools and models for space researchers. Several databases in the field of space science are integrated and an efficient retrieve system is developing. Common tools for data visualization, deep processing (e.g., smoothing and filtering tools), analysis (e.g., FFT analysis tool and minimum variance analysis tool) and mining (e.g., proton event correlation analysis tool) are also integrated to help the researchers to better utilize the data. The space weather models on SSC include magnetic storm forecast model, multi-station middle and upper atmospheric climate model, solar energetic particle propagation model and so on. All the services above-mentioned are based on the e-Science infrastructures of CAS e.g. cloud storage and cloud computing. SSC provides its users with self-service storage and computing resources at the same time.At present, the prototyping of SSC is underway and the platform is expected to be put into trial operation in August 2014. We hope that as SSC develops, our vision of Digital Space may come true someday.

  11. [Determination of soluble solids content in Nanfeng Mandarin by Vis/NIR spectroscopy and UVE-ICA-LS-SVM].

    PubMed

    Sun, Tong; Xu, Wen-Li; Hu, Tian; Liu, Mu-Hua

    2013-12-01

    The objective of the present research was to assess soluble solids content (SSC) of Nanfeng mandarin by visible/near infrared (Vis/NIR) spectroscopy combined with new variable selection method, simplify prediction model and improve the performance of prediction model for SSC of Nanfeng mandarin. A total of 300 Nanfeng mandarin samples were used, the numbers of Nanfeng mandarin samples in calibration, validation and prediction sets were 150, 75 and 75, respectively. Vis/NIR spectra of Nanfeng mandarin samples were acquired by a QualitySpec spectrometer in the wavelength range of 350-1000 nm. Uninformative variables elimination (UVE) was used to eliminate wavelength variables that had few information of SSC, then independent component analysis (ICA) was used to extract independent components (ICs) from spectra that eliminated uninformative wavelength variables. At last, least squares support vector machine (LS-SVM) was used to develop calibration models for SSC of Nanfeng mandarin using extracted ICs, and 75 prediction samples that had not been used for model development were used to evaluate the performance of SSC model of Nanfeng mandarin. The results indicate t hat Vis/NIR spectroscopy combinedwith UVE-ICA-LS-SVM is suitable for assessing SSC o f Nanfeng mandarin, and t he precision o f prediction ishigh. UVE--ICA is an effective method to eliminate uninformative wavelength variables, extract important spectral information, simplify prediction model and improve the performance of prediction model. The SSC model developed by UVE-ICA-LS-SVM is superior to that developed by PLS, PCA-LS-SVM or ICA-LS-SVM, and the coefficient of determination and root mean square error in calibration, validation and prediction sets were 0.978, 0.230%, 0.965, 0.301% and 0.967, 0.292%, respectively.

  12. Establishment and characterization of scleroderma fibroblast clonal cell lines by introduction of the hTERT gene

    PubMed Central

    Kapanadze, Bagrat; Morris, Erin; Smith, Edwin; Trojanowska, Maria

    2010-01-01

    Abstract Lack of an adequate experimental model has hindered the ability to fully understand scleroderma (SSc) pathogenesis. Current SSc research is based on the study of cultured fibroblasts from skin biopsies. In depth characterization of the SSc fibroblast phenotype is hindered by the limited lifespan and heterogeneity of these cells. The goal of this study was to isolate high collagen-producing fibroblasts from SSc biopsies and extend their lifespan with hTERT immortalization to enable characterization of their phenotype. Fibroblasts from two pairs of closely matched normal and SSc biopsies were infected with an hTERT lentivirus. Infected colonies were isolated, cultured into clonal cell lines and analysed with respect to profibrotic gene expression. The mRNA levels of nine profibrotic genes were measured by quantitative real-time PCR. Protein levels were assessed by Western blot. The hTERT SSc clones were heterogeneous with regards to expression of the profibrotic genes measured. A subset of the SSc clones showed elevated expression levels of collagen I, connective tissue growth factor and thrombospondin 1 mRNA, while expression of other genes was not significantly changed. Elevated expression of collagen I protein and mRNA was correlative with elevated expression of connective tissue growth factor. Several hTERT clones expressed high levels of pSmad1, Smad1 and TGF-βRI indicative of altered TGF-β signalling. A portion of SSc clones expressed several profibrotic genes. This study demonstrates that select characteristics of the SSc phenotype are expressed in a subset of activated fibroblasts in culture. The clonal SSc cell lines may present a new and useful model to investigate the mechanisms involved in SSc fibrosis. PMID:19432820

  13. Establishment and characterization of scleroderma fibroblast clonal cell lines by introduction of the hTERT gene.

    PubMed

    Kapanadze, Bagrat; Morris, Erin; Smith, Edwin; Trojanowska, Maria

    2010-05-01

    Lack of an adequate experimental model has hindered the ability to fully understand scleroderma (SSc) pathogenesis. Current SSc research is based on the study of cultured fibroblasts from skin biopsies. In depth characterization of the SSc fibroblast phenotype is hindered by the limited lifespan and heterogeneity of these cells. The goal of this study was to isolate high collagen-producing fibroblasts from SSc biopsies and extend their lifespan with hTERT immortalization to enable characterization of their phenotype. Fibroblasts from two pairs of closely matched normal and SSc biopsies were infected with an hTERT lentivirus. Infected colonies were isolated, cultured into clonal cell lines and analysed with respect to profibrotic gene expression. The mRNA levels of nine profibrotic genes were measured by quantitative real-time PCR. Protein levels were assessed by Western blot. The hTERT SSc clones were heterogeneous with regards to expression of the profibrotic genes measured. A subset of the SSc clones showed elevated expression levels of collagen I, connective tissue growth factor and thrombospondin 1 mRNA, while expression of other genes was not significantly changed. Elevated expression of collagen I protein and mRNA was correlative with elevated expression of connective tissue growth factor. Several hTERT clones expressed high levels of pSmad1, Smad1 and TGF-betaRI indicative of altered TGF-beta signalling. A portion of SSc clones expressed several profibrotic genes. This study demonstrates that select characteristics of the SSc phenotype are expressed in a subset of activated fibroblasts in culture. The clonal SSc cell lines may present a new and useful model to investigate the mechanisms involved in SSc fibrosis.

  14. Biobjective planning of GEO debris removal mission with multiple servicing spacecrafts

    NASA Astrophysics Data System (ADS)

    Jing, Yu; Chen, Xiao-qian; Chen, Li-hu

    2014-12-01

    The mission planning of GEO debris removal with multiple servicing spacecrafts (SScs) is studied in this paper. Specifically, the SScs are considered to be initially on the GEO belt, and they should rendezvous with debris of different orbital slots and different inclinations, remove them to the graveyard orbit and finally return to their initial locations. Three key problems should be resolved here: task assignment, mission sequence planning and transfer trajectory optimization for each SSc. The minimum-cost, two-impulse phasing maneuver is used for each rendezvous. The objective is to find a set of optimal planning schemes with minimum fuel cost and travel duration. Considering this mission as a hybrid optimal control problem, a mathematical model is proposed. A modified multi-objective particle swarm optimization is employed to address the model. Numerous examples are carried out to demonstrate the effectiveness of the model and solution method. In this paper, single-SSc and multiple-SSc scenarios with the same amount of fuel are compared. Numerous experiments indicate that for a definite GEO debris removal mission, that which alternative (single-SSc or multiple-SSc) is better (cost less fuel and consume less travel time) is determined by many factors. Although in some cases, multiple-SSc scenarios may perform worse than single-SSc scenarios, the extra costs are considered worth the gain in mission safety and robustness.

  15. Statistical self-similarity of hotspot seamount volumes modeled as self-similar criticality

    USGS Publications Warehouse

    Tebbens, S.F.; Burroughs, S.M.; Barton, C.C.; Naar, D.F.

    2001-01-01

    The processes responsible for hotspot seamount formation are complex, yet the cumulative frequency-volume distribution of hotspot seamounts in the Easter Island/Salas y Gomez Chain (ESC) is found to be well-described by an upper-truncated power law. We develop a model for hotspot seamount formation where uniform energy input produces events initiated on a self-similar distribution of critical cells. We call this model Self-Similar Criticality (SSC). By allowing the spatial distribution of magma migration to be self-similar, the SSC model recreates the observed ESC seamount volume distribution. The SSC model may have broad applicability to other natural systems.

  16. Common measure of quality of life for people with systemic sclerosis across seven European countries: a cross-sectional study.

    PubMed

    Ndosi, Mwidimi; Alcacer-Pitarch, Begonya; Allanore, Yannick; Del Galdo, Francesco; Frerix, Marc; García-Díaz, Sílvia; Hesselstrand, Roger; Kendall, Christine; Matucci-Cerinic, Marco; Mueller-Ladner, Ulf; Sandqvist, Gunnel; Torrente-Segarra, Vicenç; Schmeiser, Tim; Sierakowska, Matylda; Sierakowska, Justyna; Sierakowski, Stanslaw; Redmond, Anthony

    2018-02-20

    The aim of this study was to adapt the Systemic Sclerosis Quality of Life Questionnaire (SScQoL) into six European cultures and validate it as a common measure of quality of life in systemic sclerosis (SSc). This was a seven-country (Germany, France, Italy, Poland, Spain, Sweden and UK) cross-sectional study. A forward-backward translation process was used to adapt the English SScQoL into target languages. SScQoL was completed by patients with SSc, then data were validated against the Rasch model. To correct local response dependency, items were grouped into the following subscales: function, emotion, sleep, social and pain and reanalysed for fit to the model, unidimensionality and cross-cultural equivalence. The adaptation of the SScQoL was seamless in all countries except Germany. Cross-cultural validation included 1080 patients with a mean age 58.0 years (SD 13.9) and 87% were women. Local dependency was evident in individual country data. Grouping items into testlets corrected the local dependency in most country specific data. Fit to the model, reliability and unidimensionality was achieved in six-country data after cross-cultural adjustment for Italy in the social subscale. The SScQoL was then calibrated into an interval level scale. The individual SScQoL items have translated well into five languages and overall, the scale maintained its construct validity, working well as a five-subscale questionnaire. Measures of quality of life in SSc can be directly compared across five countries (France, Poland Spain, Sweden and UK). Data from Italy are also comparable with the other five countries although require an adjustment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Amelioration of tissue fibrosis by toll-like receptor 4 knockout in murine models of systemic sclerosis.

    PubMed

    Takahashi, Takehiro; Asano, Yoshihide; Ichimura, Yohei; Toyama, Tetsuo; Taniguchi, Takashi; Noda, Shinji; Akamata, Kaname; Tada, Yayoi; Sugaya, Makoto; Kadono, Takafumi; Sato, Shinichi

    2015-01-01

    Bleomycin-induced fibrosis and the tight skin (TSK/+) mouse are well-established experimental murine models of human systemic sclerosis (SSc). Growing evidence has demonstrated the pivotal role of Toll-like receptors (TLRs) in several autoimmune inflammatory diseases, including SSc. This study was undertaken to determine the role of TLR-4 in the fibrotic processes in these murine models. We generated a murine model of bleomycin-induced SSc using TLR-4(-/-) mice and TLR-4(-/-) ;TSK/+ mice. The mechanisms by which TLR-4 contributes to pathologic tissue fibrosis were investigated in these 2 models by histologic examination, hydroxyproline assay, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and flow cytometry. Dermal and lung fibrosis was attenuated in bleomycin-treated TLR-4(-/-) mice compared with their wild-type counterparts. Inflammatory cell infiltration, expression of various inflammatory cytokines, and pathologic angiogenesis induced by bleomycin treatment were suppressed with TLR-4 deletion. Furthermore, the increased expression of interleukin-6 (IL-6) in fibroblasts, endothelial cells, and immune cells in response to bleomycin in vivo and to lipopolysaccharide in vitro was notably abrogated in the absence of TLR-4. Moreover, TLR-4 deletion was associated with alleviated B cell activation and skew toward a Th2/Th17 response against bleomycin treatment. Importantly, in TSK/+ mice, another SSc murine model, TLR-4 abrogation attenuated hypodermal fibrosis. These results indicate the pivotal contribution of TLR-4 to the pathologic tissue fibrosis of SSc murine models. Our results indicate the critical role of TLR-4 signaling in the development of tissue fibrosis, suggesting that biomolecular TLR-4 targeting might be a potential therapeutic approach to SSc. Copyright © 2015 by the American College of Rheumatology.

  18. Central and Eastern United States (CEUS) Seismic Source Characterization (SSC) for Nuclear Facilities Project

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

    Kevin J. Coppersmith; Lawrence A. Salomone; Chris W. Fuller

    2012-01-31

    This report describes a new seismic source characterization (SSC) model for the Central and Eastern United States (CEUS). It will replace the Seismic Hazard Methodology for the Central and Eastern United States, EPRI Report NP-4726 (July 1986) and the Seismic Hazard Characterization of 69 Nuclear Plant Sites East of the Rocky Mountains, Lawrence Livermore National Laboratory Model, (Bernreuter et al., 1989). The objective of the CEUS SSC Project is to develop a new seismic source model for the CEUS using a Senior Seismic Hazard Analysis Committee (SSHAC) Level 3 assessment process. The goal of the SSHAC process is to representmore » the center, body, and range of technically defensible interpretations of the available data, models, and methods. Input to a probabilistic seismic hazard analysis (PSHA) consists of both seismic source characterization and ground motion characterization. These two components are used to calculate probabilistic hazard results (or seismic hazard curves) at a particular site. This report provides a new seismic source model. Results and Findings The product of this report is a regional CEUS SSC model. This model includes consideration of an updated database, full assessment and incorporation of uncertainties, and the range of diverse technical interpretations from the larger technical community. The SSC model will be widely applicable to the entire CEUS, so this project uses a ground motion model that includes generic variations to allow for a range of representative site conditions (deep soil, shallow soil, hard rock). Hazard and sensitivity calculations were conducted at seven test sites representative of different CEUS hazard environments. Challenges and Objectives The regional CEUS SSC model will be of value to readers who are involved in PSHA work, and who wish to use an updated SSC model. This model is based on a comprehensive and traceable process, in accordance with SSHAC guidelines in NUREG/CR-6372, Recommendations for Probabilistic Seismic Hazard Analysis: Guidance on Uncertainty and Use of Experts. The model will be used to assess the present-day composite distribution for seismic sources along with their characterization in the CEUS and uncertainty. In addition, this model is in a form suitable for use in PSHA evaluations for regulatory activities, such as Early Site Permit (ESPs) and Combined Operating License Applications (COLAs). Applications, Values, and Use Development of a regional CEUS seismic source model will provide value to those who (1) have submitted an ESP or COLA for Nuclear Regulatory Commission (NRC) review before 2011; (2) will submit an ESP or COLA for NRC review after 2011; (3) must respond to safety issues resulting from NRC Generic Issue 199 (GI-199) for existing plants and (4) will prepare PSHAs to meet design and periodic review requirements for current and future nuclear facilities. This work replaces a previous study performed approximately 25 years ago. Since that study was completed, substantial work has been done to improve the understanding of seismic sources and their characterization in the CEUS. Thus, a new regional SSC model provides a consistent, stable basis for computing PSHA for a future time span. Use of a new SSC model reduces the risk of delays in new plant licensing due to more conservative interpretations in the existing and future literature. Perspective The purpose of this study, jointly sponsored by EPRI, the U.S. Department of Energy (DOE), and the NRC was to develop a new CEUS SSC model. The team assembled to accomplish this purpose was composed of distinguished subject matter experts from industry, government, and academia. The resulting model is unique, and because this project has solicited input from the present-day larger technical community, it is not likely that there will be a need for significant revision for a number of years. See also Sponsors Perspective for more details. The goal of this project was to implement the CEUS SSC work plan for developing a regional CEUS SSC model. The work plan, formulated by the project manager and a technical integration team, consists of a series of tasks designed to meet the project objectives. This report was reviewed by a participatory peer review panel (PPRP), sponsor reviewers, the NRC, the U.S. Geological Survey, and other stakeholders. Comments from the PPRP and other reviewers were considered when preparing the report. The SSC model was completed at the end of 2011.« less

  19. Applicability of a numerical model to predict vertical distribution of suspended sediment concentration along the depth in Dithmarschen Bight

    NASA Astrophysics Data System (ADS)

    Rahbani, M.

    2012-04-01

    A three dimensional numerical model of Delft3d-flow was developed to simulate the current velocity and sediment transport of Piep tidal channel system. This channel system is part of Dithmarschen Bight located in the German North Sea coast. It consists of two main channel namely Norderpiep, and Süderpiep. These two channels conjunct together to form Piep channel near the land on tidal flat. The source of the required field data for this study was those collected under "Prediction of Medium Term Coastal Morphodynamics", known as the PROMORPH project. It was executed during the period May 1999 to June 2002. Those measured data used for calibration and validation of the model were current velocity and suspended sediment concentration (SSC). Current velocities were collected using ADCP devise. Suspended sediment concentration data was prepared by converting the measured values of light transmission. These data was collected using transmissometer. On the basis of some in situ mechanical sampler data an equation was developed to convert light transmission to the SSC. Field data were carried out at several stations along the width of three cross sections from the surface to the bottom, taking into account the limitations. To verify the performance of the calibrated model, its results were compared with the field data. The comparison between the modeled and measured current velocity shows an accuracy of about 0.2 m/s. Factor of two of measured SSC were used to evaluate the performance of the model regarding these values. Some dissimilarity was found between the modeled SSC and those of the field data.To verify the cause of this dissimilarity, two comparing procedures were carried out. First the evolution of the vertical profile of the SSC from the model and those from the field were prepared and compared. In another procedure the snapshot of distribution of SSC at each cross section during different phases of a tidal cycle were prepared using the model results and compared with those derived from the field. It was found that the predicted SSC values are in good agreement with the field data during the periods of flood phase and low slack water. However, spatial dissimilarities are observed in the distribution of the SSC, during the periods of high slack water and the ebb phase. It was also found that the model could not simulate the peak SSC during the ebb current at Piep cross section which is located near the land. An insufficient supply of sediment from the tidal flat area in the model was considered to be responsible. several parameters and/or factors found to be responsible among them the usage of constant settling velocity and also constant erosion rate. The input of different values of the critical bed shear stress for erosion for the tidal flat areas and the tidal channel eastward of the cross section did improve the model results.

  20. Shape prior modeling using sparse representation and online dictionary learning.

    PubMed

    Zhang, Shaoting; Zhan, Yiqiang; Zhou, Yan; Uzunbas, Mustafa; Metaxas, Dimitris N

    2012-01-01

    The recently proposed sparse shape composition (SSC) opens a new avenue for shape prior modeling. Instead of assuming any parametric model of shape statistics, SSC incorporates shape priors on-the-fly by approximating a shape instance (usually derived from appearance cues) by a sparse combination of shapes in a training repository. Theoretically, one can increase the modeling capability of SSC by including as many training shapes in the repository. However, this strategy confronts two limitations in practice. First, since SSC involves an iterative sparse optimization at run-time, the more shape instances contained in the repository, the less run-time efficiency SSC has. Therefore, a compact and informative shape dictionary is preferred to a large shape repository. Second, in medical imaging applications, training shapes seldom come in one batch. It is very time consuming and sometimes infeasible to reconstruct the shape dictionary every time new training shapes appear. In this paper, we propose an online learning method to address these two limitations. Our method starts from constructing an initial shape dictionary using the K-SVD algorithm. When new training shapes come, instead of re-constructing the dictionary from the ground up, we update the existing one using a block-coordinates descent approach. Using the dynamically updated dictionary, sparse shape composition can be gracefully scaled up to model shape priors from a large number of training shapes without sacrificing run-time efficiency. Our method is validated on lung localization in X-Ray and cardiac segmentation in MRI time series. Compared to the original SSC, it shows comparable performance while being significantly more efficient.

  1. Distinct Properties of Human M-CSF and GM-CSF Monocyte-Derived Macrophages to Simulate Pathological Lung Conditions In Vitro: Application to Systemic and Inflammatory Disorders with Pulmonary Involvement.

    PubMed

    Lescoat, Alain; Ballerie, Alice; Augagneur, Yu; Morzadec, Claudie; Vernhet, Laurent; Fardel, Olivier; Jégo, Patrick; Jouneau, Stéphane; Lecureur, Valérie

    2018-03-17

    Macrophages play a central role in the pathogenesis of inflammatory and fibrotic lung diseases. However, alveolar macrophages (AM) are poorly available in humans to perform in vitro studies due to a limited access to broncho-alveolar lavage (BAL). In this study, to identify the best alternative in vitro model for human AM, we compared the phenotype of AM obtained from BAL of patients suffering from three lung diseases (lung cancers, sarcoidosis and Systemic Sclerosis (SSc)-associated interstitial lung disease) to human blood monocyte-derived macrophages (MDMs) differentiated with M-CSF or GM-CSF. The expression of eight membrane markers was evaluated by flow cytometry. Globally, AM phenotype was closer to GM-CSF MDMs. However, the expression levels of CD163, CD169, CD204, CD64 and CD36 were significantly higher in SSc-ILD than in lung cancers. Considering the expression of CD204 and CD36, the phenotype of SSc-AM was closer to MDMs, from healthy donors or SSc patients, differentiated by M-CSF rather than GM-CSF. The comparative secretion of IL-6 by SSc-MDMs and SSc-AM is concordant with these phenotypic considerations. Altogether, these results support the M-CSF MDM model as a relevant in vitro alternative to simulate AM in fibrotic disorders such as SSc.

  2. The role of sublithospheric gravitational instability on oceanic intraplate volcanism

    NASA Astrophysics Data System (ADS)

    Ballmer, M. D.; van Hunen, J.; Ito, G.; Tackley, P. J.; Bianco, T. A.

    2009-12-01

    Some intraplate volcano chains in the Pacific violate the predictions of the hotspot hypothesis for geographic age progressions. One mechanism invoked to explain these observations is small-scale sublithospheric convection (SSC). We explore this concept in fully thermo-chemical, 3D-numerical models. Melting due to SSC is shown to emerge along hot-lines of length >1000 km parallel to plate motion and not just at a fixed spot; therefore volcanism occurs in chains but not with hotspot-like linear age progressions. Our models predict many of the key observations along the Pukapuka ridges, and the volcano groups associated with the Marshalls, Gilberts, Cook-Australs, Wake seamounts and Marshall Islands. SSC volcanism may further play a role for volcanism at major mantle plumes - such as the Hawaiian plume. Plume models have successfully predicted most of the first-order observations at Hawaii hotspot. However, the details of plume-plate interaction and the origin of secondary volcanism still remain to be understood. Small-scale convection (SSC) in the 'pancake' of the Hawaii plume is a possible candidate for lithospheric thinning downstream Hawaii. Low asthenospheric viscosities and lateral density heterogeneity are triggers for SSC - and are both provided by the Hawaiian plume. SSC should also already be developed before the arrival of the Hawaiian plume, which hits mature oceanic lithosphere (of age ~90 Myrs) with important effects on plume-plate interaction and magma generation.

  3. The impact of Fli1 deficiency on the pathogenesis of systemic sclerosis

    PubMed Central

    Asano, Yoshihide; Bujor, Andreea M.; Trojanowska, Maria

    2013-01-01

    Systemic sclerosis (SSc) is an autoimmune inflammatory disease with unknown etiology characterized by microvascular injury and fibrosis of the skin and internal organs. A growing body of evidence suggests that deficiency of the transcription factor Fli1 (Friend leukemia integration-1) has a pivotal role in the pathogenesis of SSc. Fli1 is expressed in fibroblasts, endothelial cells, and immune cells, and has important roles in the activation, differentiation, development, and survival of these cells. Previous studies demonstrated that Fli1 is downregulated in SSc fibroblasts by an epigenetic mechanism and a series of experiments with Fli1-deficient animal models revealed that Fli1 deficiency in fibroblasts and endothelial cells reproduces the histopathologic features of fibrosis and vasculopathy in SSc, respectively. In this article, we review the impact of Fli1 deficiency on the pathogenesis of SSc and discuss a new therapeutic strategy for SSc by targeting the transcription factor Fli1. PMID:20663647

  4. Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial lung disease: reversal by caveolin-1 scaffolding domain peptide.

    PubMed

    Tourkina, Elena; Bonner, Michael; Oates, James; Hofbauer, Ann; Richard, Mathieu; Znoyko, Sergei; Visconti, Richard P; Zhang, Jing; Hatfield, Corey M; Silver, Richard M; Hoffman, Stanley

    2011-07-01

    Interstitial lung disease (ILD) is a major cause of morbidity and mortality in scleroderma (systemic sclerosis, or SSc). Fibrocytes are a monocyte-derived cell population implicated in the pathogenesis of fibrosing disorders. Given the recently recognized importance of caveolin-1 in regulating function and signaling in SSc monocytes, in the present study we examined the role of caveolin-1 in the migration and/or trafficking and phenotype of monocytes and fibrocytes in fibrotic lung disease in human patients and an animal model. These studies fill a gap in our understanding of how monocytes and fibrocytes contribute to SSc-ILD pathology. We found that C-X-C chemokine receptor type 4-positive (CXCR4+)/collagen I-positive (ColI+), CD34+/ColI+ and CD45+/ColI+ cells are present in SSc-ILD lungs, but not in control lungs, with CXCR4+ cells being most prevalent. Expression of CXCR4 and its ligand, stromal cell-derived factor 1 (CXCL12), are also highly upregulated in SSc-ILD lung tissue. SSc monocytes, which lack caveolin-1 and therefore overexpress CXCR4, exhibit almost sevenfold increased migration toward CXCL12 compared to control monocytes. Restoration of caveolin-1 function by administering the caveolin scaffolding domain (CSD) peptide reverses this hypermigration. Similarly, transforming growth factor β-treated normal monocytes lose caveolin-1, overexpress CXCR4 and exhibit 15-fold increased monocyte migration that is CSD peptide-sensitive. SSc monocytes exhibit a different phenotype than normal monocytes, expressing high levels of ColI, CD14 and CD34. Because ColI+/CD14+ cells are prevalent in SSc blood, we looked for such cells in lung tissue and confirmed their presence in SSc-ILD lungs but not in normal lungs. Finally, in the bleomycin model of lung fibrosis, we show that CSD peptide diminishes fibrocyte accumulation in the lungs. Our results suggest that low caveolin-1 in SSc monocytes contributes to ILD via effects on cell migration and phenotype and that the hyperaccumulation of fibrocytes in SSc-ILD may result from the altered phenotype and migratory activity of their monocyte precursors.

  5. Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial lung disease: reversal by caveolin-1 scaffolding domain peptide

    PubMed Central

    2011-01-01

    Interstitial lung disease (ILD) is a major cause of morbidity and mortality in scleroderma (systemic sclerosis, or SSc). Fibrocytes are a monocyte-derived cell population implicated in the pathogenesis of fibrosing disorders. Given the recently recognized importance of caveolin-1 in regulating function and signaling in SSc monocytes, in the present study we examined the role of caveolin-1 in the migration and/or trafficking and phenotype of monocytes and fibrocytes in fibrotic lung disease in human patients and an animal model. These studies fill a gap in our understanding of how monocytes and fibrocytes contribute to SSc-ILD pathology. We found that C-X-C chemokine receptor type 4-positive (CXCR4+)/collagen I-positive (ColI+), CD34+/ColI+ and CD45+/ColI+ cells are present in SSc-ILD lungs, but not in control lungs, with CXCR4+ cells being most prevalent. Expression of CXCR4 and its ligand, stromal cell-derived factor 1 (CXCL12), are also highly upregulated in SSc-ILD lung tissue. SSc monocytes, which lack caveolin-1 and therefore overexpress CXCR4, exhibit almost sevenfold increased migration toward CXCL12 compared to control monocytes. Restoration of caveolin-1 function by administering the caveolin scaffolding domain (CSD) peptide reverses this hypermigration. Similarly, transforming growth factor β-treated normal monocytes lose caveolin-1, overexpress CXCR4 and exhibit 15-fold increased monocyte migration that is CSD peptide-sensitive. SSc monocytes exhibit a different phenotype than normal monocytes, expressing high levels of ColI, CD14 and CD34. Because ColI+/CD14+ cells are prevalent in SSc blood, we looked for such cells in lung tissue and confirmed their presence in SSc-ILD lungs but not in normal lungs. Finally, in the bleomycin model of lung fibrosis, we show that CSD peptide diminishes fibrocyte accumulation in the lungs. Our results suggest that low caveolin-1 in SSc monocytes contributes to ILD via effects on cell migration and phenotype and that the hyperaccumulation of fibrocytes in SSc-ILD may result from the altered phenotype and migratory activity of their monocyte precursors. PMID:21722364

  6. Cross-Validation of Suspended Sediment Concentrations Derived from Satellite Imagery and Numerical Modeling of the 1997 New Year's Flood on the Feather River, CA

    NASA Astrophysics Data System (ADS)

    Kilham, N. E.

    2009-12-01

    Image analysis was applied to assess suspended sediment concentrations (SSC) predicted by a numerical model of 2D hydraulics and sediment transport (Telemac-2D), coupled to a solver for the advection-diffusion equation (SISYPHE) and representing 18 days of flooding over 70 kilometers of the lower Feather-Yuba Rivers. Sisyphe treats the suspended load as a tracer, removed from the flow if the bed shear velocity, u* is lower than an empirically derived threshold (ud* = 7.8E-3 m s-1). Agreement between model (D50 = 0.03 mm) and image-derived SSC (mg L-1) suggests that image interpretation could prove to be a viable approach for verifying spatially-distributed models of floodplain sediment transport if imagery is acquired for a particular flood and at a sufficient spatial and radiometric resolution. However, remotely derived SSC represents the integrated concentration of suspended sediment at the water surface. Hence, comparing SSC magnitudes derived from imagery and numerical modeling requires that a relationship is first established between the total suspended load and the portion of this load suspended within the optical range of the sensor (e.g., Aalto, 1995). Using the optical depth (0.5 m) determined from radiative transfer modeling, surface SSC measured from a 1/14/97 Landsat TM5 image (30 m) were converted to depth-integrated SSC with the Rouse (1937) equation. Surface concentrations were derived using a look-up table for the sensor to convert endmember fractions obtained from a spectral mixture analysis of the image. A two-endmember model (2.0 and 203 mg L-1) was used, with synthetic endmembers derived from optical and radiative transfer modeling and inversion of field spectra collected from the Sacramento and Feather Rivers and matched to measured SSC values. Remotely sensed SSC patterns were then compared to the Telemac results for the same day and time. Modeled concentrations are a function of both the rating curve boundary conditions, and the transport and deposition calculations. At each of three upstream channel boundaries, hourly SSC was derived from instantaneous discharge and SSC records at USGS gages for winter months (December-April) following dam closure on the Feather, Yuba, and Bear Rivers (r2 = 0.61; r2 = 0.81; r2 = 0.55). Model channel concentrations declined downstream from about 90 mg L-1 to 40 mg L-1 as sediment input was depleted through decanting of river water overbank, advection through floodplain channels, and deposition onto the floodplain. Similar downstream declines in the image values suggest that bed and bank erosion downstream of the major gages did not contribute much new sediment two weeks following the flood peak. Model predicted concentrations agree with image derived concentrations to within 10 mg L-1, although the model predicts a more rapid drawdown of floodplain flow than is apparent from the image. Aalto, R., 1995. Discordance between suspended sediment diffusion theory and observed sediment concentration profiles in rivers. M.S., University of Washington, Seattle, WA. Rouse, H.R., 1937. Modern conceptions of the mechanics of turbulence. Transactions, American Society of Civil Engineers, 102: 463-543.

  7. Multiband variability studies and novel broadband SED modeling of Mrk 501 in 2009

    NASA Astrophysics Data System (ADS)

    Ahnen, M. L.; Ansoldi, S.; Antonelli, L. A.; Antoranz, P.; Babic, A.; Banerjee, B.; Bangale, P.; Barres de Almeida, U.; Barrio, J. A.; Becerra González, J.; Bednarek, W.; Bernardini, E.; Berti, A.; Biasuzzi, B.; Biland, A.; Blanch, O.; Bonnefoy, S.; Bonnoli, G.; Borracci, F.; Bretz, T.; Buson, S.; Carosi, A.; Chatterjee, A.; Clavero, R.; Colin, P.; Colombo, E.; Contreras, J. L.; Cortina, J.; Covino, S.; Da Vela, P.; Dazzi, F.; De Angelis, A.; De Lotto, B.; de Oña Wilhelmi, E.; Di Pierro, F.; Doert, M.; Domínguez, A.; Dominis Prester, D.; Dorner, D.; Doro, M.; Einecke, S.; Eisenacher Glawion, D.; Elsaesser, D.; Engelkemeier, M.; Fallah Ramazani, V.; Fernández-Barral, A.; Fidalgo, D.; Fonseca, M. V.; Font, L.; Frantzen, K.; Fruck, C.; Galindo, D.; García López, R. J.; Garczarczyk, M.; Garrido Terrats, D.; Gaug, M.; Giammaria, P.; Godinović, N.; González Muñoz, A.; Gora, D.; Guberman, D.; Hadasch, D.; Hahn, A.; Hanabata, Y.; Hayashida, M.; Herrera, J.; Hose, J.; Hrupec, D.; Hughes, G.; Idec, W.; Kodani, K.; Konno, Y.; Kubo, H.; Kushida, J.; La Barbera, A.; Lelas, D.; Lindfors, E.; Lombardi, S.; Longo, F.; López, M.; López-Coto, R.; Majumdar, P.; Makariev, M.; Mallot, K.; Maneva, G.; Manganaro, M.; Mannheim, K.; Maraschi, L.; Marcote, B.; Mariotti, M.; Martínez, M.; Mazin, D.; Menzel, U.; Miranda, J. M.; Mirzoyan, R.; Moralejo, A.; Moretti, E.; Nakajima, D.; Neustroev, V.; Niedzwiecki, A.; Nievas Rosillo, M.; Nilsson, K.; Nishijima, K.; Noda, K.; Nogués, L.; Overkemping, A.; Paiano, S.; Palacio, J.; Palatiello, M.; Paneque, D.; Paoletti, R.; Paredes, J. M.; Paredes-Fortuny, X.; Pedaletti, G.; Peresano, M.; Perri, L.; Persic, M.; Poutanen, J.; Prada Moroni, P. G.; Prandini, E.; Puljak, I.; Reichardt, I.; Rhode, W.; Ribó, M.; Rico, J.; Rodriguez Garcia, J.; Saito, T.; Satalecka, K.; Schröder, S.; Schultz, C.; Schweizer, T.; Shore, S. N.; Sillanpää, A.; Sitarek, J.; Snidaric, I.; Sobczynska, D.; Stamerra, A.; Steinbring, T.; Strzys, M.; Surić, T.; Takalo, L.; Tavecchio, F.; Temnikov, P.; Terzić, T.; Tescaro, D.; Teshima, M.; Thaele, J.; Torres, D. F.; Toyama, T.; Treves, A.; Vanzo, G.; Verguilov, V.; Vovk, I.; Ward, J. E.; Will, M.; Wu, M. H.; Zanin, R.; Abeysekara, A. U.; Archambault, S.; Archer, A.; Benbow, W.; Bird, R.; Buchovecky, M.; Buckley, J. H.; Bugaev, V.; Connolly, M. P.; Cui, W.; Dickinson, H. J.; Falcone, A.; Feng, Q.; Finley, J. P.; Fleischhack, H.; Flinders, A.; Fortson, L.; Gillanders, G. H.; Griffin, S.; Grube, J.; Hütten, M.; Hanna, D.; Holder, J.; Humensky, T. B.; Kaaret, P.; Kar, P.; Kelley-Hoskins, N.; Kertzman, M.; Kieda, D.; Krause, M.; Krennrich, F.; Lang, M. J.; Maier, G.; McCann, A.; Moriarty, P.; Mukherjee, R.; Nieto, D.; O'Brien, S.; Ong, R. A.; Otte, N.; Park, N.; Perkins, J.; Pichel, A.; Pohl, M.; Popkow, A.; Pueschel, E.; Quinn, J.; Ragan, K.; Reynolds, P. T.; Richards, G. T.; Roache, E.; Rovero, A. C.; Rulten, C.; Sadeh, I.; Santander, M.; Sembroski, G. H.; Shahinyan, K.; Telezhinsky, I.; Tucci, J. V.; Tyler, J.; Wakely, S. P.; Weinstein, A.; Wilcox, P.; Wilhelm, A.; Williams, D. A.; Zitzer, B.; Razzaque, S.; Villata, M.; Raiteri, C. M.; Aller, H. D.; Aller, M. F.; Larionov, V. M.; Arkharov, A. A.; Blinov, D. A.; Efimova, N. V.; Grishina, T. S.; Hagen-Thorn, V. A.; Kopatskaya, E. N.; Larionova, L. V.; Larionova, E. G.; Morozova, D. A.; Troitsky, I. S.; Ligustri, R.; Calcidese, P.; Berdyugin, A.; Kurtanidze, O. M.; Nikolashvili, M. G.; Kimeridze, G. N.; Sigua, L. A.; Kurtanidze, S. O.; Chigladze, R. A.; Chen, W. P.; Koptelova, E.; Sakamoto, T.; Sadun, A. C.; Moody, J. W.; Pace, C.; Pearson, R.; Yatsu, Y.; Mori, Y.; Carraminyana, A.; Carrasco, L.; de la Fuente, E.; Norris, J. P.; Smith, P. S.; Wehrle, A.; Gurwell, M. A.; Zook, A.; Pagani, C.; Perri, M.; Capalbi, M.; Cesarini, A.; Krimm, H. A.; Kovalev, Y. Y.; Kovalev, Yu. A.; Ros, E.; Pushkarev, A. B.; Lister, M. L.; Sokolovsky, K. V.; Kadler, M.; Piner, G.; Lähteenmäki, A.; Tornikoski, M.; Angelakis, E.; Krichbaum, T. P.; Nestoras, I.; Fuhrmann, L.; Zensus, J. A.; Cassaro, P.; Orlati, A.; Maccaferri, G.; Leto, P.; Giroletti, M.; Richards, J. L.; Max-Moerbeck, W.; Readhead, A. C. S.

    2017-07-01

    Context. We present an extensive study of the BL Lac object Mrk 501 based on a data set collected during the multi-instrument campaign spanning from 2009 March 15 to 2009 August 1, which includes, among other instruments, MAGIC, VERITAS, Whipple 10 m, and Fermi-LAT to cover the γ-ray range from 0.1 GeV to 20 TeV; RXTE and Swift to cover wavelengths from UV tohard X-rays; and GASP-WEBT, which provides coverage of radio and optical wavelengths. Optical polarization measurements were provided for a fraction of the campaign by the Steward and St. Petersburg observatories. We evaluate the variability of the source and interband correlations, the γ-ray flaring activity occurring in May 2009, and interpret the results within two synchrotron self-Compton (SSC) scenarios. Aims: The multiband variability observed during the full campaign is addressed in terms of the fractional variability, and the possible correlations are studied by calculating the discrete correlation function for each pair of energy bands where the significance was evaluated with dedicated Monte Carlo simulations. The space of SSC model parameters is probed following a dedicated grid-scan strategy, allowing for a wide range of models to be tested and offering a study of the degeneracy of model-to-data agreement in the individual model parameters, hence providing a less biased interpretation than the "single-curve SSC model adjustment" typically reported in the literature. Methods: We find an increase in the fractional variability with energy, while no significant interband correlations of flux changes are found on the basis of the acquired data set. The SSC model grid-scan shows that the flaring activity around May 22 cannot be modeled adequately with a one-zone SSC scenario (using an electron energy distribution with two breaks), while it can be suitably described within a two (independent) zone SSC scenario. Here, one zone is responsible for the quiescent emission from the averaged 4.5-month observing period, while the other one, which is spatially separated from the first, dominates the flaring emission occurring at X-rays and very-high-energy (>100 GeV, VHE) γ rays. The flaring activity from May 1, which coincides with a rotation of the electric vector polarization angle (EVPA), cannot be satisfactorily reproduced by either a one-zone or a two-independent-zone SSC model, yet this is partially affected by the lack of strictly simultaneous observations and the presence of large flux changes on sub-hour timescales (detected at VHE γ rays). Results: The higher variability in the VHE emission and lack of correlation with the X-ray emission indicate that, at least during the 4.5-month observing campaign in 2009, the highest energy (and most variable) electrons that are responsible for the VHE γ rays do not make a dominant contribution to the 1 keV emission. Alternatively, there could be a very variable component contributing to the VHE γ-ray emission in addition to that coming from the SSC scenario. The studies with our dedicated SSC grid-scan show that there is some degeneracy in both the one-zone and the two-zone SSC scenarios probed, with several combinations of model parameters yielding a similar model-to-data agreement, and some parameters better constrained than others. The observed γ-ray flaring activity, with the EVPA rotation coincident with the first γ-ray flare, resembles those reported previously for low frequency peaked blazars, hence suggesting that there are many similarities in the flaring mechanisms of blazars with different jet properties.

  8. Development of a five-year mortality model in systemic sclerosis patients by different analytical approaches.

    PubMed

    Beretta, Lorenzo; Santaniello, Alessandro; Cappiello, Francesca; Chawla, Nitesh V; Vonk, Madelon C; Carreira, Patricia E; Allanore, Yannick; Popa-Diaconu, D A; Cossu, Marta; Bertolotti, Francesca; Ferraccioli, Gianfranco; Mazzone, Antonino; Scorza, Raffaella

    2010-01-01

    Systemic sclerosis (SSc) is a multiorgan disease with high mortality rates. Several clinical features have been associated with poor survival in different populations of SSc patients, but no clear and reproducible prognostic model to assess individual survival prediction in scleroderma patients has ever been developed. We used Cox regression and three data mining-based classifiers (Naïve Bayes Classifier [NBC], Random Forests [RND-F] and logistic regression [Log-Reg]) to develop a robust and reproducible 5-year prognostic model. All the models were built and internally validated by means of 5-fold cross-validation on a population of 558 Italian SSc patients. Their predictive ability and capability of generalisation was then tested on an independent population of 356 patients recruited from 5 external centres and finally compared to the predictions made by two SSc domain experts on the same population. The NBC outperformed the Cox-based classifier and the other data mining algorithms after internal cross-validation (area under receiving operator characteristic curve, AUROC: NBC=0.759; RND-F=0.736; Log-Reg=0.754 and Cox= 0.724). The NBC had also a remarkable and better trade-off between sensitivity and specificity (e.g. Balanced accuracy, BA) than the Cox-based classifier, when tested on an independent population of SSc patients (BA: NBC=0.769, Cox=0.622). The NBC was also superior to domain experts in predicting 5-year survival in this population (AUROC=0.829 vs. AUROC=0.788 and BA=0.769 vs. BA=0.67). We provide a model to make consistent 5-year prognostic predictions in SSc patients. Its internal validity, as well as capability of generalisation and reduced uncertainty compared to human experts support its use at bedside. Available at: http://www.nd.edu/~nchawla/survival.xls.

  9. One-zone synchrotron self-Compton model for the core emission of Centaurus A revisited

    NASA Astrophysics Data System (ADS)

    Petropoulou, M.; Lefa, E.; Dimitrakoudis, S.; Mastichiadis, A.

    2014-02-01

    Aims: We investigate the role of the second synchrotron self-Compton (SSC) photon generation to the multiwavelength emission from the compact regions of sources that are characterized as misaligned blazars. For this, we focus on the nearest high-energy emitting radio galaxy Centaurus A and we revisit the one-zone SSC model for its core emission. Methods: We have calculated analytically the peak luminosities of the first and second SSC components by first deriving the steady-state electron distribution in the presence of synchrotron and SSC cooling, and then by using appropriate expressions for the positions of the spectral peaks. We have also tested our analytical results against those derived from a numerical code where the full emissivities and cross-sections were used. Results: We show that the one-zone SSC model cannot account for the core emission of Centaurus A above a few GeV, where the peak of the second SSC component appears. We thus propose an alternative explanation for the origin of the high-energy (≳0.4 GeV) and TeV emission, where these are attributed to the radiation emitted by a relativistic proton component through photohadronic interactions with the photons produced by the primary leptonic component. We show that the required proton luminosities are not extremely high, i.e. ~1043 erg/s, provided that the injection spectra are modelled by a power law with a high value of the lower energy cutoff. Finally, we find that the contribution of the core emitting region of Cen A to the observed neutrino and ultra-high-energy cosmic-ray fluxes is negligible.

  10. Optimal mission planning of GEO on-orbit refueling in mixed strategy

    NASA Astrophysics Data System (ADS)

    Chen, Xiao-qian; Yu, Jing

    2017-04-01

    The mission planning of GEO on-orbit refueling (OOR) in Mixed strategy is studied in this paper. Specifically, one SSc will be launched to an orbital slot near the depot when multiple GEO satellites are reaching their end of lives. The SSc replenishes fuel from the depot and then extends the lifespan of the target satellites via refueling. In the mixed scenario, only some of the target satellites could be served by the SSc, and the remaining ones will be fueled by Pseudo SScs (the target satellite which has already been refueled by the SSc and now has sufficient fuel for its operation as well as the fuel to refuel other target satellites is called Pseudo SSc here). The mission sequences and fuel mass of the SSc and Pseudo SScs, the dry mass of the SSc are used as design variables, whereas the economic benefit of the whole mission is used as design objective. The economic cost and benefit models are stated first, and then a mathematical optimization model is proposed. A comprehensive solution method involving enumeration, particle swarm optimization and modification is developed. Numerical examples are carried out to demonstrate the effectiveness of the model and solution method. Economic efficiencies of different OOR strategies are compared and discussed. The mixed strategy would perform better than the other strategies only when the target satellites satisfy some conditions. This paper presents an available mixed strategy scheme for users and analyzes its advantages and disadvantages by comparing with some other OOR strategies, providing helpful references to decision makers. The best strategy in practical applications depends on the specific demands and user preference.

  11. Work Productivity in Scleroderma – Analysis from the UCLA Scleroderma Quality of Life Study

    PubMed Central

    Singh, Manjit K.; Clements, Philip J.; Furst, Daniel E.; Maranian, Paul; Khanna, Dinesh

    2011-01-01

    Objective To examine the productivity of patients with scleroderma (SSc) both outside and within the home in a large observational cohort. Methods 162 patients completed the Work Productivity Survey. Patients indicated whether or not they were employed outside of the home, how many days/month they missed work (employment or household work) due to SSc and how many days/month productivity was decreased ≥ 50%. Patients also completed other patient-reported outcome measures. We developed binomial regression models to assess the predictors of days missed from work (paid employment or household activities). The covariates included: type of SSc, education, physician and patient global assessments, HAQ-DI, FACIT-Fatigue, and Center of Epidemiologic Studies Depression Scale – Short Form (CESD). Results The average age of patients was 51.8 years and 51% had limited SSc. Of 37% patients employed outside of the home, patients reported missing 2.6 days/month of work and had 2.5 days per month productivity reduced by half. Of the 102 patients who were not employed, 39.4% were unable to work due to their SSc. When we assessed patients for household activities (N = 162), patients missed an average of 8 days of housework/month and had productivity reduced by average of 6 days/month. In the regression models, patients with lower education and poor assessment of overall health by physician were more likely to miss work outside the home. Patients with limited SSc and high HAQ-DI were more likely to miss work at home. Conclusion SSc has a major impact on productivity at home and at work. Nearly 40% of patients reported disability due to their SSc. PMID:22012885

  12. Registry of the Spanish Network for Systemic Sclerosis

    PubMed Central

    Simeón-Aznar, C.P.; Fonollosa-Plá, V.; Tolosa-Vilella, Carles; Espinosa-Garriga, G.; Campillo-Grau, M.; Ramos-Casals, M.; García-Hernández, F.J.; Castillo-Palma, M.J.; Sánchez-Román, J.; Callejas-Rubio, J.L.; Ortego-Centeno, N.; Egurbide-Arberas, M.V.; Trapiellla-Martínez, L.; Caminal-Montero, L.; Sáez-Comet, L.; Velilla-Marco, J.; Camps-García, M.T.; de Ramón-Garrido, E.; Esteban-Marcos, E.M.; Pallarés-Ferreres, L.; Navarrete-Navarrete, N.; Vargas-Hitos, J.A.; de la Torre, R. Gómez; Salvador-Cervello, G.; Rios-Blanco, J.J.; Vilardell-Tarrés, M.

    2015-01-01

    Abstract Systemic sclerosis (SSc) is a rare, multisystem disease showing a large individual variability in disease progression and prognosis. In the present study, we assess survival, causes of death, and risk factors of mortality in a large series of Spanish SSc patients. Consecutive SSc patients fulfilling criteria of the classification by LeRoy were recruited in the survey. Kaplan–Meier and Cox proportional-hazards models were used to analyze survival and to identify predictors of mortality. Among 879 consecutive patients, 138 (15.7%) deaths were registered. Seventy-six out of 138 (55%) deceased patients were due to causes attributed to SSc, and pulmonary hypertension (PH) was the leading cause in 23 (16.6%) patients. Survival rates were 96%, 93%, 83%, and 73% at 5, 10, 20, and 30 years after the first symptom, respectively. Survival rates for diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc were 91%, 86%, 64%, and 39%; and 97%, 95%, 85%, and 81% at 5, 10, 20, and 30 years, respectively (log-rank: 67.63, P < 0.0001). The dcSSc subset, male sex, age at disease onset older than 65 years, digital ulcers, interstitial lung disease (ILD), PH, heart involvement, scleroderma renal crisis (SRC), presence of antitopoisomerase I and absence of anticentromere antibodies, and active capillaroscopic pattern showed reduced survival rate. In a multivariate analysis, older age at disease onset, dcSSc, ILD, PH, and SRC were independent risk factors for mortality. In the present study involving a large cohort of SSc patients, a high prevalence of disease-related causes of death was demonstrated. Older age at disease onset, dcSSc, ILD, PH, and SRC were identified as independent prognostic factors. PMID:26512564

  13. Survival and causes of death in systemic sclerosis patients: a single center registry report from Iran.

    PubMed

    Poormoghim, Hadi; Andalib, Elham; Jalali, Arash; Ghaderi, Afshin; Ghorbannia, Ali; Mojtabavi, Nazanin

    2016-07-01

    The aims of the study were to determine prognostic factors for survival and causes of death in a cohort of patients with systemic sclerosis (SSc). This was a cohort study of SSc patients in single rheumatologic center from January 1998 to August 2012. They fulfilled the American College of Rheumatology classification criteria for SSc or had calcinosis Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia or sine sclerosis. Causes of death were classified as SSc related and non-SSc related. Kaplan-Meier and Cox proportional hazard regression models were used in univariate and multivariate analysis to analyse survival in subgroups and determine prognostic factors of survival. The study includes 220 patients (192 female, 28 male). Out of thirty-two (14.5 %) who died, seventeen (53.1 %) deaths were SSc related and in nine (28.1 %) non-SSc-related causes, and in six (18.8 %) of patients causes of death were not defined. Overall survival rate was 92.6 % (95 % CI 87.5-95.7 %) after 5 years and 82.3 % (95 % CI 73.4-88.4 %) after 10 years. Pulmonary involvement was a major SSc-related cause of death, occurred in seven (41.1 %) patients. Cardiovascular events were leading cause of in overall death (11) 34.3 % and 6 in non-SSc-related death. Independent risk factors for mortality were age >50 at diagnosis (HR 5.10) advance pulmonary fibrosis (HR 11.5), tendon friction rub at entry (HR 6.39), arthritis (HR 3.56). In this first Middle Eastern series of SSc registry, pulmonary and cardiac involvements were the leading cause of SSc-related death.

  14. Improved resolution in extracellular vesicle populations using 405 instead of 488 nm side scatter

    PubMed Central

    McVey, Mark J.; Spring, Christopher M.; Kuebler, Wolfgang M.

    2018-01-01

    ABSTRACT Improvements in identification and assessment of extracellular vesicles (EVs) have fuelled a recent surge in EV publications investigating their roles as biomarkers and mediators of disease. Meaningful scientific comparisons are, however, hampered by difficulties in accurate, reproducible enumeration and characterization of EVs in biological fluids. High-sensitivity flow cytometry (FCM) is presently the most commonly applied strategy to assess EVs, yet its utility is limited by variant ability to resolve smaller EVs. Here, we propose the use of 405 nm (violet) wavelength lasers in place of 488 nm (blue) for side scatter (SSC) detection to obtain greater resolution of EVs using high-sensitivity FCM. To test this hypothesis, we modelled EV resolution by violet versus blue SSC in silico and compared resolution of reference beads and biological EVs from plasma and bronchoalveolar lavage (BAL) fluid using either violet or blue wavelength SSC EV detection. Mie scatter modelling predicted that violet as compared to blue SSC increases resolution of small (100–500 nm) spherical particles with refractive indices (1.34–1.46) similar to EVs by approximately twofold in terms of light intensity and by nearly 20% in SSC signal quantum efficiency. Resolution of reference beads was improved by violet instead of blue SSC with two- and fivefold decreases in coefficients of variation for particles of 300–500 nm and 180–240 nm size, respectively. Resolution was similarly improved for detection of EVs from plasma or BAL fluid. Violet SSC detection for high-sensitivity FCM allows for significantly greater resolution of EVs in plasma and BAL compared to conventional blue SSC and particularly improves resolution of smaller EVs. Notably, the proposed strategy is readily implementable and inexpensive for machines already equipped with 405 nm SSC or the ability to accommodate 405/10 nm bandpass filters in their violet detector arrays. PMID:29696076

  15. Estimating suspended sediment using acoustics in a fine-grained riverine system, Kickapoo Creek at Bloomington, Illinois

    USGS Publications Warehouse

    Manaster, Amanda D.; Domanski, Marian M.; Straub, Timothy D.; Boldt, Justin A.

    2016-08-18

    Acoustic technologies have the potential to be used as a surrogate for measuring suspended-sediment concentration (SSC). This potential was examined in a fine-grained (97-100 percent fines) riverine system in central Illinois by way of installation of an acoustic instrument. Acoustic data were collected continuously over the span of 5.5 years. Acoustic parameters were regressed against SSC data to determine the accuracy of using acoustic technology as a surrogate for measuring SSC in a fine-grained riverine system. The resulting regressions for SSC and sediment acoustic parameters had coefficients of determination ranging from 0.75 to 0.97 for various events and configurations. The overall Nash-Sutcliffe model-fit efficiency was 0.95 for the 132 observed and predicted SSC values determined using the sediment acoustic parameter regressions. The study of using acoustic technologies as a surrogate for measuring SSC in fine-grained riverine systems is ongoing. The results at this site are promising in the realm of surrogate technology.

  16. Correlations of turbidity to suspended-sediment concentration in the Toutle River Basin, near Mount St. Helens, Washington, 2010-11

    USGS Publications Warehouse

    Uhrich, Mark A.; Kolasinac, Jasna; Booth, Pamela L.; Fountain, Robert L.; Spicer, Kurt R.; Mosbrucker, Adam R.

    2014-01-01

    Researchers at the U.S. Geological Survey, Cascades Volcano Observatory, investigated alternative methods for the traditional sample-based sediment record procedure in determining suspended-sediment concentration (SSC) and discharge. One such sediment-surrogate technique was developed using turbidity and discharge to estimate SSC for two gaging stations in the Toutle River Basin near Mount St. Helens, Washington. To provide context for the study, methods for collecting sediment data and monitoring turbidity are discussed. Statistical methods used include the development of ordinary least squares regression models for each gaging station. Issues of time-related autocorrelation also are evaluated. Addition of lagged explanatory variables was used to account for autocorrelation in the turbidity, discharge, and SSC data. Final regression model equations and plots are presented for the two gaging stations. The regression models support near-real-time estimates of SSC and improved suspended-sediment discharge records by incorporating continuous instream turbidity. Future use of such models may potentially lower the costs of sediment monitoring by reducing time it takes to collect and process samples and to derive a sediment-discharge record.

  17. A sampling approach for predicting the eating quality of apples using visible-near infrared spectroscopy.

    PubMed

    Martínez Vega, Mabel V; Sharifzadeh, Sara; Wulfsohn, Dvoralai; Skov, Thomas; Clemmensen, Line Harder; Toldam-Andersen, Torben B

    2013-12-01

    Visible-near infrared spectroscopy remains a method of increasing interest as a fast alternative for the evaluation of fruit quality. The success of the method is assumed to be achieved by using large sets of samples to produce robust calibration models. In this study we used representative samples of an early and a late season apple cultivar to evaluate model robustness (in terms of prediction ability and error) on the soluble solids content (SSC) and acidity prediction, in the wavelength range 400-1100 nm. A total of 196 middle-early season and 219 late season apples (Malus domestica Borkh.) cvs 'Aroma' and 'Holsteiner Cox' samples were used to construct spectral models for SSC and acidity. Partial least squares (PLS), ridge regression (RR) and elastic net (EN) models were used to build prediction models. Furthermore, we compared three sub-sample arrangements for forming training and test sets ('smooth fractionator', by date of measurement after harvest and random). Using the 'smooth fractionator' sampling method, fewer spectral bands (26) and elastic net resulted in improved performance for SSC models of 'Aroma' apples, with a coefficient of variation CVSSC = 13%. The model showed consistently low errors and bias (PLS/EN: R(2) cal = 0.60/0.60; SEC = 0.88/0.88°Brix; Biascal = 0.00/0.00; R(2) val = 0.33/0.44; SEP = 1.14/1.03; Biasval = 0.04/0.03). However, the prediction acidity and for SSC (CV = 5%) of the late cultivar 'Holsteiner Cox' produced inferior results as compared with 'Aroma'. It was possible to construct local SSC and acidity calibration models for early season apple cultivars with CVs of SSC and acidity around 10%. The overall model performance of these data sets also depend on the proper selection of training and test sets. The 'smooth fractionator' protocol provided an objective method for obtaining training and test sets that capture the existing variability of the fruit samples for construction of visible-NIR prediction models. The implication is that by using such 'efficient' sampling methods for obtaining an initial sample of fruit that represents the variability of the population and for sub-sampling to form training and test sets it should be possible to use relatively small sample sizes to develop spectral predictions of fruit quality. Using feature selection and elastic net appears to improve the SSC model performance in terms of R(2), RMSECV and RMSEP for 'Aroma' apples. © 2013 Society of Chemical Industry.

  18. Retrieval of suspended sediment concentrations using Landsat-8 OLI satellite images in the Orinoco River (Venezuela)

    NASA Astrophysics Data System (ADS)

    Yepez, Santiago; Laraque, Alain; Martinez, Jean-Michel; De Sa, Jose; Carrera, Juan Manuel; Castellanos, Bartolo; Gallay, Marjorie; Lopez, Jose L.

    2018-01-01

    In this study, 81 Landsat-8 scenes acquired from 2013 to 2015 were used to estimate the suspended sediment concentration (SSC) in the Orinoco River at its main hydrological station at Ciudad Bolivar, Venezuela. This gauging station monitors an upstream area corresponding to 89% of the total catchment area where the mean discharge is of 33,000 m3·s-1. SSC spatial and temporal variabilities were analyzed in relation to the hydrological cycle and to local geomorphological characteristics of the river mainstream. Three types of atmospheric correction models were evaluated to correct the Landsat-8 images: DOS, FLAASH, and L8SR. Surface reflectance was compared with monthly water sampling to calibrate a SSC retrieval model using a bootstrapping resampling. A regression model based on surface reflectance at the Near-Infrared wavelengths showed the best performance: R2 = 0.92 (N = 27) for the whole range of SSC (18 to 203 mg·l-1) measured at this station during the studied period. The method offers a simple new approach to estimate the SSC along the lower Orinoco River and demonstrates the feasibility and reliability of remote sensing images to map the spatiotemporal variability in sediment transport over large rivers.

  19. SAM Photovoltaic Model Technical Reference 2016 Update

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

    Gilman, Paul; DiOrio, Nicholas A; Freeman, Janine M

    This manual describes the photovoltaic performance model in the System Advisor Model (SAM) software, Version 2016.3.14 Revision 4 (SSC Version 160). It is an update to the 2015 edition of the manual, which describes the photovoltaic model in SAM 2015.1.30 (SSC 41). This new edition includes corrections of errors in the 2015 edition and descriptions of new features introduced in SAM 2016.3.14, including: 3D shade calculator Battery storage model DC power optimizer loss inputs Snow loss model Plane-of-array irradiance input from weather file option Support for sub-hourly simulations Self-shading works with all four subarrays, and uses same algorithm for fixedmore » arrays and one-axis tracking Linear self-shading algorithm for thin-film modules Loss percentages replace derate factors. The photovoltaic performance model is one of the modules in the SAM Simulation Core (SSC), which is part of both SAM and the SAM SDK. SAM is a user-friedly desktop application for analysis of renewable energy projects. The SAM SDK (Software Development Kit) is for developers writing their own renewable energy analysis software based on SSC. This manual is written for users of both SAM and the SAM SDK wanting to learn more about the details of SAM's photovoltaic model.« less

  20. Comparative characterization of sewage sludge compost and soil: Heavy metal leaching characteristics.

    PubMed

    Fang, Wen; Wei, Yonghong; Liu, Jianguo

    2016-06-05

    The leaching and accumulation of heavy metals are major concerns following the land application of sewage sludge compost (SSC). We comparatively characterized SSC, the reference soil, and the SSC amended soil to investigate their similarities and differences regarding heavy metal leaching behavior and then to evaluate the effect of SSC land application on the leaching behavior of soil. Results showed that organic matter, including both of particulate organic matter (POM) and dissolved organic matter (DOM), were critical factors influencing heavy metal leaching from both of SSC and the soil. When SSC was applied to soil at the application rate of 48t/ha, the increase of DOM content slightly enhanced heavy metal leaching from the amended soil over the applicable pH domain (6

  1. The sustainability and performance measurement on supply chain in services industry: A literature review

    NASA Astrophysics Data System (ADS)

    Leksono, Eko Budi; Suparno, Vanany, Iwan

    2017-11-01

    The services industry growth has been significant relation with economic growth. A new paradigm is needed for services sector development. The supply chain and performance measurement able to sustain of services industry growth. The supply chain implementation in the services industry called service supply chain (SSC). The globalization and stakeholder pressure makes operation of SSC should more attention to sustainability issue which consists of economic, social and environment simultaneously on SSC. Furthermore, services industry can develop by implementation of the sustainable SSC and its performance measurement. The sustainable SSC implementation can minimize of negative operation effect to environment and social, and maximize of profit. Sustainable service supply chain performance measurements (SSSCPM) are still less explored. The purpose of this paper is to review the literature in the field SSC, SSSC, SSC performance measurement (SSCPM) and SSSCPM for identification of the SSSCPM frameworks and indicators. Beside, the result of review able to look opportunities for develop a new framework for SSSCPM at the operational level, tactical and strategic, multiplayer and close loop, the effectiveness of the integration and development of modeling and simulation for evaluation in the future.

  2. Increased dermal collagen bundle alignment in systemic sclerosis is associated with a cell migration signature and role of Arhgdib in directed fibroblast migration on aligned ECMs

    PubMed Central

    Lafyatis, Robert; Burkly, Linda C.

    2017-01-01

    Systemic sclerosis (SSc) is a devastating disease affecting the skin and internal organs. Dermal fibrosis manifests early and Modified Rodnan Skin Scores (MRSS) correlate with disease progression. Transcriptomics of SSc skin biopsies suggest the role of the in vivo microenvironment in maintaining the pathological myofibroblasts. Therefore, defining the structural changes in dermal collagen in SSc patients could inform our understanding of fibrosis pathogenesis. Here, we report a method for quantitative whole-slide image analysis of dermal collagen from SSc patients, and our findings of more aligned dermal collagen bundles in diffuse cutaneous SSc (dcSSc) patients. Using the bleomycin-induced mouse model of SSc, we identified a distinct high dermal collagen bundle alignment gene signature, characterized by a concerted upregulation in cell migration, adhesion, and guidance pathways, and downregulation of spindle, replication, and cytokinesis pathways. Furthermore, increased bundle alignment induced a cell migration gene signature in fibroblasts in vitro, and these cells demonstrated increased directed migration on aligned ECM fibers that is dependent on expression of Arhgdib (Rho GDP-dissociation inhibitor 2). Our results indicate that increased cell migration is a cellular response to the increased collagen bundle alignment featured in fibrotic skin. Moreover, many of the cell migration genes identified in our study are shared with human SSc skin and may be new targets for therapeutic intervention. PMID:28662216

  3. A method for simulating sediment incipient motion varying with time and space in an ocean model (FVCOM): development and validation

    NASA Astrophysics Data System (ADS)

    Zhu, Zichen; Wang, Yongzhi; Bian, Shuhua; Hu, Zejian; Liu, Jianqiang; Liu, Lejun

    2017-11-01

    We modified the sediment incipient motion in a numerical model and evaluated the impact of this modification using a study case of the coastal area around Weihai, China. The modified and unmodified versions of the model were validated by comparing simulated and observed data of currents, waves, and suspended sediment concentrations (SSC) measured from July 25th to July 26th, 2006. A fitted Shields diagram was introduced into the sediment model so that the critical erosional shear stress could vary with time. Thus, the simulated SSC patterns were improved to more closely reflect the observed values, so that the relative error of the variation range decreased by up to 34.5% and the relative error of simulated temporally averaged SSC decreased by up to 36%. In the modified model, the critical shear stress values of the simulated silt with a diameter of 0.035 mm and mud with a diameter of 0.004 mm varied from 0.05 to 0.13 N/m2, and from 0.05 to 0.14 N/m 2, respectively, instead of remaining constant in the unmodified model. Besides, a method of applying spatially varying fractions of the mixed grain size sediment improved the simulated SSC distribution to fit better to the remote sensing map and reproduced the zonal area with high SSC between Heini Bay and the erosion groove in the modified model. The Relative Mean Absolute Error was reduced by between 6% and 79%, depending on the regional attributes when we used the modified method to simulate incipient sediment motion. But the modification achieved the higher accuracy in this study at a cost of computation speed decreasing by 1.52%.

  4. Application of dimensionless sediment rating curves to predict suspended-sediment concentrations, bedload, and annual sediment loads for rivers in Minnesota

    USGS Publications Warehouse

    Ellison, Christopher A.; Groten, Joel T.; Lorenz, David L.; Koller, Karl S.

    2016-10-27

    Consistent and reliable sediment data are needed by Federal, State, and local government agencies responsible for monitoring water quality, planning river restoration, quantifying sediment budgets, and evaluating the effectiveness of sediment reduction strategies. Heightened concerns about excessive sediment in rivers and the challenge to reduce costs and eliminate data gaps has guided Federal and State interests in pursuing alternative methods for measuring suspended and bedload sediment. Simple and dependable data collection and estimation techniques are needed to generate hydraulic and water-quality information for areas where data are unavailable or difficult to collect.The U.S. Geological Survey, in cooperation with the Minnesota Pollution Control Agency and the Minnesota Department of Natural Resources, completed a study to evaluate the use of dimensionless sediment rating curves (DSRCs) to accurately predict suspended-sediment concentrations (SSCs), bedload, and annual sediment loads for selected rivers and streams in Minnesota based on data collected during 2007 through 2013. This study included the application of DSRC models developed for a small group of streams located in the San Juan River Basin near Pagosa Springs in southwestern Colorado to rivers in Minnesota. Regionally based DSRC models for Minnesota also were developed and compared to DSRC models from Pagosa Springs, Colorado, to evaluate which model provided more accurate predictions of SSCs and bedload in Minnesota.Multiple measures of goodness-of-fit were developed to assess the effectiveness of DSRC models in predicting SSC and bedload for rivers in Minnesota. More than 600 dimensionless ratio values of SSC, bedload, and streamflow were evaluated and delineated according to Pfankuch stream stability categories of “good/fair” and “poor” to develop four Minnesota-based DSRC models. The basis for Pagosa Springs and Minnesota DSRC model effectiveness was founded on measures of goodness-of-fit that included proximity of the model(s) fitted line to the 95-percent confidence intervals of the site-specific model, Nash-Sutcliffe Efficiency values, model biases, and deviation of annual sediment loads from each model to the annual sediment loads calculated from measured data.Composite plots comparing Pagosa Springs DSRCs, Minnesota DSRCs, site-specific regression models, and measured data indicated that regionally developed DSRCs (Minnesota DSRC models) more closely approximated measured data for nearly every site. Pagosa Springs DSRC models had markedly larger exponents (slopes) when compared to the Minnesota DSRC models and the site-specific regression models, and over-represent SSC and bedload at streamflows exceeding bankfull. The Nash-Sutcliffe Efficiency values for the Minnesota DSRC model for suspended-sediment concentrations closely matched Nash-Sutcliffe Efficiency values of the site-specific regression models for 12 out of 16 sites. Nash-Sutcliffe Efficiency values associated with Minnesota DSRCs were greater than those associated with Pagosa Springs DSRCs for every site except the Whitewater River near Beaver, Minnesota site. Pagosa Springs DSRC models were less accurate than the mean of the measured data at predicting SSC values for one-half of the sites for good/fair stability sites and one-half of the sites for poor stability sites. Relative model biases were calculated and determined to be substantial (greater than 5 percent) for Pagosa Springs and Minnesota models, with Minnesota models having a lower mean model bias. For predicted annual suspended-sediment loads (SSL), the Minnesota DSRC models for good/fair and poor stream stability sites more closely approximated the annual SSLs calculated from the measured data as compared to the Pagosa Springs DSRC model.Results of data analyses indicate that DSRC models developed using data collected in Minnesota were more effective at compensating for differences in individual stream characteristics across a variety of basin sizes and flow regimes than DSRC models developed using data collected for Pagosa Springs, Colorado. Minnesota DSRC models retained a substantial portion of the unique sediment signatures for most rivers, although deviations were observed for streams with limited sediment supply and for rivers in southeastern Minnesota, which had markedly larger regression exponents. Compared to Pagosa Springs DSRC models, Minnesota DSRC models had regression slopes that more closely matched the slopes of site-specific regression models, had greater Nash-Sutcliffe Efficiency values, had lower model biases, and approximated measured annual sediment loads more closely. The results presented in this report indicate that regionally based DSRCs can be used to estimate reasonably accurate values of SSC and bedload.Practitioners are cautioned that DSRC reliability is dependent on representative measures of bankfull streamflow, SSC, and bedload. It is, therefore, important that samples of SSC and bedload, which will be used for estimating SSC and bedload at the bankfull streamflow, are collected over a range of conditions that includes the ascending and descending limbs of the event hydrograph. The use of DSRC models may have substantial limitations for certain conditions. For example, DSRC models should not be used to predict SSC and sediment loads for extreme streamflows, such as those that exceed twice the bankfull streamflow value because this constitutes conditions beyond the realm of current (2016) empirical modeling capability. Also, if relations between SSC and streamflow and between bedload and streamflow are not statistically significant, DSRC models should not be used to predict SSC or bedload, as this could result in large errors. For streams that do not violate these conditions, DSRC estimates of SSC and bedload can be used for stream restoration planning and design, and for estimating annual sediment loads for streams where little or no sediment data are available.

  5. South-South cooperation as a mechanism to strengthen public health services in Africa: experiences, challenges and a call for concerted action.

    PubMed

    Olu, Olushayo; Petu, Amos; Ovberedjo, Martin; Muhongerwa, Diane

    2017-01-01

    Implementation of new models of development cooperation have been on the increase lately. Coupled with this are calls for use of horizontal development cooperation mechanisms such as South-South Cooperation (SSC) as a way to enhance aid effectiveness in the health sector of developing countries. In this case series, we review recent experiences in the application of SSC initiatives to two public health situations in Africa to demonstrate the veracity of this new paradigm. Our review highlight the immense benefits associated with the use of SSC for health and provide evidence for increasing use of horizontal development coordination mechanisms to strengthen public health services delivery and socioeconomic development among African countries. Opportunities for SSC among African countries include in the areas of disease prevention and control, production of medical products and essential medicines, harmonization of regulatory processes, and health workforce development among others. However, pitfalls such as poor coordination, inadequate political commitment, lack of conducive policy environments, language barrier and inadequate financing opportunities for SSC initiatives present major dilemma for the use of SSC mechanisms. We conclude that the need for a paradigm shift from vertical to horizontal development cooperation needs no further proof but a call to action. We call on the concerned stakeholders to support the establishment of a systematic approach for use of SSC mechanisms in the health sector of Africa, designation of an African Centre of Excellence for SSC in public health and development of a regional mechanism for monitoring and evaluation of SSC initiatives in Africa.

  6. South-South cooperation as a mechanism to strengthen public health services in Africa: experiences, challenges and a call for concerted action

    PubMed Central

    Olu, Olushayo; Petu, Amos; Ovberedjo, Martin; Muhongerwa, Diane

    2017-01-01

    Implementation of new models of development cooperation have been on the increase lately. Coupled with this are calls for use of horizontal development cooperation mechanisms such as South-South Cooperation (SSC) as a way to enhance aid effectiveness in the health sector of developing countries. In this case series, we review recent experiences in the application of SSC initiatives to two public health situations in Africa to demonstrate the veracity of this new paradigm. Our review highlight the immense benefits associated with the use of SSC for health and provide evidence for increasing use of horizontal development coordination mechanisms to strengthen public health services delivery and socioeconomic development among African countries. Opportunities for SSC among African countries include in the areas of disease prevention and control, production of medical products and essential medicines, harmonization of regulatory processes, and health workforce development among others. However, pitfalls such as poor coordination, inadequate political commitment, lack of conducive policy environments, language barrier and inadequate financing opportunities for SSC initiatives present major dilemma for the use of SSC mechanisms. We conclude that the need for a paradigm shift from vertical to horizontal development cooperation needs no further proof but a call to action. We call on the concerned stakeholders to support the establishment of a systematic approach for use of SSC mechanisms in the health sector of Africa, designation of an African Centre of Excellence for SSC in public health and development of a regional mechanism for monitoring and evaluation of SSC initiatives in Africa. PMID:29158863

  7. Use of acoustic backscatter to estimate continuous suspended sediment and phosphorus concentrations in the Barton River, northern Vermont, 2010-2013

    USGS Publications Warehouse

    Medalie, Laura; Chalmers, Ann T.; Kiah, Richard G.; Copans, Benjamin

    2014-01-01

    The U.S. Geological Survey, in cooperation with the Vermont Department of Environmental Conservation, investigated the use of acoustic backscatter to estimate concentrations of suspended sediment and total phosphorus at the Barton River near Coventry, Vermont. The hypothesis was that acoustic backscatter—the reflection of sound waves off objects back to the source from which they came—measured by an acoustic Doppler profiler (ADP) and recorded as ancillary data for the calculation of discharge, also could be used to generate a continuous concentration record of suspended sediment and phosphorus at the streamgage, thereby deriving added value from the instrument. Suspended-sediment and phosphorus concentrations are of particular interest in Vermont, where impairment of surface waters by suspended sediments and phosphorus is a major concern. Regression models for estimating suspended-sediment concentrations (SSCs) and total phosphorus concentrations evaluated several independent variables: measured backscatter (MB), water-corrected backscatter (WCB), sediment-corrected backscatter (SCB), discharge, fluid-absorption coefficient, sediment-driven acoustic attenuation coefficient, and discharge hysteresis. The best regression equations for estimating SSC used backscatter as the predictor, reflecting the direct relation between acoustic backscatter and SSC. Backscatter was a better predictor of SSC than discharge in part because hysteresis between SSC and backscatter was less than for SSC and discharge. All three backscatter variables—MB, WCB, and SCB—performed equally as predictors of SSC and phosphorus concentrations at the Barton River site. The similar abilities to predict SSC among backscatter terms may partially be attributed to the low values and narrow range of the sediment-driven acoustic attenuation in the Barton River. The regression based on SCB was selected for estimating SSC because it removes potential bias caused by attenuation and temperature fluctuations. The best regression model for estimating phosphorus concentrations included terms for discharge and discharge hysteresis. The finding that discharge hysteresis was a significant predictor of phosphorus concentrations might be related to preferential sorption of phosphorus to fine-grained sediments, which have been found to be particularly sensitive to hysteresis. Regression models designed to estimate phosphorus concentrations had less predictive power than the models for SSCs. Data from the Barton River did not fully support one of the study’s hypotheses—that backscatter is mostly caused by sands, and attenuation is mostly caused by fines. Sands, fines, and total SSCs in the Barton River all related better to backscatter than to sediment-driven acoustic attenuation. The weak relation between SSC and sediment-driven acoustic attenuation may be related to the low values and narrow range of SSCs and sediment attenuations observed at Barton River. A weak relation between SSC and sediment-driven acoustic attenuation also suggests that the diameters of the fine-sized suspended sediments in the Barton River may be predominantly greater than 20 micrometers (μm). Long-term changes in the particle-size distribution (PSD) were not observed in Barton River; however, some degree of within-storm changes in sediment source and possibly PSD were inferred from the hysteresis between SSC and SCB.

  8. Spectral Characteristics of Salinized Soils during Microbial Remediation Processes.

    PubMed

    Ma, Chuang; Shen, Guang-rong; Zhi, Yue-e; Wang, Zi-jun; Zhu, Yun; Li, Xian-hua

    2015-09-01

    In this study, the spectral reflectance of saline soils, the associated soil salt content (SSC) and the concentrations of salt ions were measured and analysed by tracing the container microbial remediation experiments for saline soil (main salt is sodium chloride) of Dongying City, Shandong Province. The sensitive spectral reflectance bands of saline soils to SSC, Cl- and Na+ in the process of microbial remediation were analysed. The average-dimension reduction of these bands was conducted by using a combination of correlation coefficient and decision coefficient, and by gradually narrowing the sampling interval method. Results showed that the tendency and magnitude of the average spectral reflectance in all bands of saline soils during the total remediation processes were nearly consistent with SSC and with Cl- coocentration, respectively. The degree of salinity of the soil, including SSC and salt ion concentrations, had a significant positive correlation with the spectral reflectance of all bands, particularly in the near-infrared band. The optimal spectral bands of SSC were 1370 to 1445 nm and 1447 to 1608 nm, whereas the optimal spectral bands of Cl- and Na+ were 1336 to 1461 nm and 1471 to 1561 nm, respectively. The relationship model among SSC, soil salt ion concentrations (Cl- and Na+) and soil spectral reflectance of the corresponding optimal spectral band was established. The largest R2 of relationship model between SSC and the average reflectance of associated optimal band reached to 0.95, and RMSEC and RMSEP were 1.076 and 0.591, respectively. Significant statistical analysis of salt factors and soil reflectance for different microbial remediation processes indicated that the spectral response characteristics and sensitivity of SSC to soil reflectance, which implied the feasibility of high spectrum test on soil microbial remediation monitoring, also provided the basis for quick nondestructive monitoring soil bioremediation process by soil spectral reflectance.

  9. Prediction of ECS and SSC Models for Flux-Limited Samples of Gamma-Ray Blazars

    NASA Technical Reports Server (NTRS)

    Lister, Matthew L.; Marscher, Alan P.

    1999-01-01

    The external Compton scattering (ECS) and synchrotron self-Compton (SSC) models make distinct predictions for the amount of Doppler boosting of high-energy gamma-rays emitted by Nazar. We examine how these differences affect the predicted properties of active galactic nucleus (AGN) samples selected on the basis of Murray emission. We create simulated flux-limited samples based on the ECS and SSC models, and compare their properties to those of identified EGRET blazars. We find that for small gamma-ray-selected samples, the two models make very similar predictions, and cannot be reliably distinguished. This is primarily due to the fact that not only the Doppler factor, but also the cosmological distance and intrinsic luminosity play a role in determining whether an AGN is included in a flux-limited gamma-ray sample.

  10. Autoantibodies in Serum of Systemic Scleroderma Patients: Peptide-Based Epitope Mapping Indicates Increased Binding to Cytoplasmic Domains of CXCR3.

    PubMed

    Recke, Andreas; Regensburger, Ann-Katrin; Weigold, Florian; Müller, Antje; Heidecke, Harald; Marschner, Gabriele; Hammers, Christoph M; Ludwig, Ralf J; Riemekasten, Gabriela

    2018-01-01

    Systemic sclerosis (SSc) is a severe chronic autoimmune disease with high morbidity and mortality. Sera of patients with SSc contain a large variety of autoantibody (aab) reactivities. Among these are functionally active aab that bind to G protein-coupled receptors (GPCR) such as C-X-C motif chemokine receptor 3 (CXCR3) and 4 (CXCR4). Aab binding to the N-terminal portion of these two GPCRs have been shown to be associated with slower disease progression in SSc, especially deterioration of lung function. Aabs binding to GPCRs exhibit functional activities by stimulating or inhibiting GPCR signaling. The specific functional activity of aabs crucially depends on the epitopes they bind to. To identify the location of important epitopes on CXCR3 recognized by aabs from SSc patients, we applied an array of 36 overlapping 18-20mer peptides covering the entire CXCR3 sequence, comparing epitope specificity of SSc patient sera ( N  = 32, with positive reactivity with CXCR3) to healthy controls ( N  = 30). Binding of SSc patient and control sera to these peptides was determined by ELISA. Using a Bayesian model approach, we found increased binding of SSc patient sera to peptides corresponding to intracellular epitopes within CXCR3, while the binding signal to extracellular portions of CXCR3 was found to be reduced. Experimentally determined epitopes showed a good correspondence to those predicted by the ABCpred tool. To verify these results and to translate them into a novel diagnostic ELISA, we combined the peptides that represent SSc-associated epitopes into a single ELISA and evaluated its potential to discriminate SSc patients ( N  = 31) from normal healthy controls ( N  = 47). This ELISA had a sensitivity of 0.61 and a specificity of 0.85. Our data reveals that SSc sera preferentially bind intracellular epitopes of CXCR3, while an extracellular epitope in the N-terminal domain that appears to be target of aabs in healthy individuals is not bound by SSc sera. Based upon our results, we could devise a novel ELISA concept that may be helpful for monitoring of SSc patients.

  11. Autoantibodies in Serum of Systemic Scleroderma Patients: Peptide-Based Epitope Mapping Indicates Increased Binding to Cytoplasmic Domains of CXCR3

    PubMed Central

    Recke, Andreas; Regensburger, Ann-Katrin; Weigold, Florian; Müller, Antje; Heidecke, Harald; Marschner, Gabriele; Hammers, Christoph M.; Ludwig, Ralf J.; Riemekasten, Gabriela

    2018-01-01

    Systemic sclerosis (SSc) is a severe chronic autoimmune disease with high morbidity and mortality. Sera of patients with SSc contain a large variety of autoantibody (aab) reactivities. Among these are functionally active aab that bind to G protein-coupled receptors (GPCR) such as C-X-C motif chemokine receptor 3 (CXCR3) and 4 (CXCR4). Aab binding to the N-terminal portion of these two GPCRs have been shown to be associated with slower disease progression in SSc, especially deterioration of lung function. Aabs binding to GPCRs exhibit functional activities by stimulating or inhibiting GPCR signaling. The specific functional activity of aabs crucially depends on the epitopes they bind to. To identify the location of important epitopes on CXCR3 recognized by aabs from SSc patients, we applied an array of 36 overlapping 18-20mer peptides covering the entire CXCR3 sequence, comparing epitope specificity of SSc patient sera (N = 32, with positive reactivity with CXCR3) to healthy controls (N = 30). Binding of SSc patient and control sera to these peptides was determined by ELISA. Using a Bayesian model approach, we found increased binding of SSc patient sera to peptides corresponding to intracellular epitopes within CXCR3, while the binding signal to extracellular portions of CXCR3 was found to be reduced. Experimentally determined epitopes showed a good correspondence to those predicted by the ABCpred tool. To verify these results and to translate them into a novel diagnostic ELISA, we combined the peptides that represent SSc-associated epitopes into a single ELISA and evaluated its potential to discriminate SSc patients (N = 31) from normal healthy controls (N = 47). This ELISA had a sensitivity of 0.61 and a specificity of 0.85. Our data reveals that SSc sera preferentially bind intracellular epitopes of CXCR3, while an extracellular epitope in the N-terminal domain that appears to be target of aabs in healthy individuals is not bound by SSc sera. Based upon our results, we could devise a novel ELISA concept that may be helpful for monitoring of SSc patients. PMID:29623076

  12. Deformable segmentation via sparse representation and dictionary learning.

    PubMed

    Zhang, Shaoting; Zhan, Yiqiang; Metaxas, Dimitris N

    2012-10-01

    "Shape" and "appearance", the two pillars of a deformable model, complement each other in object segmentation. In many medical imaging applications, while the low-level appearance information is weak or mis-leading, shape priors play a more important role to guide a correct segmentation, thanks to the strong shape characteristics of biological structures. Recently a novel shape prior modeling method has been proposed based on sparse learning theory. Instead of learning a generative shape model, shape priors are incorporated on-the-fly through the sparse shape composition (SSC). SSC is robust to non-Gaussian errors and still preserves individual shape characteristics even when such characteristics is not statistically significant. Although it seems straightforward to incorporate SSC into a deformable segmentation framework as shape priors, the large-scale sparse optimization of SSC has low runtime efficiency, which cannot satisfy clinical requirements. In this paper, we design two strategies to decrease the computational complexity of SSC, making a robust, accurate and efficient deformable segmentation system. (1) When the shape repository contains a large number of instances, which is often the case in 2D problems, K-SVD is used to learn a more compact but still informative shape dictionary. (2) If the derived shape instance has a large number of vertices, which often appears in 3D problems, an affinity propagation method is used to partition the surface into small sub-regions, on which the sparse shape composition is performed locally. Both strategies dramatically decrease the scale of the sparse optimization problem and hence speed up the algorithm. Our method is applied on a diverse set of biomedical image analysis problems. Compared to the original SSC, these two newly-proposed modules not only significant reduce the computational complexity, but also improve the overall accuracy. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Estimating concentrations of fine-grained and total suspended sediment from close-range remote sensing imagery

    USGS Publications Warehouse

    Mosbrucker, Adam; Spicer, Kurt R.; Christianson, Tami; Uhrich, Mark A.

    2015-01-01

    Fluvial sediment, a vital surface water resource, is hazardous in excess. Suspended sediment, the most prevalent source of impairment of river systems, can adversely affect flood control, navigation, fisheries and aquatic ecosystems, recreation, and water supply (e.g., Rasmussen et al., 2009; Qu, 2014). Monitoring programs typically focus on suspended-sediment concentration (SSC) and discharge (SSQ). These time-series data are used to study changes to basin hydrology, geomorphology, and ecology caused by disturbances. The U.S. Geological Survey (USGS) has traditionally used physical sediment sample-based methods (Edwards and Glysson, 1999; Nolan et al., 2005; Gray et al., 2008) to compute SSC and SSQ from continuous streamflow data using a sediment transport-curve (e.g., Walling, 1977) or hydrologic interpretation (Porterfield, 1972). Accuracy of these data is typically constrained by the resources required to collect and analyze intermittent physical samples. Quantifying SSC using continuous instream turbidity is rapidly becoming common practice among sediment monitoring programs. Estimations of SSC and SSQ are modeled from linear regression analysis of concurrent turbidity and physical samples. Sediment-surrogate technologies such as turbidity promise near real-time information, increased accuracy, and reduced cost compared to traditional physical sample-based methods (Walling, 1977; Uhrich and Bragg, 2003; Gray and Gartner, 2009; Rasmussen et al., 2009; Landers et al., 2012; Landers and Sturm, 2013; Uhrich et al., 2014). Statistical comparisons among SSQ computation methods show that turbidity-SSC regression models can have much less uncertainty than streamflow-based sediment transport-curves or hydrologic interpretation (Walling, 1977; Lewis, 1996; Glysson et al., 2001; Lee et al., 2008). However, computation of SSC and SSQ records from continuous instream turbidity data is not without challenges; some of these include environmental fouling, calibration, and data range among sensors. Of greatest interest to many programs is a hysteresis in the relationship between turbidity and SSC, attributed to temporal variation of particle size distribution (Landers and Sturm, 2013; Uhrich et al., 2014). This phenomenon causes increased uncertainty in regression-estimated values of SSC, due to changes in nephelometric reflectance off the varying grain sizes in suspension (Uhrich et al., 2014). Here, we assess the feasibility and application of close-range remote sensing to quantify SSC and particle size distribution of a disturbed, and highly-turbid, river system. We use a consumer-grade digital camera to acquire imagery of the river surface and a depth-integrating sampler to collect concurrent suspended-sediment samples. We then develop two empirical linear regression models to relate image spectral information to concentrations of fine sediment (clay to silt) and total suspended sediment. Before presenting our regression model development, we briefly summarize each data-acquisition method.

  14. [Characteristic wavelengths selection of soluble solids content of pear based on NIR spectral and LS-SVM].

    PubMed

    Fan, Shu-xiang; Huang, Wen-qian; Li, Jiang-bo; Zhao, Chun-jiang; Zhang, Bao-hua

    2014-08-01

    To improve the precision and robustness of the NIR model of the soluble solid content (SSC) on pear. The total number of 160 pears was for the calibration (n=120) and prediction (n=40). Different spectral pretreatment methods, including standard normal variate (SNV) and multiplicative scatter correction (MSC) were used before further analysis. A combination of genetic algorithm (GA) and successive projections algorithm (SPA) was proposed to select most effective wavelengths after uninformative variable elimination (UVE) from original spectra, SNV pretreated spectra and MSC pretreated spectra respectively. The selected variables were used as the inputs of least squares-support vector machine (LS-SVM) model to build models for de- termining the SSC of pear. The results indicated that LS-SVM model built using SNVE-UVE-GA-SPA on 30 characteristic wavelengths selected from full-spectrum which had 3112 wavelengths achieved the optimal performance. The correlation coefficient (Rp) and root mean square error of prediction (RMSEP) for prediction sets were 0.956, 0.271 for SSC. The model is reliable and the predicted result is effective. The method can meet the requirement of quick measuring SSC of pear and might be important for the development of portable instruments and online monitoring.

  15. Modeling the Influence of Early Skin-to-Skin Contact on Exclusive Breastfeeding in a Sample of Hispanic Immigrant Women.

    PubMed

    Linares, Ana M; Wambach, Karen; Rayens, Mary K; Wiggins, Amanda; Coleman, Elizabeth; Dignan, Mark B

    2017-10-01

    Using data from a longitudinal study of breastfeeding in Hispanics, this study evaluated the influence of early skin-to-skin contact (SSC) on initiation and sustained exclusive breastfeeding (EBF) at 1 month postpartum. Two-thirds of the women in the sample participated in early SSC. At discharge, over half of the women were EBF; this proportion decreased to one-third at 1 month postpartum. Controlling for demographic and clinical variables in the model, participation in early SSC was associated with a greater than sevenfold increase in the odds of EBF at discharge (p = .005) but was not predictive of EBF at 1 month post-discharge (p = .7). Younger maternal age and increased prenatal infant feeding intention were associated with an increased likelihood of EBF across both timepoints. Promoting early SSC may help with initiation of EBF, while further breastfeeding support may be needed to maintain EBF following discharge for this vulnerable population.

  16. Reasons for Not Participating in Scleroderma Patient Support Groups: A Cross-Sectional Study.

    PubMed

    Gumuchian, Stephanie T; Delisle, Vanessa C; Peláez, Sandra; Malcarne, Vanessa L; El-Baalbaki, Ghassan; Kwakkenbos, Linda; Jewett, Lisa R; Carrier, Marie-Eve; Pépin, Mia; Thombs, Brett D

    2018-02-01

    Peer-led support groups are an important resource for many people with scleroderma (systemic sclerosis; SSc). Little is known, however, about barriers to participation. The objective of this study was to identify reasons why some people with SSc do not participate in SSc support groups. A 21-item survey was used to assess reasons for nonattendance among SSc patients in Canada and the US. Exploratory factor analysis (EFA) was conducted, using the software MPlus 7, to group reasons for nonattendance into themes. A total of 242 people (202 women) with SSc completed the survey. EFA results indicated that a 3-factor model best described the data (χ 2 [150] = 302.7; P < 0.001; Comparative Fit Index = 0.91, Tucker-Lewis Index = 0.88, root mean square error of approximation = 0.07, factor intercorrelations 0.02-0.43). The 3 identified themes, reflecting reasons for not attending SSc support groups were personal reasons (9 items; e.g., already having enough support), practical reasons (7 items; e.g., no local support groups available), and beliefs about support groups (5 items; e.g., support groups are too negative). On average, respondents rated 4.9 items as important or very important reasons for nonattendance. The 2 items most commonly rated as important or very important were 1) already having enough support from family, friends, or others, and 2) not knowing of any SSc support groups offered in my area. SSc organizations may be able to address limitations in accessibility and concerns about SSc support groups by implementing online support groups, better informing patients about support group activities, and training support group facilitators. © 2017, American College of Rheumatology.

  17. Genome-wide association study for the level of serum electrolytes in Italian Large White pigs.

    PubMed

    Bovo, S; Schiavo, G; Mazzoni, G; Dall'Olio, S; Galimberti, G; Calò, D G; Scotti, E; Bertolini, F; Buttazzoni, L; Samorè, A B; Fontanesi, L

    2016-10-01

    Calcium, magnesium and phosphorus are essential electrolytes involved in a large number of biological processes. Imbalance of these minerals in blood may indicate clinically relevant conditions and are important in inferring acute or chronic pathologies in humans and animals. In this work, we carried out a genome-wide association study (GWAS) for the level of these three electrolytes in the serum of 843 performance-tested Italian Large White pigs. All pigs were genotyped with the Illumina PorcineSNP60 BeadChip, and GWAS was carried out using genome-wide efficient mixed-model association. For the level of Ca(2+) , eight single nucleotide polymorphisms (SNPs) were significant, considering a false discovery rate (FDR) < 0.05, and another eight were above the moderate association threshold (Pnominal value  < 5.00E-05). These SNPs are distributed in four porcine chromosomes (SSC): SSC8, SSC11, SSC12 and SSC13. In particular, a few putative different signals of association detected on SSC13 and one on SSC12 were in genes or close to genes involved in calcium metabolism (P2RY1, RAP2B, SLC9A9, C3orf58, TSC22D2, PLCH1 and CACNB1). Only one SNP (on SSC7) and six SNPs (on SSC2 and SSC7) showed moderate association with the level of magnesium and phosphorus respectively. The association signals for these two latter minerals might identify genes not known thus far for playing a role in their biological functions and regulations. In conclusion, our GWAS contributed to increased knowledge on the role that calcium, magnesium and phosphorus may play in the genetically determined physiological mechanisms affecting the natural variability of mineral levels in mammalian blood. © 2016 Stichting International Foundation for Animal Genetics.

  18. Prediction and forecast of Suspended Sediment Concentration (SSC) on the Upper Yangtze basin

    NASA Astrophysics Data System (ADS)

    Matos, José Pedro; Hassan, Marwan; Lu, Xixi; Franca, Mário J.

    2017-04-01

    Sediment transport in suspension may represent 90% or more of the global annual flux of sediment. For instance, more than 99% of the sediment supplied to the sea by the Yangtze River is suspended load. Suspended load is an important component for understanding channel dynamics and landscape evolution. Sediments transported in suspension are a major source of nutrients for aquatic organisms in riparian and floodplain habitats, and play a beneficial role acting as a sink in the carbon cycle. Excess of fine sediments may also have adverse effects. It can impair fish spawning by riverbed clogging, disturb foraging efficiency of hunting of river fauna, cause algae and benthos scouring, reduce or inhibit exchanges through the hyporheic region. Accumulation of fine sediments in reservoirs reduces storage capacity. Although fine sediment dynamics has been the focus of many studies, the current knowledge of sediment sources, transfer, and storage is inadequate to address fine sediment dynamics in the landscape. The theoretical derivation of a complete model for suspended sediment transport at the basin scale, incorporating small scale processes of production and transport, is hindered because the underlying mechanisms are produced at different non-similar scales. Availability of long-term reliable data on suspended sediment dynamics is essential to improve our knowledge on transport processes and to develop reliable sediment prediction models. Over the last 60 years, the Yangtze River Commission has been measuring the daily Suspended Sediment Concentration (SSC) at the Pingshan station. This dataset provides a unique opportunity to examine temporal variability and controls of fine sediment dynamics in the Upper Yangtze basin. The objective of this study is to describe temporal variation of fine sediment dynamics at the Pingshan station making use of the extensive sediment monitoring program undertaken at that location. We test several strategies of prediction and forecast applied to the long time series of SSC and streamflow. By changing the base variables between strategies, we improve our understanding of the phenomena driving SSC. Prediction and forecasts are obtained from the various input data sets based on a novel probabilistic data-driven technique, the Generalized Pareto Uncertainty (GPU), which requires very little parametrization. Addressing uncertainty explicitly, this methodology recognizes the stochastic nature of SSC. The GPU was inspired in machine learning concepts and benefits from advances in multi-objective optimization techniques to discard most explicit assumptions about the nature of the uncertainty being modeled. Assumptions that do remain are the need to specify a model for eventual non-stationarity of the series and that there are enough observations to conveniently model the uncertainty. In this contribution, several models are tested with conditioned inputs to focus on specific processes leading affecting SSC. For example, the influence of seasonal and local contributions to SSC can be separated by conditioning the probability estimation on seasonal and local drivers. Probabilistic forecasting models for SSC that account for different drivers of the phenomena are discussed.

  19. Sweet taste in apple: the role of sorbitol, individual sugars, organic acids and volatile compounds.

    PubMed

    Aprea, Eugenio; Charles, Mathilde; Endrizzi, Isabella; Laura Corollaro, Maria; Betta, Emanuela; Biasioli, Franco; Gasperi, Flavia

    2017-03-21

    Sweetness is one of the main drivers of consumer preference, and thus is given high priority in apple breeding programmes. Due to the complexity of sweetness evaluation, soluble solid content (SSC) is commonly used as an estimation of this trait. Nevertheless, it has been demonstrated that SSC and sweet taste are poorly correlated. Though individual sugar content may vary greatly between and within apple cultivars, no previous study has tried to investigate the relationship between the amount of individual sugars, or ratios of these, and apple sweetness. In this work, we quantified the major sugars (sucrose, glucose, fructose, xylose) and sorbitol and explored their influence on perceived sweetness in apple; we also related this to malic acid content, SSC and volatile compounds. Our data confirmed that the correlation between sweetness and SSC is weak. We found that sorbitol content correlates (similarly to SSC) with perceived sweetness better than any other single sugar or total sugar content. The single sugars show no differentiable importance in determining apple sweetness. Our predictive model based on partial least squares regression shows that after sorbitol and SSC, the most important contribution to apple sweetness is provided by several volatile compounds, mainly esters and farnesene.

  20. Sweet taste in apple: the role of sorbitol, individual sugars, organic acids and volatile compounds

    NASA Astrophysics Data System (ADS)

    Aprea, Eugenio; Charles, Mathilde; Endrizzi, Isabella; Laura Corollaro, Maria; Betta, Emanuela; Biasioli, Franco; Gasperi, Flavia

    2017-03-01

    Sweetness is one of the main drivers of consumer preference, and thus is given high priority in apple breeding programmes. Due to the complexity of sweetness evaluation, soluble solid content (SSC) is commonly used as an estimation of this trait. Nevertheless, it has been demonstrated that SSC and sweet taste are poorly correlated. Though individual sugar content may vary greatly between and within apple cultivars, no previous study has tried to investigate the relationship between the amount of individual sugars, or ratios of these, and apple sweetness. In this work, we quantified the major sugars (sucrose, glucose, fructose, xylose) and sorbitol and explored their influence on perceived sweetness in apple; we also related this to malic acid content, SSC and volatile compounds. Our data confirmed that the correlation between sweetness and SSC is weak. We found that sorbitol content correlates (similarly to SSC) with perceived sweetness better than any other single sugar or total sugar content. The single sugars show no differentiable importance in determining apple sweetness. Our predictive model based on partial least squares regression shows that after sorbitol and SSC, the most important contribution to apple sweetness is provided by several volatile compounds, mainly esters and farnesene.

  1. Planar seismic source characterization models developed for probabilistic seismic hazard assessment of Istanbul

    NASA Astrophysics Data System (ADS)

    Gülerce, Zeynep; Buğra Soyman, Kadir; Güner, Barış; Kaymakci, Nuretdin

    2017-12-01

    This contribution provides an updated planar seismic source characterization (SSC) model to be used in the probabilistic seismic hazard assessment (PSHA) for Istanbul. It defines planar rupture systems for the four main segments of the North Anatolian fault zone (NAFZ) that are critical for the PSHA of Istanbul: segments covering the rupture zones of the 1999 Kocaeli and Düzce earthquakes, central Marmara, and Ganos/Saros segments. In each rupture system, the source geometry is defined in terms of fault length, fault width, fault plane attitude, and segmentation points. Activity rates and the magnitude recurrence models for each rupture system are established by considering geological and geodetic constraints and are tested based on the observed seismicity that is associated with the rupture system. Uncertainty in the SSC model parameters (e.g., b value, maximum magnitude, slip rate, weights of the rupture scenarios) is considered, whereas the uncertainty in the fault geometry is not included in the logic tree. To acknowledge the effect of earthquakes that are not associated with the defined rupture systems on the hazard, a background zone is introduced and the seismicity rates in the background zone are calculated using smoothed-seismicity approach. The state-of-the-art SSC model presented here is the first fully documented and ready-to-use fault-based SSC model developed for the PSHA of Istanbul.

  2. Suspended sediment diffusion mechanisms in the Yangtze Estuary influenced by wind fields

    NASA Astrophysics Data System (ADS)

    Wang, Lihua; Zhou, Yunxuan; Shen, Fang

    2018-01-01

    The complexity of suspended sediment concentration (SSC) distribution and diffusion has been widely recognized because it is influenced by sediment supply and various hydrodynamic forcing conditions that vary over space and over time. Sediment suspended by waves and transported by currents are the dominant sediment transport mechanisms in estuarine and coastal areas. However, it is unclear to what extent the SSC distribution is impacted by each hydrodynamic factor. Research on the quantitative influence of wind fields on the SSC diffusion range will contribute to a better understanding of the characteristics of sediment transport change and sedimentary geomorphic evolution. This study determined SSC from three Envisat Medium-Resolution Imaging Spectrometer acquisitions, covering the Yangtze Estuary and adjacent water area under the same season and tidal conditions but with varying wind conditions. SSC was examined based on the Semi-Empirical Radiative Transfer model, which has been well validated with the observation data. Integrating the corresponding wind field information from European Centre for Medium-Range Weather Forecasts further facilitated the discussion of wind fields affecting SSC, and in turn the influence of water and suspended sediment transportation and diffusion in the Yangtze estuarine and coastal area. The results demonstrated that the SSC present much more distinctive fluvial features in the inner estuary and wind fields are one of the major factors controlling the range of turbid water diffusion.

  3. The importance of skin–to–skin contact for early initiation of breastfeeding in Nigeria and Bangladesh

    PubMed Central

    Singh, Kavita; Khan, Shane M; Carvajal–Aguirre, Liliana; Brodish, Paul; Amouzou, Agbessi; Moran, Allisyn

    2017-01-01

    Background Skin–to–skin contact (SSC) between mother and newborn offers numerous protective effects, however it is an intervention that has been under–utilized. Our objectives are to understand which newborns in Bangladesh and Nigeria receive SSC and whether SSC is associated with the early initiation of breastfeeding. Methods Demographic and Health Survey (DHS) data were used to study the characteristics of newborns receiving SSC for non–facility births in Nigeria (DHS 2013) and for both facility and non–facility births in Bangladesh (DHS 2014). Multivariable logistic regression was used to study the association between SSC and early initiation of breastfeeding after controlling for key socio–demographic, maternal and newborn–related factors. Results Only 10% of newborns in Nigeria and 26% of newborns in Bangladesh received SSC. In the regression models, SSC was significantly associated with the early initiation of breastfeeding in both countries (OR = 1.42, 95% CI 1.15–1.76 for Nigeria; OR = 1.27, 95% CI 1.04–1.55, for Bangladesh). Findings from the regression analysis for Bangladesh revealed that newborns born by Cesarean section had a 67% lower odds of early initiation of breastfeeding than those born by normal delivery (OR = 0.33, 95% CI 0.26–0.43). Also in Bangladesh newborns born in a health facility had a 30% lower odds of early initiation of breastfeeding than those born in non–facility environments (OR = 0.70, 95% CI 0.53–0.92). Early initiation of breastfeeding was significantly associated with parity, urban residence and wealth in Nigeria. Geographic area was significant in the regression analyses for both Bangladesh and Nigeria. Conclusions Coverage of SSC is very low in the two countries, despite its benefits for newborns without complications. SSC has the potential to save newborn lives. There is a need to prioritize training of health providers on the implementation of essential newborn care including SSC. Community engagement is also needed to ensure that all women and their families regardless of residence, socio–economic status, place or type of delivery, understand the benefits of SSC and early initiation of breastfeeding. PMID:29423182

  4. The importance of skin-to-skin contact for early initiation of breastfeeding in Nigeria and Bangladesh.

    PubMed

    Singh, Kavita; Khan, Shane M; Carvajal-Aguirre, Liliana; Brodish, Paul; Amouzou, Agbessi; Moran, Allisyn

    2017-12-01

    Skin-to-skin contact (SSC) between mother and newborn offers numerous protective effects, however it is an intervention that has been under-utilized. Our objectives are to understand which newborns in Bangladesh and Nigeria receive SSC and whether SSC is associated with the early initiation of breastfeeding. Demographic and Health Survey (DHS) data were used to study the characteristics of newborns receiving SSC for non-facility births in Nigeria (DHS 2013) and for both facility and non-facility births in Bangladesh (DHS 2014). Multivariable logistic regression was used to study the association between SSC and early initiation of breastfeeding after controlling for key socio-demographic, maternal and newborn-related factors. Only 10% of newborns in Nigeria and 26% of newborns in Bangladesh received SSC. In the regression models, SSC was significantly associated with the early initiation of breastfeeding in both countries (OR = 1.42, 95% CI 1.15-1.76 for Nigeria; OR = 1.27, 95% CI 1.04-1.55, for Bangladesh). Findings from the regression analysis for Bangladesh revealed that newborns born by Cesarean section had a 67% lower odds of early initiation of breastfeeding than those born by normal delivery (OR = 0.33, 95% CI 0.26-0.43). Also in Bangladesh newborns born in a health facility had a 30% lower odds of early initiation of breastfeeding than those born in non-facility environments (OR = 0.70, 95% CI 0.53-0.92). Early initiation of breastfeeding was significantly associated with parity, urban residence and wealth in Nigeria. Geographic area was significant in the regression analyses for both Bangladesh and Nigeria. Coverage of SSC is very low in the two countries, despite its benefits for newborns without complications. SSC has the potential to save newborn lives. There is a need to prioritize training of health providers on the implementation of essential newborn care including SSC. Community engagement is also needed to ensure that all women and their families regardless of residence, socio-economic status, place or type of delivery, understand the benefits of SSC and early initiation of breastfeeding.

  5. Scleroderma prevalence: demographic variations in a population-based sample.

    PubMed

    Bernatsky, S; Joseph, L; Pineau, C A; Belisle, P; Hudson, M; Clarke, A E

    2009-03-15

    To estimate the prevalence of systemic sclerosis (SSc) using population-based administrative data, and to assess the sensitivity of case ascertainment approaches. We ascertained SSc cases from Quebec physician billing and hospitalization databases (covering approximately 7.5 million individuals). Three case definition algorithms were compared, and statistical methods accounting for imperfect case ascertainment were used to estimate SSc prevalence and case ascertainment sensitivity. A hierarchical Bayesian latent class regression model that accounted for possible between-test dependence conditional on disease status estimated the effect of patient characteristics on SSc prevalence and the sensitivity of the 3 ascertainment algorithms. Accounting for error inherent in both the billing and the hospitalization data, we estimated SSc prevalence in 2003 at 74.4 cases per 100,000 women (95% credible interval [95% CrI] 69.3-79.7) and 13.3 cases per 100,000 men (95% CrI 11.1-16.1). Prevalence was higher for older individuals, particularly in urban women (161.2 cases per 100,000, 95% CrI 148.6-175.0). Prevalence was lowest in young men (in rural areas, as low as 2.8 cases per 100,000, 95% CrI 1.4-4.8). In general, no single algorithm was very sensitive, with point estimates for sensitivity ranging from 20-73%. We found marked differences in SSc prevalence according to age, sex, and region. In general, no single case ascertainment approach was very sensitive for SSc. Therefore, using data from multiple sources, with adjustment for the imperfect nature of each, is an important strategy in population-based studies of SSc and similar conditions.

  6. Branch-Based Model for the Diameters of the Pulmonary Airways: Accounting for Departures From Self-Consistency and Registration Errors

    PubMed Central

    Neradilek, Moni B.; Polissar, Nayak L.; Einstein, Daniel R.; Glenny, Robb W.; Minard, Kevin R.; Carson, James P.; Jiao, Xiangmin; Jacob, Richard E.; Cox, Timothy C.; Postlethwait, Edward M.; Corley, Richard A.

    2017-01-01

    We examine a previously published branch-based approach for modeling airway diameters that is predicated on the assumption of self-consistency across all levels of the tree. We mathematically formulate this assumption, propose a method to test it and develop a more general model to be used when the assumption is violated. We discuss the effect of measurement error on the estimated models and propose methods that take account of error. The methods are illustrated on data from MRI and CT images of silicone casts of two rats, two normal monkeys, and one ozone-exposed monkey. Our results showed substantial departures from self-consistency in all five subjects. When departures from self-consistency exist, we do not recommend using the self-consistency model, even as an approximation, as we have shown that it may likely lead to an incorrect representation of the diameter geometry. The new variance model can be used instead. Measurement error has an important impact on the estimated morphometry models and needs to be addressed in the analysis. PMID:22528468

  7. [Temperature compensation for portable Vis/NIR spectrometer measurement of apple fruit soluble solids contents].

    PubMed

    Wang, Jia-hua; Qi, Shu-ye; Tang, Zhi-hui; Jia, Shou-xing; Li, Yong-yu

    2012-05-01

    Visible (Vis)/near infrared (NIR) spectroscopy has been used successfully to measure soluble solids content (SSC) in fruit. However, for practical implementation, the NIR technique needs to be able to compensate for fruit temperature fluctuations, as it was observed that the sample temperature affects the NIR spectrum. A portable Vis/NIR spectrometer was used to collect diffused transmittance spectra of apples at different temperatures (0-30 degrees C). The spectral data of apple at 20 degrees C was used to develop a norm partial least squares (PLS) model. Slope/bias technique was found to well suits to control the accuracy of the calibration model for SSC concerning temperature fluctuations. The correctional PLS models were used to predict the SSC of apple at 0, 10 and 30 degrees C, respectively. The correctional method was found to perform well with Q values of 0.810, 0.822 and 0.802, respectively. When no precautions are taken, the Q value on the SSC may be as small as 0.525-0.680. The results obtained highlight the potential of portable Vis/NIR instruments for assessing internal quality of fruits on site under varying weather conditions.

  8. [Application of characteristic NIR variables selection in portable detection of soluble solids content of apple by near infrared spectroscopy].

    PubMed

    Fan, Shu-Xiang; Huang, Wen-Qian; Li, Jiang-Bo; Guo, Zhi-Ming; Zhaq, Chun-Jiang

    2014-10-01

    In order to detect the soluble solids content(SSC)of apple conveniently and rapidly, a ring fiber probe and a portable spectrometer were applied to obtain the spectroscopy of apple. Different wavelength variable selection methods, including unin- formative variable elimination (UVE), competitive adaptive reweighted sampling (CARS) and genetic algorithm (GA) were pro- posed to select effective wavelength variables of the NIR spectroscopy of the SSC in apple based on PLS. The back interval LS- SVM (BiLS-SVM) and GA were used to select effective wavelength variables based on LS-SVM. Selected wavelength variables and full wavelength range were set as input variables of PLS model and LS-SVM model, respectively. The results indicated that PLS model built using GA-CARS on 50 characteristic variables selected from full-spectrum which had 1512 wavelengths achieved the optimal performance. The correlation coefficient (Rp) and root mean square error of prediction (RMSEP) for prediction sets were 0.962, 0.403°Brix respectively for SSC. The proposed method of GA-CARS could effectively simplify the portable detection model of SSC in apple based on near infrared spectroscopy and enhance the predictive precision. The study can provide a reference for the development of portable apple soluble solids content spectrometer.

  9. Study on for soluble solids contents measurement of grape juice beverage based on Vis/NIRS and chemomtrics

    NASA Astrophysics Data System (ADS)

    Wu, Di; He, Yong

    2007-11-01

    The aim of this study is to investigate the potential of the visible and near infrared spectroscopy (Vis/NIRS) technique for non-destructive measurement of soluble solids contents (SSC) in grape juice beverage. 380 samples were studied in this paper. Smoothing way of Savitzky-Golay and standard normal variate were applied for the pre-processing of spectral data. Least-squares support vector machines (LS-SVM) with RBF kernel function was applied to developing the SSC prediction model based on the Vis/NIRS absorbance data. The determination coefficient for prediction (Rp2) of the results predicted by LS-SVM model was 0. 962 and root mean square error (RMSEP) was 0. 434137. It is concluded that Vis/NIRS technique can quantify the SSC of grape juice beverage fast and non-destructively.. At the same time, LS-SVM model was compared with PLS and back propagation neural network (BP-NN) methods. The results showed that LS-SVM was superior to the conventional linear and non-linear methods in predicting SSC of grape juice beverage. In this study, the generation ability of LS-SVM, PLS and BP-NN models were also investigated. It is concluded that LS-SVM regression method is a promising technique for chemometrics in quantitative prediction.

  10. MiR-30a-3p Negatively Regulates BAFF Synthesis in Systemic Sclerosis and Rheumatoid Arthritis Fibroblasts

    PubMed Central

    Philippe, Lucas; Gong, Ya-Zhuo; Bahram, Seiamak; Cetin, Semih; Pfeffer, Sébastien; Gottenberg, Jacques-Eric; Wachsmann, Dominique; Georgel, Philippe; Sibilia, Jean

    2014-01-01

    We evaluated micro (mi) RNA-mediated regulation of BAFF expression in fibroblasts using two concomitant models: (i) synovial fibroblasts (FLS) isolated from healthy controls (N) or Rheumatoid Arthritis (RA) patients; (ii) human dermal fibroblasts (HDF) isolated from healthy controls (N) or Systemic Sclerosis (SSc) patients. Using RT-qPCR and ELISA, we first showed that SScHDF synthesized and released BAFF in response to Poly(I:C) or IFN-γ treatment, as previously observed in RAFLS, whereas NHDF released BAFF preferentially in response to IFN-γ. Next, we demonstrated that miR-30a-3p expression was down regulated in RAFLS and SScHDF stimulated with Poly(I:C) or IFN-γ. Moreover, we demonstrated that transfecting miR-30a-3p mimic in Poly(I:C)- and IFN-γ-activated RAFLS and SScHDF showed a strong decrease on BAFF synthesis and release and thus B cells survival in our model. Interestingly, FLS and HDF isolated from healthy subjects express higher levels of miR-30a-3p and lower levels of BAFF than RAFLS and SScHDF. Transfection of miR-30a-3p antisense in Poly(I:C)- and IFN-γ-activated NFLS and NHDF upregulated BAFF secretion, confirming that this microRNA is a basal repressors of BAFF expression in cells from healthy donors. Our data suggest a critical role of miR-30a-3p in the regulation of BAFF expression, which could have a major impact in the regulation of the autoimmune responses occurring in RA and SSc. PMID:25360821

  11. Hyperspectral imaging for predicting the allicin and soluble solid content of garlic with variable selection algorithms and chemometric models.

    PubMed

    Rahman, Anisur; Faqeerzada, Mohammad A; Cho, Byoung-Kwan

    2018-03-14

    Allicin and soluble solid content (SSC) in garlic is the responsible for its pungent flavor and odor. However, current conventional methods such as the use of high-pressure liquid chromatography and a refractometer have critical drawbacks in that they are time-consuming, labor-intensive and destructive procedures. The present study aimed to predict allicin and SSC in garlic using hyperspectral imaging in combination with variable selection algorithms and calibration models. Hyperspectral images of 100 garlic cloves were acquired that covered two spectral ranges, from which the mean spectra of each clove were extracted. The calibration models included partial least squares (PLS) and least squares-support vector machine (LS-SVM) regression, as well as different spectral pre-processing techniques, from which the highest performing spectral preprocessing technique and spectral range were selected. Then, variable selection methods, such as regression coefficients, variable importance in projection (VIP) and the successive projections algorithm (SPA), were evaluated for the selection of effective wavelengths (EWs). Furthermore, PLS and LS-SVM regression methods were applied to quantitatively predict the quality attributes of garlic using the selected EWs. Of the established models, the SPA-LS-SVM model obtained an Rpred2 of 0.90 and standard error of prediction (SEP) of 1.01% for SSC prediction, whereas the VIP-LS-SVM model produced the best result with an Rpred2 of 0.83 and SEP of 0.19 mg g -1 for allicin prediction in the range 1000-1700 nm. Furthermore, chemical images of garlic were developed using the best predictive model to facilitate visualization of the spatial distributions of allicin and SSC. The present study clearly demonstrates that hyperspectral imaging combined with an appropriate chemometrics method can potentially be employed as a fast, non-invasive method to predict the allicin and SSC in garlic. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

  12. Association of interleukin-1 family cytokines single nucleotide polymorphisms with susceptibility to systemic sclerosis: an independent case-control study and a meta-analysis.

    PubMed

    Huang, Xiao-Lei; Wu, Guo-Cui; Wang, Yu-Jie; Yang, Xiao-Ke; Yang, Guo-Jun; Tao, Jin-Hui; Duan, Yu; Yan, Jun-Wei; Li, Xiang-Pei; Ye, Dong-Qing; Wang, Jing

    2016-08-01

    The aim of our study was to investigate the association of five single nucleotide polymorphisms in interleukin-1 (IL-1) gene with susceptibility to systemic sclerosis (SSc) in a Chinese population. A total of 58 SSc patients and 113 healthy controls were enrolled. TaqMan allele discrimination assay was performed to detect the genotyping of IL-1A -889C/T (rs1800587), IL-1B -511C/T (rs16944), IL-18 -607C/A (rs1946518), IL-18 -137G/C (rs187238) and IL-33 rs7044343. The association between these SNPs and SSc risk was analyzed. Furthermore, a meta-analysis of relevant studies on the association of IL-1A -889C/T (rs1800587) and IL-1B -511C/T (rs16944) with the susceptibility to SSc was performed. Through the genotyping, significant associations for SSc were found for: IL-1A -889C/T genotype frequencies (P = 0.000), dominant model (P = 0.000), recessive model (P = 0.001) and allele T frequency (P = 0.000). Among SSc patients, dyspnea was significantly associated with IL-18 -607C/A genotype frequency and IL-33 rs7044343 allele frequency (P = 0.037, P = 0.042, respectively). In addition, elevated erythrocyte sedimentation rate was significantly associated with IL-18 -137G/C (rs187238) genotype and allele frequency (P = 0.019, P = 0.006, respectively). While meta-analysis showed there was no significant association between IL-1A -889C/T polymorphism and SSc, for IL-1B -511C/T (rs16944), significant associations were found in the comparison of allele C versus T (OR 1.267, 95 % CI 1.016-1.580) by combined different outcomes. Results showed that IL-1A -889C/T (rs1800587) was associated with SSc susceptibility in the Chinese population. However, this association was not supported by a meta-analysis of all relevant studies. Further investigations are required to verify our findings.

  13. Forecasting tidal marsh elevation and habitat change through fusion of Earth observations and a process model

    USGS Publications Warehouse

    Byrd, Kristin B.; Windham-Myers, Lisamarie; Leeuw, Thomas; Downing, Bryan D.; Morris, James T.; Ferner, Matthew C.

    2016-01-01

    Reducing uncertainty in data inputs at relevant spatial scales can improve tidal marsh forecasting models, and their usefulness in coastal climate change adaptation decisions. The Marsh Equilibrium Model (MEM), a one-dimensional mechanistic elevation model, incorporates feedbacks of organic and inorganic inputs to project elevations under sea-level rise scenarios. We tested the feasibility of deriving two key MEM inputs—average annual suspended sediment concentration (SSC) and aboveground peak biomass—from remote sensing data in order to apply MEM across a broader geographic region. We analyzed the precision and representativeness (spatial distribution) of these remote sensing inputs to improve understanding of our study region, a brackish tidal marsh in San Francisco Bay, and to test the applicable spatial extent for coastal modeling. We compared biomass and SSC models derived from Landsat 8, DigitalGlobe WorldView-2, and hyperspectral airborne imagery. Landsat 8-derived inputs were evaluated in a MEM sensitivity analysis. Biomass models were comparable although peak biomass from Landsat 8 best matched field-measured values. The Portable Remote Imaging Spectrometer SSC model was most accurate, although a Landsat 8 time series provided annual average SSC estimates. Landsat 8-measured peak biomass values were randomly distributed, and annual average SSC (30 mg/L) was well represented in the main channels (IQR: 29–32 mg/L), illustrating the suitability of these inputs across the model domain. Trend response surface analysis identified significant diversion between field and remote sensing-based model runs at 60 yr due to model sensitivity at the marsh edge (80–140 cm NAVD88), although at 100 yr, elevation forecasts differed less than 10 cm across 97% of the marsh surface (150–200 cm NAVD88). Results demonstrate the utility of Landsat 8 for landscape-scale tidal marsh elevation projections due to its comparable performance with the other sensors, temporal frequency, and cost. Integration of remote sensing data with MEM should advance regional projections of marsh vegetation change by better parameterizing MEM inputs spatially. Improving information for coastal modeling will support planning for ecosystem services, including habitat, carbon storage, and flood protection.

  14. Branch-Based Model for the Diameters of the Pulmonary Airways: Accounting for Departures From Self-Consistency and Registration Errors

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

    Neradilek, Moni B.; Polissar, Nayak L.; Einstein, Daniel R.

    2012-04-24

    We examine a previously published branch-based approach to modeling airway diameters that is predicated on the assumption of self-consistency across all levels of the tree. We mathematically formulate this assumption, propose a method to test it and develop a more general model to be used when the assumption is violated. We discuss the effect of measurement error on the estimated models and propose methods that account for it. The methods are illustrated on data from MRI and CT images of silicone casts of two rats, two normal monkeys and one ozone-exposed monkey. Our results showed substantial departures from self-consistency inmore » all five subjects. When departures from selfconsistency exist we do not recommend using the self-consistency model, even as an approximation, as we have shown that it may likely lead to an incorrect representation of the diameter geometry. Measurement error has an important impact on the estimated morphometry models and needs to be accounted for in the analysis.« less

  15. Digital ulcers and cutaneous subsets of systemic sclerosis: Clinical, immunological, nailfold capillaroscopy, and survival differences in the Spanish RESCLE Registry.

    PubMed

    Tolosa-Vilella, Carles; Morera-Morales, Maria Lluisa; Simeón-Aznar, Carmen Pilar; Marí-Alfonso, Begoña; Colunga-Arguelles, Dolores; Callejas Rubio, José Luis; Rubio-Rivas, Manuel; Freire-Dapena, Maika; Guillén-Del Castillo, Alfredo; Iniesta-Arandia, Nerea; Castillo-Palma, Maria Jesús; Egurbide-Arberas, Marivi; Trapiellla-Martínez, Luis; Vargas-Hitos, José A; Todolí-Parra, José Antonio; Rodriguez-Carballeira, Mónica; Marin-Ballvé, Adela; Pla-Salas, Xavier; Rios-Blanco, Juan José; Fonollosa-Pla, Vicent

    2016-10-01

    Digital ulcers (DU) are the most common vascular complication of systemic sclerosis (SSc). We compared the characteristics between patients with prior or current DU with those never affected and evaluated whether a history of DU may be a predictor of vascular, organ involvement, and/or death in patients with SSc. Data from SSc patients with or without prior or current DU were collected by 19 referral centers in an ongoing registry of Spanish SSc patients, named Registro de ESCLErodermia (RESCLE). Demographics, organ involvement, autoimmunity features, nailfold capillary pattern, survival time, and causes of death were analyzed to identify DU related characteristics and survival of the entire series and according to the following cutaneous subsets-diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and SSc sine scleroderma (ssSSc). Out of 1326, 552 patients enrolled in the RESCLE registry had prior or current DU, 88% were women, the mean age was 50 ± 16 years, and the mean disease duration from first SSc symptom was 7.6 ± 9.6 years. Many significant differences were observed in the univariate analysis between patients with and without prior/current DU. Multivariate analysis identified that history of prior/current DU in patients with SSc was independently associated to younger age at SSc diagnosis, diffuse cutaneous SSc, peripheral vascular manifestations such Raynaud's phenomenon, telangiectasia, and acro-osteolysis but no other vascular features such as pulmonary arterial hypertension or scleroderma renal crisis. DU was also associated to calcinosis cutis, interstitial lung disease, as well as worse survival. Multivariate analysis performed in the cutaneous subsets showed that prior/current DU were independently associated: (1) in dcSSc, to younger age at SSc diagnosis, presence of telangiectasia and calcinosis and rarely a non-SSc pattern on nailfold capillaroscopy; (2) in lcSSc, to younger age at SSc diagnosis, presence of Raynaud's phenomenon as well as calcinosis cutis, interstitial lung disease, and higher incidence of death from all causes; and (3) in ssSSc, to younger age at first SSc symptom and greater incidence of death from all causes. Digital ulcers develop in patients with SSc younger at diagnosis, mainly in patients with dcSSc and lcSSc, and they are associated to other peripheral vascular manifestations such as Raynaud's phenomenon, telangiectasia, and acro-osteolysis but also to calcinosis, and interstitial lung disease. History of DU in SSc leads to worse survival, also noticeable for lcSSc and ssSSc subsets but not for dcSSc patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Simulating supersymmetry at the SSC

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

    Barnett, R.M.; Haber, H.E.

    1984-08-01

    Careful study of supersymmetric signatures at the SSC is required in order to distinguish them from Standard Model physics backgrounds. To this end, we have created an efficient, accurate computer program which simulates supersymmetric particle production and decay (or other new particles). We have incorporated the full matrix elements, keeping track of the polarizations of all intermediate states. (At this time hadronization of final-state partons is ignored). Using Monte Carlo techniques this program can generate any desired final-state distribution or individual events for Lego plots. Examples of the results of our study of supersymmetry at SSC are provided.

  17. Self-Consistent Model of Magnetospheric Electric Field, Ring Current, Plasmasphere, and Electromagnetic Ion Cyclotron Waves: Initial Results

    NASA Technical Reports Server (NTRS)

    Gamayunov, K. V.; Khazanov, G. V.; Liemohn, M. W.; Fok, M.-C.; Ridley, A. J.

    2009-01-01

    Further development of our self-consistent model of interacting ring current (RC) ions and electromagnetic ion cyclotron (EMIC) waves is presented. This model incorporates large scale magnetosphere-ionosphere coupling and treats self-consistently not only EMIC waves and RC ions, but also the magnetospheric electric field, RC, and plasmasphere. Initial simulations indicate that the region beyond geostationary orbit should be included in the simulation of the magnetosphere-ionosphere coupling. Additionally, a self-consistent description, based on first principles, of the ionospheric conductance is required. These initial simulations further show that in order to model the EMIC wave distribution and wave spectral properties accurately, the plasmasphere should also be simulated self-consistently, since its fine structure requires as much care as that of the RC. Finally, an effect of the finite time needed to reestablish a new potential pattern throughout the ionosphere and to communicate between the ionosphere and the equatorial magnetosphere cannot be ignored.

  18. Systematic review of systemic sclerosis-specific instruments for the EULAR Outcome Measures Library: An evolutional database model of validated patient-reported outcomes.

    PubMed

    Ingegnoli, Francesca; Carmona, Loreto; Castrejon, Isabel

    2017-04-01

    The EULAR Outcome Measures Library (OML) is a freely available database of validated patient-reported outcomes (PROs). The aim of this study was to provide a comprehensive review of validated PROs specifically developed for systemic sclerosis (SSc) to feed the EULAR OML. A sensitive search was developed in Medline and Embase to identify all validation studies, cohort studies, reviews, or meta-analyses in which the objective were the development or validation of specific PROs evaluating organ involvement, disease activity or damage in SSc. A reviewer screened title and abstracts, selected the studies, and collected data concerning validation using ad hoc forms based on the COSMIN checklist. From 13,140 articles captured, 74 met the predefined criteria. After excluding two instruments as they were unavailable in English the selected 23 studies provided information on seven SSc-specific PROs on different SSc domains: burden of illness (symptom burden index), functional status (Scleroderma Assessment Questionnaire), functional ability (scleroderma Functional Score), Raynaud's phenomenon (Raynaud's condition score), mouth involvement (Mouth Handicap in SSc), gastro-intestinal involvement (University of California Los Angeles-Scleroderma Clinical Trial Consortium Gastro-Intestinal tract 2.0), and skin involvement (skin self-assessment). Each of them is partially validated and has different psychometric requirements. Seven SSc-specific PROs have a minimum validation and were included in the EULAR OML. Further development in the area of disease-specific PROs in SSc is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Sweet taste in apple: the role of sorbitol, individual sugars, organic acids and volatile compounds

    PubMed Central

    Aprea, Eugenio; Charles, Mathilde; Endrizzi, Isabella; Laura Corollaro, Maria; Betta, Emanuela; Biasioli, Franco; Gasperi, Flavia

    2017-01-01

    Sweetness is one of the main drivers of consumer preference, and thus is given high priority in apple breeding programmes. Due to the complexity of sweetness evaluation, soluble solid content (SSC) is commonly used as an estimation of this trait. Nevertheless, it has been demonstrated that SSC and sweet taste are poorly correlated. Though individual sugar content may vary greatly between and within apple cultivars, no previous study has tried to investigate the relationship between the amount of individual sugars, or ratios of these, and apple sweetness. In this work, we quantified the major sugars (sucrose, glucose, fructose, xylose) and sorbitol and explored their influence on perceived sweetness in apple; we also related this to malic acid content, SSC and volatile compounds. Our data confirmed that the correlation between sweetness and SSC is weak. We found that sorbitol content correlates (similarly to SSC) with perceived sweetness better than any other single sugar or total sugar content. The single sugars show no differentiable importance in determining apple sweetness. Our predictive model based on partial least squares regression shows that after sorbitol and SSC, the most important contribution to apple sweetness is provided by several volatile compounds, mainly esters and farnesene. PMID:28322320

  20. Impact of mussel bioengineering on fine-grained sediment dynamics in a coastal lagoon: A numerical modelling investigation

    NASA Astrophysics Data System (ADS)

    Forsberg, Pernille L.; Lumborg, Ulrik; Bundgaard, Klavs; Ernstsen, Verner B.

    2017-12-01

    Rødsand lagoon in southeast Denmark is a non-tidal coastal lagoon. It is home to a wide range of marine flora and fauna and part of the Natura 2000 network. An increase in turbidity through elevated levels of suspended sediment concentration (SSC) within the lagoon may affect the ecosystem health due to reduced light penetration. Increasing SSC levels within Rødsand lagoon could be caused by increasing storm intensity or by a sediment spill from dredging activities west of the lagoon in relation to the planned construction of the Fehmarnbelt fixed link between Denmark and Germany. The aim of the study was to investigate the impact of a mussel reef on sediment import and SSC in a semi-enclosed lagoon through the development of a bioengineering modelling application that makes it possible to include the filtrating effect of mussels in a numerical model of the lagoonal system. The numerical implementation of an exterior mussel reef generated a reduction in the SSC in the vicinity of the reef, through the adjacent inlet and in the western part of the lagoon. The mussel reef reduced the sediment import to Rødsand lagoon by 13-22% and reduced the SSC within Rødsand lagoon by 5-9% depending on the filtration rate and the reef length. The results suggest that the implementation of a mussel reef has the potential to relieve the pressure of increasing turbidity levels within a semi-enclosed lagoonal system. However, further assessment and development of the bioengineering application and resulting ecosystem impacts are necessary prior to actual implementation.

  1. Exploring the origin of broad-band emissions of Mrk 501 with a two-zone model

    NASA Astrophysics Data System (ADS)

    Lei, Maichang; Yang, Chuyuan; Wang, Jiancheng; Yang, Xiaolin

    2018-06-01

    We propose a two-zone synchrotron self-Compton (SSC) model, including an inner gamma-ray emitting region with spherical shape and a conical radio emitting region located at the extended jet, to alleviate the long-standing "bulk Lorentz factor crisis" in blazars. In this model, the spectral energy distributions (SEDs) of blazars are produced by considering the gamma-ray emitting region inverse Compton scattering of both the synchrotron photons itself and the ambient photons from the radio emitting region. Applying the model to Mrk 501, we obtain that the radio emitting region has a comoving length of ˜0.15 pc and is located at sub-parsec scale from the central engine by modeling the radio data; the flux of the Compton scattering of the ambient photons is so low that it can be neglected safely. The characteristic hard gamma-ray spectrum can be explained by the superposition of two SSC processes, and the model can approximately explain the very high energy (VHE) data. The insights into the spectral shape and the inter-band correlations under the flaring state will provide us with a diagnostic for the bulk Lorentz factor of radio emitting region, where the low and upper limits of 8 and 15 are preferred, and for the two-zone SSC model itself. In addition, our two-zone SSC model shows that the gamma-ray emitting region creates flare on the timescale of merely a few hours, and the long time outbursts more likely originate from the extended radio emitting region.

  2. Exploring the origin of broad-band emissions of Mrk 501 with a two-zone model

    NASA Astrophysics Data System (ADS)

    Lei, Maichang; Yang, Chuyuan; Wang, Jiancheng; Yang, Xiaolin

    2018-04-01

    We propose a two-zone synchrotron self-Compton (SSC) model, including an inner gamma-ray emitting region with spherical shape and a conical radio emitting region located at the extended jet, to alleviate the long-standing "bulk Lorentz factor crisis" in blazars. In this model, the spectral energy distributions (SEDs) of blazars are produced by considering the gamma-ray emitting region inverse Compton scattering of both the synchrotron photons itself and the ambient photons from the radio emitting region. Applying the model to Mrk 501, we obtain that the radio emitting region has a comoving length of ˜0.15 pc and is located at sub-parsec scale from the central engine by modeling the radio data; the flux of the Compton scattering of the ambient photons is so low that it can be neglected safely. The characteristic hard gamma-ray spectrum can be explained by the superposition of two SSC processes, and the model can approximately explain the very high energy (VHE) data. The insights into the spectral shape and the inter-band correlations under the flaring state will provide us with a diagnostic for the bulk Lorentz factor of radio emitting region, where the low and upper limits of 8 and 15 are preferred, and for the two-zone SSC model itself. In addition, our two-zone SSC model shows that the gamma-ray emitting region creates flare on the timescale of merely a few hours, and the long time outbursts more likely originate from the extended radio emitting region.

  3. [The diagnostic significance of nailfold video-capillaroscopy in systemic sclerosis].

    PubMed

    Li, Lin-Guang; Zhang, Jiang-Lin; Liu, Xiu-Hua; Huang, Feng

    2012-05-01

    To observe nailfold capillary changes in a cohort of connective tissue disease (CTD) with Raynaud's phenomenon (RP) and to explore the diagnostic value of nailfold video-capillaroscopy (NVC) in systemic sclerosis (SSc). Sixty CTD patients with RP divided into SSc group (n = 36) and non-SSc group (n = 24) were referred to an experienced operator for NVC. The patients had decreased capillary loops in SSc group with the capillary diameter more enlarged in SSc group than non-SSc group. The number of patients in SSc group with giant capillaries was 14, while 3 in non-SSc group. There were 23 patients with haemorrhages in SSc group and 9 in non-SSc group. The number of patients with severe effusion was 15 in SSc group, while 2 in non-SSc group. By using the ROC curves, indexes with AUC at least 0.7 of the input capillary diameter, the output capillary diameter, the middle capillary diameter, blood color and effusion for the diagnostic cutoff points were 18.5 µm, 24.5 µm, 19.5µm, deep red and severe effusion. With at least 2 out of the top 3 indexes, the diagnostic sensitivity and specificity of SSc were higher. CTD Patients with RP of SSc have less capillary loops, more enlarged capillaries, more giant capillaries, more severe effusion and more haemorrhages than non-SSc patients. The characteristics of nailfold capillary changes in SSc patients with RP can be helpful for the diagnosis and the differential diagnosis of SSc.

  4. Symplectic multiparticle tracking model for self-consistent space-charge simulation

    DOE PAGES

    Qiang, Ji

    2017-01-23

    Symplectic tracking is important in accelerator beam dynamics simulation. So far, to the best of our knowledge, there is no self-consistent symplectic space-charge tracking model available in the accelerator community. In this paper, we present a two-dimensional and a three-dimensional symplectic multiparticle spectral model for space-charge tracking simulation. This model includes both the effect from external fields and the effect of self-consistent space-charge fields using a split-operator method. Such a model preserves the phase space structure and shows much less numerical emittance growth than the particle-in-cell model in the illustrative examples.

  5. Symplectic multiparticle tracking model for self-consistent space-charge simulation

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

    Qiang, Ji

    Symplectic tracking is important in accelerator beam dynamics simulation. So far, to the best of our knowledge, there is no self-consistent symplectic space-charge tracking model available in the accelerator community. In this paper, we present a two-dimensional and a three-dimensional symplectic multiparticle spectral model for space-charge tracking simulation. This model includes both the effect from external fields and the effect of self-consistent space-charge fields using a split-operator method. Such a model preserves the phase space structure and shows much less numerical emittance growth than the particle-in-cell model in the illustrative examples.

  6. Self-consistent asset pricing models

    NASA Astrophysics Data System (ADS)

    Malevergne, Y.; Sornette, D.

    2007-08-01

    We discuss the foundations of factor or regression models in the light of the self-consistency condition that the market portfolio (and more generally the risk factors) is (are) constituted of the assets whose returns it is (they are) supposed to explain. As already reported in several articles, self-consistency implies correlations between the return disturbances. As a consequence, the alphas and betas of the factor model are unobservable. Self-consistency leads to renormalized betas with zero effective alphas, which are observable with standard OLS regressions. When the conditions derived from internal consistency are not met, the model is necessarily incomplete, which means that some sources of risk cannot be replicated (or hedged) by a portfolio of stocks traded on the market, even for infinite economies. Analytical derivations and numerical simulations show that, for arbitrary choices of the proxy which are different from the true market portfolio, a modified linear regression holds with a non-zero value αi at the origin between an asset i's return and the proxy's return. Self-consistency also introduces “orthogonality” and “normality” conditions linking the betas, alphas (as well as the residuals) and the weights of the proxy portfolio. Two diagnostics based on these orthogonality and normality conditions are implemented on a basket of 323 assets which have been components of the S&P500 in the period from January 1990 to February 2005. These two diagnostics show interesting departures from dynamical self-consistency starting about 2 years before the end of the Internet bubble. Assuming that the CAPM holds with the self-consistency condition, the OLS method automatically obeys the resulting orthogonality and normality conditions and therefore provides a simple way to self-consistently assess the parameters of the model by using proxy portfolios made only of the assets which are used in the CAPM regressions. Finally, the factor decomposition with the self-consistency condition derives a risk-factor decomposition in the multi-factor case which is identical to the principal component analysis (PCA), thus providing a direct link between model-driven and data-driven constructions of risk factors. This correspondence shows that PCA will therefore suffer from the same limitations as the CAPM and its multi-factor generalization, namely lack of out-of-sample explanatory power and predictability. In the multi-period context, the self-consistency conditions force the betas to be time-dependent with specific constraints.

  7. Induction of Scleroderma Fibrosis in Skin-Humanized Mice by Administration of Anti-Platelet-Derived Growth Factor Receptor Agonistic Autoantibodies.

    PubMed

    Luchetti, Michele M; Moroncini, Gianluca; Jose Escamez, Maria; Svegliati Baroni, Silvia; Spadoni, Tatiana; Grieco, Antonella; Paolini, Chiara; Funaro, Ada; Avvedimento, Enrico V; Larcher, Fernando; Del Rio, Marcela; Gabrielli, Armando

    2016-09-01

    To describe a skin-SCID mouse chimeric model of systemic sclerosis (SSc; scleroderma) fibrosis based on engraftment of ex vivo-bioengineered skin using skin cells derived either from scleroderma patients or from healthy donors. Three-dimensional bioengineered skin containing human keratinocytes and fibroblasts isolated from skin biopsy specimens from healthy donors or SSc patients was generated ex vivo and then grafted onto the backs of SCID mice. The features of the skin grafts were analyzed by immunohistochemistry, and the functional profile of the graft fibroblasts was defined before and after treatment with IgG from healthy controls or SSc patients. Two procedures were used to investigate the involvement of platelet-derived growth factor receptor (PDGFR): 1) nilotinib, a tyrosine kinase inhibitor, was administered to mice before injection of IgG from SSc patient sera (SSc IgG) into the grafts, and 2) human anti-PDGFR monoclonal antibodies were injected into the grafts. Depending on the type of bioengineered skin grafted, the regenerated human skin exhibited either the typical scleroderma phenotype or the healthy human skin architecture. Treatment of animals carrying healthy donor skin grafts with SSc IgG resulted in the appearance of a bona fide scleroderma phenotype, as confirmed by increased collagen deposition and fibroblast activation markers. Results of the experiments involving administration of nilotinib or monoclonal antibodies confirmed the involvement of PDGFR. Our results provide the first in vivo demonstration of the fibrotic properties of anti-PDGFR agonistic antibodies. This bioengineered skin-humanized mouse model can be used to test in vivo the progression of the disease and to monitor response to antifibrotic drugs. © 2016, American College of Rheumatology.

  8. Mapping QTL affecting a systemic sclerosis-like disorder in a cross between UCD-200 and red jungle fowl chickens.

    PubMed

    Ek, Weronica; Sahlqvist, Anna-Stina; Crooks, Lucy; Sgonc, Roswitha; Dietrich, Hermann; Wick, Georg; Ekwall, Olov; Andersson, Leif; Carlborg, Örjan; Kämpe, Olle; Kerje, Susanne

    2012-10-01

    Systemic sclerosis (SSc) or scleroderma is a rare, autoimmune, multi-factorial disease characterized by early microvascular alterations, inflammation, and fibrosis. Chickens from the UCD-200 line develop a hereditary SSc-like disease, showing all the hallmarks of the human disorder, which makes this line a promising model to study genetic factors underlying the disease. A backcross was generated between UCD-200 chickens and its wild ancestor - the red jungle fowl and a genome-scan was performed to identify loci affecting early (21 days of age) and late (175 days of age) ischemic lesions of the comb. A significant difference in frequency of disease was observed between sexes in the BC population, where the homogametic males were more affected than females, and there was evidence for a protective W chromosome effect. Three suggestive disease predisposing loci were mapped to chromosomes 2, 12 and 14. Three orthologues of genes implicated in human SSc are located in the QTL region on chromosome 2, TGFRB1, EXOC2-IRF4 and COL1A2, as well as CCR8, which is more generally related to immune function. IGFBP3 is also located within the QTL on chromosome 2 and earlier studies have showed increased IGFBP3 serum levels in SSc patients. To our knowledge, this study is the first to reveal a potential genetic association between IGFBP3 and SSc. Another gene with an immunological function, SOCS1, is located in the QTL region on chromosome 14. These results illustrate the usefulness of the UCD-200 chicken as a model of human SSc and motivate further in-depth functional studies of the implicated candidate genes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Sediment transport-based metrics of wetland stability

    USGS Publications Warehouse

    Ganju, Neil K.; Kirwan, Matthew L.; Dickhudt, Patrick J.; Guntenspergen, Glenn R.; Cahoon, Donald R.; Kroeger, Kevin D.

    2015-01-01

    Despite the importance of sediment availability on wetland stability, vulnerability assessments seldom consider spatiotemporal variability of sediment transport. Models predict that the maximum rate of sea level rise a marsh can survive is proportional to suspended sediment concentration (SSC) and accretion. In contrast, we find that SSC and accretion are higher in an unstable marsh than in an adjacent stable marsh, suggesting that these metrics cannot describe wetland vulnerability. Therefore, we propose the flood/ebb SSC differential and organic-inorganic suspended sediment ratio as better vulnerability metrics. The unstable marsh favors sediment export (18 mg L−1 higher on ebb tides), while the stable marsh imports sediment (12 mg L−1 higher on flood tides). The organic-inorganic SSC ratio is 84% higher in the unstable marsh, and stable isotopes indicate a source consistent with marsh-derived material. These simple metrics scale with sediment fluxes, integrate spatiotemporal variability, and indicate sediment sources.

  10. All-cause Healthcare Costs and Mortality in Patients with Systemic Sclerosis with Lung Involvement.

    PubMed

    Fischer, Aryeh; Kong, Amanda M; Swigris, Jeffrey J; Cole, Ashley L; Raimundo, Karina

    2018-02-01

    Patients with systemic sclerosis (SSc) often develop interstitial lung disease (ILD) and/or pulmonary arterial hypertension (PAH). The effect of ILD and PAH on healthcare costs among patients with SSc is not well described. The objective of this analysis was to describe healthcare costs in patients with newly diagnosed SSc and SSc patients newly diagnosed with ILD and/or PAH in the United States. This retrospective cohort analysis was conducted in the Truven Health MarketScan Commercial and Medicare Supplemental healthcare claims databases from 2003 to 2014. Based on International Classification of Diseases-9-Clinical Modification diagnosis codes on medical claims, patients were classified into 3 groups: incident SSc, SSc with incident ILD (SSc-ILD), and SSc with incident PAH (SSc-PAH). Patients were required to have continuous enrollment for 5 years to measure all-cause healthcare costs. Costs (adjusted to US$) were reported overall and by service type and year following diagnosis. Because of the overlap between groups, statistical comparisons were not conducted. There were 1957 patients with incident SSc, 219 with incident SSc-ILD, and 108 patients with incident SSc-PAH. Average (mean ± SD) all-cause healthcare costs over followup were higher for patients with incident SSc-ILD ($191,107 ± $322,193) or patients with incident SSc-PAH ($254,425 ± $240,497), compared to patients with incident SSc ($101,839 ± $167,155). Average annual costs over the 5-year period ranged from $18,513 to $23,268 for patients with incident SSc, from $31,285 to $55,446 for patients with incident SSc-ILD, and from $44,454 to $63,320 for patients with incident SSc-PAH. Costs tended to be the highest in the fifth year of followup. Among patients with SSc, ILD and PAH can result in substantial increases in healthcare costs.

  11. Development and Validation of the Body Concealment Scale for Scleroderma.

    PubMed

    Jewett, Lisa R; Malcarne, Vanessa L; Kwakkenbos, Linda; Harcourt, Diana; Rumsey, Nichola; Körner, Annett; Steele, Russell J; Hudson, Marie; Baron, Murray; Haythornthwaite, Jennifer A; Heinberg, Leslie; Wigley, Fredrick M; Thombs, Brett D

    2016-08-01

    Body concealment is a component of social avoidance among people with visible differences from disfiguring conditions, including systemic sclerosis (SSc). The study objective was to develop a measure of body concealment related to avoidance behaviors in SSc. Initial items for the Body Concealment Scale for Scleroderma (BCSS) were selected using item analysis in a development sample of 93 American SSc patients. The factor structure of the BCSS was evaluated in 742 Canadian patients with single-factor, 2-factor, and bifactor confirmatory factor analysis models. Convergent and divergent validity were assessed by comparing the BCSS total score with the Brief-Satisfaction with Appearance Scale (Brief-SWAP) and measures of depressive symptoms and pain. A 2-factor model (Comparative Fit Index [CFI] 0.99, Tucker-Lewis Index [TLI] 0.98, Root Mean Square Error of Approximation [RMSEA] 0.08) fit substantially better than a 1-factor model (CFI 0.95, TLI 0.94, RMSEA 0.15) for the 9-item BCSS, but the Concealment with Clothing and Concealment of Hands factors were highly correlated (α = 0.79). The bifactor model (CFI 0.99, TLI 0.99, RMSEA 0.08) also fit well. In the bifactor model, the omega coefficient was high for the general factor (ω = 0.80), but low for the Concealment with Clothing (ω = 0.01) and Concealment of Hands (ω = 0.33) factors. The BCSS total score correlated more strongly with the Brief-SWAP Social Discomfort (r = 0.59) and Dissatisfaction with Appearance (r = 0.53) subscales than with measures of depressive symptoms and pain. The BCSS sum score is a valid indicator of body concealment in SSc that extends the concepts of body concealment and avoidance beyond the realms of body shape and weight to concerns of individuals with visible differences from SSc. © 2016, American College of Rheumatology.

  12. Nondestructive quantification of the soluble-solids content and the available acidity of apples by Fourier-transform near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Ying, Yibin; Liu, Yande; Tao, Yang

    2005-09-01

    This research evaluated the feasibility of using Fourier-transform near-infrared (FT-NIR) spectroscopy to quantify the soluble-solids content (SSC) and the available acidity (VA) in intact apples. Partial least-squares calibration models, obtained from several preprocessing techniques (smoothing, derivative, etc.) in several wave-number ranges were compared. The best models were obtained with the high coefficient determination (r) 0.940 for the SSC and a moderate r of 0.801 for the VA, root-mean-square errors of prediction of 0.272% and 0.053%, and root-mean-square errors of calibration of 0.261% and 0.046%, respectively. The results indicate that the FT-NIR spectroscopy yields good predictions of the SSC and also showed the feasibility of using it to predict the VA of apples.

  13. The Hadronic Origin of the Hard Gamma-Ray Spectrum from Blazar 1ES 1101-232

    NASA Astrophysics Data System (ADS)

    Cao, Gang; Wang, Jiancheng

    2014-03-01

    The very hard γ-ray spectrum from distant blazars challenges the traditional synchrotron self-Compton (SSC) model, which may indicate that there is a contribution from an additional high-energy component beyond the SSC emission. In this paper, we study the possible origin of the hard γ-ray spectrum from distant blazars. We develop a model to explain the hard γ-ray spectrum from blazar 1ES 1101-232. In the model, the optical and X-ray radiation would come from the synchrotron radiation of primary electrons and secondary pairs and the GeV emission would be produced by the SSC process, however, the hard γ-ray spectrum would originate from the decay of neutral pion produced through proton-photon interactions with the synchrotron radiation photons within the jet. Our model can explain the observed spectral energy distribution of 1ES 1101-232 well, especially the very hard γ-ray spectrum. However, our model requires a very large proton power to efficiently produce the γ-ray through proton-photon interactions.

  14. Relations between continuous real-time turbidity data and discrete suspended-sediment concentration samples in the Neosho and Cottonwood Rivers, east-central Kansas, 2009-2012

    USGS Publications Warehouse

    Foster, Guy M.

    2014-01-01

    The Neosho River and its primary tributary, the Cottonwood River, are the primary sources of inflow to the John Redmond Reservoir in east-central Kansas. Sedimentation rate in the John Redmond Reservoir was estimated as 743 acre-feet per year for 1964–2006. This estimated sedimentation rate is more than 80 percent larger than the projected design sedimentation rate of 404 acre-feet per year, and resulted in a loss of 40 percent of the conservation pool since its construction in 1964. To reduce sediment input into the reservoir, the Kansas Water Office implemented stream bank stabilization techniques along an 8.3 mile reach of the Neosho River during 2010 through 2011. The U.S. Geological Survey, in cooperation with the Kansas Water Office and funded in part through the Kansas State Water Plan Fund, operated continuous real-time water-quality monitors upstream and downstream from stream bank stabilization efforts before, during, and after construction. Continuously measured water-quality properties include streamflow, specific conductance, water temperature, and turbidity. Discrete sediment samples were collected from June 2009 through September 2012 and analyzed for suspended-sediment concentration (SSC), percentage of sediments less than 63 micrometers (sand-fine break), and loss of material on ignition (analogous to amount of organic matter). Regression models were developed to establish relations between discretely measured SSC samples, and turbidity or streamflow to estimate continuously SSC. Continuous water-quality monitors represented between 96 and 99 percent of the cross-sectional variability for turbidity, and had slopes between 0.91 and 0.98. Because consistent bias was not observed, values from continuous water-quality monitors were considered representative of stream conditions. On average, turbidity-based SSC models explained 96 percent of the variance in SSC. Streamflow-based regressions explained 53 to 60 percent of the variance. Mean squared prediction error for turbidity-based regression relations ranged from -32 to 48 percent, whereas mean square prediction error for streamflow-based regressions ranged from -69 to 218 percent. These models are useful for evaluating the variability of SSC during rapidly changing conditions, computing loads and yields to assess SSC transport through the watershed, and for providing more accurate load estimates compared to streamflow-only based estimation methods used in the past. These models can be used to evaluate the efficacy of streambank stabilization efforts.

  15. Evaluating turbidity and suspended-sediment concentration relations from the North Fork Toutle River basin near Mount St. Helens, Washington; annual, seasonal, event, and particle size variations - a preliminary analysis.

    USGS Publications Warehouse

    Uhrich, Mark A.; Spicer, Kurt R.; Mosbrucker, Adam; Christianson, Tami

    2015-01-01

    Regression of in-stream turbidity with concurrent sample-based suspended-sediment concentration (SSC) has become an accepted method for producing unit-value time series of inferred SSC (Rasmussen et al., 2009). Turbidity-SSC regression models are increasingly used to generate suspended-sediment records for Pacific Northwest rivers (e.g., Curran et al., 2014; Schenk and Bragg, 2014; Uhrich and Bragg, 2003). Recent work developing turbidity-SSC models for the North Fork Toutle River in Southwest Washington (Uhrich et al., 2014), as well as other studies (Landers and Sturm, 2013, Merten et al., 2014), suggests that models derived from annual or greater datasets may not adequately reflect shorter term changes in turbidity-SSC relations, warranting closer inspection of such relations. In-stream turbidity measurements and suspended-sediment samples have been collected from the North Fork Toutle River since 2010. The study site, U.S. Geological Survey (USGS) streamgage 14240525 near Kid Valley, Washington, is 13 river km downstream of the debris avalanche emplaced by the 1980 eruption of Mount St. Helens (Lipman and Mullineaux, 1981), and 2 river km downstream of the large sediment retention structure (SRS) built from 1987–1989 to mitigate the associated sediment hazard. The debris avalanche extends roughly 25 km down valley from the edifice of the volcano and is the primary source of suspended sediment moving past the streamgage (NF Toutle-SRS). Other significant sources are debris flow events and sand deposits upstream of the SRS, which are periodically remobilized and transported downstream. Also, finer material often is derived from the clay-rich original debris avalanche deposit, while coarser material can derive from areas such as fluvially reworked terraces.

  16. Improving health outcomes of children through effective parenting: model and methods.

    PubMed

    Okafor, Martha; Sarpong, Daniel F; Ferguson, Aneeqah; Satcher, David

    2013-12-23

    This article reports on the design, development, testing and presentation of preliminary evidence of a translational, culturally relevant parenting education model, titled Smart and Secured Children (SSC). SSC, a quality parenting curriculum, prepares disparate African American parents as leaders for transforming their parenting behaviors and leading their peers and community in changing existing parenting culture. The article recommends expanded utility of identified promising processes, approaches and practices to engage African American parents to lead in addressing health inequity conditions in their families and communities. It adds to the growing scientific literature on the association between parent-child relationship quality and a wide variety of children physical, emotional and social outcomes. SSC applied principles of developmental theories; community based participatory research (CBPR), and iterative Delphi method between the community stakeholders, parents and researchers. The delivery approach of SSC was revamped from professional-led to parent-led content presentation and delivery methods using a conversational learning approach, referred to as 'conversepedia'. Parents' leadership development training and delivery of this curriculum in social supportive groups improved their mental wellbeing, parenting capacity and leadership skills. Parents do matter and can choose positive influence in their lives and are capable of reversing negative peer influence.

  17. Improving Health Outcomes of Children through Effective Parenting: Model and Methods

    PubMed Central

    Okafor, Martha; Sarpong, Daniel F.; Ferguson, Aneeqah; Satcher, David

    2013-01-01

    This article reports on the design, development, testing and presentation of preliminary evidence of a translational, culturally relevant parenting education model, titled Smart and Secured Children (SSC). SSC, a quality parenting curriculum, prepares disparate African American parents as leaders for transforming their parenting behaviors and leading their peers and community in changing existing parenting culture. The article recommends expanded utility of identified promising processes, approaches and practices to engage African American parents to lead in addressing health inequity conditions in their families and communities. It adds to the growing scientific literature on the association between parent–child relationship quality and a wide variety of children physical, emotional and social outcomes. SSC applied principles of developmental theories; community based participatory research (CBPR), and iterative Delphi method between the community stakeholders, parents and researchers. The delivery approach of SSC was revamped from professional-led to parent-led content presentation and delivery methods using a conversational learning approach, referred to as ‘conversepedia’. Parents’ leadership development training and delivery of this curriculum in social supportive groups improved their mental wellbeing, parenting capacity and leadership skills. Parents do matter and can choose positive influence in their lives and are capable of reversing negative peer influence. PMID:24366048

  18. Clinical and laboratory features of systemic sclerosis complicated with localized scleroderma.

    PubMed

    Toki, Sayaka; Motegi, Sei-ichiro; Yamada, Kazuya; Uchiyama, Akihiko; Kanai, Sahori; Yamanaka, Masayoshi; Ishikawa, Osamu

    2015-03-01

    Localized scleroderma (LSc) primarily affects skin, whereas systemic sclerosis (SSc) affects skin and various internal organs. LSc and SSc are considered to be basically different diseases, and there is no transition between them. However, LSc and SSc have several common characteristics, including endothelial cell dysfunction, immune activation, and excess fibrosis of the skin, and there exist several SSc cases complicated with LSc during the course of SSc. Clinical and laboratory characteristics of SSc patients with LSc remain unclear. We investigated the clinical and laboratory features of 8 SSc patients with LSc among 220 SSc patients (3.6%). The types of LSc included plaque (5/8), guttate (2/8), and linear type (1/8). All cases were diagnosed as having SSc within 5 years before or after the appearance of LSc. In three cases of SSc with LSc (37.5%), LSc skin lesions preceded clinical symptoms of SSc. Young age, negative antinuclear antibody, and positive anti-RNA polymerase III antibody were significantly prevalent in SSc patients with LSc. The positivity of anticentromere antibody tended to be prevalent in SSc patients without LSc. No significant difference in the frequency of complications, such as interstitial lung disease, reflux esophagitis, and pulmonary artery hypertension, was observed. The awareness of these characteristic of SSc with LSc are essential to establish an early diagnosis and treatment. © 2015 Japanese Dermatological Association.

  19. From Localized Scleroderma to Systemic Sclerosis: Coexistence or Possible Evolution.

    PubMed

    Dilia, Giuggioli; Michele, Colaci; Emanuele, Cocchiara; Amelia, Spinella; Federica, Lumetti; Clodoveo, Ferri

    2018-01-01

    Systemic sclerosis (SSc) and localized scleroderma (LoS) are two different diseases that may share some features. We evaluated the relationship between SSc and LoS in our case series of SSc patients. We analysed the clinical records of 330 SSc patients, in order to find the eventual occurrence of both the two diseases. Eight (2.4%) female patients presented both the two diagnoses in their clinical histories. Six developed LoS prior to SSc; in 4/6 cases, the presence of autoantibodies was observed before SSc diagnosis. Overall, the median time interval between LoS and SSc diagnosis was 18 (range 0-156) months. LoS and SSc are two distinct clinical entities that may coexist. Moreover, as anecdotally reported in pediatric populations, we suggested the possible development of SSc in adult patients with LoS, particularly in presence of Raynaud's phenomenon or antinuclear antibodies before the SSc onset.

  20. Self-Stigma in People With Mental Illness

    PubMed Central

    Watson, Amy C.; Corrigan, Patrick; Larson, Jonathon E.; Sells, Molly

    2007-01-01

    Persons with mental illnesses such as schizophrenia may internalize mental illness stigma and experience diminished self-esteem and self-efficacy. In this article, we describe a model of self-stigma and examine a hierarchy of mediational processes within the model. Seventy-one individuals with serious mental illness were recruited from a community support program at an outpatient psychiatry department of a community hospital. All participants completed the Self-Stigma of Mental Illness Scale along with measures of group identification (GI), perceived legitimacy (PL), self-esteem, and self-efficacy. Models examining the steps involved in self-stigma process were tested. Specifically, after conducting preliminary bivariate analyses, we examine stereotype agreement as a mediator of GI and PL on stigma self-concurrence (SSC); SSC as a mediator of GI and PL on self-efficacy; and SSC as a mediator of GI and PL on self-esteem. Findings provide partial support for the proposed mediational processes and point to GI, PL, and stereotype agreement as areas to be considered for intervention. PMID:17255118

  1. Factors associated with gingival inflammation among adults with systemic sclerosis.

    PubMed

    Yuen, H K; Weng, Y; Reed, S G; Summerlin, L M; Silver, R M

    2014-02-01

    To identify factors associated with increased gingival inflammation in adults with systemic sclerosis (SSc, scleroderma). In this cross-sectional study, forty-eight adults with SSc received assessment of gingival inflammation using Löe and Silness gingival index (LSGI), measurement of oral aperture and evaluation of manual dexterity to perform oral hygiene using the Toothbrushing Ability Test, as well as completion of an oral health-related questionnaire. Three explanatory variables in the final multiple predictor models for the LSGI outcome were statistically significant--manual dexterity to perform oral hygiene, flossing in the evening and SSc subtype, with higher (i.e., worse) LSGI score among those with impaired manual dexterity, not flossing in the evening and diffuse form of SSc. In addition, posterior teeth had higher LSGI scores compared with that of the anterior teeth after adjusting for other variables. Results suggest that dental health professionals take manual dexterity into consideration when educating patients with SSc to improve their oral hygiene and educate them on paying more attention on cleaning their posterior teeth and the importance of flossing in the evening--especially those who only floss once a day or less often. © 2013 John Wiley & Sons A/S.

  2. Performance of the new ACR/EULAR classification criteria for systemic sclerosis in clinical practice.

    PubMed

    Jordan, Suzana; Maurer, Britta; Toniolo, Martin; Michel, Beat; Distler, Oliver

    2015-08-01

    The preliminary classification criteria for SSc lack sensitivity for mild/early SSc patients, therefore, the new ACR/EULAR classification criteria for SSc were developed. The objective of this study was to evaluate the performance of the new classification criteria for SSc in clinical practice in a cohort of mild/early patients. Consecutive patients with a clinical diagnosis of SSc, based on expert opinion, were prospectively recruited and assessed according to the EULAR Scleroderma Trials and Research group (EUSTAR) and very early diagnosis of SSc (VEDOSS) recommendations. In some patients, missing values were retrieved retrospectively from the patient's records. Patients were grouped into established SSc (fulfilling the old ACR criteria) and mild/early SSc (not fulfilling the old ACR criteria). The new ACR/EULAR criteria were applied to all patients. Of the 304 patients available for the final analysis, 162/304 (53.3%) had established SSc and 142/304 (46.7%) had mild/early SSc. All 162 established SSc patients fulfilled the new ACR/EULAR classification criteria. The remaining 142 patients had mild/early SSc. Eighty of these 142 patients (56.3%) fulfilled the new ACR/EULAR classification criteria. Patients with mild/early SSc not fulfilling the new classification criteria were most often suffering from RP, had SSc-characteristic autoantibodies and had an SSc pattern on nailfold capillaroscopy. Taken together, the sensitivity of the new ACR/EULAR classification criteria for the overall cohort was 242/304 (79.6%) compared with 162/304 (53.3%) for the ACR criteria. In this cohort with a focus on mild/early SSc, the new ACR/EULAR classification criteria showed higher sensitivity and classified more patients as definite SSc patients than the ACR criteria. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Field-scale application of spent sulfidic caustic as a source of alternative electron donor for autotrophic denitrification.

    PubMed

    Lee, Jae-Ho; Park, Jeung-Jin; Choi, Gi-Choong; Byun, Im-Gyu; Park, Tae-Joo; Lee, Tae-Ho

    2013-01-01

    Biological reuse of spent sulfidic caustic (SSC) originating from oil refineries is a promising method for the petrochemical industry because of low handling cost. SSC typically contains high concentrations of sulfur, with the most dominant sulfur compounds being sulfide (S(2-)). SSC is also characterized by a high pH and elevated alkalinity up to 5-15% by weight. Because of these characteristics, SSC can be used for denitrification of NO3(-)-N in the biological nitrogen removal process as both the electron donor and buffering agent in sulfur-utilizing autotrophic denitrification. In this study, two kinds of SSC (SSC I, SSC II) produced from two petrochemical companies were used for autotrophic denitrification in a field-scale wastewater treatment plant (WWTP). The effluent total nitrogen (TN) concentration in this process was about 10.5 mg/L without any external carbon sources and the nitrification efficiency was low, about 93.0%, because of alkalinity deficiency in the influent. The injection of SSC I, but not SSC II, promoted nitrification efficiency, which was attributed to the difference in the NaOH/S ratio between SSC I and II. SSC was injected based on sulfide concentration of SSC required to denitrify NO3(-)-N in the WWTP. SSC I had higher NaOH/S than SSC II and thus could supply more alkalinity for nitrification than SSC II. On the other hand, additional TN removal of about 9.0% was achieved with the injection of both SSCs. However, denitrification efficiency was not proportionally increased with increasing SSC injection because of NO3(-)-N deficiency in the anoxic tank due to the limited capacity of the recycling pump. For the same reason, sulfate concentration, which is the end product of sulfur-utilizing autotrophic denitrificaiton in the effluent, was also not increased with increasing SSC injection.

  4. Suspended sediment concentration in the Lower Sea Scheldt (Belgium): long term trends and relation to mud disposal

    NASA Astrophysics Data System (ADS)

    Depreiter, Davy; van Holland, Gijsbert; Lanckriet, Thijs; Beirinckx, Kirsten; Vanlede, Joris; Maris, Tom

    2015-04-01

    In this presentation, results from different monitoring and research projects (OMES, MONEOS, Flexible Disposal and Marine-Fluvial mud ratio) will be integrated to increase the insight in the trends and relation between mud disposal and the increasing sediment concentrations (SSC) in the Lower Sea Scheldt. In the Scheldt Estuary, major projects have been carried out in the past decade, among which the third deepening of the navigation channel and the opening of the Deurganck dock. Maintenance dredging is carried out to guarantee a minimum navigation depth. A rising trend in the volume of mud dredged in the Lower Sea Scheldt is observed since 2006, the year after the opening of the Deurganck Dock. The trend is explained by increasing mud volumes dredged in this dock and on a nearby sill. This volume culminated in 2011 (4.8 million m³) when the depth of this dock was increased to its design depth. The dredged mud is disposed upstream, quickly to be resuspended. Near the mud disposal location, yearly averaged SSC (measured at 4.5 m above bed) tripled between 2005 and 2011 (108 to 348 mg/L), and SSC peaks increased even stronger. A multivariate regression model indicated a strong correlation between mud disposal volumes and timing and observed SSC. Mud disposal volumes and SSC where somewhat lower again after 2011. The SSC increase raises an alert with regard to the risk for a regime shift towards a hyperturbid system. Increasing SSC may indeed decrease the hydraulic resistance initiating a feedback mechanism that results in further increasing SSC values. It thus appears that more mud is being circulated: the Deurganck dock acts as mud sink, from which the mud is - after dredging and disposal - resuspended. The mud may have different sources: fluvial or marine influx. The increasing SSC might not only be related to the mud disposal, but also to changing tidal characteristics that enhance the influx of marine suspended sediments. To elucidate this, an analysis of the marine fraction in soil and suspended sediments has also been performed.

  5. Effects of electric field methods on modeling the midlatitude ionospheric electrodynamics and inner magnetosphere dynamics

    DOE PAGES

    Yu, Yiqun; Jordanova, Vania Koleva; Ridley, Aaron J.; ...

    2017-05-10

    Here, we report a self-consistent electric field coupling between the midlatitude ionospheric electrodynamics and inner magnetosphere dynamics represented in a kinetic ring current model. This implementation in the model features another self-consistency in addition to its already existing self-consistent magnetic field coupling with plasma. The model is therefore named as Ring current-Atmosphere interaction Model with Self-Consistent magnetic (B) and electric (E) fields, or RAM-SCB-E. With this new model, we explore, by comparing with previously employed empirical Weimer potential, the impact of using self-consistent electric fields on the modeling of storm time global electric potential distribution, plasma sheet particle injection, andmore » the subauroral polarization streams (SAPS) which heavily rely on the coupled interplay between the inner magnetosphere and midlatitude ionosphere. We find the following phenomena in the self-consistent model: (1) The spatially localized enhancement of electric field is produced within 2.5 < L < 4 during geomagnetic active time in the dusk-premidnight sector, with a similar dynamic penetration as found in statistical observations. (2) The electric potential contours show more substantial skewing toward the postmidnight than the Weimer potential, suggesting the resistance on the particles from directly injecting toward the low-L region. (3) The proton flux indeed indicates that the plasma sheet inner boundary at the dusk-premidnight sector is located further away from the Earth than in the Weimer potential, and a “tongue” of low-energy protons extends eastward toward the dawn, leading to the Harang reversal. (4) SAPS are reproduced in the subauroral region, and their magnitude and latitudinal width are in reasonable agreement with data.« less

  6. Effects of electric field methods on modeling the midlatitude ionospheric electrodynamics and inner magnetosphere dynamics

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

    Yu, Yiqun; Jordanova, Vania Koleva; Ridley, Aaron J.

    Here, we report a self-consistent electric field coupling between the midlatitude ionospheric electrodynamics and inner magnetosphere dynamics represented in a kinetic ring current model. This implementation in the model features another self-consistency in addition to its already existing self-consistent magnetic field coupling with plasma. The model is therefore named as Ring current-Atmosphere interaction Model with Self-Consistent magnetic (B) and electric (E) fields, or RAM-SCB-E. With this new model, we explore, by comparing with previously employed empirical Weimer potential, the impact of using self-consistent electric fields on the modeling of storm time global electric potential distribution, plasma sheet particle injection, andmore » the subauroral polarization streams (SAPS) which heavily rely on the coupled interplay between the inner magnetosphere and midlatitude ionosphere. We find the following phenomena in the self-consistent model: (1) The spatially localized enhancement of electric field is produced within 2.5 < L < 4 during geomagnetic active time in the dusk-premidnight sector, with a similar dynamic penetration as found in statistical observations. (2) The electric potential contours show more substantial skewing toward the postmidnight than the Weimer potential, suggesting the resistance on the particles from directly injecting toward the low-L region. (3) The proton flux indeed indicates that the plasma sheet inner boundary at the dusk-premidnight sector is located further away from the Earth than in the Weimer potential, and a “tongue” of low-energy protons extends eastward toward the dawn, leading to the Harang reversal. (4) SAPS are reproduced in the subauroral region, and their magnitude and latitudinal width are in reasonable agreement with data.« less

  7. Effects of electric field methods on modeling the midlatitude ionospheric electrodynamics and inner magnetosphere dynamics

    NASA Astrophysics Data System (ADS)

    Yu, Yiqun; Jordanova, Vania K.; Ridley, Aaron J.; Toth, Gabor; Heelis, Roderick

    2017-05-01

    We report a self-consistent electric field coupling between the midlatitude ionospheric electrodynamics and inner magnetosphere dynamics represented in a kinetic ring current model. This implementation in the model features another self-consistency in addition to its already existing self-consistent magnetic field coupling with plasma. The model is therefore named as Ring current-Atmosphere interaction Model with Self-Consistent magnetic (B) and electric (E) fields, or RAM-SCB-E. With this new model, we explore, by comparing with previously employed empirical Weimer potential, the impact of using self-consistent electric fields on the modeling of storm time global electric potential distribution, plasma sheet particle injection, and the subauroral polarization streams (SAPS) which heavily rely on the coupled interplay between the inner magnetosphere and midlatitude ionosphere. We find the following phenomena in the self-consistent model: (1) The spatially localized enhancement of electric field is produced within 2.5 < L < 4 during geomagnetic active time in the dusk-premidnight sector, with a similar dynamic penetration as found in statistical observations. (2) The electric potential contours show more substantial skewing toward the postmidnight than the Weimer potential, suggesting the resistance on the particles from directly injecting toward the low-L region. (3) The proton flux indeed indicates that the plasma sheet inner boundary at the dusk-premidnight sector is located further away from the Earth than in the Weimer potential, and a "tongue" of low-energy protons extends eastward toward the dawn, leading to the Harang reversal. (4) SAPS are reproduced in the subauroral region, and their magnitude and latitudinal width are in reasonable agreement with data.

  8. Esophageal Motor Abnormalities in Patients With Scleroderma: Heterogeneity, Risk Factors, and Effects on Quality of Life.

    PubMed

    Crowell, Michael D; Umar, Sarah B; Griffing, W Leroy; DiBaise, John K; Lacy, Brian E; Vela, Marcelo F

    2017-02-01

    Systemic scleroderma (SSc) is associated with esophageal aperistalsis and hypotensive esophagogastric junction pressure, although there could be a gradation in esophageal motor dysfunction. We characterized esophageal motor function by high-resolution esophageal manometry (HRM) and assessed associations between SSc severity, health-related quality of life (HRQOL), and HRM findings in patients. We performed a prospective study of 200 patients with SSc and 102 patients without SSc (controls) who underwent HRM at Mayo Clinic Arizona from May 2006 through January 2015. We used data on integrated relaxation pressure, distal contractile integral, and distal latency to classify esophageal motility disorders according to the Chicago Classification v 3.0. A subset of subjects (n = 122) completed SSc-specific gastrointestinal symptom and HRQOL questionnaires. HRM findings, symptoms, and HRQOL data were compared among diffuse SSc, limited SSc, and control subjects. Categorical variables were compared by using the χ 2 or Fisher exact test; continuous variables were compared by using Mann-Whitney or Kruskal-Wallis test. Multivariable logistic regression was used to assess the association between severity of esophageal dysmotility and baseline clinical factors. Among patients with SSc, 83 had diffuse SSc (42%), and 117 had limited SSc (58%). Absent contractility was more frequent in patients with SSc than in controls (56% vs 13%; P < .001). HRM findings varied among the patients; absent contractility (56%) was the most frequent diagnosis, followed by normal motility (26%) and ineffective esophageal motility (10%). Classic scleroderma esophagus (esophagogastric junction pressure with absent contractility) was only observed in 33% of patients (34% with diffuse SSc vs 32% limited SSc) (P = .880). Severe esophageal dysmotility was associated with disease duration, interstitial lung disease, and higher gastrointestinal symptom scores (P < .001). HRQOL was decreased in patients with SSc and severe esophageal dysmotility. Although severe dysmotility is more common in patients with SSc than in controls, we observed the so-called scleroderma esophagus in only one-third of patients with SSc. Esophageal motor function appears to be heterogeneous in SSc. Esophageal dysmotility reduces HRQOL in patients with SSc. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  9. Quality effort decision in service supply chain with quality preference based on quantum game

    NASA Astrophysics Data System (ADS)

    Zhang, Cuihua; Xing, Peng; Wang, Jianwei

    2015-04-01

    Service quality preference behaviors of both members are considered in service supply chain (SSC) including a service integrator and a service provider with stochastic demand. Through analysis of service quality cost and revenue, the utility functions are established on service quality effort degree and service quality preference level in integrated and decentralized SSC. Nash equilibrium and quantum game are used to optimize the models. By comparing the different solutions, the optimal strategies are obtained in SSC with quality preference. Then some numerical examples are studied and the changing trend of service quality effort is further analyzed by the influence of the entanglement operator and quality preferences.

  10. Immunohistochemical and morphometric evaluation of COX-1 and COX-2 in the remodeled lung in idiopathic pulmonary fibrosis and systemic sclerosis* ,**

    PubMed Central

    Parra, Edwin Roger; Lin, Flavia; Martins, Vanessa; Rangel, Maristela Peres; Capelozzi, Vera Luiza

    2013-01-01

    OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival. METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival. RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP), and low COX-1 expression in alveolar septa. CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that. PMID:24473763

  11. Clinical pattern of systemic sclerosis in Central Ukraine. Association between clinical manifestations of systemic sclerosis and hypertension.

    PubMed

    Semenov, Viktor; Kuryata, Olexandr; Lysunets, Tatiana

    2018-01-01

    Systemic sclerosis (SSc) is a rare disease of connective tissue, manifestations of which may vary in different geographical areas. We aimed to describe the clinical portrait of patients with SSc in Dnipropetrovsk region and to investigate how initial clinical and laboratory characteristics are connected with the presence of hypertension in SSc onset. Patients were enrolled to this study from the registry of SSc patients, established in the Rheumatology Department, Mechnikov Dnipropetrovsk Regional Clinic, Dnipro. This registry contains histories of new cases of SSc from 1993 to 2014. Patients are followed-up and receive treatment according to EULAR and local standards. Diagnosis of SSc was based on ACR and EULAR Criteria for systemic Sclerosis. Two patients developed scleroderma renal crisis during follow-up. This report is a cross-sectional study. We analysed only data of the first visit to a rheumatologist. In total 148 patients (median age [IQR] - 47 [40; 52] years) fulfilled the inclusion criteria. Male/female ratio was 1 : 20.1. The most frequent clinical signs were Raynaud's phenomenon and arthritis. The prevalence of skin lesion in dcSSc patients was twice as high as in lcSSc patients. Pulmonary fibrosis occurred significantly more commonly in dcSSc patients. Hypertension occurred in 26-33% in both groups. Patients with hypertension at the SSc onset were seven years older than normotensive patients. More hypertensive patients were classified as lcSSc. Mean GFR was dramatically lower in hypertensive patients. The most common clinical form in our study was diffuse cutaneous subset of SSc. Hypertension in patients with SSc may be associated with local cutaneous subset of SSc and renal impairment. The strongest predictors of clinical form of SSc are signs of fibrosis (skin lesion and pulmonary fibrosis) and inflammation (arthritis and elevated CRP).

  12. The stretch-shortening cycle : a model to study naturally occurring neuromuscular fatigue.

    PubMed

    Nicol, Caroline; Avela, Janne; Komi, Paavo V

    2006-01-01

    Neuromuscular fatigue has traditionally been examined using isolated forms of either isometric, concentric or eccentric actions. However, none of these actions are naturally occurring in human (or animal) ground locomotion. The basic muscle function is defined as the stretch-shortening cycle (SSC), where the preactivated muscle is first stretched (eccentric action) and then followed by the shortening (concentric) action. As the SSC taxes the skeletal muscles very strongly mechanically, its influence on the reflex activation becomes apparent and very different from the isolated forms of muscle actions mentioned above. The ground contact phases of running, jumping and hopping etc. are examples of the SSC for leg extensor muscles; similar phases can also be found for the upper-body activities. Consequently, it is normal and expected that the fatigue phenomena should be explored during SSC activities. The fatigue responses of repeated SSC actions are very versatile and complex because the fatigue does not depend only on the metabolic loading, which is reportedly different among muscle actions. The complexity of SSC fatigue is well reflected by the recovery patterns of many neuromechanical parameters. The basic pattern of SSC fatigue response (e.g. when using the complete exhaustion model of hopping or jumping) is the bimodality showing an immediate reduction in performance during exercise, quick recovery within 1-2 hours, followed by a secondary reduction, which may often show the lowest values on the second day post-exercise when the symptoms of muscle soreness/damage are also greatest. The full recovery may take 4-8 days depending on the parameter and on the severity of exercise. Each subject may have their own time-dependent bimodality curve. Based on the reviewed literature, it is recommended that the fatigue protocol is 'completely' exhaustive to reduce the important influence of inter-subject variability in the fatigue responses. The bimodality concept is especially apparent for stretch reflex responses, measured either in passive or active conditions. Interestingly, the reflex responses follow parallel changes with some of the pure mechanical parameters, such as yielding of the braking force during an initial ground contact of running or hopping. The mechanism of SSC fatigue and especially the bimodal response of performance deterioration and its recovery are often difficult to explain. The immediate post-exercise reduction in most of the measured parameters and their partial recovery 1-2 hours post-exercise can be explained primarily to be due to metabolic fatigue induced by exercise. The secondary reduction in these parameters takes place when the muscle soreness is highest. The literature gives several suggestions including the possible structural damage of not only the extrafusal muscle fibres, but also the intrafusal ones. Temporary changes in structural proteins and muscle-tendon interaction may be related to the fatigue-induced force reduction. Neural adjustments in the supraspinal level could naturally be operative, although many studies quoted in this article emphasise more the influences of exhaustive SSC fatigue on the fusimotor-muscle spindle system. It is, however, still puzzling why the functional recovery lasts several days after the disappearance of muscle soreness. Unfortunately, this and many other possible mechanisms need more thorough testing in animal models provided that the SSC actions can be truly performed as they appear in normal human locomotion.

  13. From Localized Scleroderma to Systemic Sclerosis: Coexistence or Possible Evolution

    PubMed Central

    Emanuele, Cocchiara; Amelia, Spinella; Clodoveo, Ferri

    2018-01-01

    Background Systemic sclerosis (SSc) and localized scleroderma (LoS) are two different diseases that may share some features. We evaluated the relationship between SSc and LoS in our case series of SSc patients. Methods We analysed the clinical records of 330 SSc patients, in order to find the eventual occurrence of both the two diseases. Results Eight (2.4%) female patients presented both the two diagnoses in their clinical histories. Six developed LoS prior to SSc; in 4/6 cases, the presence of autoantibodies was observed before SSc diagnosis. Overall, the median time interval between LoS and SSc diagnosis was 18 (range 0–156) months. Conclusions LoS and SSc are two distinct clinical entities that may coexist. Moreover, as anecdotally reported in pediatric populations, we suggested the possible development of SSc in adult patients with LoS, particularly in presence of Raynaud's phenomenon or antinuclear antibodies before the SSc onset. PMID:29666638

  14. Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry.

    PubMed

    Denton, Christopher P; Krieg, Thomas; Guillevin, Loic; Schwierin, Barbara; Rosenberg, Daniel; Silkey, Mariabeth; Zultak, Maurice; Matucci-Cerinic, Marco

    2012-05-01

    The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies.

  15. Dysregulated expression of MIG/CXCL9, IP-10/CXCL10 and CXCL16 and their receptors in systemic sclerosis

    PubMed Central

    2011-01-01

    Introduction Systemic sclerosis (SSc) is characterized by fibrosis and microvascular abnormalities including dysregulated angiogenesis. Chemokines, in addition to their chemoattractant properties, have the ability to modulate angiogenesis. Chemokines lacking the enzyme-linked receptor (ELR) motif, such as monokine induced by interferon-γ (IFN-γ) (MIG/CXCL9) and IFN-inducible protein 10 (IP-10/CXCL10), inhibit angiogenesis by binding CXCR3. In addition, CXCL16 promotes angiogenesis by binding its unique receptor CXCR6. In this study, we determined the expression of these chemokines and receptors in SSc skin and serum. Methods Immunohistology and enzyme-linked immunosorbent assays (ELISAs) were used to determine chemokine and chemokine receptor expression in the skin and serum, respectively, of SSc and normal patients. Endothelial cells (ECs) were isolated from SSc skin biopsies and chemokine and chemokine receptor expression was determined by quantitative PCR and immunofluorescence staining. Results Antiangiogenic IP-10/CXCL10 and MIG/CXCL9 were elevated in SSc serum and highly expressed in SSc skin. However, CXCR3, the receptor for these chemokines, was decreased on ECs in SSc vs. normal skin. CXCL16 was elevated in SSc serum and increased in SSc patients with early disease, pulmonary arterial hypertension, and those that died during the 36 months of the study. In addition, its receptor CXCR6 was overexpressed on ECs in SSc skin. At the mRNA and protein levels, CXCR3 was decreased while CXCR6 was increased on SSc ECs vs. human microvascular endothelial cells (HMVECs). Conclusions These results show that while the expression of MIG/CXCL9 and IP-10/CXCL10 are elevated in SSc serum, the expression of CXCR3 is downregulated on SSc dermal ECs. In contrast, CXCL16 and CXCR6 are elevated in SSc serum and on SSc dermal ECs, respectively. In all, these findings suggest angiogenic chemokine receptor expression is likely regulated in an effort to promote angiogenesis in SSc skin. PMID:21303517

  16. LIDT-DD: A New Self-Consistent Debris Disc Model Including Radiation Pressure and Coupling Dynamical and Collisional Evolution

    NASA Astrophysics Data System (ADS)

    Kral, Q.; Thebault, P.; Charnoz, S.

    2014-01-01

    The first attempt at developing a fully self-consistent code coupling dynamics and collisions to study debris discs (Kral et al. 2013) is presented. So far, these two crucial mechanisms were studied separately, with N-body and statistical collisional codes respectively, because of stringent computational constraints. We present a new model named LIDT-DD which is able to follow over long timescales the coupled evolution of dynamics (including radiation forces) and collisions in a self-consistent way.

  17. Synchrotron and Synchrotron Self-Compton Spectral Signatures and Blazar Emission Models

    NASA Technical Reports Server (NTRS)

    Chiang, James; Boettcher, Markus; White, Nicholas E. (Technical Monitor)

    2002-01-01

    We find that energy losses due to synchrotron self-Compton (BBC) emission in Blazar jets can produce distinctive signatures in the time-averaged synchrotron and SSC spectra of these objects. For a fairly broad range of particle injection distributions, SSC-loss-dominated synchrotron emission exhibits a spectral dependence Fv approximately v (exp -3/2). The presence or absence of this dependence in the optical and ultraviolet spectra of flat-spectrum radio quasars such as PC 279 and in the soft X-ray spectra of high-frequency BL Lac objects such as Mark 501 gives a robust measure of the importance of SSC losses. Furthermore, for partially cooled particle distributions, spectral breaks of varying sizes can appear in the synchrotron and SSC spectra and will be related to the spectral indices of the emission below the break. These spectral signatures place constraints on the size scale and the nonthermal particle content of the emitting plasma, as well as the observer orientation relative to the jet axis.

  18. Self-consistent chaos in a mean-field Hamiltonian model of fluids and plasmas

    NASA Astrophysics Data System (ADS)

    del-Castillo-Negrete, D.; Firpo, Marie-Christine

    2002-11-01

    We present a mean-field Hamiltonian model that describes the collective dynamics of marginally stable fluids and plasmas. In plasmas, the model describes the self-consistent evolution of electron holes and clumps in phase space. In fluids, the model describes the dynamics of vortices with negative and positive circulation in shear flows. The mean-field nature of the system makes it a tractable model to study the dynamics of large degrees-of-freedom, coupled Hamiltonian systems. Here we focus in the role of self-consistent chaos in the formation and destruction of phase space coherent structures. Numerical simulations in the finite N and in the Narrow kinetic limit (where N is the number of particles) show the existence of coherent, rotating dipole states. We approximate the dipole as two macroparticles, and show that the N = 2 limit has a family of rotating integrable solutions described by a one degree-of-freedom nontwist Hamiltonian. The coherence of the dipole is explained in terms of a parametric resonance between the rotation frequency of the macroparticles and the oscillation frequency of the self-consistent mean field. For a class of initial conditions, the mean field exhibits a self-consistent, elliptic-hyperbolic bifurcation that leads to the destruction of the dipole and violent mixing of the phase space.

  19. Identification of Cadherin 11 as a Mediator of Dermal Fibrosis and Possible Role in Systemic Sclerosis

    PubMed Central

    Wu, Minghua; Pedroza, Mesias; Lafyatis, Robert; George, Anuh-Teresa; Mayes, Maureen D.; Assassi, Shervin; Tan, Filemon K.; Brenner, Michael B.; Agarwal, Sandeep K.

    2014-01-01

    Objective Systemic sclerosis (SSc) is a chronic autoimmune disease clinically manifesting as progressive fibrosis of the skin and internal organs. Recent microarray studies demonstrated that cadherin 11 (Cad-11) expression is increased in the affected skin of patients with SSc. The purpose of this study was to examine our hypothesis that Cad-11 is a mediator of dermal fibrosis. Methods Biopsy samples of skin from SSc patients and healthy control subjects were used for real-time quantitative polymerase chain reaction analysis to assess Cad-11 expression and for immunohistochemistry to determine the expression pattern of Cad-11. To determine whether Cad-11 is a mediator of dermal fibrosis, Cad-11–deficient mice and anti–Cad-11 monoclonal antibodies (mAb) were used in the bleomycin-induced dermal fibrosis model. In vitro studies with dermal fibroblasts and bone marrow–derived macrophages were used to determine the mechanisms by which Cad-11 contributes to the development of tissue fibrosis. Results Levels of messenger RNA for Cad-11 were increased in skin biopsy samples from patients with SSc and correlated with the modified Rodnan skin thickness scores. Cad-11 expression was localized to dermal fibroblasts and macrophages in SSc skin. Cad-11–knockout mice injected with bleomycin had markedly attenuated dermal fibrosis, as quantified by measurements of skin thickness, collagen levels, myofibroblast accumulation, and profibrotic gene expression, in lesional skin as compared to the skin of wild-type mice. In addition, anti–Cad-11 mAb decreased fibrosis at various time points in the bleomycin-induced dermal fibrosis model. In vitro studies demonstrated that Cad-11 regulated the production of transforming growth factor β (TGFβ) by macrophages and the migration of fibroblasts. Conclusion These data demonstrate that Cad-11 is a mediator of dermal fibrosis and TGFβ production and suggest that Cad-11 may be a therapeutic target in SSc. PMID:24757152

  20. THE GERMLINE STEM CELL NICHE UNIT IN MAMMALIAN TESTES

    PubMed Central

    Oatley, Jon M.; Brinster, Ralph L.

    2014-01-01

    This review addresses current understanding of the germline stem cell niche unit in mammalian testes. Spermatogenesis is a classic model of tissue-specific stem cell function relying on self-renewal and differentiation of spermatogonial stem cells (SSCs). These fate decisions are influenced by a niche microenvironment composed of a growth factor milieu that is provided by several testis somatic support cell populations. Investigations over the last two decades have identified key determinants of the SSC niche including cytokines that regulate SSC functions and support cells providing these factors, adhesion molecules that influence SSC homing, and developmental heterogeneity of the niche during postnatal aging. Emerging evidence suggests that Sertoli cells are a key support cell population influencing the formation and function of niches by secreting soluble factors and possibly orchestrating contributions of other support cells. Investigations with mice have shown that niche influence on SSC proliferation differs during early postnatal development and adulthood. Moreover, there is mounting evidence of an age-related decline in niche function, which is likely influenced by systemic factors. Defining the attributes of stem cell niches is key to developing methods to utilize these cells for regenerative medicine. The SSC population and associated niche comprise a valuable model system for study that provides fundamental knowledge about the biology of tissue-specific stem cells and their capacity to sustain homeostasis of regenerating tissue lineages. While the stem cell is essential for maintenance of all self-renewing tissues and has received considerable attention, the role of niche cells is at least as important and may prove to be more receptive to modification in regenerative medicine. PMID:22535892

  1. An Observational Cohort Study Examining the Effect of the Duration of Skin-to-Skin Contact on the Physiological Parameters of the Neonate in a Neonatal Intensive Special Care Unit.

    PubMed

    Jones, Hannah; Santamaria, Nick

    2018-06-01

    Focus on skin-to-skin contact (SSC) as a family-centered care intervention in Neonatal Intensive Special Care (NISC) Units continues to increase. Previously, SSC has been shown to improve neonatal physiological stability, support brain development, and promote bonding and attachment. Limited research exists investigating SSC duration and neonatal physiological responses. This study examined the relationship between SSC duration and the neonate's oxygen saturation, heart rate (HR), respiratory rate (RR), and temperature. An observational cohort study was conducted at The Royal Women's Hospital NISC Unit in Melbourne, Australia. For each neonate participant, 1 SSC with their parent was studied (parent convenience) and neonatal physiological parameters recorded, with a bivariate correlation used to explore the relationship between the duration of SSC and the percentage of time during SSC that the neonate's physiological variables remained within a target range. No correlation existed between the duration of SSC and the neonatal physiological variables of oxygen saturation, HR, RR, and temperature. However, neonatal oxygen requirement was more often reduced across the duration of SSC. Due to previously documented benefits to neonates physiologically from SSC, and our supportive finding that SSC reduces neonatal oxygen requirement, we believe that this study adds to the evidence to support promotion of SSC in NISC Units. The duration of SSC does not appear to negatively impact the physiological effects to the neonate. Thus, SSC should be encouraged in all NISC Units to be conducted for the length of time the parent is able. This study should be repeated with a larger sample size.

  2. Modelling postharvest quality of blueberry affected by biological variability using image and spectral data.

    PubMed

    Hu, Meng-Han; Dong, Qing-Li; Liu, Bao-Lin

    2016-08-01

    Hyperspectral reflectance and transmittance sensing as well as near-infrared (NIR) spectroscopy were investigated as non-destructive tools for estimating blueberry firmness, elastic modulus and soluble solid content (SSC). Least squares-support vector machine models were established from these three spectra based on samples from three cultivars viz. Bluecrop, Duke and M2 and two harvest years viz. 2014 and 2015 for predicting blueberry postharvest quality. One-cultivar reflectance models (establishing model using one cultivar) derived better results than the corresponding transmittance and NIR models for predicting blueberry firmness with few cultivar effects. Two-cultivar NIR models (establishing model using two cultivars) proved to be suitable for estimating blueberry SSC with correlations over 0.83. Rp (RMSEp ) values of the three-cultivar reflectance models (establishing model using 75% of three cultivars) were 0.73 (0.094) and 0.73 (0.186), respectively , for predicting blueberry firmness and elastic modulus. For SSC prediction, the three-cultivar NIR model was found to achieve an Rp (RMSEp ) value of 0.85 (0.090). Adding Bluecrop samples harvested in 2014 could enhance the three-cultivar model robustness for firmness and elastic modulus. The above results indicated the potential for using spatial and spectral techniques to develop robust models for predicting blueberry postharvest quality containing biological variability. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  3. Osteopontin in Systemic Sclerosis and its Role in Dermal Fibrosis

    PubMed Central

    Wu, Minghua; Schneider, Daniel J.; Mayes, Maureen D; Assassi, Shervin; Arnett, Frank C.; Tan, Filemon K.; Blackburn, Michael R.; Agarwal, Sandeep K.

    2012-01-01

    Osteopontin (OPN) is a matricellular protein with proinflammatory and profibrotic properties. Previous reports demonstrate a role for OPN in wound healing and pulmonary fibrosis. Herein, we determined if OPN levels are increased in a large cohort of systemic sclerosis (SSc) patients and if OPN contributes dermal fibrosis. Plasma OPN levels were increased in SSc patients, including patients with limited and diffuse disease, compared to healthy controls. Immunohistology demonstrated OPN on fibroblast-like and inflammatory cells in SSc skin and lesional skin from mice in the bleomycin-induced dermal fibrosis model. OPN deficient (OPN−/−) mice developed less dermal fibrosis compared to wild-type mice in the bleomycin-induced dermal fibrosis model. Additional in vivo studies demonstrated that lesional skin from OPN−/− mice had fewer Mac-3+ cells, fewer myofibroblasts, decreased TGF-beta (TGFβ) and genes in the TGFβ pathway and decreased numbers of cells expressing phosphorylated SMAD2 (pSMAD) and ERK. In vitro, OPN−/− dermal fibroblasts had decreased migratory capacity but similar phosphorylation of SMAD2 by TGFβ. Finally, TGFβ production by OPN deficient macrophages was reduced compared to wild type. These data demonstrate an important role for OPN in the development of dermal fibrosis and suggest that OPN may be a novel therapeutic target in SSc. PMID:22402440

  4. Testicular tissue cryopreservation and spermatogonial stem cell transplantation to restore fertility: from bench to bedside

    PubMed Central

    2014-01-01

    Male infertility management has made significant progress during the past three decades, especially after the introduction of intracytoplasmic sperm injection in 1992. However, many boys and men still suffer from primary testicular failure due to acquired or genetic causes. New and novel treatments are needed to address these issues. Spermatogenesis originates from spermatogonial stem cells (SSCs) that reside in the testis. Many of these men lack SSCs or have lost SSCs over time as a result of specific medical conditions or toxic exposures. Loss of SSCs is critical in prepubertal boys who suffer from cancer and are going through gonadotoxic cancer treatments, as there is no option of sperm cryopresrvation due to sexual immaturity. The development of SSC transplantation in a mouse model to repopulate spermatozoa in depleted testes has opened new avenues of research in other animal models, including non-human primates. Recent advances in cryopreservation and in vitro propagation of human SSCs offer promise for human SSC autotransplantation in the near future. Ongoing research is focusing on safety and technical issues of human SSC autotransplantation. This is the time to counsel parents and boys at risk of infertility on the possibility of cryopreserving and banking a small amount of testis tissue for potential future use in SSC transplantation. PMID:25157677

  5. Skin-to-skin care for procedural pain in neonates.

    PubMed

    Johnston, Celeste; Campbell-Yeo, Marsha; Disher, Timothy; Benoit, Britney; Fernandes, Ananda; Streiner, David; Inglis, Darlene; Zee, Rebekah

    2017-02-16

    Skin-to-skin care (SSC), often referred to as 'kangaroo care' (KC) due to its similarity with marsupial behaviour of ventral maternal-infant contact, is one non-pharmacological intervention for pain control in infants. The primary objectives were to determine the effect of SSC alone on pain from medical or nursing procedures in neonates compared to no intervention, sucrose or other analgesics, or additions to simple SSC such as rocking; and to determine the effects of the amount of SSC (duration in minutes), method of administration (e.g. who provided the SSC) of SSC in reducing pain from medical or nursing procedures in neonatesThe secondary objectives were to determine the safety of SSC care for relieving procedural pain in infants; and to compare the SSC effect in different postmenstrual age subgroups of infants. For this update, we used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1); MEDLINE via PubMed (1966 to 25 February 2016); Embase (1980 to 25 February 2016); and CINAHL (1982 to 25 February 2016). We also searched clinical trials' databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials. Studies with randomisation or quasi-randomisation, double- or single-blinded, involving term infants (≥ 37 completed weeks' postmenstrual age (PMA) to a maximum of 44 weeks' PMA and preterm infants (< 37 completed weeks PMA) receiving SSC for painful procedures conducted by healthcare professionals. The main outcome measures were physiological or behavioural pain indicators and composite pain scores. A mean difference (MD) with 95% confidence interval (CI) using a fixed-effect model was reported for continuous outcome measures. We included variations on type of tissue-damaging procedure, provider of care, and duration of SSC. Twenty-five studies (n = 2001 infants) were included. Nineteen studies (n = 1065) used heel lance as the painful procedure, one study combined venepuncture and heel stick (n = 50), three used intramuscular injection (n = 776), one used 'vaccination' (n = 60), and one used tape removal (n = 50). The studies were generally strong and had low or uncertain risk of bias. Blinding of the intervention was not possible, making them subject to high risk, depending on the method of scoring outcomes.Seventeen studies (n = 810) compared SSC to a no-treatment control. Although 15 studies measured heart rate during painful procedures, data from only five studies (n = 161) could be combined for a mean difference (MD) of -10.78 beats per minute (95% CI -13.63 to -7.93) favouring SSC. Meta-analysis of four studies (n = 120) showed no difference in heart rate following the painful procedure (MD 0.08, 95% CI -4.39 to 4.55). Two studies (n = 38) reported heart rate variability with no significant differences. Two studies (n = 101) in a meta-analysis on oxygen saturation at 30 and 60 seconds following the painful procedure did not show a difference. Duration of crying meta-analysis was performed on four studies (n = 133): two (n = 33) investigated response to heel lance (MD = -34.16, 95% CI -42.86 to -25.45), and two (n = 100) following IM injection (MD = -8.83, 95% CI -14.63 to -3.02), favouring SSC. Five studies, one consisting of two substudies (n = 267), used the Premature Infant Pain Profile (PIPP) as a primary outcome, which favoured SCC at 30 seconds (MD -3.21, 95% CI -3.94 to -2.47), at 60 seconds (3 studies; n = 156) (MD -1.64, 95% CI -2.86 to -0.43), and at 90 seconds (n = 156) (MD -1.28, 95% CI -2.53 to -0.04); but at 120 seconds there was no difference (n = 156) (MD 0.07, 95% CI -1.11 to 1.25). No studies on return of heart rate to baseline level, cortisol levels, and facial actions could be combined for meta-analysis findings.Eight studies compared SSC to another intervention with or without a no-treatment control. Two cross-over studies (n = 80) compared mother versus other provider (father, another female) on PIPP scores at 30, 60, 90, and 120 seconds with no significant difference. When SSC was compared to other interventions, there were not enough similar studies to pool results in an analysis. One study compared SSC (n = 640) with and without dextrose and found that the combination was most effective and that SSC alone was more effective than dextrose alone. Similarly, in another study SSC was more effective than oral glucose for heart rate (n = 95). SSC either in combination with breastfeeding or alone was favoured over a no-treatment control, but not different to breastfeeding. One study compared SSC alone and in combination with both sucrose and breastfeeding on heart rate (HR), NIPS scores, and crying time (n = 127). The combinations were more effective than SSC alone for NIPS and crying. Expressed breast milk was compared to SSC in one study (n = 50) and found both equally effective on PIPP scores. There were not enough participants with similar outcomes and painful procedures to compare age groups or duration of SSC. No adverse events were reported in any of the studies. SSC appears to be effective as measured by composite pain indicators with both physiological and behavioural indicators and, independently, using heart rate and crying time; and safe for a single painful procedure. Purely behavioural indicators tended to favour SSC but with facial actions there is greater possibility of observers not being blinded. Physiological indicators were mixed although the common measure of heart rate favoured SSC. Two studies compared mother-providers to others, with non-significant results. There was more heterogeneity in the studies with behavioural or composite outcomes. There is a need for replication studies that use similar, clearly defined outcomes. Studies examining optimal duration of SSC, gestational age groups, repeated use, and long-term effects of SSC are needed. Of interest would be to study synergistic effects of SSC with other interventions.

  6. Clinical pattern of systemic sclerosis in Central Ukraine. Association between clinical manifestations of systemic sclerosis and hypertension

    PubMed Central

    Kuryata, Olexandr; Lysunets, Tatiana

    2018-01-01

    Objectives Systemic sclerosis (SSc) is a rare disease of connective tissue, manifestations of which may vary in different geographical areas. We aimed to describe the clinical portrait of patients with SSc in Dnipropetrovsk region and to investigate how initial clinical and laboratory characteristics are connected with the presence of hypertension in SSc onset. Material and methods Patients were enrolled to this study from the registry of SSc patients, established in the Rheumatology Department, Mechnikov Dnipropetrovsk Regional Clinic, Dnipro. This registry contains histories of new cases of SSc from 1993 to 2014. Patients are followed-up and receive treatment according to EULAR and local standards. Diagnosis of SSc was based on ACR and EULAR Criteria for systemic Sclerosis. Two patients developed scleroderma renal crisis during follow-up. This report is a cross-sectional study. We analysed only data of the first visit to a rheumatologist. Results In total 148 patients (median age [IQR] – 47 [40; 52] years) fulfilled the inclusion criteria. Male/female ratio was 1 : 20.1. The most frequent clinical signs were Raynaud’s phenomenon and arthritis. The prevalence of skin lesion in dcSSc patients was twice as high as in lcSSc patients. Pulmonary fibrosis occurred significantly more commonly in dcSSc patients. Hypertension occurred in 26–33% in both groups. Patients with hypertension at the SSc onset were seven years older than normotensive patients. More hypertensive patients were classified as lcSSc. Mean GFR was dramatically lower in hypertensive patients. Conclusions The most common clinical form in our study was diffuse cutaneous subset of SSc. Hypertension in patients with SSc may be associated with local cutaneous subset of SSc and renal impairment. The strongest predictors of clinical form of SSc are signs of fibrosis (skin lesion and pulmonary fibrosis) and inflammation (arthritis and elevated CRP). PMID:29686439

  7. CD16-positive circulating monocytes and fibrotic manifestations of systemic sclerosis.

    PubMed

    Lescoat, Alain; Lecureur, Valérie; Roussel, Mikael; Sunnaram, Béatrice Ly; Ballerie, Alice; Coiffier, Guillaume; Jouneau, Stéphane; Fardel, Olivier; Fest, Thierry; Jégo, Patrick

    2017-07-01

    The objective of this study is to assess the association of clinical manifestations of systemic sclerosis (SSc) with the absolute count of circulating blood monocyte subpopulations according to their membrane expression of CD16. Forty-eight consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in this cross-sectional study. CD16+ monocyte absolute count was defined by flow cytometry and confronted to the clinical characteristics of SSc patients. Twenty-three healthy donors (HD) were randomly selected for comparison. SSc patients had an increased number of total circulating blood monocytes compared to HD (p < 0.001). The CD16- subpopulation absolute count was increased in SSc patients compared to HD (p < 0.001) but was similar in limited SSc (lSSc) and diffuse SSc (dSSc). On the contrary, the CD16+ population absolute count was increased in dSSc compared to both HD and lSSc patients (dSSc 0.071 Giga/L (±0.034) vs HD 0.039 Giga/L (±0.030), p < 0.01, and dSSc 0.071 Giga/L (±0.034) vs lSSc 0.048 Giga/L (±0.024), p < 0.05). The CD16+ monocyte subpopulation absolute count was significantly correlated with the severity of skin fibrosis evaluated by the modified Rodnan skin score (p < 0.001). The CD16+ monocyte subpopulation was also associated with pulmonary fibrosis (p < 0.05), with the severity of the restrictive ventilatory defect evaluated by total lung capacity (p < 0.05) and with the pulmonary function impairment reflected by diffusing capacity of the lungs for carbon monoxyde measures (p < 0.01). These results suggest that CD16+ monocytes are associated with the main fibrotic manifestations of SSc and their role in the pathogenesis of fibrosis in this autoimmune disorder should therefore be further considered.

  8. Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis

    PubMed Central

    Mayes, Maureen D.; Bossini-Castillo, Lara; Gorlova, Olga; Martin, José Ezequiel; Zhou, Xiaodong; Chen, Wei V.; Assassi, Shervin; Ying, Jun; Tan, Filemon K.; Arnett, Frank C.; Reveille, John D.; Guerra, Sandra; Teruel, María; Carmona, Francisco David; Gregersen, Peter K.; Lee, Annette T.; López-Isac, Elena; Ochoa, Eguzkine; Carreira, Patricia; Simeón, Carmen Pilar; Castellví, Iván; González-Gay, Miguel Ángel; Ortego-Centeno, Norberto; Ríos, Raquel; Callejas, José Luis; Navarrete, Nuria; García Portales, Rosa; Camps, María Teresa; Fernández-Nebro, Antonio; González-Escribano, María F.; Sánchez-Román, Julio; García-Hernández, Francisco José; Castillo, María Jesús; Aguirre, María Ángeles; Gómez-Gracia, Inmaculada; Fernández-Gutiérrez, Benjamín; Rodríguez-Rodríguez, Luis; Vicente, Esther; Andreu, José Luis; Fernández de Castro, Mónica; García de la Peña, Paloma; López-Longo, Francisco Javier; Martínez, Lina; Fonollosa, Vicente; Espinosa, Gerard; Tolosa, Carlos; Pros, Anna; Rodríguez Carballeira, Mónica; Narváez, Francisco Javier; Rubio Rivas, Manel; Ortiz Santamaría, Vera; Díaz, Bernardino; Trapiella, Luis; Freire, María del Carmen; Sousa, Adrián; Egurbide, María Victoria; Fanlo Mateo, Patricia; Sáez-Comet, Luis; Díaz, Federico; Hernández, Vanesa; Beltrán, Emma; Román-Ivorra, José Andrés; Grau, Elena; Alegre Sancho, Juan José; Blanco García, Francisco J.; Oreiro, Natividad; Fernández Sueiro, Luis; Zhernakova, Alexandra; Padyukov, Leonid; Alarcón-Riquelme, Marta; Wijmenga, Cisca; Brown, Matthew; Beretta, Lorenzo; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg H.W.; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Hesselstrand, Roger; Nordin, Annika; Airó, Paolo; Lunardi, Claudio; Shiels, Paul; van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Wigley, Fredrick M.; Hummers, Laura K.; Varga, John; Hinchcliff, Monique E.; Baron, Murray; Hudson, Marie; Pope, Janet E.; Furst, Daniel E.; Khanna, Dinesh; Phillips, Kristin; Schiopu, Elena; Segal, Barbara M.; Molitor, Jerry A.; Silver, Richard M.; Steen, Virginia D.; Simms, Robert W.; Lafyatis, Robert A.; Fessler, Barri J.; Frech, Tracy M.; AlKassab, Firas; Docherty, Peter; Kaminska, Elzbieta; Khalidi, Nader; Jones, Henry Niall; Markland, Janet; Robinson, David; Broen, Jasper; Radstake, Timothy R.D.J.; Fonseca, Carmen; Koeleman, Bobby P.; Martin, Javier

    2014-01-01

    In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci. PMID:24387989

  9. Alteration of microcirculation is a hallmark of very early systemic sclerosis patients: a laser speckle contrast analysis.

    PubMed

    Della Rossa, Alessandra; Cazzato, Massimiliano; d'Ascanio, Anna; Tavoni, Antonio; Bencivelli, Walter; Pepe, Pasquale; Mosca, Marta; Baldini, Chiara; Rossi, Marco; Bombardieri, Stefano

    2013-01-01

    To investigate blood flow and microvascular reactivity by laser speckle perfusion imager (Perimed, Jarfalla) in consecutive patients affected by Raynaud's phenomenon at baseline and following dynamic stimulations. Skin blood flow in the dorsum of the hand was measured at baseline and after cold test and post-occlusive hyperemia test in 56 consecutive subjects affected by Raynaud's phenomenon (RP), 20 primary (PRP) and 36 secondary to systemic sclerosis (SSc). Twenty healthy subjects (HS) were studied as controls. After cold test, SSc had a significant reduction of blood flow (-58%) as compared to HS (-19%) (p=0.01). Recovery time was significantly higher in SSc (58 minutes) as compared to HS (18 minutes) and PRP (19 minutes) (p=0.006 and 0.0016, respectively). Peak flow after ischaemic test was significantly reduced in SSc (+237%) as compared to PRP (+485%) (p=0.0068). Post-ischaemic hyperemic area under the curve (AUC) was blunted in SSc (79U/sec) compared to PRP (167 U/sec) (p=0.0126). Proximal distal gradient was noticed in 74% of HS, 45% of PRP and 36% of SSc (p=0.01). Homogeneous pattern of flux distribution was significantly different between HS (95%), PRP (80%), and SSc (16%) (p<0.0001). Among SSc patients, a significant difference in ischaemic challenge was shown between patients with early-SSc versus patients with definite-SSc. Our preliminary results indicate a clearcut alteration of the dynamic of microcirculation in SSc-RP as compared to PRP and HS. Among SSc patients, early-SSc is a separate entity as compared to established disease.

  10. An analysis of the kangaroo care intervention using neonatal EEG complexity: a preliminary study.

    PubMed

    Kaffashi, F; Scher, M S; Ludington-Hoe, S M; Loparo, K A

    2013-02-01

    Skin-to-skin contact (SSC) promotes physiological stability and interaction between parents and infants. Temporal analyses of predictability in EEG-sleep time series can elucidate functional brain maturation between SSC and non-SSC cohorts at similar post-menstrual ages (PMAs). Sixteen EEG-sleep studies were performed on eight preterm infants who received 8 weeks of SSC, and compared with two non-SSC cohorts at term (N=126) that include a preterm group corrected to term age and a full term group. Two time series measures of predictability were used for comparisons. The SSC premature neonate group had increased complexity when compared to the non-SSC premature neonate group at the same PMA. Discriminant analysis shows that SSC neonates at 40 weeks PMA are closer to the full term neonate non-SSC group than to the premature non-SSC group at the same PMA; suggesting that the KC intervention accelerates neurophysiological maturation of premature neonates. Based on the hypothesis that EEG-derived complexity increases with neurophysiological maturation as supported by previously published research, SSC accelerates brain maturation in healthy preterm infants as quantified by time series measures of predictability when compared to a similar non-SSC group. Times series methods that quantify predictability of EEG sleep in neonates can provide useful information about altered neural development after developmental care interventions such as SSC. Analyses of this type may be helpful in assessing other neuroprotection strategies. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  11. Quench simulation studies of TAC jelly roll superferric dipole corrector elements for the SSC

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

    Lopez, G.

    Using the computer program SSC-DTAC-T, which is a modification of the quench computer program SSC-RR to model Jelly Roll coils, the quench behavior of the dipole corrector element (TAC design with Jelly Roll winding) is studied. The simulations are made as a function of the length of the magnet, the copper-to-superconducting ratio, and the thickness of insulation surrounding the wires. The magnet is self-protected with all listed considerations. In addition, this implies that other corrector multipoles (quadrupole, sextupole, octupole, etc.), which use the same conductor winding technique, are self-protected. A passive protection system should work for these elements. 9 refs.,more » 18 figs., 1 tab.« less

  12. Metabolomic profile of systemic sclerosis patients.

    PubMed

    Murgia, Federica; Svegliati, Silvia; Poddighe, Simone; Lussu, Milena; Manzin, Aldo; Spadoni, Tatiana; Fischetti, Colomba; Gabrielli, Armando; Atzori, Luigi

    2018-05-16

    Systemic sclerosis (SSc) is an autoimmune disease of unknown aetiology characterized by vascular lesions, immunological alterations and diffuse fibrosis of the skin and internal organs. Since recent evidence suggests that there is a link between metabolomics and immune mediated disease, serum metabolic profile of SSc patients and healthy controls was investigated by 1 H-NMR and GC-MS techniques. The results indicated a lower level of aspartate, alanine, choline, glutamate, and glutarate in SSc patients compared with healthy controls. Moreover, comparing patients affected by limited SSc (lcSSc) and diffuse SSc (dcSSc), 6 discriminant metabolites were identified. The multivariate analysis performed using all the metabolites significantly different revealed glycolysis, gluconeogenesis, energetic pathways, glutamate metabolism, degradation of ketone bodies and pyruvate metabolism as the most important networks. Aspartate, alanine and citrate yielded a high area under receiver-operating characteristic (ROC) curves (AUC of 0.81; CI 0.726-0.93) for discriminating SSc patients from controls, whereas ROC curve generated with acetate, fructose, glutamate, glutamine, glycerol and glutarate (AUC of 0.84; CI 0.7-0.98) discriminated between lcSSc and dcSSc. These results indicated that serum NMR-based metabolomics profiling method is sensitive and specific enough to distinguish SSc from healthy controls and provided a feasible diagnostic tool for the diagnosis and classification of the disease.

  13. Modeling the spectral energy distribution of the radio galaxy IC310

    NASA Astrophysics Data System (ADS)

    Fraija, N.; Marinelli, A.; Galván-Gámez, A.; Aguilar-Ruiz, E.

    2017-03-01

    The radio galaxy IC310 located in the Perseus Cluster is one of the brightest objects in the radio and X-ray bands, and one of the closest active galactic nuclei observed in very-high energies. In GeV - TeV γ-rays, IC310 was detected in low and high flux states by the MAGIC telescopes from October 2009 to February 2010. Taking into account that the spectral energy distribution (SED) up to a few GeV seems to exhibit a double-peak feature and that a single-zone synchrotron self-Compton (SSC) model can explain all of the multiwavelength emission except for the non-simultaneous MAGIC emission, we interpret, in this work, the multifrequency data set of the radio galaxy IC310 in the context of homogeneous hadronic and leptonic models. In the leptonic framework, we present a multi-zone SSC model with two electron populations to explain the whole SED whereas for the hadronic model, we propose that a single-zone SSC model describes the SED up to a few GeVs and neutral pion decay products resulting from pγ interactions could describe the TeV - GeV γ-ray spectra. These interactions occur when Fermi-accelerated protons interact with the seed photons around the SSC peaks. We show that, in the leptonic model the minimum Lorentz factor of second electron population is exceedingly high γe ∼ 105 disfavoring this model, and in the hadronic model the required proton luminosity is not extremely high ∼1044 erg/s, provided that charge neutrality between the number of electrons and protons is given. Correlating the TeV γ-ray and neutrino spectra through photo-hadronic interactions, we find that the contribution of the emitting region of IC310 to the observed neutrino and ultra-high-energy cosmic ray fluxes are negligible.

  14. [Improving apple fruit quality predictions by effective correction of Vis-NIR laser diffuse reflecting images].

    PubMed

    Qing, Zhao-shen; Ji, Bao-ping; Shi, Bo-lin; Zhu, Da-zhou; Tu, Zhen-hua; Zude, Manuela

    2008-06-01

    In the present study, improved laser-induced light backscattering imaging was studied regarding its potential for analyzing apple SSC and fruit flesh firmness. Images of the diffuse reflection of light on the fruit surface were obtained from Fuji apples using laser diodes emitting at five wavelength bands (680, 780, 880, 940 and 980 nm). Image processing algorithms were tested to correct for dissimilar equator and shape of fruit, and partial least squares (PLS) regression analysis was applied to calibrate on the fruit quality parameter. In comparison to the calibration based on corrected frequency with the models built by raw data, the former improved r from 0. 78 to 0.80 and from 0.87 to 0.89 for predicting SSC and firmness, respectively. Comparing models based on mean value of intensities with results obtained by frequency of intensities, the latter gave higher performance for predicting Fuji SSC and firmness. Comparing calibration for predicting SSC based on the corrected frequency of intensities and the results obtained from raw data set, the former improved root mean of standard error of prediction (RMSEP) from 1.28 degrees to 0.84 degrees Brix. On the other hand, in comparison to models for analyzing flesh firmness built by means of corrected frequency of intensities with the calibrations based on raw data, the former gave the improvement in RMSEP from 8.23 to 6.17 N x cm(-2).

  15. Doubly self-consistent field theory of grafted polymers under simple shear in steady state.

    PubMed

    Suo, Tongchuan; Whitmore, Mark D

    2014-03-21

    We present a generalization of the numerical self-consistent mean-field theory of polymers to the case of grafted polymers under simple shear. The general theoretical framework is presented, and then applied to three different chain models: rods, Gaussian chains, and finitely extensible nonlinear elastic (FENE) chains. The approach is self-consistent at two levels. First, for any flow field, the polymer density profile and effective potential are calculated self-consistently in a manner similar to the usual self-consistent field theory of polymers, except that the calculation is inherently two-dimensional even for a laterally homogeneous system. Second, through the use of a modified Brinkman equation, the flow field and the polymer profile are made self-consistent with respect to each other. For all chain models, we find that reasonable levels of shear cause the chains to tilt, but it has very little effect on the overall thickness of the polymer layer, causing a small decrease for rods, and an increase of no more than a few percent for the Gaussian and FENE chains. Using the FENE model, we also probe the individual bond lengths, bond correlations, and bond angles along the chains, the effects of the shear on them, and the solvent and bonded stress profiles. We find that the approximations needed within the theory for the Brinkman equation affect the bonded stress, but none of the other quantities.

  16. Interval follow up of a 4-day pilot program to implement the WHO surgical safety checklist at a Congolese hospital.

    PubMed

    White, Michelle C; Peterschmidt, Jennifer; Callahan, James; Fitzgerald, J Edward; Close, Kristin L

    2017-06-29

    The World Health Organisation Surgical Safety Checklist (SSC) improves surgical outcomes and the research question is no longer 'does the SSC work?' but, 'how to make the SSC work?' Evidence for implementation strategies in low-income countries is sparse and existing strategies are heavily based on long-term external support. Short but effective implementation programs are required if widespread scale up is to be achieved. We designed and delivered a four-day pilot SSC training course at a single hospital centre in the Republic of Congo, and evaluated the implementation after one year. We hypothesised that participants would still be using the checklist over 50% of the time. We taught the four-day SSC training course at Dolisie hospital in February 2014, and undertook a mixed methods impact evaluation based on the Kirkpatrick model in May 2015. SSC implementation was evaluated using self-reported questionnaire with a 3 point Likert scale to assess six key process measures. Learning, behaviour, organisational change and facilitators and inhibitors to change were evaluated with questionnaires, interviews and focus group discussion. Seventeen individuals participated in the training and seven (40%) were available for impact evaluation at 15 months. No participant had used the SSC prior to training. Over half the participants were following the six processes measures always or most of the time: confirmation of patient identity and the surgical procedure (57%), assessment of difficult intubation risk (72%), assessment of the risk of major blood loss (86%), antibiotic prophylaxis given before skin incision (86%), use of a pulse oximeter (86%), and counting sponges and instruments (71%). All participants reported positive improvements in teamwork, organisation and safe anesthesia. Most participants reported they worked in helpful, supportive and respectful atmosphere; and could speak up if they saw something that might harm a patient. However, less than half felt able to challenge those in authority. Our study demonstrates that a 4-day pilot course for SSC implementation resulted in over 50% of participants using the SSC at 15 months, positive changes in learning, behaviour and organisational change, but less impact on hierarchical culture. The next step is to test our novel implementation strategy in a larger hospital setting.

  17. Pulling it all together: the self-consistent distribution of neutral tori in Saturn's Magnetosphere based on all Cassini observations

    NASA Astrophysics Data System (ADS)

    Smith, H. T.; Richardson, J. D.

    2017-12-01

    Saturn's magnetosphere is unique in that the plumes from the small icy moon, Enceladus, serve at the primary source for heavy particles in Saturn's magnetosphere. The resulting co-orbiting neutral particles interact with ions, electrons, photons and other neutral particles to generate separate H2O, OH and O tori. Characterization of these toroidal distributions is essential for understanding Saturn magnetospheric sources, composition and dynamics. Unfortunately, limited direct observations of these features are available so modeling is required. A significant modeling challenge involves ensuring that either the plasma and neutral particle populations are not simply input conditions but can provide feedback to each population (i.e. are self-consistent). Jurac and Richardson (2005) executed such a self-consistent model however this research was performed prior to the return of Cassini data. In a similar fashion, we have coupled a 3-D neutral particle model (Smith et al. 2004, 2005, 2006, 2007, 2009, 2010) with a plasma transport model (Richardson 1998; Richardson & Jurac 2004) to develop a self-consistent model which is constrained by all available Cassini observations and current findings on Saturn's magnetosphere and the Enceladus plume source resulting in much more accurate neutral particle distributions. We present a new self-consistent model of the distribution of the Enceladus-generated neutral tori that is validated by all available observations. We also discuss the implications for source rate and variability.

  18. CXCL4 in undifferentiated connective tissue disease at risk for systemic sclerosis (SSc) (previously referred to as very early SSc).

    PubMed

    Valentini, Gabriele; Riccardi, Antonella; Vettori, Serena; Irace, Rosaria; Iudici, Michele; Tolone, Salvatore; Docimo, Ludovico; Bocchino, Marialuisa; Sanduzzi, Alessandro; Cozzolino, Domenico

    2017-08-01

    The aim of the study was to evaluate CXCL4 levels in undifferentiated connective tissue disease at risk for SSc (UCTD-SSc-risk) and confirm its increase and investigate its prognostic value. Serum CXCL4 levels were measured in 45 patients and 24 controls. CXCL4 was significantly higher in UCTD-SSc-risk patients than in controls. It resulted higher in patients with a shorter disease duration and in those lacking capillaroscopic alterations. We confirm that CXCL4 levels are increased in UCTD-risk-SSc patients. Further studies are needed to investigate the role of CXCL4 assessment in UCTD-risk-SSc.

  19. The Italian version of the Mouth Handicap in Systemic Sclerosis scale (MHISS) is valid, reliable and useful in assessing oral health-related quality of life (OHRQoL) in systemic sclerosis (SSc) patients.

    PubMed

    Maddali Bongi, S; Del Rosso, A; Miniati, I; Galluccio, F; Landi, G; Tai, G; Matucci-Cerinic, M

    2012-09-01

    In systemic sclerosis (SSc), mouth and face involvement leads to problems in oral health-related quality of life (OHRQoL). Mouth Handicap in Systemic Sclerosis scale (MHISS) is a 12-item questionnaire specifically quantifying mouth disability in SSc, organized in 3 subscales. Our aim was to validate Italian version of MHISS, by assessing its test-retest reliability and internal and external consistency in Italian SSc patients. Forty SSc patients (7 dSSc, 33 lSSc; age and disease duration: 57.27 ± 11.41, 9.4 ± 4.4 years; 22 with sicca syndrome) were evaluated with MHISS. MHISS was translated following a forward-backward translation procedure, with independent translations and counter-translation. Test-retest reliability was evaluated, comparing the results of two administrations, with intraclass correlation coefficient (ICC). Internal consistency was assessed by Cronbach's α and external consistency by comparison with mouth opening. MHISS has a good test-retest reliability (ICC: 0.93) and internal consistency (Cronbach's α:0.99). A good external consistency was confirmed by correlation with mouth opening (rho: -0,3869, p: 0.0137). Total MHISS score was 17.65 ± 5.20, with scores of subscale 1 (reduced mouth opening) of 6.60 ± 2.85 and scores of subscales 2 (sicca syndrome) and 3 (aesthetic concerns) of 7.82 ± 2.59 and 3.22 ± 1.14. Total and subscale 2 scores are higher in dSSc than in lSSc. This result may be due to the higher presence of sicca syndrome in dSSc than in lSSc (p = 0.0109). Our results support validity and reliability in Italian SSc patients of MHISS, specifically measuring SSc OHRQoL.

  20. Changes in macrophage transcriptome associate with systemic sclerosis and mediate GSDMA contribution to disease risk

    PubMed Central

    Koturan, Surya; Ko, Jeong-Hun; Fonseca, Carmen; Harmston, Nathan; Game, Laurence; Martin, Javier; Ong, Voon; Abraham, David J; Denton, Christopher P; Behmoaras, Jacques; Petretto, Enrico

    2018-01-01

    Objectives Several common and rare risk variants have been reported for systemic sclerosis (SSc), but the effector cell(s) mediating the function of these genetic variants remains to be elucidated. While innate immune cells have been proposed as the critical targets to interfere with the disease process underlying SSc, no studies have comprehensively established their effector role. Here we investigated the contribution of monocyte-derived macrophages (MDMs) in mediating genetic susceptibility to SSc. Methods We carried out RNA sequencing and genome-wide genotyping in MDMs from 57 patients with SSc and 15 controls. Our differential expression and expression quantitative trait locus (eQTL) analysis in SSc was further integrated with epigenetic, expression and eQTL data from skin, monocytes, neutrophils and lymphocytes. Results We identified 602 genes upregulated and downregulated in SSc macrophages that were significantly enriched for genes previously implicated in SSc susceptibility (P=5×10−4), and 270 cis-regulated genes in MDMs. Among these, GSDMA was reported to carry an SSc risk variant (rs3894194) regulating expression of neighbouring genes in blood. We show that GSDMA is upregulated in SSc MDMs (P=8.4×10−4) but not in the skin, and is a significant eQTL in SSc macrophages and lipopolysaccharide/interferon gamma (IFNγ)-stimulated monocytes. Furthermore, we identify an SSc macrophage transcriptome signature characterised by upregulation of glycolysis, hypoxia and mTOR signalling and a downregulation of IFNγ response pathways. Conclusions Our data further establish the link between macrophages and SSc, and suggest that the contribution of the rs3894194 risk variant to SSc susceptibility can be mediated by GSDMA expression in macrophages. PMID:29348297

  1. The differential expression of VEGF, VEGFR-2, and GLUT-1 proteins in disease subtypes of systemic sclerosis.

    PubMed

    Davies, Christine Ann; Jeziorska, Maria; Freemont, Anthony J; Herrick, Ariane L

    2006-02-01

    Our aim was to evaluate (a) whether there is differential expression of the endothelial regulator vascular endothelial growth factor (VEGF), its receptor (VEGFR-2), and the hypoxia-associated glucose transporter molecule, GLUT-1, in skin biopsies from different disease subtypes of systemic sclerosis (SSc) and (b) whether they associate with dermal calcinosis, a significant complication of SSc. Skin punch biopsies were taken from the forearms of 66 SSc patients including 18 with limited cutaneous disease without calcinosis (lcSSc), 23 with calcinosis (lcSSc/cal), and 25 with diffuse cutaneous disease (dcSSc) and from 12 healthy control subjects. The histological appearance of the skin was graded as G0 (normal), G1 (dermal edema), or G2 or G3 (increasing fibrotic changes). Immunohistochemistry was performed with antibodies to VEGF, VEGFR-2, and GLUT-1. Staining was assessed in the epidermis, microvessels, and fibroblasts. The Kruskal-Wallis 1-way analysis of variance was used to compare the data between disease groups. VEGF protein was located in the epidermis and in dermal endothelial cells, pericytes, fibroblasts, and inflammatory cells. In dcSSc only, there was a significant increase in VEGF staining intensity in the keratinocytes and pericytes and the lowest percentage of microvessels with VEGF-positive endothelial cells. GLUT-1 protein was located in the epidermis, erythrocytes, and perineurium. In both lcSSc/cal and dcSSC, but not lcSSc, there were significant increases in GLUT-1 staining intensity of keratinocytes. We propose that in patients with dcSSc, there is a net increase in unbound VEGF in skin that may account for the raised levels of VEGF in serum reported by others. Increased GLUT-1 expression in lcSSc/cal and dcSSc indicates that hypoxia is an associated factor.

  2. Decline in suspended sediment concentration delivered by the Changjiang (Yangtze) River into the East China Sea between 1956 and 2013

    NASA Astrophysics Data System (ADS)

    Dai, Zhijun; Fagherazzi, Sergio; Mei, Xuefei; Gao, Jinjuan

    2016-09-01

    The temporal evolution of suspended sediment concentration (SSC) in a river debouching into the ocean provides vital insights into erosion processes in the watershed and dictates the evolution of the inner continental shelf. While the delivery of sediment from rivers to the ocean has received special attention in the recent past, few studies focused on the variability and dynamics of river SSC, especially in the Changjiang (Yangtze) river, China, the longest river in Asia. Here, variations in SSC delivered by the Changjiang River to the East China Sea and possible causes of its variability were detected based on a long-term time series of daily SSC and monthly water discharge measured at the Datong gauging station. The SSC data are further compared to a hydrological analysis of yearly precipitation covering the entire catchment. The results indicate the presence of a decline in SSC in the period 1956-2013, which can be divided into three phases: (i) high SSC (0.69 kg/m3) in the wet season and low SSC (0.2 kg/m3) in the dry season from 1956 to 1970; (ii) relative high SSC (0.58 kg/m3) in the wet season and low SSC (0.15 kg/m3) in the dry season from 1971 to 2002; and (iii) low SSC (0.19 kg/m3) in the wet season and very low SSC (0.09 kg/m3) in the dry season after 2002. These three periods have a mean yearly SSC values of 0.62, 0.42, and 0.18 kg/m3, respectively. Compared with 1956-1970, the slope of the rating curve between SSC and water discharge decreased, respectively, by 2% and 30% during the period 1971-2002 and 2002-2013. Soil erosion, dam construction, and banks reinforcement along the Changjiang River are the main causes of SSC variations. Fluctuations in water discharge are also controlling the SSC long-term variations. Specifically, from 1956 to 1970, the effect of soil erosion overrules that of dam impoundment, which is likely responsible for the high SSC; during the period 1970-2002, the influence of dam impoundment increases while that of soil erosion decreases, which together produce a small reduction in SSC. Since 2002, the impact of soil erosion further decreases and large-scale sediment trapping behind the Three Gorges Dam is responsible for the occurrence of extremely low SSC. The results presented herein for the Changjiang River can inform a better management strategy of sediment resources and water quality for both the river and the coast. Our conclusions can be well applied to other rivers discharging in the ocean subject to similar human activities.

  3. Disaster Response and Preparedness Application: Emergency Environmental Response Tool (EERT)

    NASA Technical Reports Server (NTRS)

    Smoot, James; Carr, Hugh; Jester, Keith

    2003-01-01

    In 2000, the National Aeronautics and Space Administration (NASA) Environmental Office at the John C. Stennis Space Center (SSC) developed an Environmental Geographic Information Systems (EGIS) database. NASA had previously developed a GIS database at SSC to assist in the NASA Environmental Office's management of the Center. This GIS became the basis for the NASA-wide EGIS project, which was proposed after the applicability of the SSC database was demonstrated. Since its completion, the SSC EGIS has aided the Environmental Office with noise pollution modeling, land cover assessment, wetlands delineation, environmental hazards mapping, and critical habitat delineation for protected species. At SSC, facility management and safety officers are responsible for ensuring the physical security of the facilities, staff, and equipment as well as for responding to environmental emergencies, such as accidental releases of hazardous materials. All phases of emergency management (planning, mitigation, preparedness, and response) depend on data reliability and system interoperability from a variety of sources to determine the size and scope of the emergency operation. Because geospatial data are now available for all NASA facilities, it was suggested that this data could be incorporated into a computerized management information program to assist facility managers. The idea was that the information system could improve both the effectiveness and the efficiency of managing and controlling actions associated with disaster, homeland security, and other activities. It was decided to use SSC as a pilot site to demonstrate the efficacy of having a baseline, computerized management information system that ultimately was referred to as the Emergency Environmental Response Tool (EERT).

  4. Influence of rheology on realignment of mantle convective structure with plate motion after a plate reorganization

    NASA Astrophysics Data System (ADS)

    van Hunen, J.; Zhong, S.

    2006-08-01

    Small-scale convection (SSC) rolls below the oceanic lithosphere have the tendency to align with the large-scale shearing direction and thus with the plate motion direction relative to the deep mantle. Understanding the timescales of and processes responsible for realignment would contribute significantly to our understanding of the unresolved phenomena in the Pacific such as gravity lineations, small-scale seismic velocity variations, and intraplate volcanism that cannot be explained by hot spots. In this study we examine the evolution of those convection rolls when this relative plate motion direction is suddenly changed, as suggested by the kink in the Hawaii-Emperor seamount chain. Using three-dimensional numerical flow models, we investigate the realignment of SSC rolls after a change in plate motion direction. From the nature of the SSC, it is expected that rheological parameters dominate the characteristics of this realignment. Our results show that this is indeed the case. We find that (1) using constraints from onset timing of SSC, realignment of rolls can occur as fast as within 20 Ma, but might also take much longer, dependent on the rheology; (2) the realignment period is strongly correlated to the sum of large-scale shear stress induced by plate motion and small-scale shear stress from the SSC itself; (3) in a mantle deforming by dislocation creep, realignment occurs faster than by diffusion creep, because dislocation creep SSC is more vigorous; and (4) activation energy has little influence on the realignment time. Possible evidence for the realignment period might come from precise age determination of intraplate volcanism or azimuthal seismic anisotropy.

  5. Clinical Features of Idiopathic Interstitial Pneumonia with Systemic Sclerosis-Related Autoantibody in Comparison with Interstitial Pneumonia with Systemic Sclerosis

    PubMed Central

    Yamakawa, Hideaki; Hagiwara, Eri; Kitamura, Hideya; Yamanaka, Yumie; Ikeda, Satoshi; Sekine, Akimasa; Baba, Tomohisa; Iso, Shinichiro; Okudela, Koji; Iwasawa, Tae; Takemura, Tamiko; Kuwano, Kazuyoshi; Ogura, Takashi

    2016-01-01

    Background Patients with idiopathic interstitial pneumonias sometimes have a few features of connective tissue disease (CTD) and yet do not fulfil the diagnostic criteria for any specific CTD. Objective This study was conducted to elucidate the characteristics, prognosis, and disease behavior in patients with interstitial lung disease (ILD) associated with systemic sclerosis (SSc)-related autoantibodies. Methods We retrospectively analyzed medical records of 72 ILD patients: 40 patients with SSc (SSc-ILD) and 32 patients with SSc-related autoantibody-positive ILD but not with CTD (ScAb-ILD), indicating lung-dominant CTD with SSc-related autoantibody. Results Patients with SSc-ILD were predominantly females and non-smokers, and most had nonspecific interstitial pneumonia confirmed by high-resolution computed tomography (HRCT) and pathological analysis. However, about half of the patients with ScAb-ILD were male and current or ex-smokers. On HRCT analysis, honeycombing was more predominant in patients with ScAb-ILD than with SSc-ILD. Pathological analysis showed the severity of vascular intimal or medial thickening in the SSc-ILD patients to be significantly higher than that in the ScAb-ILD patients. Survival curves showed that the patients with ScAb-ILD had a significantly poorer outcome than those with SSc-ILD. Conclusion Data from this study suggest that lung-dominant CTD with SSc-related autoantibody is a different disease entity from SSc-ILD. PMID:27564852

  6. Sudden clearing of estuarine waters upon crossing the threshold from transport to supply regulation of sediment transport as an erodible sediment pool is depleted: San Francisco Bay, 1999

    USGS Publications Warehouse

    Schoellhamer, David H.

    2011-01-01

    The quantity of suspended sediment in an estuary is regulated either by transport, where energy or time needed to suspend sediment is limiting, or by supply, where the quantity of erodible sediment is limiting. This paper presents a hypothesis that suspended-sediment concentration (SSC) in estuaries can suddenly decrease when the threshold from transport to supply regulation is crossed as an erodible sediment pool is depleted. This study was motivated by a statistically significant 36% step decrease in SSC in San Francisco Bay from water years 1991–1998 to 1999–2007. A quantitative conceptual model of an estuary with an erodible sediment pool and transport or supply regulation of sediment transport is developed. Model results confirm that, if the regulation threshold was crossed in 1999, SSC would decrease rapidly after water year 1999 as observed. Estuaries with a similar history of a depositional sediment pulse followed by erosion may experience sudden clearing.

  7. Mapping and predicting mortality from systemic sclerosis.

    PubMed

    Elhai, Muriel; Meune, Christophe; Boubaya, Marouane; Avouac, Jérôme; Hachulla, Eric; Balbir-Gurman, Alexandra; Riemekasten, Gabriela; Airò, Paolo; Joven, Beatriz; Vettori, Serena; Cozzi, Franco; Ullman, Susanne; Czirják, László; Tikly, Mohammed; Müller-Ladner, Ulf; Caramaschi, Paola; Distler, Oliver; Iannone, Florenzo; Ananieva, Lidia P; Hesselstrand, Roger; Becvar, Radim; Gabrielli, Armando; Damjanov, Nemanja; Salvador, Maria J; Riccieri, Valeria; Mihai, Carina; Szücs, Gabriella; Walker, Ulrich A; Hunzelmann, Nicolas; Martinovic, Duska; Smith, Vanessa; Müller, Carolina de Souza; Montecucco, Carlo Maurizio; Opris, Daniela; Ingegnoli, Francesca; Vlachoyiannopoulos, Panayiotis G; Stamenkovic, Bojana; Rosato, Edoardo; Heitmann, Stefan; Distler, Jörg H W; Zenone, Thierry; Seidel, Matthias; Vacca, Alessandra; Langhe, Ellen De; Novak, Srdan; Cutolo, Maurizio; Mouthon, Luc; Henes, Jörg; Chizzolini, Carlo; Mühlen, Carlos Alberto von; Solanki, Kamal; Rednic, Simona; Stamp, Lisa; Anic, Branimir; Santamaria, Vera Ortiz; De Santis, Maria; Yavuz, Sule; Sifuentes-Giraldo, Walter Alberto; Chatelus, Emmanuel; Stork, Jiri; Laar, Jacob van; Loyo, Esthela; García de la Peña Lefebvre, Paloma; Eyerich, Kilian; Cosentino, Vanesa; Alegre-Sancho, Juan Jose; Kowal-Bielecka, Otylia; Rey, Grégoire; Matucci-Cerinic, Marco; Allanore, Yannick

    2017-11-01

    To determine the causes of death and risk factors in systemic sclerosis (SSc). Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Skin-to-skin care for procedural pain in neonates.

    PubMed

    Johnston, Celeste; Campbell-Yeo, Marsha; Fernandes, Ananda; Inglis, Darlene; Streiner, David; Zee, Rebekah

    2014-01-23

    Skin-to-skin care (SSC), otherwise known as Kangaroo Care (KC) due to its similarity with marsupial behaviour of ventral maternal-infant contact, is one non-pharmacological intervention for pain control in infants. The primary objectives were to determine the effect of SSC alone on pain from medical or nursing procedures in neonates undergoing painful procedures compared to no intervention, sucrose or other analgesics, or additions to simple SSC such as rocking; and the effects of the amount of SSC (duration in minutes) and the method of administration (who provided the SSC, positioning of caregiver and neonate pair).The secondary objectives were to determine the incidence of untoward effects of SSC and to compare the SSC effect in different postmenstrual age subgroups of infants. The standard methods of the Cochrane Neonatal Collaborative Review Group were used. Databases searched in August 2011: Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library); Evidence-Based Medicine Reviews; MEDLINE (1950 onwards); PubMed (1975 onwards); EMBASE (1974 onwards); CINAHL (1982 onwards); Web of Science (1980 onwards); LILACS database (1982 onwards); SCIELO database (1982 onwards); PsycInfo (1980 onwards); AMED (1985 onwards); Dissertation-Abstracts International (1980 onwards). Searches were conducted throughout September 2012. Studies with randomisation or quasi-randomisation, double or single-blinded, involving term infants (> 37 completed weeks postmenstrual age (PMA)) to a maximum of 44 weeks PMA and preterm infants (< 37 completed weeks PMA) receiving SSC for painful procedures conducted by doctors, nurses, or other healthcare professionals. The main outcome measures were physiological or behavioural pain indicators and composite pain scores. A weighted mean difference (WMD) with 95% confidence interval (CI) using a fixed-effect model was reported for continuous outcome measures. We included variations on type of tissue-damaging procedure, provider of care, and duration of SSC. Nineteen studies (n = 1594 infants) were included. Fifteen studies (n = 744) used heel lance as the painful procedure, one study combined venepuncture and heel stick (n = 50), two used intramuscular injection, and one used 'vaccination' (n = 80). The studies that were included were generally strong and free from bias.Eleven studies (n = 1363) compared SSC alone to a no-treatment control. Although 11 studies measured heart rate during painful procedures, data from only four studies (n = 121) could be combined to give a mean difference (MD) of 0.35 beats per minute (95% CI -6.01 to 6.71). Three other studies that were not included in meta-analyses also reported no difference in heart rate after the painful procedure. Two studies reported heart rate variability outcomes and found no significant differences. Five studies used the Premature Infant Pain Profile (PIPP) as a primary outcome, which favoured SCC at 30 seconds (n = 268) (MD -3.21, 95% CI -3.94 to -2.48), 60 seconds (n = 164) (MD -1.85, 95% CI -3.03 to -0.68), and 90 seconds (n = 163) (MD -1.34, 95% CI -2.56 to -0.13), but at 120 seconds (n = 157) there was no difference. No studies provided findings on return of heart rate to baseline level, oxygen saturation, cortisol levels, duration of crying, and facial actions that could be combined for analysis.Eight studies compared SSC to another intervention with or without a no-treatment control. Two cross-over studies (n = 80) compared mother versus other provider on PIPP scores at 30, 60, 90, and 120 seconds with no significant difference. When SSC was compared to other interventions, there were not enough similar studies to pool results in an analysis. One study compared SSC with and without dextrose and found that the combination was most effective and that SSC alone was more effective than dextrose alone. Similarly, in another study SSC was more effective than oral glucose for heart rate but not oxygen saturation. SSC either in combination with breastfeeding or alone was favoured over a no-treatment control, but was not different to breastfeeding. There were not enough participants with similar outcomes and painful procedures to compare age groups or duration of SSC. No adverse events were reported in any of the studies. SSC appears to be effective, as measured by composite pain indicators and including both physiological and behavioural indicators, and safe for a single painful procedure such as a heel lance. Purely behavioural indicators tended to favour SSC but there remains questionable bias regarding behavioural indicators. Physiological indicators were typically not different between conditions. Only two studies compared mother providers to others, with non-significant results. There was more heterogeneity in the studies with behavioural or composite outcomes. There is a need for replication studies that use similar, clearly defined outcomes. New studies examining optimal duration of SSC, gestational age groups, repeated use, and long-term effects of SSC are needed.

  9. Current Approaches to the Treatment of Systemic-Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH).

    PubMed

    Sobanski, Vincent; Launay, David; Hachulla, Eric; Humbert, Marc

    2016-02-01

    Pulmonary arterial hypertension (PAH) is a severe condition causing significant morbidity and mortality in patients with systemic sclerosis (SSc). Despite the use of specific treatments, SSc-PAH survival remains poorer than in idiopathic PAH (IPAH). Recent therapeutic advances in PAH show a lower magnitude of response in SSc-PAH and a higher risk of adverse events, as compared to IPAH. The multifaceted underlying mechanisms and the multisystem nature of SSc probably explain part of the worse outcomes in SSc-PAH compared to IPAH. This review describes the current management of SSc-PAH with an emphasis on the impact of the different organ involvements in the prognosis and treatment response. An earlier detection of PAH and a better characterization of the clinical phenotypes of SSc-PAH are warranted in clinical practice and future trials. Determinants of prognosis, surrogate markers of clinical improvement or worsening, and relevance of the common endpoints used in clinical trials should be evaluated in this specific population. A multidisciplinary approach in expert referral centers is mandatory for SSc-PAH management.

  10. Cost-effectiveness evaluation of bovine tuberculosis surveillance in wildlife in France (Sylvatub system) using scenario trees.

    PubMed

    Rivière, Julie; Le Strat, Yann; Hendrikx, Pascal; Dufour, Barbara

    2017-01-01

    Bovine tuberculosis (bTB) is a common disease in cattle and wildlife, with health, zoonotic and economic implications. Infected wild animals, and particularly reservoirs, could hinder eradication of bTB from cattle populations, which could have an important impact on international cattle trade. Therefore, surveillance of bTB in wildlife is of particular importance to better understand the epidemiological role of wild species and to adapt the control measures. In France, a bTB surveillance system for free-ranging wildlife, the Sylvatub system, has been implemented since 2011. It relies on three surveillance components (SSCs) (passive surveillance on hunted animals (EC-SSC), passive surveillance on dead or dying animals (SAGIR-SSC) and active surveillance (PSURV-SSC)). The effectiveness of the Sylvatub system was previously assessed, through the estimation of its sensitivity (i.e. the probability of detecting at least one case of bTB infection by each SSC, specie and risk-level area). However, to globally assess the performance of a surveillance system, the measure of its sensitivity is not sufficient, as other factors such as economic or socio-economic factors could influence the effectiveness. We report here an estimation of the costs of the surveillance activities of the Sylvatub system, and of the cost-effectiveness of each surveillance component, by specie and risk-level, based on scenario tree modelling with the same tree structure as used for the sensitivity evaluation. The cost-effectiveness of the Sylvatub surveillance is better in higher-risk departments, due in particular to the higher probability of detecting the infection (sensitivity). Moreover, EC-SSC, which has the highest unit cost, is more efficient than the surveillance enhanced by the SAGIR-SSC, due to its better sensitivity. The calculation of the cost-effectiveness ratio shows that PSURV-SSC remains the most cost-effective surveillance component of the Sylvatub system, despite its high cost in terms of coordination, sample collection and laboratory analysis.

  11. Cost-effectiveness evaluation of bovine tuberculosis surveillance in wildlife in France (Sylvatub system) using scenario trees

    PubMed Central

    2017-01-01

    Bovine tuberculosis (bTB) is a common disease in cattle and wildlife, with health, zoonotic and economic implications. Infected wild animals, and particularly reservoirs, could hinder eradication of bTB from cattle populations, which could have an important impact on international cattle trade. Therefore, surveillance of bTB in wildlife is of particular importance to better understand the epidemiological role of wild species and to adapt the control measures. In France, a bTB surveillance system for free-ranging wildlife, the Sylvatub system, has been implemented since 2011. It relies on three surveillance components (SSCs) (passive surveillance on hunted animals (EC-SSC), passive surveillance on dead or dying animals (SAGIR-SSC) and active surveillance (PSURV-SSC)). The effectiveness of the Sylvatub system was previously assessed, through the estimation of its sensitivity (i.e. the probability of detecting at least one case of bTB infection by each SSC, specie and risk-level area). However, to globally assess the performance of a surveillance system, the measure of its sensitivity is not sufficient, as other factors such as economic or socio-economic factors could influence the effectiveness. We report here an estimation of the costs of the surveillance activities of the Sylvatub system, and of the cost-effectiveness of each surveillance component, by specie and risk-level, based on scenario tree modelling with the same tree structure as used for the sensitivity evaluation. The cost-effectiveness of the Sylvatub surveillance is better in higher-risk departments, due in particular to the higher probability of detecting the infection (sensitivity). Moreover, EC-SSC, which has the highest unit cost, is more efficient than the surveillance enhanced by the SAGIR-SSC, due to its better sensitivity. The calculation of the cost-effectiveness ratio shows that PSURV-SSC remains the most cost-effective surveillance component of the Sylvatub system, despite its high cost in terms of coordination, sample collection and laboratory analysis. PMID:28800642

  12. On the origin of X-ray spectra in luminous blazars

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

    Sikora, Marek; Janiak, Mateusz; Nalewajko, Krzysztof

    2013-11-26

    Gamma-ray luminosities of some quasar-associated blazars imply jet powers reaching values comparable to the accretion power even if assuming very strong Doppler boosting and very high efficiency of gamma-ray production. With much lower radiative efficiencies of protons than of electrons, and the recent reports of very strong coupling of electrons with shock-heated protons indicated by particle-in-cell simulations, the leptonic models seem to be strongly favored over the hadronic ones. However, the electron-proton coupling combined with the external-radiation-Compton (ERC) models of gamma-ray production in leptonic models predict extremely hard X-ray spectra, with energy indices α x ~ 0. This is inconsistentmore » with the observed 2-10 keV slopes of blazars, which cluster around α x ~ 0.6. This problem can be resolved by assuming that electrons can be efficiently cooled down radiatively to non-relativistic energies, or that blazar spectra are entirely dominated by the synchrotron self-Compton (SSC) component up to at least 10 keV. Here, we show that the required cooling can be sufficiently efficient only at distances r < 0.03 pc. SSC spectra, on the other hand, can be produced roughly co-spatially with the observed synchrotron and ERC components, which are most likely located roughly at a parsec scale. We show that the dominant SSC component can also be produced much further than the dominant synchrotron and ERC components, at distances of gsim 10 pc. Hence, depending on the spatial distribution of the energy dissipation along the jet, one may expect to see γ-ray/optical events with either correlated or uncorrelated X-rays. In all cases the number of e +e – pairs per proton is predicted to be very low. The direct verification of the proposed SSC scenario, and particularly the question of the co-spatiality of the SSC component with other spectral components, requires sensitive observations in the hard X-ray band. Lastly, this is now possible with the deployment of the NuSTAR satellite, providing the required sensitivity to monitor the details of the hard X-ray spectra of blazars in the range where the ERC component is predicted to start dominating over the SSC component.« less

  13. Quench simulation studies of the TAC Jelly Roll superferric dipole corrector elements for the SSC

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

    Lopez, G.

    Using the computer program SSC-DTAC-T, which is a modification of the quench computer program SSC-RR, to model Jelly Roll coils, the quench behavior of the dipole corrector element (TAC design with Jelly roll winding) is studied. The simulations are made as a function of the length of the magnet, the copper to superconducting ratio, and the thickness of insulation surrounding the wires. The magnet is quite well self-protected under all of these considerations. In addition, this implies that the other corrector multipoles (quadrupole, sextupole, octupole, etc.) which use the same conductor winding technique are self-protected. A passive protection system ismore » likely to work for these elements. 6 refs., 2 figs., 1 tab.« less

  14. A Meta-ethnography: Skin-to-Skin Holding From the Caregiver's Perspective.

    PubMed

    Vittner, Dorothy; Casavant, Sharon; McGrath, Jacqueline M

    2015-06-01

    Although the benefits of skin-to-skin care (SSC) are well documented in the literature, practices in the clinical setting remain inconsistent. Although nurses' reported knowledge about SSC has improved, confusion still exists regarding safety and appropriateness. Existing qualitative literature primarily focuses on parents' experiences; yet it is crucial to describe the essence of professional caregivers' experiences to enhance facilitation and implementation of SSC. Most studies surrounding the caregiver's perspective and SSC have focused on barriers that impede implementation or examined the experience from the organizational perspective and general group experiences rather than individual personal experiences with SSC. This meta-ethnography integrated the findings from several discrete studies into a salient interpretative perspective, creating a relevant understanding of the process of SSC as a means of enhancing facilitation and implementation of SSC with hospitalized infants. An ethnographic meta-synthesis of qualitative literature was completed. As a result of this synthesis, the caregivers' experiences were separated into themes to articulate the phenomena juxtaposed from the 8 original studies that influence facilitation of SSC for the parent-infant dyad. Qualitative data analysis uncovered 4 overarching themes: (1) varying thresholds of getting started; (2) defining adequate resources; (3) navigating the demands and complexity of the infant; and (4) balancing parental readiness with infant needs. This ethnographic meta-synthesis confirms nurses have good intentions in supporting SSC practices, yet struggle to meet competing demands in their daily practice. Innovative and practical translations of SSC are needed to normalize SSC as the daily standard for premature infants.

  15. Microbial and metabolic multi-omic correlations in systemic sclerosis patients.

    PubMed

    Bellocchi, Chiara; Fernández-Ochoa, Álvaro; Montanelli, Gaia; Vigone, Barbara; Santaniello, Alessandro; Milani, Christian; Quirantes-Piné, Rosa; Borrás-Linares, Isabel; Ventura, Marco; Segura-Carrettero, Antonio; Alarcón-Riquelme, Marta Eugenia; Beretta, Lorenzo

    2018-06-01

    Intestinal microbiota has been associated with systemic autoimmune diseases, yet the functional consequences of these associations are elusive. We characterized the fecal microbiota (16S rRNA gene amplification and sequencing) and the plasma metabolome (high-performance liquid chromatography coupled to mass spectrometry) in 59 patients with systemic sclerosis (SSc) and 28 healthy controls (HCs). Microbial and metabolic data were cross-correlated to find meaningful associations after extensive data mining analysis and internal validation. Our data show that a reduced model of nine bacteria is capable of differentiating HCs from SSc patients. SSc gut microbiota is characterized by a reduction in protective butyrate-producing bacteria and by an increase in proinflammatory noxious genera, especially Desulfovibrio. From the metabolic point of view, a multivariate model with 17 metabolite intermediates well distinguished cases from controls. The most interesting peaks we found were identified as glycerophospholipid metabolites and benzene derivatives. The microbial and metabolic data showed significant interactions between Desulfovibrio and alpha-N-phenylacetyl-l-glutamine and 2,4-dinitrobenzenesulfonic acid. Our data suggest that in SSc, intestinal microbiota is characterized by proinflammatory alterations subtly entwined with the metabolic state. Desulfovibrio is a relevant actor in gut dysbiosis that may promote intestinal damage and influence amino acid metabolism. © 2018 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

  16. Chitinase 1 Is a Biomarker for and Therapeutic Target in Scleroderma-Associated Interstitial Lung Disease That Augments TGF-β1 Signaling

    PubMed Central

    Lee, Chun Geun; Herzog, Erica L.; Ahangari, Farida; Zhou, Yang; Gulati, Mridu; Lee, Chang-Min; Peng, Xueyan; Feghali-Bostwick, Carol; Jimenez, Sergio A.; Varga, John; Elias, Jack A.

    2014-01-01

    Interstitial lung disease (ILD) with pulmonary fibrosis is an important manifestation in systemic sclerosis (SSc, scleroderma) where it portends a poor prognosis. However, biomarkers that predict the development and or severity of SSc-ILD have not been validated, and the pathogenetic mechanisms that engender this pulmonary response are poorly understood. In this study, we demonstrate in two different patient cohorts that the levels of chitotriosidase (Chit1) bioactivity and protein are significantly increased in the circulation and lungs of SSc patients compared with demographically matched controls. We also demonstrate that, compared with patients without lung involvement, patients with ILD show high levels of circulating Chit1 activity that correlate with disease severity. Murine modeling shows that in comparison with wild-type mice, bleomycin-induced pulmonary fibrosis was significantly reduced in Chit1−/− mice and significantly enhanced in lungs from Chit1 overexpressing transgenic animals. In vitro studies also demonstrated that Chit1 interacts with TGF-β1 to augment fibroblast TGF-β receptors 1 and 2 expression and TGF-β–induced Smad and MAPK/ERK activation. These studies indicate that Chit1 is potential biomarker for ILD in SSc and a therapeutic target in SSc-associated lung fibrosis and demonstrate that Chit1 augments TGF-β1 effects by increasing receptor expression and canonical and noncanonical TGF-β1 signaling. PMID:22826322

  17. Nailfold capillaroscopy abnormalities as predictors of mortality in patients with systemic sclerosis.

    PubMed

    Kayser, Cristiane; Sekiyama, Juliana Y; Próspero, Lucas C; Camargo, Cintia Z; Andrade, Luis E C

    2013-01-01

    Peripheral microangiopathy is a hallmark of systemic sclerosis (SSc) and can be early detected by nailfold capillaroscopy (NFC). This study aimed to examine whether more severe peripheral microangiopathy at NFC are predictive factor for death in SSc patients. 135 SSc patients who performed NFC between June 2001 and July 2009 were included. The following NFC parameters were evaluated: number of capillary loops/mm, avascular score (scored from 0 to 3), and number of enlarged and giant capillary loops. Univariate and multivariate regression models were used to analyse the association of mortality with NFC and clinical parameters. At the time of the analysis (August 2010), 123 patients were alive, and 12 were dead. By univariate analysis, male gender, forced vital capacity <75% predicted, higher number of giant capillary loops, and an avascular score >1.5 on NFC were associated with a significantly increase risk of death. By multivariate analysis, an avascular score >1.5 was the only independent predictor of death (hazard ratio 2.265). Survival rates from diagnosis at 1, 5 and 10 years were lower in patients with avascular score >1.5 (97%, 86%, and 59%, respectively) compared with those with avascular score ≤1.5 (97%, 97%, and 91% respectively) (p=0.009 by log rank test). Avascular scores higher than 1.5 at NFC was an independent predictor of death in SSc, suggesting that NFC can be useful for predicting SSc outcome.

  18. Skin-to-Skin Contact Facilitates More Equal Parenthood - A Qualitative Study From Fathers' Perspective.

    PubMed

    Olsson, Emma; Eriksson, Mats; Anderzén-Carlsson, Agneta

    A descriptive design was used where 20 fathers of premature infants were interviewed using a semi-structured interview-guide. The guide contained the following five topics: the fathers' feelings about and experiences of using skin-to-skin contact (SSC), the physical environment at the Neonatal Intensive Care unit, staff attitudes, and whether SSC had any impact on the relationship with their partner and other children in the family. The interviews were analyzed using directed qualitative content analysis and the results compared with those of a qualitative systematic review by Anderzén-Carlsson and colleagues. The result shows that the fathers' overall experience of SSC was positive and as in the aforementioned review, they described experiences that were both gratifying and challenging. They felt more included and just as important as the mother because SSC and the demands placed on them by the premature birth helped them to achieve more equal parenthood. The fathers' overall experiences of SSC were positive as they felt included in their infants' care and just as important as the mothers. To a great degree the theoretical model tested was supported, although some weaknesses and differences were identified. It is important to include fathers in neonatal care and recognize that they feel equally important as mothers in caring for premature infants. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. (Not) talking about sex: a systematic comparison of sexual impairment in women with systemic sclerosis and other chronic disease samples.

    PubMed

    Knafo, Ruby; Thombs, Brett D; Jewett, Lisa; Hudson, Marie; Wigley, Fred; Haythornthwaite, Jennifer A

    2009-10-01

    Sexual impairment in women with SSc has received little attention. The objective of this study was to compare levels of sexual impairment in women with SSc with samples of women with medical illnesses for which sexual impairment has been researched more extensively. SSc patients completed the Sexual Relationships subscale of the Psychosocial Adjustment to Illness Scale-Self-Report (PAIS-SR). A systematic review was conducted to select comparison samples. Sexual Relationships subscale scores from SSc patients were compared with scores from comparison samples (breast or gynaecological cancer and HIV) using t-tests and Hedges's g to calculate effect sizes. Samples from 138 female SSc patients were analysed (28.3% diffuse; mean age 52.1 +/- 12.3 years; mean time since diagnosis 9.0 +/- 8.3 years). Women with dcSSc (6.1 +/- 4.2) reported significantly greater sexual impairment (P < 0.05) than those with lcSSc (4.4 +/- 4.2), three breast cancer samples (1.8 +/- 0.1, 3.4 +/- 3.9, 1.6 +/- 0.6) and two samples of HIV-positive female patients (4.4 +/- 3.8, 4.5 +/- 3.9). Scores in dcSSc were similar to one sample of HIV-positive women (5.8 +/- 4.1) and gynaecological cancer patients (7.3 +/- 4.3). Scores in lcSSc were significantly higher than two breast cancer samples, similar to one breast cancer sample and two HIV-positive samples, and significantly lower (P < 0.05) than in one HIV sample and gynaecological cancer. Women with SSc, particularly those with dcSSc, have high levels of sexual impairment compared with women with other chronic diseases, where sexual function has received greater attention. Further research is needed on sexual function among women with SSc.

  20. Influence of antibody profile in clinical features and prognosis in a cohort of Spanish patients with systemic sclerosis.

    PubMed

    Iniesta Arandia, Nerea; Simeón-Aznar, Carmen Pilar; Guillén Del Castillo, Alfredo; Colunga Argüelles, Dolores; Rubio-Rivas, Manuel; Trapiella Martínez, Luis; García Hernández, Francisco José; Sáez Comet, Luis; Egurbide Arberas, María Victoria; Ortego-Centeno, Norberto; Freire, Mayka; Marí Alfonso, Begoña; Vargas Hitos, José Antonio; Ríos Blanco, Juan José; Todolí Parra, José Antonio; Rodríguez-Carballeira, Monica; Marín Ballvé, Adela; Chamorro Fernández, Antonio Javier; Pla Salas, Xavier; Madroñero Vuelta, Ana Belen; Ruiz Muñoz, Manuel; Fonollosa Pla, Vicent; Espinosa, Gerard

    2017-01-01

    To assess the clinical manifestations and prognosis of Spanish patients with systemic sclerosis (SSc) according to their immunological profile. From the Spanish Scleroderma Study Group or RESCLE (Registro de ESCLErodermia as Spanish nomenclature) Registry we selected those patients in which anti-centromere (ACA), anti-topoisomerase I (ATA), and anti-RNA polymerase III (ARA) antibodies had been determined, and a single positivity for each SSc specific antibody was detected. Demographic, clinical, laboratory, and survival data were compared according to the serologic status of these antibodies. Overall, 209 SSc patients were included. In 128 (61%) patients ACA was the only positive antibody, 46 (22%) were only positive for ATA, and 35 (17%) for ARA. Of note, the three groups were mutually exclusive. In univariate analysis, patients with ACA presented more frequently limited cutaneous SSc (lcSSc) (p<0.001), whereas diffuse cutaneous SSc (dcSSc) was the most frequent subtype in patients with ATA (54%) and ARA (62%) (both p<0.001). Positive patients for ARA showed the highest prevalence of joint involvement (p<0.001) and those from ATA group had a higher prevalence of interstitial lung disease (ILD) (p<0.001). Scleroderma renal crisis was more frequent in the ARA group (p<0.001). In multivariate analysis, ACA were associated with female gender and were protective for dcSSc and ILD. ATA were found to be protective for lcSSc and they were independently associated with interstitial reticular pattern. ARA positivity was independently associated with dcSSc. We did not find differences in mortality between the three groups. In Spanish SSc patients, the presence of SSc specific antibodies conferred a distinctive clinical profile.

  1. Abscisic acid ameliorates the systemic sclerosis fibroblast phenotype in vitro

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

    Bruzzone, Santina, E-mail: santina.bruzzone@unige.it; Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova; Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova

    Highlights: Black-Right-Pointing-Pointer ABA is an endogenous hormone in humans, regulating different cell responses. Black-Right-Pointing-Pointer ABA reverts some of the functions altered in SSc fibroblasts to a normal phenotype. Black-Right-Pointing-Pointer UV-B irradiation increases ABA content in SSc cultures. Black-Right-Pointing-Pointer SSc fibroblasts could benefit from exposure to ABA and/or to UV-B. -- Abstract: The phytohormone abscisic acid (ABA) has been recently identified as an endogenous hormone in humans, regulating different cell functions, including inflammatory processes, insulin release and glucose uptake. Systemic sclerosis (SSc) is a chronic inflammatory disease resulting in fibrosis of skin and internal organs. In this study, we investigated themore » effect of exogenous ABA on fibroblasts obtained from healthy subjects and from SSc patients. Migration of control fibroblasts induced by ABA was comparable to that induced by transforming growth factor-{beta} (TGF-{beta}). Conversely, migration toward ABA, but not toward TGF-{beta}, was impaired in SSc fibroblasts. In addition, ABA increased cell proliferation in fibroblasts from SSc patients, but not from healthy subjects. Most importantly, presence of ABA significantly decreased collagen deposition by SSc fibroblasts, at the same time increasing matrix metalloproteinase-1 activity and decreasing the expression level of tissue inhibitor of metalloproteinase (TIMP-1). Thus, exogenously added ABA appeared to revert some of the functions altered in SSc fibroblasts to a normal phenotype. Interestingly, ABA levels in plasma from SSc patients were found to be significantly lower than in healthy subjects. UV-B irradiation induced an almost 3-fold increase in ABA content in SSc cultures. Altogether, these results suggest that the fibrotic skin lesions in SSc patients could benefit from exposure to high(er) ABA levels.« less

  2. Doubly self-consistent field theory of grafted polymers under simple shear in steady state

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

    Suo, Tongchuan; Whitmore, Mark D., E-mail: mark-whitmore@umanitoba.ca

    2014-03-21

    We present a generalization of the numerical self-consistent mean-field theory of polymers to the case of grafted polymers under simple shear. The general theoretical framework is presented, and then applied to three different chain models: rods, Gaussian chains, and finitely extensible nonlinear elastic (FENE) chains. The approach is self-consistent at two levels. First, for any flow field, the polymer density profile and effective potential are calculated self-consistently in a manner similar to the usual self-consistent field theory of polymers, except that the calculation is inherently two-dimensional even for a laterally homogeneous system. Second, through the use of a modified Brinkmanmore » equation, the flow field and the polymer profile are made self-consistent with respect to each other. For all chain models, we find that reasonable levels of shear cause the chains to tilt, but it has very little effect on the overall thickness of the polymer layer, causing a small decrease for rods, and an increase of no more than a few percent for the Gaussian and FENE chains. Using the FENE model, we also probe the individual bond lengths, bond correlations, and bond angles along the chains, the effects of the shear on them, and the solvent and bonded stress profiles. We find that the approximations needed within the theory for the Brinkman equation affect the bonded stress, but none of the other quantities.« less

  3. Angiogenic T cell expansion correlates with severity of peripheral vascular damage in systemic sclerosis.

    PubMed

    Manetti, Mirko; Pratesi, Sara; Romano, Eloisa; Bellando-Randone, Silvia; Rosa, Irene; Guiducci, Serena; Fioretto, Bianca Saveria; Ibba-Manneschi, Lidia; Maggi, Enrico; Matucci-Cerinic, Marco

    2017-01-01

    The mechanisms underlying endothelial cell injury and defective vascular repair in systemic sclerosis (SSc) remain unclear. Since the recently discovered angiogenic T cells (Tang) may have an important role in the repair of damaged endothelium, this study aimed to analyze the Tang population in relation to disease-related peripheral vascular features in SSc patients. Tang (CD3+CD31+CXCR4+) were quantified by flow cytometry in peripheral blood samples from 39 SSc patients and 18 healthy controls (HC). Circulating levels of the CXCR4 ligand stromal cell-derived factor (SDF)-1α and proangiogenic factors were assessed in paired serum samples by immunoassay. Serial skin sections from SSc patients and HC were subjected to CD3/CD31 and CD3/CXCR4 double immunofluorescence. Circulating Tang were significantly increased in SSc patients with digital ulcers (DU) compared either with SSc patients without DU or with HC. Tang levels were significantly higher in SSc patients with late nailfold videocapillaroscopy (NVC) pattern than in those with early/active NVC patterns and in HC. No difference in circulating Tang was found when comparing either SSc patients without DU or patients with early/active NVC patterns and HC. In SSc peripheral blood, Tang percentage was inversely correlated to levels of SDF-1α and CD34+CD133+VEGFR-2+ endothelial progenitor cells (EPC), and positively correlated to levels of vascular endothelial growth factor and matrix metalloproteinase-9. Tang were frequently detected in SSc dermal perivascular inflammatory infiltrates. In summary, our findings demonstrate for the first time that Tang cells are selectively expanded in the circulation of SSc patients displaying severe peripheral vascular complications like DU. In SSc, Tang may represent a potentially useful biomarker reflecting peripheral vascular damage severity. Tang expansion may be an ineffective attempt to compensate the need for increased angiogenesis and EPC function. Further studies are required to clarify the function of Tang cells and investigate the mechanisms responsible for their change in SSc.

  4. Full self-consistency versus quasiparticle self-consistency in diagrammatic approaches: Exactly solvable two-site Hubbard model

    DOE PAGES

    Kutepov, A. L.

    2015-07-22

    Self-consistent solutions of Hedin's equations (HE) for the two-site Hubbard model (HM) have been studied. They have been found for three-point vertices of increasing complexity (Γ = 1 (GW approximation), Γ₁ from the first-order perturbation theory, and the exact vertex Γ E). Comparison is made between the cases when an additional quasiparticle (QP) approximation for Green's functions is applied during the self-consistent iterative solving of HE and when QP approximation is not applied. Results obtained with the exact vertex are directly related to the present open question—which approximation is more advantageous for future implementations, GW + DMFT or QPGW +more » DMFT. It is shown that in a regime of strong correlations only the originally proposed GW + DMFT scheme is able to provide reliable results. Vertex corrections based on Perturbation Theory systematically improve the GW results when full self-consistency is applied. The application of QP self-consistency combined with PT vertex corrections shows similar problems to the case when the exact vertex is applied combined with QP sc. An analysis of Ward Identity violation is performed for all studied in this work's approximations and its relation to the general accuracy of the schemes used is provided.« less

  5. Full self-consistency versus quasiparticle self-consistency in diagrammatic approaches: exactly solvable two-site Hubbard model.

    PubMed

    Kutepov, A L

    2015-08-12

    Self-consistent solutions of Hedin's equations (HE) for the two-site Hubbard model (HM) have been studied. They have been found for three-point vertices of increasing complexity (Γ = 1 (GW approximation), Γ1 from the first-order perturbation theory, and the exact vertex Γ(E)). Comparison is made between the cases when an additional quasiparticle (QP) approximation for Green's functions is applied during the self-consistent iterative solving of HE and when QP approximation is not applied. The results obtained with the exact vertex are directly related to the present open question-which approximation is more advantageous for future implementations, GW + DMFT or QPGW + DMFT. It is shown that in a regime of strong correlations only the originally proposed GW + DMFT scheme is able to provide reliable results. Vertex corrections based on perturbation theory (PT) systematically improve the GW results when full self-consistency is applied. The application of QP self-consistency combined with PT vertex corrections shows similar problems to the case when the exact vertex is applied combined with QP sc. An analysis of Ward Identity violation is performed for all studied in this work's approximations and its relation to the general accuracy of the schemes used is provided.

  6. The re-incarnation, re-interpretation and re-demise of the transition probability model.

    PubMed

    Koch, A L

    1999-05-28

    There are two classes of models for the cell cycle that have both a deterministic and a stochastic part; they are the transition probability (TP) models and sloppy size control (SSC) models. The hallmark of the basic TP model are two graphs: the alpha and beta plots. The former is the semi-logarithmic plot of the percentage of cell divisions yet to occur, this results in a horizontal line segment at 100% corresponding to the deterministic phase and a straight line sloping tail corresponding to the stochastic part. The beta plot concerns the differences of the age-at-division of sisters (the beta curve) and gives a straight line parallel to the tail of the alpha curve. For the SC models the deterministic part is the time needed for the cell to accumulate a critical amount of some substance(s). The variable part differs in the various variants of the general model, but they do not give alpha and beta curves with linear tails as postulated by the TP model. This paper argues against TP and for an elaboration of SSC type of model. The main argument against TP is that it assumes that the probability of the transition from the stochastic phase is time invariant even though it is certain that the cells are growing and metabolizing throughout the cell cycle; a fact that should make the transition probability be variable. The SSC models presume that cell division is triggered by the cell's success in growing and not simply the result of elapsed time. The extended model proposed here to accommodate the predictions of the SSC to the straight tailed parts of the alpha and beta plots depends on the existence of a few percent of the cell in a growing culture that are not growing normally, these are growing much slower or are temporarily quiescent. The bulk of the cells, however, grow nearly exponentially. Evidence for a slow growing component comes from experimental analyses of population size distributions for a variety of cell types by the Collins-Richmond technique. These subpopulations existence is consistent with the new concept that there are a large class of rapidly reversible mutations occurring in many organisms and at many loci serving a large range of purposes to enable the cell to survive environmental challenges. These mutations yield special subpopulations of cells within a population. The reversible mutational changes, relevant to the elaboration of SSC models, produce slow-growing cells that are either very large or very small in size; these later revert to normal growth and division. The subpopulations, however, distort the population distribution in such a way as to fit better the exponential tails of the alpha and beta curves of the TP model.

  7. Subjective Confidence in Perceptual Judgments: A Test of the Self-Consistency Model

    ERIC Educational Resources Information Center

    Koriat, Asher

    2011-01-01

    Two questions about subjective confidence in perceptual judgments are examined: the bases for these judgments and the reasons for their accuracy. Confidence in perceptual judgments has been claimed to rest on qualitatively different processes than confidence in memory tasks. However, predictions from a self-consistency model (SCM), which had been…

  8. Systematic approach to understanding the pathogenesis of systemic sclerosis.

    PubMed

    Zuo, Xiaoxia; Zhang, Lihua; Luo, Hui; Li, Yisha; Zhu, Honglin

    2017-10-01

    Systemic sclerosis (SSc) is a complex heterogeneous autoimmune disease. Progressive organ fibrosis is a major contributor to SSc mortality. Despite extensive efforts, the underlying mechanism of SSc remains unclear. Efforts to understand the pathogenesis of SSc have included genomics, epigenetics, transcriptomic, proteomic and metabolomic studies in the last decade. This review focuses on recent studies in SSc research based on multi-omics. The combination of these technologies can help us understand the pathogenesis of SSc. This review aims to provide important information for disease identification, therapeutic targets and potential biomarkers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Nailfold capillaroscopy in primary biliary cirrhosis: a useful tool for the early diagnosis of scleroderma.

    PubMed

    Tovoli, Francesco; Granito, Alessandro; Giampaolo, Luca; Frisoni, Magda; Volta, Umberto; Fusconi, Marco; Masi, Chiara; Lenzi, Marco

    2014-03-01

    Primary biliary cirrhosis (PBC) is frequently associated with other autoimmune diseases, including systemic sclerosis (SSc). In the last years many efforts have been dedicated to the research of widely accepted criteria for the early diagnosis of SSc. Since studies on the prevalence of early SSc in PBC patients are lacking, our aim was to investigate its hitherto unknown prevalence in a large cohort of PBC patients. We studied 80 PBC patients and 72 patients with other chronic liver diseases. Diagnostic workup included research into signs of connective tissue disease, determination of autoantibody profile, and examination of capillary abnormalities through nailfold videocapillaroscopy. Ten PBC patients (12.5%) satisfied diagnostic criteria for early SSc and 5 (6.3%) had definite SSc. None of the patients in the control group were diagnosed either with early or definite SSc. No differences were observed in terms of aminotransferases, alkaline phosphatase, and liver function tests between PBC patients with and without associated SSc. Early SSc is significantly frequent in PBC patients. The detection of early SSc in PBC patients may lead to a prompt treatment of its complications, preventing inabilities and preserving the chance of liver transplantation.

  10. Longitudinal variation in lateral trapping of fine sediment in tidal estuaries: observations and a 3D exploratory model

    NASA Astrophysics Data System (ADS)

    Chen, Wei; de Swart, Huib E.

    2018-03-01

    This study investigates the longitudinal variation of lateral entrapment of suspended sediment, as is observed in some tidal estuaries. In particular, field data from the Yangtze Estuary are analysed, which reveal that in one cross-section, two maxima of suspended sediment concentration (SSC) occur close to the south and north sides, while in a cross-section 2 km down-estuary, only one SSC maximum on the south side is present. This pattern is found during both spring tide and neap tide, which are characterised by different intensities of turbulence. To understand longitudinal variation in lateral trapping of sediment, results of a new three-dimensional exploratory model are analysed. The hydrodynamic part contains residual flow due to fresh water input, density gradients and Coriolis force and due to channel curvature-induced leakage. Moreover, the model includes a spatially varying eddy viscosity that accounts for variation of intensity of turbulence over the spring-neap cycle. By imposing morphodynamic equilibrium, the two-dimensional distribution of sediment in the domain is obtained analytically by a novel procedure. Results reveal that the occurrence of the SSC maxima near the south side of both cross-sections is due to sediment entrapment by lateral density gradients, while the second SSC maximum near the north side of the first cross-section is by sediment transport due to curvature-induced leakage. Coriolis deflection of longitudinal flow also contributes the trapping of sediment near the north side. This mechanism is important in the upper estuary, where the flow due to lateral density gradients is weak.

  11. Intraplate volcanism with complex age-distance patterns: A case for small-scale sublithospheric convection

    NASA Astrophysics Data System (ADS)

    Ballmer, M. D.; van Hunen, J.; Ito, G.; Bianco, T. A.; Tackley, P. J.

    2009-06-01

    Many volcano chains in the Pacific do not follow the most fundamental predictions of hot spot theory in terms of geographic age progressions. One possible explanation for non-hot spot intraplate volcanism is small-scale sublithospheric convection (SSC), and we explore this concept using 3-D numerical models that simulate melting with rheology laws that account for the effects of dehydration. SSC spontaneously self-organizes beneath relatively mature oceanic lithosphere. Whenever this lithosphere is sufficiently young and thin, SSC replaces the shallow layer of harzburgite, which was formed by partial melting at the mid-ocean ridge, with fresh peridotite. This mechanism enables magma generation without any preexisting thermochemical anomalies. However, the additional effect of melting-induced dehydration to stiffen the harzburgite requires lower background viscosities to allow for vigorous SSC, overturn of the compositional stratification, and related magmatism. The intrinsic stiffness of the dehydrated harzburgite furthermore restricts penetration of SSC into very shallow and cooler levels. On the one hand, such a restriction precludes high degrees of melting, but on the other hand, it slows asthenospheric cooling and thus prolongs the duration of melting (to ˜25 Ma). Volcanism over such an elongated melting anomaly continues for at least 10-20 Ma and occurs on seafloor ages of ˜20 to ˜60 Ma. These seafloor ages increase with increasing mantle temperature due to the effect of forming a thicker harzburgite layer from more extensive mid-ocean ridge melting. The long durations of volcanism predicted reconcile observations of extended activity of individual seamounts and synchronous activity over great distances along some volcanic chains. SSC thus gives an explanation for previously enigmatic volcano ages along the Line Islands and the Gilbert and Pukapuka ridges, as well as along the individual subchains of the Wakes, Marshalls, and Cook-Australs.

  12. Comparison of the basin-scale effect of dredging operations and natural estuarine processes on suspended sediment concentration

    USGS Publications Warehouse

    Schoellhamer, D.H.

    2002-01-01

    Suspended sediment concentration (SSC) data from San Pablo Bay, California, were analyzed to compare the basin-scale effect of dredging and disposal of dredged material (dredging operations) and natural estuarine processes. The analysis used twelve 3-wk to 5-wk periods of mid-depth and near-bottom SSC data collected at Point San Pablo every 15 min from 1993-1998. Point San Pablo is within a tidal excursion of a dredged-material disposal site. The SSC data were compared to dredging volume, Julian day, and hydrodynamic and meteorological variables that could affect SSC. Kendall's ??, Spearman's ??, and weighted (by the fraction of valid data in each period) Spearman's ??w correlation coefficients of the variables indicated which variables were significantly correlated with SSC. Wind-wave resuspension had the greatest effect on SSC. Median water-surface elevation was the primary factor affecting mid-depth SSC. Greater depths inhibit wind-wave resuspension of bottom sediment and indicate greater influence of less turbid water from down estuary. Seasonal variability in the supply of erodible sediment is the primary factor affecting near-bottom SSC. Natural physical processes in San Pablo Bay are more areally extensive, of equal or longer duration, and as frequent as dredging operations (when occurring), and they affect SSC at the tidal time scale. Natural processes control SSC at Point San Pablo even when dredging operations are occurring.

  13. Transcriptional response of soybean suspension-cultured cells induced by Nod factors obtained from Bradyrhizobium japonicum USDA110.

    PubMed

    Hakoyama, Tsuneo; Yokoyama, Tadashi; Kouchi, Hiroshi; Tsuchiya, Ken-ichi; Kaku, Hisatoshi; Arima, Yasuhiro

    2002-11-01

    Genes responding to Nod factors were picked up by the application of a differential display method for soybean suspension-cultured cells. Forty-five cDNA fragments derived from such genes were detected. Seven fragments (ssc1-ssc7) were successfully cloned. The putative product of genes corresponding to ssc1 was estimated to be a disease-resistance protein relating to the induction of the plant defense response against pathogens, and that corresponding to ssc7 was a sucrose transporter. Amino acid sequences deduced from full-length cDNA corresponding to ssc2 and ssc4 were investigated, and it was shown that these polypeptides were equipped with a leucine zipper motif and with phosphorylation sites that were targeted by tyrosin kinase and cAMP-dependent protein kinase, respectively. In a differential display experiment, the transcriptional levels of three genes corresponding to ssc2, ssc3 and ssc5 were estimated to be up-regulated at 6 h after initiation of the treatment and the remaining four were estimated to be down-regulated. However, transcription of the genes corresponding to all ssc was clearly repressed within 2 h after initiation of the treatment. Five of them were restored to their transcriptional level 6 h after initiation of the treatment, although the others were repressed throughout the experimental period.

  14. A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study.

    PubMed

    Ingegnoli, Francesca; Boracchi, Patrizia; Gualtierotti, Roberta; Smith, Vanessa; Cutolo, Maurizio; Foeldvari, Ivan

    2015-11-01

    Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% CI 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% CI 0.28-2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% CI 0.34-3.56. This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of scleroderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Hyperspectral Imaging for Predicting the Internal Quality of Kiwifruits Based on Variable Selection Algorithms and Chemometric Models.

    PubMed

    Zhu, Hongyan; Chu, Bingquan; Fan, Yangyang; Tao, Xiaoya; Yin, Wenxin; He, Yong

    2017-08-10

    We investigated the feasibility and potentiality of determining firmness, soluble solids content (SSC), and pH in kiwifruits using hyperspectral imaging, combined with variable selection methods and calibration models. The images were acquired by a push-broom hyperspectral reflectance imaging system covering two spectral ranges. Weighted regression coefficients (BW), successive projections algorithm (SPA) and genetic algorithm-partial least square (GAPLS) were compared and evaluated for the selection of effective wavelengths. Moreover, multiple linear regression (MLR), partial least squares regression and least squares support vector machine (LS-SVM) were developed to predict quality attributes quantitatively using effective wavelengths. The established models, particularly SPA-MLR, SPA-LS-SVM and GAPLS-LS-SVM, performed well. The SPA-MLR models for firmness (R pre  = 0.9812, RPD = 5.17) and SSC (R pre  = 0.9523, RPD = 3.26) at 380-1023 nm showed excellent performance, whereas GAPLS-LS-SVM was the optimal model at 874-1734 nm for predicting pH (R pre  = 0.9070, RPD = 2.60). Image processing algorithms were developed to transfer the predictive model in every pixel to generate prediction maps that visualize the spatial distribution of firmness and SSC. Hence, the results clearly demonstrated that hyperspectral imaging has the potential as a fast and non-invasive method to predict the quality attributes of kiwifruits.

  16. Performance and Structural Evolution of Nano-Scale Infiltrated Solid Oxide Fuel Cell Cathodes

    NASA Astrophysics Data System (ADS)

    Call, Ann Virginia

    Nano-structured mixed ionic and electronic conducting (MIEC) materials have garnered intense interest in electrode development for solid oxide fuel cells due to their high surface areas which allow for effective catalytic activity and low polarization resistances. In particular, composite solid oxide fuel cell (SOFC) cathodes consisting of ionic conducting scaffolds infiltrated with MIEC nanoparticles have exhibited some of the lowest reported polarization resistances. In order for cells utilizing nanostructured moRPhologies to be viable for commercial implementation, more information on their initial performance and long term stability is necessary. In this study, symmetric cell cathodes were prepared via wet infiltration of Sr0.5Sm 0.5CoO3 (SSC) nano-particles via a nitrate process into porous Ce0.9Gd0.1O1.95 (GDC) scaffolds to be used as a model system to investigate performance and structural evolution. Detailed analysis of the cells and cathodes was carried out using electrochemical impedance spectroscopy (EIS). Initial polarization resistances (RP) as low as 0.11 O cm2 at 600ºC were obtained for these SSC-GDC cathodes, making them an ideal candidate for studying high performance nano-structured electrodes. The present results show that the infiltrated cathode microstructure has a direct impact on the initial performance of the cell. Small initial particle sizes and high infiltration loadings (up to 30 vol% SSC) improved initial RP. A simple microstructure-based electrochemical model successfully explained these trends in RP. Further understanding of electrode performance was gleaned from fitting EIS data gathered under varying temperatures and oxygen partial pressures to equivalent circuit models. Both RQ and Gerischer impedance elements provided good fits to the main response in the EIS data, which was associated with the combination of oxygen surface exchange and oxygen diffusion in the electrode. A gas diffusion response was also observed at relatively low pO2. The cells were subjected to life testing at temperatures between 650°C and 800°C for as long as 1500 h. EIS measurements, carried out periodically during the life tests, were done in air at 600°C, a typical expected intermediate-temperature SOFC operating temperature. These were accelerated tests because the aging temperatures > 600ºC should accelerate most degradation processes such as nano-particle coarsening. Long-term RP versus time data was fitted to a combined surface resistance and coarsening kinetics model, and a t0.25 power law coarsening model was found to provide the best fits to the data, suggesting that surface diffusion is the dominant mass transport pathway in SSC-GDC infiltrated cathodes. That is, cathode degradation was due primarily to the coarsening-induced decrease in active SSC surface area. Scanning electron microscopy (SEM) performed after electrochemical life testing confirmed the extent of coarsening of the SSC nanoparticles. The model is used to make predictions regarding long-term stability of infiltrated SSC electrodes, and is also compared with prior results on a similar perovskite MIEC electrode, LSCF. An important new finding is that increasing infiltration loadings yields a marked decrease in the long term degradation rate. Predictions based on accelerated life tests found the lowest possible operating temperature while achieving a degradation rate of 0.5% per kh is 595°C, corresponding to an initial particle size of 40 nm.

  17. Integration of RAM-SCB into the Space Weather Modeling Framework

    DOE PAGES

    Welling, Daniel; Toth, Gabor; Jordanova, Vania Koleva; ...

    2018-02-07

    We present that numerical simulations of the ring current are a challenging endeavor. They require a large set of inputs, including electric and magnetic fields and plasma sheet fluxes. Because the ring current broadly affects the magnetosphere-ionosphere system, the input set is dependent on the ring current region itself. This makes obtaining a set of inputs that are self-consistent with the ring current difficult. To overcome this challenge, researchers have begun coupling ring current models to global models of the magnetosphere-ionosphere system. This paper describes the coupling between the Ring current Atmosphere interaction Model with Self-Consistent Magnetic field (RAM-SCB) tomore » the models within the Space Weather Modeling Framework. Full details on both previously introduced and new coupling mechanisms are defined. Finally, the impact of self-consistently including the ring current on the magnetosphere-ionosphere system is illustrated via a set of example simulations.« less

  18. Integration of RAM-SCB into the Space Weather Modeling Framework

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

    Welling, Daniel; Toth, Gabor; Jordanova, Vania Koleva

    We present that numerical simulations of the ring current are a challenging endeavor. They require a large set of inputs, including electric and magnetic fields and plasma sheet fluxes. Because the ring current broadly affects the magnetosphere-ionosphere system, the input set is dependent on the ring current region itself. This makes obtaining a set of inputs that are self-consistent with the ring current difficult. To overcome this challenge, researchers have begun coupling ring current models to global models of the magnetosphere-ionosphere system. This paper describes the coupling between the Ring current Atmosphere interaction Model with Self-Consistent Magnetic field (RAM-SCB) tomore » the models within the Space Weather Modeling Framework. Full details on both previously introduced and new coupling mechanisms are defined. Finally, the impact of self-consistently including the ring current on the magnetosphere-ionosphere system is illustrated via a set of example simulations.« less

  19. Systemic sclerosis with normal or nonspecific nailfold capillaroscopy.

    PubMed

    Fichel, Fanny; Baudot, Nathalie; Gaitz, Jean-Pierre; Trad, Salim; Barbe, Coralie; Francès, Camille; Senet, Patricia

    2014-01-01

    In systemic sclerosis (SSc), a specific nailfold videocapillaroscopy (NVC) pattern is observed in 90% of cases and seems to be associated with severity and progression of the disease. To describe the characteristics of SSc patients with normal or nonspecific (normal/nonspecific) NVC. In a retrospective cohort study, clinical features and visceral involvements of 25 SSc cases with normal/nonspecific NVC were compared to 63 SSc controls with the SSc-specific NVC pattern. Normal/nonspecific NVC versus SSc-specific NVC pattern was significantly associated with absence of skin sclerosis (32 vs. 6.3%, p = 0.004), absence of telangiectasia (47.8 vs. 17.3%, p = 0.006) and absence of sclerodactyly (60 vs. 25.4%, p = 0.002), and less frequent severe pulmonary involvement (26.3 vs. 58.2%, p = 0.017). Normal/nonspecific NVC in SSc patients appears to be associated with less severe skin involvement and less frequent severe pulmonary involvement. © 2014 S. Karger AG, Basel.

  20. Severe Hypothyroidism due to the Loss of Therapeutic Efficacy of l-Thyroxine in a Patient with Esophageal Complication Associated with Systemic Sclerosis.

    PubMed

    Lobasso, Antonio; Nappi, Liliana; Barbieri, Letizia; Peirce, Carmela; Ippolito, Serena; Arpaia, Debora; Rossi, Francesca Wanda; de Paulis, Amato; Biondi, Bernadette

    2017-01-01

    Thyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with systemic autoimmune diseases as systemic sclerosis (SSc). Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score. Asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to l-thyroxine (l-T4) malabsorption in patients with Hashimoto's thyroiditis (HT) and SSc. Here, we report a case of a 56-year-old female affected by both SSc and HT who developed severe hypothyroidism due to the loss of therapeutic efficacy of l-T4. Therapeutic failure resulted from the altered l-T4 absorption because of SSc esophageal complications. Clinical findings improved after the administration of oral liquid l-T4. Thyroid function completely normalized with a full clinical recovery, the disappearance of the pericardial effusion and the improvement of the pulmonary pressure. A recognition of a poor absorption is crucial in patients with hypothyroidism and SSc to reduce the risk of the subsequent adverse events. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because the systemic complications of these dysfunctions may worsen the prognosis of hypothyroid SSc/HT patients.

  1. Paclitaxel modulates TGFbeta signaling in scleroderma skin grafts in immunodeficient mice.

    PubMed

    Liu, Xialin; Zhu, Shoukang; Wang, Tao; Hummers, Laura; Wigley, Fredrick M; Goldschmidt-Clermont, Pascal J; Dong, Chunming

    2005-12-01

    Systemic sclerosis (SSc) is characterized by excessive fibrosis and obliterative vascular lesions. Abnormal TGFbeta activation is implicated in the pathogenesis of SSc. Aberrant TGFbeta/Smad signaling can be controlled by stabilization of microtubules with paclitaxel. SSc and healthy human skin biopsies were incubated in the presence or absence of paclitaxel followed by transplantation into severe combined immunodeficient mice. TGFbeta signaling, fibrosis, and neovessel formation were evaluated by quantitative RT-PCR and immunohistochemical staining. Paclitaxel markedly suppressed Smad2 and Smad3 phosphorylation and collagen deposition in SSc grafts. As a result, the autonomous maintenance/reconstitution of the SSc phenotype was prevented. Remarkably, SSc grafts showed a 2-fold increase in neovessel formation relative to normal grafts, regardless of paclitaxel treatment. Angiogenesis in SSc grafts was associated with a substantial increase in mouse PECAM-1 expression, indicating the mouse origin of the neovascular cells. Low-dose paclitaxel can significantly suppress TGFbeta/Smad activity and lessen fibrosis in SCID mice. Transplantation of SSc skin into SCID mice elicits a strong angiogenesis-an effect not affected by paclitaxel. Although prolonged chemotherapy with paclitaxel at higher doses is associated with pro-fibrotic and anti-angiogenic changes, the findings described here indicate that low-dose paclitaxel may have therapeutic benefits for SSc via modulating TGFbeta signaling.

  2. Gammadelta receptor bearing T cells in scleroderma: enhanced interaction with vascular endothelial cells in vitro.

    PubMed

    Kahaleh, M B; Fan, P S; Otsuka, T

    1999-05-01

    In view of the documented perivascular mononuclear cell infiltration in the involved organs in scleroderma (SSc) and the reported accumulation of gammadelta-T cells in SSc skin and lung, we evaluated gammadelta-T cell interaction with endothelial cells (EC) in vitro. gammadelta- and alphabeta-T cells were isolated from BPMN of SSc patients with early diffuse disease and of matched control subjects by an immunomagnetic method after stimulation with mycobacterium lysate and interleukin-2 for 2 weeks. Lymphocyte adhesion, proliferation, and cytotoxicity to EC were investigated. SSc gammadelta-T cells adhered to cultured EC and proliferated at higher rates than control cells. Furthermore, significant EC cytotoxicity by SSc gammadelta was seen. The cytotoxicity was blocked by addition of anti-gammadelta-TCR antibody and by anti-granzyme A antibody but not by anti-MHC class I and II antibodies. Expression of granzyme A mRNA was seen in five/five SSc gammadelta-T cells and in one/five control cells. alphabeta-T cells from both SSc and control subjects were significantly less interactive with EC than gammadelta-T cells. The data demonstrate EC recognition by SSc gammadelta-T cells and propose gammadelta-T cells as a possible effector cell type in the immune pathogenesis of SSc. Copyright 1999 Academic Press.

  3. A portable dermatoscope for easy, rapid examination of periungual nailfold capillary changes in patients with systemic sclerosis.

    PubMed

    Muroi, Eiji; Hara, Toshihide; Yanaba, Koichi; Ogawa, Fumihide; Yoshizaki, Ayumi; Takenaka, Motoi; Shimizu, Kazuhiro; Sato, Shinichi

    2011-12-01

    Microvascular lesions are a predominant feature in systemic sclerosis (SSc) and seem to play a central pathogenic role. The presence of nailfold capillary abnormalities is useful in diagnosing SSc. Capillaroscopy, however, usually requires special equipment and may be time consuming. Dermatoscope has been presented as a new diagnostic tool for quick and efficient examination of nailfold capillaries for circumstances when standard microscope equipment is not available. To assess the practical utility of dermatoscope for assessment of capillary morphology in patients with SSc, 83 Japanese patients with SSc (68 women, 15 men) and 68 healthy controls were examined in the study. Twenty-one patients (16 women, 5 men) had diffuse cutaneous SSc and 62 (52 women, 10 men) had limited cutaneous SSc. Enlarged capillaries and hemorrhages were evaluated in all 10 fingers with either naked eyes or DermLite(®) DL100 dermatoscope. Enlarged capillaries and hemorrhages were significantly more frequently detected with dermatoscope than without it. These findings were observed most frequently in the fourth finger. The presence of two or more enlarged capillaries in one or more fingers showed 83.1% sensitivity and 100% specificity for SSc. Among patients with SSc with anti-topoisomerase I antibody, the disease duration correlated negatively with the dermatoscopic number of enlarged capillaries and hemorrhages. Dermatoscope allows the easy and rapid identification of capillary nailfold morphological changes in SSc and should be routinely used for diagnosing SSc.

  4. Systemic sclerosis complicated with localized scleroderma-like lesions induced by Köbner phenomenon.

    PubMed

    Saigusa, Ryosuke; Asano, Yoshihide; Yamashita, Takashi; Takahashi, Takehiro; Nakamura, Kouki; Miura, Shunsuke; Ichimura, Yohei; Toyama, Tetsuo; Taniguchi, Takashi; Sumida, Hayakazu; Tamaki, Zenshiro; Miyazaki, Miki; Yoshizaki, Ayumi; Sato, Shinichi

    2018-03-01

    Scleroderma is a chronic disease of unknown etiology characterized by skin fibrosis and is divided into two clinical entities: systemic sclerosis (SSc) and localized scleroderma (LSc). In general, LSc is rarely complicated with SSc, but a certain portion of SSc patients manifests bilateral symmetric LSc-like lesions on the trunk and extremities. We investigated SSc patients with LSc-like lesions to clarify the underlying pathophysiology. Nine SSc cases complicated with LSc-like lesions were clinically and histologically characterized. SSc patients with LSc-like lesions exhibited multiple progressive hyper- and/or hypo-pigmented plaques with mild sclerosis symmetrically distributed on the trunk and extremities, especially abdominal region. In histological assessment, epidermal IL-1α expression was elevated in both forearms and LSc-like lesions of these patients to a greater extent than in forearms of control patients (SSc patients without LSc-like lesions). Of note, the infiltration and degranulation of mast cells were evident throughout the dermis of LSc-like lesions, while detectable to a lesser extent in forearms of SSc patients with LSc-like lesions and control patients. The epidermis of SSc patients with LSc-like lesions seems to possess an inflammatory phenotype, leading to the activation of mast cells in the dermis of mechanically stressed skin. Köbner phenomenon may be involved in the induction of LSc-like lesions in a certain subset of SSc. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  5. Scleroderma dermal microvascular endothelial cells exhibit defective response to pro-angiogenic chemokines

    PubMed Central

    Rabquer, Bradley J.; Ohara, Ray A.; Stinson, William A.; Campbell, Phillip L.; Amin, M. Asif; Balogh, Beatrix; Zakhem, George; Renauer, Paul A.; Lozier, Ann; Arasu, Eshwar; Haines, G. Kenneth; Kahaleh, Bashar; Schiopu, Elena; Khanna, Dinesh; Koch, Alisa E.

    2016-01-01

    Objectives. Angiogenesis plays a critical role in SSc (scleroderma). The aim of this study was to examine the expression of growth-regulated protein-γ (Gro-γ/CXCL3), granulocyte chemotactic protein 2 (GCP-2/CXCL6) and their receptor CXCR2 in endothelial cells (ECs) isolated from SSc skin and determine whether these cells mount an angiogenic response towards pro-angiogenic chemokines. The downstream signalling pathways as well as the pro-angiogenic transcription factor inhibitor of DNA-binding protein 1 (Id-1) were also examined. Methods. Skin biopsies were obtained from patients with dcSSc. ECs were isolated via magnetic positive selection. Angiogenesis was measured by EC chemotaxis assay. Results. Gro-γ/CXCL3 and GCP-2/CXCL6 were minimally expressed in both skin types but elevated in SSc serum. Pro-angiogenic chemokine mRNA was greater in SSc ECs than in normal ECs. SSc ECs did not migrate to vascular endothelial growth factor (VEGF), Gro-γ/CXCL3, GCP-2/CXCL6 or CXCL16. The signalling pathways stimulated by these chemokines were also dysregulated. Id-1 mRNA in SSc ECs was lower compared with normal ECs, and overexpression of Id-1 in SSc ECs increased their ability to migrate towards VEGF and CXCL16. Conclusion. Our results show that SSc ECs are unable to respond to pro-angiogenic chemokines despite their increased expression in serum and ECs. This might be due to the differences in the signalling pathways activated by these chemokines in normal vs SSc ECs. In addition, the lower expression of Id-1 also decreases the angiogenic response. The inability of pro-angiogenic chemokines to promote EC migration provides an additional mechanism for the impaired angiogenesis that characterizes SSc. PMID:26705326

  6. Intrinsic Deregulation of Vascular Smooth Muscle and Myofibroblast Differentiation in Mesenchymal Stromal Cells from Patients with Systemic Sclerosis.

    PubMed

    Hegner, Björn; Schaub, Theres; Catar, Rusan; Kusch, Angelika; Wagner, Philine; Essin, Kirill; Lange, Claudia; Riemekasten, Gabriela; Dragun, Duska

    2016-01-01

    Obliterative vasculopathy and fibrosis are hallmarks of systemic sclerosis (SSc), a severe systemic autoimmune disease. Bone marrow-derived mesenchymal stromal cells (MSCs) from SSc patients may harbor disease-specific abnormalities. We hypothesized disturbed vascular smooth muscle cell (VSMC) differentiation with increased propensity towards myofibroblast differentiation in response to SSc-microenvironment defining growth factors and determined responsible mechanisms. We studied responses of multipotent MSCs from SSc-patients (SSc-MSCs) and healthy controls (H-MSCs) to long-term exposure to CTGF, b-FGF, PDGF-BB or TGF-β1. Differentiation towards VSMC and myofibroblast lineages was analyzed on phenotypic, biochemical, and functional levels. Intracellular signaling studies included analysis of TGF-β receptor regulation, SMAD, AKT, ERK1/2 and autocrine loops. VSMC differentiation towards both, contractile and synthetic VSMC phenotypes in response to CTGF and b-FGF was disturbed in SSc-MSCs. H-MSCs and SSc-MSCs responded equally to PDGF-BB with prototypic fibroblastic differentiation. TGF-β1 initiated myofibroblast differentiation in both cell types, yet with striking phenotypic and functional differences: In relation to H-MSC-derived myofibroblasts induced by TGF-β1, those obtained from SSc-MSCs expressed more contractile proteins, migrated towards TGF-β1, had low proliferative capacity, and secreted higher amounts of collagen paralleled by reduced MMP expression. Higher levels of TGF-β receptor 1 and enhanced canonical and noncanonical TGF-β signaling in SSc-MSCs accompanied aberrant differentiation response of SSc-MSCs in comparison to H-MSCs. Deregulated VSMC differentiation with a shift towards myofibroblast differentiation expands the concept of disturbed endogenous regenerative capacity of MSCs from SSc patients. Disease related intrinsic hyperresponsiveness to TGF-β1 with increased collagen production may represent one responsible mechanism. Better understanding of repair barriers and harnessing beneficial differentiation processes in MSCs could widen options of autologous MSC application in SSc patients.

  7. Comparison of salivary cortisol, heart rate, and oxygen saturation between early skin-to-skin contact with different initiation and duration times in healthy, full-term infants.

    PubMed

    Takahashi, Yuki; Tamakoshi, Koji; Matsushima, Miyoko; Kawabe, Tsutomu

    2011-03-01

    There are few studies that compare the physiological and biological efficacies between different early skin-to-skin contacts (SSC) post birth. To investigate physiologically and biochemically how early SSC with different initiation and duration time influence the stress post birth for full-term infants. Non-experimental study. Study I; Thirty-two infants who began SSC 5 min or less [birth SSC, mean initiation time (standard deviation): 1.6 (1.1) min] after birth and 36 infants who did so more than 5 min [very early SSC, 26.3 (5.0) min] in heart rate (HR) and oxygen saturation (SpO(2)) analysis. Study II; Eighteen infants who underwent SSC for 60 min or less [mean initiation time: 7.5 (12.2) min] and 61 infants who did so for more than 60 min [15.3 (12.5) min] in salivary cortisol analysis. HR and SpO(2) measured for 30 min post birth. Salivary cortisol concentration measured at 1 min, 60 min, and 120 min post birth. Birth SSC group reached HR stability of 120-160 bpm significantly faster than very early SSC group by Kaplan-Meier analysis (P=0.001 by log-rank test). As for SpO(2) stability of 92% and 96%, no significantly between-group difference was found. Salivary cortisol levels were significantly lower between 60 and 120 min after birth in SSC group, continuing for more than 60 min compared with SSC group for 60 min or less after adjustment for salivary cortisol level at 1 min besides the infant stress factors (P=0.046). Earlier SSC beginning within 5 min post birth and longer SSC continuing for more than 60 min within 120 min post birth are beneficial for stability of cardiopulmonary dynamics and the reduction of infant stress during the early period post birth. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  8. Lung Transplant Outcomes in Systemic Sclerosis with Significant Esophageal Dysfunction. A Comprehensive Single-Center Experience

    PubMed Central

    Schwab, Kristin; Saggar, Rajeev; Duffy, Erin; Elashoff, David; Tseng, Chi-Hong; Weigt, Sam; Charan, Deepshikha; Abtin, Fereidoun; Johannes, Jimmy; Derhovanessian, Ariss; Conklin, Jeffrey; Ghassemi, Kevin; Khanna, Dinesh; Siddiqui, Osama; Ardehali, Abbas; Hunter, Curtis; Kwon, Murray; Biniwale, Reshma; Lo, Michelle; Volkmann, Elizabeth; Torres Barba, David; Belperio, John A.; Mahrer, Thomas; Furst, Daniel E.; Kafaja, Suzanne; Clements, Philip; Shino, Michael; Gregson, Aric; Kubak, Bernard; Lynch, Joseph P.; Ross, David

    2016-01-01

    Rationale: Consideration of lung transplantation in patients with systemic sclerosis (SSc) remains guarded, often due to the concern for esophageal dysfunction and the associated potential for allograft injury and suboptimal post–lung transplantation outcomes. Objectives: The purpose of this study was to systematically report our single-center experience regarding lung transplantation in the setting of SSc, with a particular focus on esophageal dysfunction. Methods: We retrospectively reviewed all lung transplants at our center from January 1, 2000 through August 31, 2012 (n = 562), comparing the SSc group (n = 35) to the following lung transplant diagnostic subsets: all non-SSc (n = 527), non-SSc diffuse fibrotic lung disease (n = 264), and a non-SSc matched group (n = 109). We evaluated post–lung transplant outcomes, including survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates. In addition, we defined severe esophageal dysfunction using esophageal manometry and esophageal morphometry criteria on the basis of chest computed tomography images. For patients with SSc referred for lung transplant but subsequently denied (n = 36), we queried the reason(s) for denial with respect to the concern for esophageal dysfunction. Measurements and Main Results: The 1-, 3-, and 5-year post–lung transplant survival for SSc was 94, 77, and 70%, respectively, and similar to the other groups. The remaining post–lung transplant outcomes evaluated were also similar between SSc and the other groups. Approximately 60% of the SSc group had severe esophageal dysfunction. Pre–lung transplant chest computed tomography imaging demonstrated significantly abnormal esophageal morphometry for SSc when compared with the matched group. Importantly, esophageal dysfunction was the sole reason for lung transplant denial in a single case. Conclusions: Relative to other lung transplant indications, our SSc group experienced comparable survival, primary graft dysfunction, acute rejection, bronchiolitis obliterans syndrome, and microbiology of respiratory isolates, despite the high prevalence of severe esophageal dysfunction. Esophageal dysfunction rarely precluded active listing for lung transplantation. PMID:27078625

  9. Modeling Trace Element Concentrations in the San Francisco Bay Estuary from Remote Measurement of Suspended Solids

    NASA Astrophysics Data System (ADS)

    Press, J.; Broughton, J.; Kudela, R. M.

    2014-12-01

    Suspended and dissolved trace elements are key determinants of water quality in estuarine and coastal waters. High concentrations of trace element pollutants in the San Francisco Bay estuary necessitate consistent and thorough monitoring to mitigate adverse effects on biological systems and the contamination of water and food resources. Although existing monitoring programs collect annual in situ samples from fixed locations, models proposed by Benoit, Kudela, & Flegal (2010) enable calculation of the water column total concentration (WCT) and the water column dissolved concentration (WCD) of 14 trace elements in the San Francisco Bay from a more frequently sampled metric—suspended solids concentration (SSC). This study tests the application of these models with SSC calculated from remote sensing data, with the aim of validating a tool for continuous synoptic monitoring of trace elements in the San Francisco Bay. Using HICO imagery, semi-analytical and empirical SSC algorithms were tested against a USGS dataset. A single-band method with statistically significant linear fit (p < 0.001) was chosen as the proxy for SSC values. The numerical models for WCT and the distribution ratio D were applied in MATLAB with terms to account for regional and seasonal effects, and results were used to calculate WCD. The modeled results were assessed against in situ data from the San Francisco Estuary Regional Monitoring Program. Quantile regression was used to evaluate model sensitivity to the distribution of regions, and outliers displaying regional aberrations were removed before robust regression was applied. Statistically significant and highly correlated results for WCT were found for 10 elements, with goodness of fit greater than or equal to that of the original models of seven elements. WCD was successfully modeled for six elements, with goodness of fit for each exceeding that of the original models. Concentrations of Arsenic, Iron, and Lead in the southern region of the Bay were found to exceed EPA water quality criteria for human health and aquatic life. The results of this study demonstrate the potential of monitoring programs using remote observation of trace element concentrations, and provide the foundation for investigation of pollutant sources and pathways over time.

  10. In situ densimetric measurements as a surrogate for suspended-sediment concentrations in the Rio Puerco, New Mexico

    USGS Publications Warehouse

    Brown, Jeb E.; Gray, John R.; Hornewer, Nancy J.

    2015-01-01

    Surrogate measurements of suspended-sediment concentration (SSC) are increasingly used to provide continuous, high-resolution, and demonstrably accurate data at a reasonable cost. Densimetric data, calculated from the difference between two in situ pressure measurements, exploit variations in real-time streamflow densities to infer SSCs. Unlike other suspendedsediment surrogate technologies based on bulk or digital optics, laser, or hydroacoustics, the accuracy of SSC data estimated using the pressure-difference (also referred to as densimetric) surrogate technology theoretically improves with increasing SCCs. Coupled with streamflow data, continuous suspended-sediment discharges can be calculated using SSC data estimated in real-time using the densimetric technology. The densimetric technology was evaluated at the Rio Puerco in New Mexico, a stream where SSC values regularly range from 10,000-200,000 milligrams per liter (mg/L) and have exceeded 500,000 mg/L. The constant-flow dual-orifice bubbler measures pressure using two precision pressure-transducer sensors at vertically aligned fixed locations in a water column. Water density is calculated from the temperature-compensated differential pressure and SSCs are inferred from the density data. A linear regression model comparing density values to field-measured SSC values yielded an R² of 0.74. Although the application of the densimetric surrogate is likely limited to fluvial systems with SSCs larger than about 10,000 mg/L, based on this and previous studies, the densimetric technology fills a void for monitoring streams with high SSCs.

  11. Turbidity and suspended sediment in the upper Esopus Creek watershed, Ulster County, New York

    USGS Publications Warehouse

    McHale, Michael R.; Siemion, Jason

    2014-01-01

    Discharge, SSC, and turbidity were strongly related at the Coldbrook site but not at every monitoring site. In general, relations between discharge and SSC and turbidity were strongest at sites with high SSCs, with the exception of Stony Clove Creek. Stony Clove Creek had high SSCs and turbidity regardless of discharge, and although concentrations and turbidity values generally increased with increasing discharge, the relation was not strong. Five of the six sites used to investigate the relations between SSC and laboratory turbidity had a coefficient of determination (r2) greater than 0.7. Relations were not as strong between SSC and the turbidity measured by in situ probes because the period of record was shorter and therefore the sample sizes were smaller. Data from in situ turbidity probes were strongly related to turbidity data measured in the laboratory for all but one of the monitoring sites where the relation was strongly leveraged by one sample. Although the in situ turbidity probes appeared to provide a good surrogate for SSC and could allow more accurate calculations of suspended-sediment load than discrete suspended-sediment samples alone, more data would be required to define the regression models throughout the range in discharge, SSCs, and turbidity levels that occur at each monitoring site. Nonetheless, the in situ probes provided much greater detail about the relation between discharge and turbidity than did the grab samples and storm samples measured in the laboratory.

  12. The Disappearing Fourth Wall: John Marburger, Science Policy, and the SSC

    NASA Astrophysics Data System (ADS)

    Crease, Robert

    2015-04-01

    John H. Marburger (1941-2011) was a skilled science administrator who had a fresh and unique approach to science policy and science leadership. His posthumously published book Science Policy up Close contains recollections of key science policy episodes in which he participated or observed closely. One was the administration of the Superconducting Supercollider (SSC); Marburger was Chairman of the Universities Research Association, the group charged with managing the SSC, from 1988-1994. Many accounts of the SSC saga attribute its demise to a combination of transitory factors: poor management, rising cost estimates, the collapse of the Soviet Union and thus of the Cold War threat, complaints by ``small science'' that the SSC's ``big science'' was consuming their budget, Congress's desire to cut spending, unwarranted contract regulations imposed by the Department of Energy (DOE) in response to environmental lapses at nuclear weapons laboratories, and so forth. Marburger tells a subtler story whose implications for science policy are more significant and far-reaching. The story involves changes in the attitude of the government towards large scientific projects that reach back to management reforms introduced by the administration of Presidents Johnson, Nixon, and Carter in the 1960s and 1970s. This experience impressed Marburger with the inevitability of public oversight of large scientific projects, and with the need for planners of such projects to establish and make public a cost and schedule tracking system that would model the project's progress and expenditures.

  13. 75 FR 32372 - Western Pacific Fishery Management Council; Public Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-08

    ... 104th Scientific and Statistical Committee (SSC) and 148th Council meetings to take recommendations and... complete scheduled business. Schedule and Agenda for 104th SSC Meeting: Tuesday, June 22, 2010, 8:30 a.m. 1... a.m. 9. Other Business A. 105th SSC Meeting 10. Summary of SSC Recommendations to the Council 148th...

  14. Enhanced photocurrent production by bio-dyes of photosynthetic macromolecules on designed TiO2 film

    PubMed Central

    Yu, Daoyong; Wang, Mengfei; Zhu, Guoliang; Ge, Baosheng; Liu, Shuang; Huang, Fang

    2015-01-01

    The macromolecular pigment-protein complex has the merit of high efficiency for light-energy capture and transfer after long-term photosynthetic evolution. Here bio-dyes of A. platensis photosystem I (PSI) and spinach light-harvesting complex II (LHCII) are spontaneously sensitized on three types of designed TiO2 films, to assess the effects of pigment-protein complex on the performance of bio-dye sensitized solar cells (SSC). Adsorption models of bio-dyes are proposed based on the 3D structures of PSI and LHCII, and the size of particles and inner pores in the TiO2 film. PSI shows its merit of high efficiency for captured energy transfer, charge separation and transfer in the electron transfer chain (ETC), and electron injection from FB to the TiO2 conducting band. After optimization, the best short current (JSC) and photoelectric conversion efficiency (η) of PSI-SSC and LHCII-SSC are 1.31 mA cm-2 and 0.47%, and 1.51 mA cm-2 and 0.52%, respectively. The potential for further improvement of this PSI based SSC is significant and could lead to better utilization of solar energy. PMID:25790735

  15. Targeting the Myofibroblast Genetic Switch: Inhibitors of Myocardin-Related Transcription Factor/Serum Response Factor–Regulated Gene Transcription Prevent Fibrosis in a Murine Model of Skin Injury

    PubMed Central

    Haak, Andrew J.; Tsou, Pei-Suen; Amin, Mohammad A.; Ruth, Jeffrey H.; Campbell, Phillip; Fox, David A.; Khanna, Dinesh; Larsen, Scott D.

    2014-01-01

    Systemic sclerosis (SSc), or scleroderma, similar to many fibrotic disorders, lacks effective therapies. Current trials focus on anti-inflammatory drugs or targeted approaches aimed at one of the many receptor mechanisms initiating fibrosis. In light of evidence that a myocardin-related transcription factor (MRTF)–and serum response factor (SRF)–regulated gene transcriptional program induced by Rho GTPases is essential for myofibroblast activation, we explored the hypothesis that inhibitors of this pathway may represent novel antifibrotics. MRTF/SRF-regulated genes show spontaneously increased expression in primary dermal fibroblasts from patients with diffuse cutaneous SSc. A novel small-molecule inhibitor of MRTF/SRF-regulated transcription (CCG-203971) inhibits expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and collagen 1 (COL1A2) in both SSc fibroblasts and in lysophosphatidic acid (LPA)–and transforming growth factor β (TGFβ)–stimulated fibroblasts. In vivo treatment with CCG-203971 also prevented bleomycin-induced skin thickening and collagen deposition. Thus, targeting the MRTF/SRF gene transcription pathway could provide an efficacious new approach to therapy for SSc and other fibrotic disorders. PMID:24706986

  16. Hysteresis in suspended sediment to turbidity relations due to changing particle size distributions

    USGS Publications Warehouse

    Landers, Mark N.; Sturm, Terry W.

    2013-01-01

    Turbidity (T) is the most ubiquitous of surrogate technologies used to estimate suspended-sediment concentration (SSC). The effects of sediment size on turbidity are well documented; however, effects from changes in particle size distributions (PSD) are rarely evaluated. Hysteresis in relations of SSC-to-turbidity (SSC~T) for single stormflow events was observed and quantified for a data set of 195 concurrent measurements of SSC, turbidity, discharge, velocity, and volumetric PSD collected during five stormflows in 2009–2010 on Yellow River at Gees Mill Road in metropolitan Atlanta, Georgia. Regressions of SSC-normalized turbidity (T/SSC) on concurrently measured PSD percentiles show an inverse, exponential influence of particle size on turbidity that is not constant across the size range of the PSD. The majority of the influence of PSD on T/SSC is from particles of fine-silt and smaller sizes (finer than 16 microns). This study shows that small changes in the often assumed stability of the PSD are significant to SSC~T relations. Changes of only 5 microns in the fine silt and smaller size fractions of suspended sediment PSD can produce hysteresis in the SSC~T rating that can increase error and produce bias. Observed SSC~T hysteresis may be an indicator of changes in sediment properties during stormflows and of potential changes in sediment sources. Trends in the PSD time series indicate that sediment transport is capacity-limited for sand-sized sediment in the channel and supply-limited for fine silt and smaller sediment from the hillslope.

  17. Survival, causes of death, and prognostic factors in systemic sclerosis: analysis of 947 Brazilian patients.

    PubMed

    Sampaio-Barros, Percival D; Bortoluzzo, Adriana B; Marangoni, Roberta G; Rocha, Luiza F; Del Rio, Ana Paula T; Samara, Adil M; Yoshinari, Natalino H; Marques-Neto, João Francisco

    2012-10-01

    To analyze survival, prognostic factors, and causes of death in a large cohort of patients with systemic sclerosis (SSc). From 1991 to 2010, 947 patients with SSc were treated at 2 referral university centers in Brazil. Causes of death were considered SSc-related and non-SSc-related. Multiple logistic regression analysis was used to identify prognostic factors. Survival at 5 and 10 years was estimated using the Kaplan-Meier method. One hundred sixty-eight patients died during the followup. Among the 110 deaths considered related to SSc, there was predominance of lung (48.1%) and heart (24.5%) involvement. Most of the 58 deaths not related to SSc were caused by infection, cardiovascular or cerebrovascular disease, and cancer. Male sex, modified Rodnan skin score (mRSS) > 20, osteoarticular involvement, lung involvement, and renal crisis were the main prognostic factors associated to death. Overall survival rate was 90% for 5 years and 84% for 10 years. Patients presented worse prognosis if they had diffuse SSc (85% vs 92% at 5 yrs, respectively, and 77% vs 87% at 10 yrs, compared to limited SSc), male sex (77% vs 90% at 5 yrs and 64% vs 86% at 10 yrs, compared to female sex), and mRSS > 20 (83% vs 90% at 5 yrs and 66% vs 86% at 10 yrs, compared to mRSS < 20). Survival was worse in male patients with diffuse SSc, and lung and heart involvement represented the main causes of death in this South American series of patients with SSc.

  18. Parental experiences of providing skin-to-skin care to their newborn infant—Part 2: A qualitative meta-synthesis

    PubMed Central

    Anderzén-Carlsson, Agneta; Lamy, Zeni C.; Tingvall, Maria; Eriksson, Mats

    2014-01-01

    Aim To synthesize and interpret qualitative research findings focusing on parental experiences of skin-to-skin care (SSC) for newborn infants. Background SSC induces many benefits for newborn infants and their parents. Three meta-analyses have been conducted on physiological outcomes, but no previous qualitative meta-synthesis on parental experiences of SSC has been identified. Design The present meta-synthesis was guided by the methodology described by Paterson and co-workers. Data sources Four databases were searched, without year or language limitations, up until December 2013. Manual searches were also performed. The searches and subsequent quality appraisal resulted in the inclusion of 29 original qualitative papers from 9 countries, reporting experiences from 401 mothers and 94 fathers. Review methods The meta-synthesis entails a meta-data analysis, analysis of meta-method, and meta-theory in the included primary studies. Based on the three analyses, the meta-synthesis represents a new interpretation of a phenomenon. The results of the meta-data analysis have been presented as a qualitative systematic review in a separate paper. Results When synthesizing and interpreting the findings from the included analyses, a theoretical model of Becoming a parent under unfamiliar circumstances emerged. Providing SSC seems to be a restorative as well as an energy-draining experience. A supportive environment has been described as facilitating the restorative experience, whereas obstacles in the environment seem to make the provision of SSC energy-draining for parents. When the process is experienced as positive, it facilitates the growth of parental self-esteem and makes the parents ready to assume full responsibility for their child. Conclusion The results show that SSC can be interpreted not only as a family-including and important health care intervention but also in terms of actually becoming a parent. The process of becoming a parent in this specific situation is influenced by external factors in three different levels; family and friends, community, and society at large. The descriptions of providing SSC are similar to what has previously been described as the natural process of becoming a mother or a father. PMID:25319747

  19. Parental experiences of providing skin-to-skin care to their newborn infant--part 2: a qualitative meta-synthesis.

    PubMed

    Anderzén-Carlsson, Agneta; Lamy, Zeni C; Tingvall, Maria; Eriksson, Mats

    2014-01-01

    To synthesize and interpret qualitative research findings focusing on parental experiences of skin-to-skin care (SSC) for newborn infants. SSC induces many benefits for newborn infants and their parents. Three meta-analyses have been conducted on physiological outcomes, but no previous qualitative meta-synthesis on parental experiences of SSC has been identified. The present meta-synthesis was guided by the methodology described by Paterson and co-workers. Four databases were searched, without year or language limitations, up until December 2013. Manual searches were also performed. The searches and subsequent quality appraisal resulted in the inclusion of 29 original qualitative papers from 9 countries, reporting experiences from 401 mothers and 94 fathers. The meta-synthesis entails a meta-data analysis, analysis of meta-method, and meta-theory in the included primary studies. Based on the three analyses, the meta-synthesis represents a new interpretation of a phenomenon. The results of the meta-data analysis have been presented as a qualitative systematic review in a separate paper. When synthesizing and interpreting the findings from the included analyses, a theoretical model of Becoming a parent under unfamiliar circumstances emerged. Providing SSC seems to be a restorative as well as an energy-draining experience. A supportive environment has been described as facilitating the restorative experience, whereas obstacles in the environment seem to make the provision of SSC energy-draining for parents. When the process is experienced as positive, it facilitates the growth of parental self-esteem and makes the parents ready to assume full responsibility for their child. The results show that SSC can be interpreted not only as a family-including and important health care intervention but also in terms of actually becoming a parent. The process of becoming a parent in this specific situation is influenced by external factors in three different levels; family and friends, community, and society at large. The descriptions of providing SSC are similar to what has previously been described as the natural process of becoming a mother or a father.

  20. Multilevel Safety Climate and Safety Performance in the Construction Industry: Development and Validation of a Top-Down Mechanism

    PubMed Central

    Gao, Ran; Chan, Albert P.C.; Utama, Wahyudi P.; Zahoor, Hafiz

    2016-01-01

    The character of construction projects exposes front-line workers to dangers and accidents. Safety climate has been confirmed to be a predictor of safety performance in the construction industry. This study aims to explore the underlying mechanisms of the relationship between multilevel safety climate and safety performance. An integrated model was developed to study how particular safety climate factors of one level affect those of other levels, and then affect safety performance from the top down. A questionnaire survey was administered on six construction sites in Vietnam. A total of 1030 valid questionnaires were collected from this survey. Approximately half of the data were used to conduct exploratory factor analysis (EFA) and the remaining data were submitted to structural equation modeling (SEM). Top management commitment (TMC) and supervisors’ expectation (SE) were identified as factors to represent organizational safety climate (OSC) and supervisor safety climate (SSC), respectively, and coworkers’ caring and communication (CCC) and coworkers’ role models (CRM) were identified as factors to denote coworker safety climate (CSC). SEM results show that OSC factor is positively related to SSC factor and CSC factors significantly. SSC factor could partially mediate the relationship between OSC factor and CSC factors, as well as the relationship between OSC factor and safety performance. CSC factors partially mediate the relationship between OSC factor and safety performance, and the relationship between SSC factor and safety performance. The findings imply that a positive safety culture should be established both at the organizational level and the group level. Efforts from all top management, supervisors, and coworkers should be provided to improve safety performance in the construction industry. PMID:27834823

  1. Responses of water environment to tidal flat reduction in Xiangshan Bay: Part II locally re-suspended sediment dynamics

    NASA Astrophysics Data System (ADS)

    Li, Li; Guan, Weibing; He, Zhiguo; Yao, Yanming; Xia, Yuezhang

    2017-11-01

    Xiangshan Bay is a semi-enclosed bay in China, in which tidal flats have been substantially reclaimed to support the development of local economies and society over previous decades. The loss of tidal flats has led to changes of tides and locally suspended sediment in the bay. The effects of tidal flat reduction on locally suspended sediment dynamics was investigated using a numerical model forced by tidal data and calibrated by observed tidal elevation and currents. The model satisfactorily reproduces observed water levels, currents, and suspended sediment concentration in the estuary, and therefore is subsequently applied to analyze the impact of tidal flat reclamation on locally suspended sediment transport. After the loss of the tidal flats from 1963 to 2010, the suspended sediment concentrations (SSC) at the bottom boundary layer were reduced/increased in the outer bay/tidal flat areas due to weakened tidal currents. In the inner bay, the SSC values near the bottom level increased from 1963 to 2003 due to the narrowed bathymetry, and then decreased from 2003 to 2010 because of the reduced tidal prism. The model scenarios suggest that: (1) a reduction of tidal flat areas appears to be the main factor for enhancing the transport of sediments up-estuary, due to the increased Eulerian velocity and tidal pumping; (2) A reduction of tidal flat areas impacts on spatial and temporal SSC distribution: reducing the SSC values in the water areas due to the reduced current; and (3) a tidal flat reduction influences the net sediment fluxes: lessening the erosion and inducing higher/lower landward/seaward sediment transportation.

  2. Twenty years of artificial directional selection have shaped the genome of the Italian Large White pig breed.

    PubMed

    Schiavo, G; Galimberti, G; Calò, D G; Samorè, A B; Bertolini, F; Russo, V; Gallo, M; Buttazzoni, L; Fontanesi, L

    2016-04-01

    In this study, we investigated at the genome-wide level if 20 years of artificial directional selection based on boar genetic evaluation obtained with a classical BLUP animal model shaped the genome of the Italian Large White pig breed. The most influential boars of this breed (n = 192), born from 1992 (the beginning of the selection program of this breed) to 2012, with an estimated breeding value reliability of >0.85, were genotyped with the Illumina Porcine SNP60 BeadChip. After grouping the boars in eight classes according to their year of birth, filtered single nucleotide polymorphisms (SNPs) were used to evaluate the effects of time on genotype frequency changes using multinomial logistic regression models. Of these markers, 493 had a PBonferroni  < 0.10. However, there was an increasing number of SNPs with a decreasing level of allele frequency changes over time, representing a continuous profile across the genome. The largest proportion of the 493 SNPs was on porcine chromosome (SSC) 7, SSC2, SSC8 and SSC18 for a total of 204 haploblocks. Functional annotations of genomic regions, including the 493 shifted SNPs, reported a few Gene Ontology terms that might underly the biological processes that contributed to increase performances of the pigs over the 20 years of the selection program. The obtained results indicated that the genome of the Italian Large White pigs was shaped by a directional selection program derived by the application of methodologies assuming the infinitesimal model that captured a continuous trend of allele frequency changes in the boar population. © 2015 Stichting International Foundation for Animal Genetics.

  3. Multilevel Safety Climate and Safety Performance in the Construction Industry: Development and Validation of a Top-Down Mechanism.

    PubMed

    Gao, Ran; Chan, Albert P C; Utama, Wahyudi P; Zahoor, Hafiz

    2016-11-08

    The character of construction projects exposes front-line workers to dangers and accidents. Safety climate has been confirmed to be a predictor of safety performance in the construction industry. This study aims to explore the underlying mechanisms of the relationship between multilevel safety climate and safety performance. An integrated model was developed to study how particular safety climate factors of one level affect those of other levels, and then affect safety performance from the top down. A questionnaire survey was administered on six construction sites in Vietnam. A total of 1030 valid questionnaires were collected from this survey. Approximately half of the data were used to conduct exploratory factor analysis (EFA) and the remaining data were submitted to structural equation modeling (SEM). Top management commitment (TMC) and supervisors' expectation (SE) were identified as factors to represent organizational safety climate (OSC) and supervisor safety climate (SSC), respectively, and coworkers' caring and communication (CCC) and coworkers' role models (CRM) were identified as factors to denote coworker safety climate (CSC). SEM results show that OSC factor is positively related to SSC factor and CSC factors significantly. SSC factor could partially mediate the relationship between OSC factor and CSC factors, as well as the relationship between OSC factor and safety performance. CSC factors partially mediate the relationship between OSC factor and safety performance, and the relationship between SSC factor and safety performance. The findings imply that a positive safety culture should be established both at the organizational level and the group level. Efforts from all top management, supervisors, and coworkers should be provided to improve safety performance in the construction industry.

  4. A Spatially Distributed Conceptual Model for Estimating Suspended Sediment Yield in Alpine catchments

    NASA Astrophysics Data System (ADS)

    Costa, Anna; Molnar, Peter; Anghileri, Daniela

    2017-04-01

    Suspended sediment is associated with nutrient and contaminant transport in water courses. Estimating suspended sediment load is relevant for water-quality assessment, recreational activities, reservoir sedimentation issues, and ecological habitat assessment. Suspended sediment concentration (SSC) along channels is usually reproduced by suspended sediment rating curves, which relate SSC to discharge with a power law equation. Large uncertainty characterizes rating curves based only on discharge, because sediment supply is not explicitly accounted for. The aim of this work is to develop a source-oriented formulation of suspended sediment dynamics and to estimate suspended sediment yield at the outlet of a large Alpine catchment (upper Rhône basin, Switzerland). We propose a novel modelling approach for suspended sediment which accounts for sediment supply by taking into account the variety of sediment sources in an Alpine environment, i.e. the spatial location of sediment sources (e.g. distance from the outlet and lithology) and the different processes of sediment production and transport (e.g. by rainfall, overland flow, snowmelt). Four main sediment sources, typical of Alpine environments, are included in our model: glacial erosion, hillslope erosion, channel erosion and erosion by mass wasting processes. The predictive model is based on gridded datasets of precipitation and air temperature which drive spatially distributed degree-day models to simulate snowmelt and ice-melt, and determine erosive rainfall. A mass balance at the grid scale determines daily runoff. Each cell belongs to a different sediment source (e.g. hillslope, channel, glacier cell). The amount of sediment entrained and transported in suspension is simulated through non-linear functions of runoff, specific for sediment production and transport processes occurring at the grid scale (e.g. rainfall erosion, snowmelt-driven overland flow). Erodibility factors identify different lithological units, while the distance from the outlet is accounted for by including sediment wave velocities. The model is calibrated and validated on the basis of continuous turbidity data measured at the outlet of the basin. In addition, SSC data measured twice per week since 1964 are used to evaluate the performance of the model over longer time scales. Our predictive model is shown to reproduce SSC dynamics of the upper Rhône basin satisfactorily. The model accounts for the spatial distribution of sediment sources (location and processes of erosion and transport) and their activation/deactivation throughout the hydrological year. Therefore, it can reproduce the effects of changes in climate on sediment fluxes. In particular, we show that observed changes in SSC in the upper Rhône basin during the last 40 years are likely a consequence of increased air temperatures in this period and the consequent acceleration of glacial erosion.

  5. ATPase domain and interdomain linker play a key role in aggregation of mitochondrial Hsp70 chaperone Ssc1.

    PubMed

    Blamowska, Marta; Sichting, Martin; Mapa, Koyeli; Mokranjac, Dejana; Neupert, Walter; Hell, Kai

    2010-02-12

    The co-chaperone Hep1 is required to prevent the aggregation of mitochondrial Hsp70 proteins. We have analyzed the interaction of Hep1 with mitochondrial Hsp70 (Ssc1) and the determinants in Ssc1 that make it prone to aggregation. The ATPase and peptide binding domain (PBD) of Hsp70 proteins are connected by a linker segment that mediates interdomain communication between the domains. We show here that the minimal Hep1 binding entity of Ssc1 consists of the ATPase domain and the interdomain linker. In the absence of Hep1, the ATPase domain with the interdomain linker had the tendency to aggregate, in contrast to the ATPase domain with the mutated linker segment or without linker, and in contrast to the PBD. The closest homolog of Ssc1, bacterial DnaK, and a Ssc1 chimera, in which a segment of the ATPase domain of Ssc1 was replaced by the corresponding segment from DnaK, did not aggregate in Delta hep1 mitochondria. The propensity to aggregate appears to be a specific property of the mitochondrial Hsp70 proteins. The ATPase domain in combination with the interdomain linker is crucial for aggregation of Ssc1. In conclusion, our results suggest that interdomain communication makes Ssc1 prone to aggregation. Hep1 counteracts aggregation by binding to this aggregation-prone conformer.

  6. ATPase Domain and Interdomain Linker Play a Key Role in Aggregation of Mitochondrial Hsp70 Chaperone Ssc1*

    PubMed Central

    Blamowska, Marta; Sichting, Martin; Mapa, Koyeli; Mokranjac, Dejana; Neupert, Walter; Hell, Kai

    2010-01-01

    The co-chaperone Hep1 is required to prevent the aggregation of mitochondrial Hsp70 proteins. We have analyzed the interaction of Hep1 with mitochondrial Hsp70 (Ssc1) and the determinants in Ssc1 that make it prone to aggregation. The ATPase and peptide binding domain (PBD) of Hsp70 proteins are connected by a linker segment that mediates interdomain communication between the domains. We show here that the minimal Hep1 binding entity of Ssc1 consists of the ATPase domain and the interdomain linker. In the absence of Hep1, the ATPase domain with the interdomain linker had the tendency to aggregate, in contrast to the ATPase domain with the mutated linker segment or without linker, and in contrast to the PBD. The closest homolog of Ssc1, bacterial DnaK, and a Ssc1 chimera, in which a segment of the ATPase domain of Ssc1 was replaced by the corresponding segment from DnaK, did not aggregate in Δhep1 mitochondria. The propensity to aggregate appears to be a specific property of the mitochondrial Hsp70 proteins. The ATPase domain in combination with the interdomain linker is crucial for aggregation of Ssc1. In conclusion, our results suggest that interdomain communication makes Ssc1 prone to aggregation. Hep1 counteracts aggregation by binding to this aggregation-prone conformer. PMID:20007714

  7. A Case Study of Infant Physiologic Response to Skin-to-Skin Contact After Surgery for Complex Congenital Heart Disease.

    PubMed

    Harrison, Tondi M; Ludington-Hoe, Susan

    2015-01-01

    Infants with complex congenital heart disease requiring surgical intervention within the first days or weeks of life may be the most seriously ill infants needing intensive nursing and medical care. Skin-to-skin contact (SSC) is well accepted and practiced as a positive therapeutic intervention in premature infants but is not routinely offered to infants in cardiac intensive care units. The physiologic effects of SSC in the congenital heart disease population must be examined before recommending incorporation of SSC into standard care routines. The purpose of this case study was to describe the physiologic response to a single session of SSC in an 18-day-old infant with hypoplastic left heart syndrome. Repeated measures of heart rate, respiratory rate, oxygen saturation, blood pressure, and temperature were recorded 30 minutes before SSC, during SSC (including interruptions for bottle and breast feedings), and 10 minutes after SSC was completed. All physiologic parameters were clinically acceptable throughout the 135-minute observation. This case study provides beginning evidence that SSC is safe in full-term infants after surgery for complex congenital heart disease. Further research with a larger sample is needed to examine the effects of SSC on infant physiology before surgery and earlier in the postoperative time period as well as on additional outcomes such as length of stay, maternal-infant interaction, and neurodevelopment.

  8. Reduced levels of S-nitrosothiols in plasma of patients with systemic sclerosis and Raynaud's phenomenon.

    PubMed

    Kundu, Devi; Abraham, David; Black, Carol M; Denton, Christopher P; Bruckdorfer, K Richard

    2014-12-01

    S-Nitrosothiols (RSNOs) are bioactive forms of nitric oxide which are involved in cell signalling and redox regulation of vascular function. Circulating S-nitrosothiols are predominantly in the form of S-nitrosoalbumin. In this study plasma concentrations of S-nitrosothiols were measured in patients with systemic sclerosis (SSc) where NO metabolism is known to be abnormal. Venous blood was collected from 16 patients with Raynaud's phenomenon (RP), 45 with systemic sclerosis (SSc) (34 patients had limited SSc (IcSSc) and 11 diffuse cutaneous disease (dcSSc)). Twenty six healthy subjects were used as controls. Plasma S-nitrosothiol concentrations were measured by chemiluminescence. The measurements were related to the extent of biological age, capillary/skin scores and disease duration. Plasma RSNO levels in patients with Raynaud's phenomenon (RP) and in those with SSc was significantly lower compared to the concentrations in control subjects. In SSc, plasma S-nitrosothiols were often below the level of detection (1nM). Low S-nitrosothiol concentrations were observed in the blood of patients with SSc and patients with RP indicating a profound disturbance of nitric oxide metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Intestinal microbiome in scleroderma: recent progress.

    PubMed

    Volkmann, Elizabeth R

    2017-11-01

    Our evolving understanding of how gut microbiota affects immune function and homeostasis has led many investigators to explore the potentially pathologic role of gut microbiota in autoimmune diseases. This review will discuss the rapidly advancing field of microbiome research in systemic sclerosis (SSc), an incurable autoimmune disease with significant gastrointestinal morbidity and mortality. Recent reports have identified common perturbations in gut microbiota across different SSc cohorts. Compared with healthy controls, patients with SSc have decreased abundance of beneficial commensal genera (e.g. Faecalibacterium, Clostridium and Bacteroides) and increased abundance of pathbiont genera (e.g. Fusobacterium, Prevotella and Erwinia). Certain genera may protect against (e.g. Bacteroides, Clostridium, and Lactobacillus), or conversely exacerbate (e.g. Fusobacterium and Prevotella) gastrointestinal symptoms in SSc. These genera represent potential targets to avert or treat gastrointestinal dysfunction in SSc. Emerging evidence suggests that alterations in gut microbiota exist in the SSc disease state; however, future basic and clinical studies are needed to ascertain the mechanism by which these alterations perpetuate inflammation and fibrosis in SSc. Therapeutic trials are also needed to investigate whether dietary interventions or fecal transplantation can restore the gut microbial balance and improve health outcomes in SSc. VIDEO ABSTRACT: http://links.lww.com/COR/A38.

  10. Systemic Sclerosis and Malignancy: A Review of Current Data

    PubMed Central

    Zeineddine, Nabil; Khoury, Lara El; Mosak, Joseph

    2016-01-01

    Systemic sclerosis (SSc) is associated with increased risk of malignancy. The organ systems most commonly affected are the lungs, the breasts and the hematological system. Risk factors predisposing a SSc patient for development of malignancy are not well defined, and the pathogenic basis of the association is yet to be explained. The incidence of malignancies in SSc patients is variable from one report to another, but most importantly, questions regarding the role of immunosuppressive therapies and the effect of autoantibodies have weak or sometimes contradictory answers in most of the currently available literature and physicians have no available guidelines to screen their SSc patients for malignancies. The lack of a concretely defined high-risk profile and the absence of malignancy screening guidelines tailored for SSc patients raise the importance of the need for more studies on the association of SSc and cancer and should incite rheumatology colleges to develop specific recommendations for the clinician to follow while approaching patients with SSc. PMID:27540435

  11. Time parameterizations and spin supplementary conditions of the Mathisson-Papapetrou-Dixon equations

    NASA Astrophysics Data System (ADS)

    Lukes-Gerakopoulos, Georgios

    2017-11-01

    The implications of two different time constraints on the Mathisson-Papapetrou-Dixon (MPD) equations are discussed under three spin supplementary conditions (SSCs). For this reason the MPD equations are revisited without specifying the affine parameter and several relations are reintroduced in their general form. The latter allows one to investigate the consequences of combining the Mathisson-Pirani (MP) SSC, the Tulczyjew-Dixon (TD) SSC and the Ohashi-Kyrian-Semerák (OKS) SSC with two affine parameter types: the proper time on one hand and the parameterizations introduced in [Gen. Relativ. Gravit. 8, 197 (1977), 10.1007/BF00763547] on the other. For the MP SSC and the TD SSC it is shown that quantities that are constant of motion for the one affine parameter are not for the other, while for the OKS SSC it is shown that the two affine parameters are the same. To clarify the relation between the two affine parameters in the case of the TD SSC the MPD equations are evolved and discussed.

  12. An Experimental Evaluation of Advanced Rotorcraft Airfoils in the NASA Ames Eleven-foot Transonic Wind Tunnel

    NASA Technical Reports Server (NTRS)

    Flemming, Robert J.

    1984-01-01

    Five full scale rotorcraft airfoils were tested in the NASA Ames Eleven-Foot Transonic Wind Tunnel for full scale Reynolds numbers at Mach numbers from 0.3 to 1.07. The models, which spanned the tunnel from floor to ceiling, included two modern baseline airfoils, the SC1095 and SC1094 R8, which have been previously tested in other facilities. Three advanced transonic airfoils, designated the SSC-A09, SSC-A07, and SSC-B08, were tested to confirm predicted performance and provide confirmation of advanced airfoil design methods. The test showed that the eleven-foot tunnel is suited to two-dimensional airfoil testing. Maximum lift coefficients, drag coefficients, pitching moments, and pressure coefficient distributions are presented. The airfoil analysis codes agreed well with the data, with the Grumman GRUMFOIL code giving the best overall performance correlation.

  13. Overview of Engineering Design and Analysis at the NASA John C. Stennis Space Center

    NASA Technical Reports Server (NTRS)

    Ryan, Harry; Congiardo, Jared; Junell, Justin; Kirkpatrick, Richard

    2007-01-01

    A wide range of rocket propulsion test work occurs at the NASA John C. Stennis Space Center (SSC) including full-scale engine test activities at test facilities A-1, A-2, B-1 and B-2 as well as combustion device research and development activities at the E-Complex (E-1, E-2, E-3 and E-4) test facilities. The propulsion test engineer at NASA SSC faces many challenges associated with designing and operating a test facility due to the extreme operating conditions (e.g., cryogenic temperatures, high pressures) of the various system components and the uniqueness of many of the components and systems. The purpose of this paper is to briefly describe the NASA SSC Engineering Science Directorate s design and analysis processes, experience, and modeling techniques that are used to design and support the operation of unique rocket propulsion test facilities.

  14. Empirical estimation of the arrival time of ICME Shocks

    NASA Astrophysics Data System (ADS)

    Shaltout, Mosalam

    Empirical estimation of the arrival time of ICME Shocks Mosalam Shaltout1 ,M.Youssef 1and R.Mawad2 1 National Research Institute of Astronomy and Geophysics (NRIAG) ,Helwan -Cairo-Egypt Email: mosalamshaltout@hotmail.com 2 Faculty of Science-Monifiia University-Physics Department-Shiben Al-Koum -Monifiia-Egypt We are got the Data of the SSC events from Preliminary Reports of the ISGI (Institut de Physique du Globe, France) .Also we are selected the same CME interval 1996-2005 from SOHO/LASCO/C2.We have estimated the arrival time of ICME shocks during solar cycle 23rd (1996-2005), we take the Sudden storm commencement SSC as a indicator of the arrival of CMEs at the Earth's Magnetosphere (ICME).Under our model ,we selected 203 ICME shock-SSC associated events, we got an imperial relation between CME velocity and their travel time, from which we obtained high correlation between them, R=0.75.

  15. Chronic Toll-like receptor 4 stimulation in skin induces inflammation, macrophage activation, transforming growth factor beta signature gene expression, and fibrosis

    PubMed Central

    2014-01-01

    Introduction The crucial role of innate immunity in the pathogenesis of systemic sclerosis (SSc) is well established, and in the past few years the hypothesis that Toll-like receptor 4 (TLR4) activation induced by endogenous ligands is involved in fibrogenesis has been supported by several studies on skin, liver, and kidney fibrosis. These findings suggest that TLR4 activation can enhance transforming growth factor beta (TGF-β) signaling, providing a potential mechanism for TLR4/Myeloid differentiation factor 88 (MyD88)-dependent fibrosis. Methods The expression of TLR4, CD14 and MD2 genes was analyzed by real-time polymerase chain reaction from skin biopsies of 24 patients with diffuse cutaneous SSc. In order to investigate the effects of the chronic skin exposure to endotoxin (Lipopolysaccharide (LPS)) in vivo we examined the expression of inflammation, TGF-β signaling and cellular markers genes by nanostring. We also identified cellular subsets by immunohistochemistry and flow cytometry. Results We found that TLR4 and its co-receptors, MD2 and CD14, are over-expressed in lesional skin from patients with diffuse cutaneous SSc, and correlate significantly with progressive or regressive skin disease as assessed by the Delta Modified Rodnan Skin Score. In vivo, a model of chronic dermal LPS exposure showed overexpression of proinflammatory chemokines, recruitment and activation of macrophages, and upregulation of TGF-β signature genes. Conclusions We delineated the role of MyD88 as necessary for the induction not only for the early phase of inflammation, but also for pro-fibrotic gene expression via activation of macrophages. Chronic LPS exposure might be a model of early stage of SSc when inflammation and macrophage activation are important pathological features of the disease, supporting a role for innate immune activation in SSc skin fibrosis. PMID:24984848

  16. Chronic Toll-like receptor 4 stimulation in skin induces inflammation, macrophage activation, transforming growth factor beta signature gene expression, and fibrosis.

    PubMed

    Stifano, Giuseppina; Affandi, Alsya J; Mathes, Allison L; Rice, Lisa M; Nakerakanti, Sashidhar; Nazari, Banafsheh; Lee, Jungeun; Christmann, Romy B; Lafyatis, Robert

    2014-07-01

    The crucial role of innate immunity in the pathogenesis of systemic sclerosis (SSc) is well established, and in the past few years the hypothesis that Toll-like receptor 4 (TLR4) activation induced by endogenous ligands is involved in fibrogenesis has been supported by several studies on skin, liver, and kidney fibrosis. These findings suggest that TLR4 activation can enhance transforming growth factor beta (TGF-β) signaling, providing a potential mechanism for TLR4/Myeloid differentiation factor 88 (MyD88)-dependent fibrosis. The expression of TLR4, CD14 and MD2 genes was analyzed by real-time polymerase chain reaction from skin biopsies of 24 patients with diffuse cutaneous SSc. In order to investigate the effects of the chronic skin exposure to endotoxin (Lipopolysaccharide (LPS)) in vivo we examined the expression of inflammation, TGF-β signaling and cellular markers genes by nanostring. We also identified cellular subsets by immunohistochemistry and flow cytometry. We found that TLR4 and its co-receptors, MD2 and CD14, are over-expressed in lesional skin from patients with diffuse cutaneous SSc, and correlate significantly with progressive or regressive skin disease as assessed by the Delta Modified Rodnan Skin Score. In vivo, a model of chronic dermal LPS exposure showed overexpression of proinflammatory chemokines, recruitment and activation of macrophages, and upregulation of TGF-β signature genes. We delineated the role of MyD88 as necessary for the induction not only for the early phase of inflammation, but also for pro-fibrotic gene expression via activation of macrophages. Chronic LPS exposure might be a model of early stage of SSc when inflammation and macrophage activation are important pathological features of the disease, supporting a role for innate immune activation in SSc skin fibrosis.

  17. The role of small-scale convection on the formation of volcanic passive margins

    NASA Astrophysics Data System (ADS)

    Van Hunen, J.; Phethean, J. J. J.

    2014-12-01

    Several models have been presented in the literature to explain volcanic passive margins (VPMs), including variation in rifting speed or history, enhanced melting from mantle plumes, and enhanced flow through the melting zone by small-scale convection (SSC) driven by lithospheric detachments. Understanding the mechanism is important to constrain the paleo-heat flow and petroleum potential of VPM. Using 2D and 3D numerical models, we investigate the influence of SSC on the rate of crust production during continental rifting. Conceptually, SSC results in up/downwellings with a typical spacing of a few-100 km, and may lead to enhanced decompression melting. Subsequent mantle depletion changes buoyancy (from latent heat consumption and compositional changes), and affects mantle dynamics under the MOR and potentially any further melting. Decompression melting leads to a colder, thermally denser residue (from consumption of latent heat of melting), but also a compositionally more buoyant one. A parameter sensitivity study of the effects of mantle viscosity, spreading rate, mantle temperature, and a range material parameters indicates that competition between thermal and compositional buoyancy determines the mantle dynamics. For mantle viscosities ηm > ~1022 Pa s, no SSC occurs, and a uniform 7-8 km-thick oceanic crust forms. For ηm < ~1021 Pa s, SSC is vigorous and can form VPMs with > 10-20 km crust. If thermal density effects dominate, a vigorous (inverted) convection may drive significant decompression melting, and create VPMs. Such dynamics could also explain the continent-dipping normal faults that are commonly observed at VPMs. After the initial rifting phase, the crustal thickness reduces significantly, but not always to a uniformly thick 7-8 km, as would be appropriate for mature oceanic basins. Transverse convection rolls may result in margin-parallel crustal thickness variation, possibly related to observations such as the East-Coast Magnetic Anomaly.

  18. Abraham Pais Prize for History of Physics Lecture: Big, Bigger, Too Big? From Los Alamos to Fermilab and the SSC

    NASA Astrophysics Data System (ADS)

    Hoddeson, Lillian

    2012-03-01

    The modern era of big science emerged during World War II. Oppenheimer's Los Alamos laboratory offered the quintessential model of a government-funded, mission-oriented facility directed by a strong charismatic leader. The postwar beneficiaries of this model included the increasingly ambitious large laboratories that participated in particle physics--in particular, Brookhaven, SLAC, and Fermilab. They carried the big science they practiced into a new realm where experiments eventually became as large and costly as entire laboratories had been. Meanwhile the available funding grew more limited causing the physics research to be concentrated into fewer and bigger experiments that appeared never to end. The next phase in American high-energy physics was the Superconducting Super Collider, the most costly pure physics project ever attempted. The SSC's termination was a tragedy for American science, but for historians it offers an opportunity to understand what made the success of earlier large high-energy physics laboratories possible, and what made the continuation of the SSC impossible. The most obvious reason for the SSC's failure was its enormous and escalating budget, which Congress would no longer support. Other factors need to be recognized however: no leader could be found with directing skills as strong as those of Wilson, Panofsky, Lederman, or Richter; the scale of the project subjected it to uncomfortable public and Congressional scrutiny; and the DOE's enforcement of management procedures of the military-industrial complex that clashed with those typical of the scientific community led to the alienation and withdrawal of many of the most creative scientists, and to the perception and the reality of poor management. These factors, exacerbated by negative pressure from scientists in other fields and a post-Cold War climate in which physicists had little of their earlier cultural prestige, discouraged efforts to gain international support. They made the SSC crucially different from its predecessors and sealed its doom.

  19. Dynamics and Self-consistent Chaos in a Mean Field Hamiltonian Model

    NASA Astrophysics Data System (ADS)

    del-Castillo-Negrete, Diego

    We study a mean field Hamiltonian model that describes the collective dynamics of marginally stable fluids and plasmas in the finite N and N-> infty kinetic limit (where N is the number of particles). The linear stability of equilibria in the kinetic model is studied as well as the initial value problem including Landau damping . Numerical simulations show the existence of coherent, rotating dipole states. We approximate the dipole as two macroparticles and show that the N=2 limit has a family of rotating integrable solutions that provide an accurate description of the dynamics. We discuss the role of self-consistent Hamiltonian chaos in the formation of coherent structures, and discuss a mechanism of "violent" mixing caused by a self-consistent elliptic-hyperbolic bifurcation in phase space.

  20. The distribution of Enceladus water-group neutrals in Saturn’s Magnetosphere

    NASA Astrophysics Data System (ADS)

    Smith, Howard T.; Richardson, John D.

    2017-10-01

    Saturn’s magnetosphere is unique in that the plumes from the small icy moon, Enceladus, serve at the primary source for heavy particles in Saturn’s magnetosphere. The resulting co-orbiting neutral particles interact with ions, electrons, photons and other neutral particles to generate separate H2O, OH and O tori. Characterization of these toroidal distributions is essential for understanding Saturn magnetospheric sources, composition and dynamics. Unfortunately, limited direct observations of these features are available so modeling is required. A significant modeling challenge involves ensuring that either the plasma and neutral particle populations are not simply input conditions but can provide feedback to each population (i.e. are self-consistent). Jurac and Richardson (2005) executed such a self-consistent model however this research was performed prior to the return of Cassini data. In a similar fashion, we have coupled a 3-D neutral particle model (Smith et al. 2004, 2005, 2006, 2007, 2009, 2010) with a plasma transport model (Richardson 1998; Richardson & Jurac 2004) to develop a self-consistent model which is constrained by all available Cassini observations and current findings on Saturn’s magnetosphere and the Enceladus plume source resulting in much more accurate neutral particle distributions. Here a new self-consistent model of the distribution of the Enceladus-generated neutral tori that is validated by all available observations. We also discuss the implications for source rate and variability.

  1. Secondary plastic closure of gastroschisis is associated with a lower incidence of mechanical ventilation.

    PubMed

    Dariel, Anne; Poocharoen, Wannisa; de Silva, Nicole; Pleasants, Hazel; Gerstle, Justin Ted

    2015-02-01

    Nonsurgical closure after primary silo placement, secondary plastic closure (SPC), has been used as an alternative to secondary surgical closure (SSC) in gastroschisis. The benefits described were closure without formal surgical procedure, cosmetic aspect, and minimization of intra-abdominal pressures. This study compared requirements for mechanical ventilation and general anesthesia, nutritional care, and outcomes between SPC and SSC. We included patients with primary staged-silo reduction with a 1-year minimum follow-up. SPC was performed at bedside with sedation using a nonadherent dressing. SSC was performed in operating room under general anesthesia using standard surgical techniques. This retrospective study included 64 patients, 23 SPC and 41 SSC. The characteristics of the two groups were comparable. Mechanical ventilation was used for 15 SPC and 41 SSC (p=0.0001) with a comparable median duration (5.5 and 6.0 days, not significant [NS]). General anesthesia was required for 9 SPC and 41 SSC (p<0.0001). Complications included one SPC and six SSC with necrotizing enterocolitis, zero SPC and four SSC with intestinal atresia, two SPC and four SSC with small bowel obstruction, zero SPC and one SSC with abdominal compartment syndrome resulting in a short bowel syndrome (NS). Median duration of parenteral nutrition (30 and 27 days), time to first feeds (14 and 14 days), time at or above minimal enteral feeding (22 and 17 days), time to full feeds (31 and 28 days), length of stay (LOS) in neonatal intensive care unit (24 and 23.5 days) and overall hospital LOS (37 and 36 days) were not statistically different between SPC and SSC patients without complications, respectively. These data were comparable for SPC and SSC patients with complications. Five SPC and six SSC developed an umbilical hernia (NS); two patients in each group required a surgical repair (NS). Plastic closure of gastroschisis after primary silo reduction is simple, safe, reproducible, and associated with a significant lower incidence of mechanical ventilation. Nutritional management and length of hospital stay were similar to conventional surgical closure for patients. Plastic closure allows nonoperative management without general anesthesia at patient's bedside, in comparison with surgical closure that must be performed under general anesthesia in the operating room. Plastic closure does not appear to be associated with more umbilical hernias in this retrospective study. Georg Thieme Verlag KG Stuttgart · New York.

  2. 40 CFR 35.6805 - Contents of an SSC.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... STATE AND LOCAL ASSISTANCE Cooperative Agreements and Superfund State Contracts for Superfund Response Actions Requirements for Administering A Superfund State Contract (ssc) § 35.6805 Contents of an SSC. The...

  3. 40 CFR 35.6805 - Contents of an SSC.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... STATE AND LOCAL ASSISTANCE Cooperative Agreements and Superfund State Contracts for Superfund Response Actions Requirements for Administering A Superfund State Contract (ssc) § 35.6805 Contents of an SSC. The...

  4. 40 CFR 35.6805 - Contents of an SSC.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... STATE AND LOCAL ASSISTANCE Cooperative Agreements and Superfund State Contracts for Superfund Response Actions Requirements for Administering A Superfund State Contract (ssc) § 35.6805 Contents of an SSC. The...

  5. 40 CFR 35.6805 - Contents of an SSC.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... STATE AND LOCAL ASSISTANCE Cooperative Agreements and Superfund State Contracts for Superfund Response Actions Requirements for Administering A Superfund State Contract (ssc) § 35.6805 Contents of an SSC. The...

  6. Fructose Malabsorption in Systemic Sclerosis

    PubMed Central

    Marie, Isabelle; Leroi, Anne-Marie; Gourcerol, Guillaume; Levesque, Hervé; Ménard, Jean-François; Ducrotte, Philippe

    2015-01-01

    Abstract The deleterious effect of fructose, which is increasingly incorporated in many beverages, dairy products, and processed foods, has been described; fructose malabsorption has thus been reported in up to 2.4% of healthy subjects, leading to digestive clinical symptoms (eg, pain, distension, diarrhea). Because digestive involvement is frequent in patients with systemic sclerosis (SSc), we hypothesized that fructose malabsorption could be responsible for intestinal manifestations in these patients. The aims of this prospective study were to: determine the prevalence of fructose malabsorption, in SSc; predict which SSc patients are at risk of developing fructose malabsorption; and assess the outcome of digestive symptoms in SSc patients after initiation of standardized low-fructose diet. Eighty consecutive patients with SSc underwent fructose breath test. All SSc patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. The prevalence of fructose malabsorption was as high as 40% in SSc patients. We also observed a marked correlation between the presence of fructose malabsorption and: higher values of GSS score of digestive symptoms (P = 0.000004); and absence of delayed gastric emptying (P = 0.007). Furthermore, in SSc patients with fructose malabsorption, the median value of GSS score of digestive symptoms was lower after initiation of standardized low-fructose diet (4 before vs. 1 after; P = 0.0009). Our study underscores that fructose malabsorption often occurs in SSc patients. Our findings are thus relevant for clinical practice, highlighting that fructose breath test is a helpful, noninvasive method by: demonstrating fructose intolerance in patients with SSc; and identifying the group of SSc patients with fructose intolerance who may benefit from low-fructose diet. Interestingly, because the present series also shows that low-fructose diet resulted in a marked decrease of gastrointestinal clinical manifestations in SSc patients with fructose malabsorption, our findings underscore that fructose malabsorption may play a significant role in the onset of gastrointestinal symptoms in these patients. Finally, we suggest that fructose malabsorption may be due to reduced fructose absorption by enterocytes, impaired enteric microbiome, and decreased intestinal permeability. PMID:26426642

  7. Structural brain differences in school-age children with and without single-suture craniosynostosis.

    PubMed

    Aldridge, Kristina; Collett, Brent R; Wallace, Erin R; Birgfeld, Craig; Austin, Jordan R; Yeh, Regina; Feil, Madison; Kapp-Simon, Kathleen A; Aylward, Elizabeth H; Cunningham, Michael L; Speltz, Matthew L

    2017-04-01

    OBJECTIVE Single-suture craniosynostosis (SSC), the premature fusion of a cranial suture, is characterized by dysmorphology of the craniofacial skeleton. Evidence to suggest that children with SSC are at an elevated risk of mild to moderate developmental delays and neurocognitive deficits is mounting, but the associations among premature suture fusion, neuroanatomy, and neurocognition are unexplained. The goals of this study were to determine 1) whether differences in the brain are present in young children with the 2 most common forms of SSC (sagittal and metopic) several years following surgical correction, and 2) whether the pattern of differences varies by affected suture (sagittal or metopic). Examination of differences in the brains of children with SSC several years after surgery may illuminate the growth trajectory of the brain after the potential constraint of the dysmorphic cranium has been relieved. METHODS The authors compared quantitative measures of the brain acquired from MR images obtained from children with sagittal or metopic craniosynostosis (n = 36) at 7 years of age to those obtained from a group of unaffected controls (n = 27) at the same age. The authors measured the volumes of the whole brain, cerebral cortex, cerebral white matter, cerebral cortex by lobe, and ventricles. Additionally, they measured the midsagittal area of the corpus callosum and its segments and of the cerebellar vermis and its component lobules. Measurements obtained from children with SSC and controls were compared using linear regression models. RESULTS No volume measures of the cerebrum or of the whole brain differed significantly between patients with SSC and controls (p > 0.05). However, ventricle volume was significantly increased in patients with SSC (p = 0.001), particularly in those with sagittal craniosynostosis (p < 0.001). In contrast, the area of the corpus callosum was significantly reduced in patients with metopic synostosis (p = 0.04), particularly in the posterior segments (p = 0.004). Similarly, the area of lobules VI-VII of the cerebellar vermis was reduced in patients with SSC (p = 0.03), with those with metopic craniosynostosis showing the greatest reduction (p = 0.01). CONCLUSIONS The lack of differences in overall brain size or regional differences in the size of the lobes of the cerebrum in children with metopic and sagittal synostosis suggests that the elevated risk of neurodevelopmental deficits is not likely to be associated with differences in the cerebral cortex. Instead, this study showed localized differences between sagittal and metopic craniosynostosis cases as compared with controls in the ventricles and in the midsagittal structures of the corpus callosum and the cerebellum. It remains to be tested whether these structural differences are associated with the increased risk for developmental delay and neurocognitive deficits in children with SSC.

  8. Whole-exome Sequencing Identifies Rare Variants in ATP8B4 as a Risk Factor for Systemic Sclerosis

    PubMed Central

    Gao, Li; Emond, Mary J; Louie, Tin; Cheadle, Chris; Berger, Alan E.; Rafaels, Nicholas; Vergara, Candelaria; Kim, Yoonhee; Taub, Margaret A.; Ruczinski, Ingo; Mathai, Stephen C.; Rich, Stephen S; Nickerson, Deborah A; Hummers, Laura K.; Bamshad, Michael J; Hassoun, Paul M.; Mathias, Rasika A; Barnes, Kathleen C.

    2015-01-01

    Objective To determine the contribution of rare variants as genetic modifiers of the expressivity, penetrance, and severity of systemic sclerosis (SSc). Methods We performed whole-exome sequencing of 78 European American systemic sclerosis patients, including 35 patients without pulmonary arterial hypertension (SSc-PAH−) and 43 patients with PAH (SSc-PAH+). Association testing of case-control probability for rare variants was performed using the aSKAT-O method with small sample adjustment by comparing all SSc patients with a reference population of 3,179 controls from the ESP 5,500 exome dataset. Replication genotyping was performed in an independent sample of 3,263 patients (415 SSc and 2,848 controls). We conducted expression profiling of mRNA from 61 SSc patients (19 SSc-PAH− and 42 SSc-PAH+) and 41 corresponding controls. Results The ATP8B4 gene was associated with a significant increase in the risk of SSc (P = 3.18 × 10−7). Among the 64 ATP8B4 variants tested, a single missense variant, c.1308C>G (F436L, rs55687265), provided the most compelling evidence for association (P = 9.35 × 10−10; OR = 6.11), which was confirmed in the replication cohort (P = 0.012; OR = 1.86) and meta-analysis (P = 1.92 x 10−7; OR = 2.5). Genes involved in E3 ubiquitin-protein ligase complex (ASB10) and cyclic nucleotide gated channelopathies (CNGB3) as well as HLA-DRB5 and HSPB2 (aka heat shock protein 27) provided additional evidence for association (P < 10−5). Differential ATP8B4 expression was observed among the SSc patients compared to the controls (P = 0.0005). Conclusion ATP8B4 may represent a putative genetic risk factor for SSc and pulmonary vascular complications. PMID:26473621

  9. Identification and characterization of microRNA in the lung tissue of pigs with different susceptibilities to PCV2 infection.

    PubMed

    Zhang, Ping; Wang, Liyuan; Li, Yanping; Jiang, Ping; Wang, Yanchao; Wang, Pengfei; Kang, Li; Wang, Yuding; Sun, Yi; Jiang, Yunliang

    2018-02-15

    Porcine circovirus type 2 (PCV2) is the primary cause of post-weaning multisystemic wasting syndrome (PMWS) and other PCV-associated diseases. According to our previous RNA-sequencing analysis, the differences in the susceptibility to PCV2 infection depended on the genetic differences between the Laiwu (LW) and Yorkshire × Landrace crossbred (YL) pigs, but the cellular microRNA (miRNA) that are differentially expressed between the LW and YL pigs before and after PCV2 infection remain to be determined. In this study, high-throughput sequencing was performed to determine the abundance and differential expression of miRNA in lung tissues from PCV2-infected and PCV2-uninfected LW and YL pigs. In total, 295 known and 95 novel miRNA were identified, and 23 known and 25 novel miRNA were significantly differentially expressed in the PCV2-infected vs. PCV2-uninfected LW pigs and/or the PCV2-infected vs. PCV2-uninfected YL pigs. The expression levels of ssc-miR-122, ssc-miR-192, ssc-miR-451, ssc-miR-486, and ssc-miR-504 were confirmed by quantitative real-time PCR (qRT-PCR). Analysis of the potential targets of the four up-regulated miRNA (i.e., ssc-miR-122, ssc-miR-192, ssc-miR-451 and ssc-miR-486) identified pathways and genes that may be important for disease resistance. Among the up-regulated miRNA, ssc-miR-122 can repress the protein expression and viral DNA replication of PCV2 and down-regulate the expression of the nuclear factor of activated T-cells 5 (NFAT5) and aminopeptidase puromycin sensitive (NPEPPS) by binding to their 3' untranslated region (3'UTR) in PK15 cells. Therefore, ssc-miR-122 may indirectly suppress PCV2 infection by targeting genes related to the host immune system, such as NFAT5 and NPEPPS.

  10. Informatics can identify systemic sclerosis (SSc) patients at risk for scleroderma renal crisis.

    PubMed

    Redd, Doug; Frech, Tracy M; Murtaugh, Maureen A; Rhiannon, Julia; Zeng, Qing T

    2014-10-01

    Electronic medical records (EMR) provide an ideal opportunity for the detection, diagnosis, and management of systemic sclerosis (SSc) patients within the Veterans Health Administration (VHA). The objective of this project was to use informatics to identify potential SSc patients in the VHA that were on prednisone, in order to inform an outreach project to prevent scleroderma renal crisis (SRC). The electronic medical data for this study came from Veterans Informatics and Computing Infrastructure (VINCI). For natural language processing (NLP) analysis, a set of retrieval criteria was developed for documents expected to have a high correlation to SSc. The two annotators reviewed the ratings to assemble a single adjudicated set of ratings, from which a support vector machine (SVM) based document classifier was trained. Any patient having at least one document positively classified for SSc was considered positive for SSc and the use of prednisone≥10mg in the clinical document was reviewed to determine whether it was an active medication on the prescription list. In the VHA, there were 4272 patients that have a diagnosis of SSc determined by the presence of an ICD-9 code. From these patients, 1118 patients (21%) had the use of prednisone≥10mg. Of these patients, 26 had a concurrent diagnosis of hypertension, thus these patients should not be on prednisone. By the use of natural language processing (NLP) an additional 16,522 patients were identified as possible SSc, highlighting that cases of SSc in the VHA may exist that are unidentified by ICD-9. A 10-fold cross validation of the classifier resulted in a precision (positive predictive value) of 0.814, recall (sensitivity) of 0.973, and f-measure of 0.873. Our study demonstrated that current clinical practice in the VHA includes the potentially dangerous use of prednisone for veterans with SSc. This present study also suggests there may be many undetected cases of SSc and NLP can successfully identify these patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Low heme oxygenase-1 levels in patients with systemic sclerosis are associated with an altered Toll-like receptor response: another role for CXCL4?

    PubMed

    van Bon, Lenny; Cossu, Marta; Scharstuhl, Alwin; Pennings, Bas W C; Vonk, Madelon C; Vreman, Hendrik J; Lafyatis, Robert L; van den Berg, Wim; Wagener, Frank A D T G; Radstake, Timothy R D J

    2016-11-01

    SSc is a disease characterized by inflammation and fibrosis. Heme Oxygenase-1 (HO-1) is a haem-degrading enzyme that mediates resolution of inflammation and is induced upon mediators abundantly present in SSc. We aimed to assess whether HO-1 expression/function is disturbed in SSc patients and could therefore be contributing to the ongoing inflammation. In total, 92 SSc patients and 48 healthy controls were included. By measuring total bilirubin in plasma in vivo, HO-activity was assessed. HO-1 expression levels were determined with western blot in monocytes before and after induction of HO-1 with cobalt protoporphyrin (CoPP) with or without CXCL4. Monocyte-derived dendritic cells (DCs) were stimulated with several Toll-like receptor (TLR) ligands with or without pre-stimulation with CoPP for 24 h. Cytokine levels were measured in the supernatants using the Luminex Bead Array. SSc patients have lower plasma levels of bilirubin, suggestive of an aberrant HO-1 function. We demonstrated low HO-1 expression in immune cells from SSc patients, whereas induction with CoPP was able to restore HO-1 levels in DCs from SSc patients, almost normalizing the increased TLR response observed in SSc. Co-exposure to CXCL4 completely abrogated CoPP-induced HO-1 expression, suggesting that the high CXCL4 levels present in SSc patients block the normal induction of HO-1 and its function. We demonstrate that HO activity in SSc patients is decreased and show its functional consequences. Since CXCL4 blocks the induction of HO-1 expression, neutralization of CXCL4 in SSc patients could have clinical benefits by diminishing overactivation of immune cells and other anti-inflammatory effects of HO-1. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Sus scrofa miR-204 and miR-4331 Negatively Regulate Swine H1N1/2009 Influenza A Virus Replication by Targeting Viral HA and NS, Respectively.

    PubMed

    Zhang, Shishuo; Wang, Ruifang; Su, Huijuan; Wang, Biaoxiong; Sizhu, Suolang; Lei, Zhixin; Jin, Meilin; Chen, Huanchun; Cao, Jiyue; Zhou, Hongbo

    2017-04-03

    The prevalence of swine pandemic H1N1/2009 influenza A virus (SIV-H1N1/2009) in pigs has the potential to generate novel reassortant viruses, posing a great threat to human health. Cellular microRNAs (miRNAs) have been proven as promising small molecules for regulating influenza A virus replication by directly targeting viral genomic RNA. In this study, we predicted potential Sus scrofa (ssc-, swine) miRNAs targeting the genomic RNA of SIV-H1N1/2009 by RegRNA 2.0, and identified ssc-miR-204 and ssc-miR-4331 to target viral HA and NS respectively through dual-luciferase reporter assays. The messenger RNA (mRNA) levels of viral HA and NS were significantly suppressed when newborn pig trachea (NPTr) cells respectively overexpressed ssc-miR-204 and ssc-miR-4331 and were infected with SIV-H1N1/2009, whereas the suppression effect could be restored when respectively decreasing endogenous ssc-miR-204 and ssc-miR-4331 with inhibitors. Because of the importance of viral HA and NS in the life cycle of influenza A virus, ssc-miR-204 and ssc-miR-4331 exhibited an inhibition effect on SIV-H1N1/2009 replication. The antiviral effect was sequence-specific of SIV-H1N1/2009, for the target sites in HA and NS of H5N1 or H9N2 influenza A virus were not conserved. Furthermore, SIV-H1N1/2009 infection reversely downregulated the expression of ssc-miR-204 and ssc-miR-4331, which might facilitate the virus replication in the host. In summary, this work will provide us some important clues for controlling the prevalence of SIV-H1N1/2009 in pig populations.

  13. The self-consistency model of subjective confidence.

    PubMed

    Koriat, Asher

    2012-01-01

    How do people monitor the correctness of their answers? A self-consistency model is proposed for the process underlying confidence judgments and their accuracy. In answering a 2-alternative question, participants are assumed to retrieve a sample of representations of the question and base their confidence on the consistency with which the chosen answer is supported across representations. Confidence is modeled by analogy to the calculation of statistical level of confidence (SLC) in testing hypotheses about a population and represents the participant's assessment of the likelihood that a new sample will yield the same choice. Assuming that participants draw representations from a commonly shared item-specific population of representations, predictions were derived regarding the function relating confidence to inter-participant consensus and intra-participant consistency for the more preferred (majority) and the less preferred (minority) choices. The predicted pattern was confirmed for several different tasks. The confidence-accuracy relationship was shown to be a by-product of the consistency-correctness relationship: It is positive because the answers that are consistently chosen are generally correct, but negative when the wrong answers tend to be favored. The overconfidence bias stems from the reliability-validity discrepancy: Confidence monitors reliability (or self-consistency), but its accuracy is evaluated in calibration studies against correctness. Simulation and empirical results suggest that response speed is a frugal cue for self-consistency, and its validity depends on the validity of self-consistency in predicting performance. Another mnemonic cue-accessibility, which is the overall amount of information that comes to mind-makes an added, independent contribution. Self-consistency and accessibility may correspond to the 2 parameters that affect SLC: sample variance and sample size.

  14. Salivary Cortisol as a Biomarker of Stress in Mothers and their Low Birth Weight Infants and Sample Collecting Challenges

    PubMed Central

    Vujičić, Ana Đorđević; Đukić, Svjetlana Maglajić

    2016-01-01

    Summary Background Salivary cortisol measurement is a non-invasive method suitable for use in neonatal research. Mother-infant separation after birth represents stress and skin-to-skin contact (SSC) has numerous benefits. The aim of the study was to measure salivary cortisol in mothers and newborns before and after SSC in order to assess the effect of SSC on mothers’ and infants’ stress and to estimate the efficacy of collecting small saliva samples in newborns. Methods Salivary cortisol was measured in 35 mother-infant pairs before and after the first and the fifth SSC in small saliva samples (50 μL) using the high sensitivity Quantitative ELISA-Kit (0.0828 nmol/L) for low cortisol levels detection. Samples were collected with eye sponge during 3 to 5 minutes. Results Cortisol level in mothers decreased after SSC: the highest levels were measured before and the lowest after SSC and the differences in values were significant during both the first (p<0.001) and the fifth SSC (p<0.001). During the first SSC the cortisol level decrease was detected in 14 (40%) and an increase in 21 (60%) newborns, and during the fifth SSC a decrease was detected in 16 (45.7%) and an increase in 19 (54.3%) newborns, without confirmed significance of the difference. Saliva sampling efficacy using eye sponge was 75%. Conclusions Cortisol level decrease in mothers proves the stress reduction during SSC, while variable cortisol levels in infants do not indicate stress reduction and imply the need for further research. The used sampling method appeared to be one of the most optimal considering the sample volume, sampling time and efficacy. PMID:28356870

  15. Procollagen Type I and III Aminoterminal Propeptide Levels and Severity of Interstitial Lung Disease in Mexican Women With Progressive Systemic Sclerosis.

    PubMed

    Gonzalez-Lopez, Laura; Rocha-Muñoz, Alberto D; Olivas-Flores, Eva M; Garcia-Gonzalez, Araceli; Peguero-Gómez, Ana R; Flores-Navarro, Juan; Villa-Manzano, Alberto I; Zavaleta-Muñiz, Soraya A; Salazar-Paramo, Mario; Mejía, Mayra; Juárez-Contreras, Pablo; Vazquez-Del Mercado, Monica; Cardona-Muñoz, Ernesto G; Trujillo-Hernández, Benjamin; Nava-Zavala, Arnulfo H; Gamez-Nava, Jorge I

    2015-09-01

    Interstitial lung disease (ILD) is a frequent complication in progressive systemic sclerosis (SSc), being present in 25% to 90% of cases. To evaluate whether serum levels of procollagen typei and iii aminoterminal propeptide (PINP and PIIINP) correlate with severity and patterns of ILD in Mexican women with SSc. Thirty three SSc patients were assessed for disease characteristics and anti-topoisomerase antibodies (topoi), and also underwent pulmonary function tests and high-resolution computed tomography (HRCT). Nineteen patients had ILD+SSc, and 14 had no lung involvement (no ILD-SSc); data were compared with those from 45 healthy controls. PINP and PIIINP were assessed in all 3 groups. Patients with SSc had higher PINP and PIIINP vs controls (P=.001, P<.001, respectively). Compared to no ILD-SSc patients, those with ILD+SSc had longer disease duration in years (P=.005), higher modified Rodnan skin score (P<.001), higher Health Assessment Questionnaire-Disability-Index scores (P<.001), higher topoi U/mL (P<.001), PINP (49.28±28.63 vs. 32.12±18.58μg/L, P=.05), and PIIINP (4.33±1.03 vs. 2.67±1.26μg/L, P<.001) levels. ILD severity based on total HRCT correlated with PINP (r=.388, P=.03) and PIIINP (P=.594, P<.001). On adjusted analysis, ILD severity was associated with disease duration (P=.037), PIIINP (P=.038), and topoi (P=.045). PINP and PIIINP are useful markers for severe ILD+SSc, suggesting they could play a role in the follow-up of this complication in SSc. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  16. Distinct mortality profile in systemic sclerosis: a death certificate study in Rio de Janeiro, Brazil (2006-2015) using a multiple causes of death analysis.

    PubMed

    de Rezende, Rodrigo Poubel Vieira; Gismondi, Ronaldo Altenburg; Maleh, Haim Cesar; de Miranda Coelho, Elisa Mendes; Vieira, Carol Sartori; Rosa, Maria Luiza Garcia; Mocarzel, Luis Otavio

    2017-12-16

    The objective of this study was to assess the mortality profile related to SSc in the state of Rio de Janeiro, Brazil. We retrospectively examined all registered deaths in the region (2006-2015 period) in which the diagnosis of SSc was mentioned on any line of the death certificates (underlying cause of death [UCD], n = 223; non-UCD, n = 151). Besides the analysis of gender, age, and the causes of death, we also compared the mortality from UCDs between individuals whose death causes included SSc (cases) and those whose death causes did not include SSc (deceased controls). For the latter comparison, we used the mortality odds ratio to approximate the cause-specific standardized mortality ratio. We identified 1495 death causes among the 374 SSc cases. The mean age at death of the SSc cases (85% women) was significantly lower than that of the controls (n = 1,294,117) (58.7 vs. 65.5 years, respectively). The main death causes were circulatory system diseases, infections, and respiratory diseases (36%, 34%, and 21% of SSc cases, respectively). Compared to the deceased controls, there were proportionally more deaths among the SSc cases from pulmonary arterial hypertension, lung fibrosis, septicemia, gastrointestinal hemorrhage, other systemic connective tissue diseases, and heart failure (for death age < 50 years). We confirmed the high burden of cardiovascular, respiratory, and infectious causes in this predominantly non-Caucasian sample of SSc patients. Of interest, the percentage of infection-related deaths in our report was about three times higher than that in SSc studies with predominantly Caucasian populations.

  17. Autoantibody against matrix metalloproteinase-3 in patients with systemic sclerosis.

    PubMed

    Nishijima, C; Hayakawa, I; Matsushita, T; Komura, K; Hasegawa, M; Takehara, K; Sato, S

    2004-11-01

    Systemic sclerosis (SSc) is characterized by multi-organ fibrosis with an autoimmune background. Although autoantibodies are detected frequently in SSc patients, the role of autoantibody in the development of fibrosis remains unknown. Connective tissue homeostasis is a balance between the synthesis and degradation of the extracellular matrix (ECM); ECM degradation is regulated mainly by matrix metalloproteinases (MMPs). Anti-MMP-1 antibody is suggested to inhibit MMP-1 and be involved in the development of the fibrosis in SSc. However, the accumulation of various ECM components in the tissue of SSc cannot be explained by the anti-MMP-1 antibody alone. In this study, we examined the presence or levels of antibody to MMP-3, a protein which degrades various ECM components relevant to SSc fibrosis. Enzyme-linked immunosorbent assay (ELISA) using human recombinant MMP-3 revealed that IgG anti-MMP-3 autoantibody levels were elevated significantly in the sera from SSc patients, but not in patients with active systemic lupus erythematosus or dermatomyositis. IgG and IgM anti-MMP-3 antibody levels were significantly higher in diffuse cutaneous SSc, a severe form, than those in limited cutaneous SSc. Consistently, IgG anti-MMP-3 antibody levels correlated significantly with fibrosis of the skin, lung and renal blood vessels. The presence of IgG anti-MMP-3 autoantibody in sera from SSc patients was confirmed by immunoblotting analysis. Remarkably, MMP-3 activity was inhibited by IgG anti-MMP-3 antibody. These results suggest that anti-MMP-3 antibody is a serological marker that reflects the severity of SSc and also suggest that it may contribute to the development of fibrosis by inhibiting MMP-3 activity and reducing the ECM turnover.

  18. 2013 American College of Rheumatology/European League against rheumatism classification criteria for systemic sclerosis outperform the 1980 criteria: data from the Canadian Scleroderma Research Group.

    PubMed

    Alhajeri, Hebah; Hudson, Marie; Fritzler, Marvin; Pope, Janet; Tatibouet, Solène; Markland, Janet; Robinson, David; Jones, Niall; Khalidi, Nader; Docherty, Peter; Kaminska, Elzbieta; Masetto, Ariel; Sutton, Evelyn; Mathieu, Jean-Pierre; Ligier, Sophie; Grodzicky, Tamara; LeClercq, Sharon; Thorne, Carter; Gyger, Geneviève; Smith, Douglas; Fortin, Paul R; Larché, Maggie; Baron, Murray

    2015-04-01

    The goal of this study was to determine the sensitivity of the new 2013 classification criteria for systemic sclerosis (SSc; scleroderma) in an independent cohort of SSc subjects and to assess the contribution of individual items of the criteria to the overall sensitivity. SSc subjects from the Canadian Scleroderma Research Group cohort were assessed. Sensitivity was determined in several subgroups of patients. In patients without the criterion of skin thickening proximal to the metacarpophalangeal (MCP) joints, we recalculated sensitivity after removing the individual criterion. A total of 724 SSc patients were included. Most were women (86%), mean age was 55.8 years, mean disease duration was 10.9 years, and 59% had limited cutaneous SSc (lcSSc). Overall, the sensitivity of the 2013 criteria was 98.3% compared to 88.3% for the 1980 criteria. This pattern was consistent among those with lcSSc (98.8% versus 85.6%), anticentromere antibodies (98.9% versus 79.8%), disease duration ≤3 years (98.7% versus 84.7%), and no skin involvement proximal to the MCP joints (97% versus 60%). In the latter subgroup, removing Raynaud's phenomenon and sclerodactyly from the criteria reduced the sensitivity to 77% and 79%, respectively. Removing both sclerodactyly and puffy fingers reduced the sensitivity to 62%. The 2013 SSc classification criteria classify more SSc patients than the 1980 criteria. The improvement in sensitivity is most striking in those with lcSSc, especially those without skin involvement proximal to the MCP joints. The addition of Raynaud's phenomenon and puffy fingers to the 2013 criteria accounts for important gains in sensitivity. Copyright © 2015 by the American College of Rheumatology.

  19. Progranulin Overproduction Due to Fli-1 Deficiency Contributes to the Resistance of Dermal Fibroblasts to Tumor Necrosis Factor in Systemic Sclerosis.

    PubMed

    Ichimura, Yohei; Asano, Yoshihide; Akamata, Kaname; Noda, Shinji; Taniguchi, Takashi; Takahashi, Takehiro; Toyama, Tetsuo; Tada, Yayoi; Sugaya, Makoto; Sato, Shinichi; Kadono, Takafumi

    2015-12-01

    Progranulin is a growth factor that is active in wound repair and is an antagonist of tumor necrosis factor (TNF) receptors, regulating fibroblast activation, angiogenesis, and inflammation. Because long-standing activation of gene programs related to wound healing is a hallmark of systemic sclerosis (SSc), we sought to investigate the role of progranulin in SSc. Progranulin expression levels in human and murine skin samples were determined by immunohistochemical analysis and quantitative reverse transcription-polymerase chain reaction. The role of progranulin in fibroblast activation was examined using a gene-silencing technique. Progranulin levels in serum obtained from 60 patients with SSc and 16 healthy control subjects were determined by enzyme-linked immunosorbent assay. Progranulin expression was increased in SSc dermal fibroblasts compared with normal dermal fibroblasts, both in vivo and in vitro. Transcription factor Fli-1, a deficiency of which is involved in the activation of SSc dermal fibroblasts, served as a potent repressor of the progranulin gene, and Fli-1(+/-) mice and bleomycin-treated wild-type mice exhibited up-regulated expression of progranulin in dermal fibroblasts. SSc dermal fibroblasts were resistant to the antifibrotic effect of TNF, but this resistance was reversed by gene silencing of progranulin. Serum progranulin levels were elevated in patients with early diffuse cutaneous SSc (dcSSc), especially in those with inflammatory skin symptoms, and were positively correlated with the C-reactive protein level. Progranulin overproduction due to Fli-1 deficiency may contribute to the constitutive activation of SSc dermal fibroblasts by antagonizing the antifibrotic effect of TNF. Progranulin may also be involved in the inflammatory process associated with progressive skin sclerosis in early dcSSc. © 2015, American College of Rheumatology.

  20. [Nailfold capillaroscopy and blood flow laser-doppler analysis of the microvascular damage in systemic sclerosis: preliminary results].

    PubMed

    Secchi, M E; Sulli, A; Pizzorni, C; Cutolo, M

    2009-01-01

    Systemic sclerosis (SSc) is characterized by altered microvascular structure and function. Nailfold videocapillaroscopy (NVC) is the tool to evaluate capillary morphological structure and laser-Doppler Blood flowmetry (LDF) can be used to estimate cutaneous blood flow of microvessels. The aim of this study was to investigate possible relationships between capillary morphology and blood flow in SSc. Twenty-seven SSc patients and 12 healthy subjects were enrolled. SSc microvascular involvement, as evaluated by NVC, was classified in three different patterns ("Early", "Active", "Late"). LDF analysis was performed at the II, III, IV, V hand fingers in both hands and both at cutaneous temperature and at 36 degrees C. Statistical evaluation was carried out by non-parametric procedures. Blood flow was found significantly lower in SSc patients when compared with healthy subjects (p<0.05). The heating of the probe to 36 degrees C induced a significant increase in peripheral blood flow in all subjects compared to baseline (p <0.05), however, the amount of variation was significantly lower in patients with SSc, compared with healthy controls (p <0.05). The SSc patients with NVC "Late" pattern, showed lower values of peripheral blood flow than patients with NVC "Active" or "Early" patterns (p<0.05). Moreover, a negative correlation between the tissue perfusion score and the progression of the SSc microangiopathy was observed, as well as between the tissue perfusion and the duration of the Raynaud's phenomenon (p <0.03). LDF can be employed to evaluate blood perfusion in the microvascular circulation in SSc patients. The blood flow changes observed with the LDF seem to correlate with the severity of microvascular damage in SSc as detected by NVC.

  1. Differential expression of stromal cell-derived factor 1 and its receptor CXCR4 in the skin and endothelial cells of systemic sclerosis patients: Pathogenetic implications.

    PubMed

    Cipriani, Paola; Franca Milia, Anna; Liakouli, Vasiliki; Pacini, Alessandra; Manetti, Mirko; Marrelli, Alessandra; Toscano, Annarita; Pingiotti, Elisa; Fulminis, Antonietta; Guiducci, Serena; Perricone, Roberto; Kahaleh, Bashar; Matucci-Cerinic, Marco; Ibba-Manneschi, Lidia; Giacomelli, Roberto

    2006-09-01

    Systemic sclerosis (SSc) is characterized by early endothelial damage evolving to vascular desertification. Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 regulate specific steps in new vessel formation. We undertook this study to determine whether an alteration of the SDF-1/CXCR4 axis might be involved in the pathogenetic mechanisms following ischemic damage during SSc. We enrolled 36 SSc patients and 15 controls. Skin biopsy samples were obtained from each subject, and the expression of SDF-1 and CXCR4 was assessed by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analyses. Furthermore, isolated microvascular endothelial cells (MVECs) from 4 patients with diffuse cutaneous SSc (dcSSc) and 3 controls were analyzed for SDF-1 and CXCR4 by confocal laser scanning microscopy, RT-PCR, and Western blotting. SDF-1 and CXCR4 were up-regulated in the skin of patients with early (edematous) SSc, both in the diffuse and limited cutaneous forms, and progressively decreased, with the lowest expression in the latest phases of both SSc subsets. MVECs from patients with dcSSc expressed significantly higher amounts of both isoforms of SDF-1 in the early stage of disease, with a progressive reduction of SDF-1 and CXCR4 in later stages. On the surface of cultured MVECs from patients with dcSSc, SDF-1 and CXCR4 colocalized in polarized areas, suggesting that they are activated in vivo and that they are under strict genetic control to retain capping function. Due to its transient expression, SDF-1 could be considered a future therapeutic target to induce new vessel formation in SSc.

  2. Factors affecting suspended-solids concentrations in South San Francisco Bay, California

    USGS Publications Warehouse

    Schoellhamer, D.H.

    1996-01-01

    Measurements of suspended-solids concentration (SSC) were made at two depths at three sites in South San Francisco Bay (South Bay) to determine the factors that affect SSC. Twenty-eight segments of reliable and continuous SSC time series data longer than 14 days were collected from late 1991 or 1992 through September 1993. Spectral analysis and singular spectrum analysis were used to relate these data segments to time series of several potential forcing factors, including diurnal and semidiurnal tides, the spring-neap tidal cycle, wind shear, freshwater runoff, and longitudinal density differences. SSC is greatest during summer when a landward wind shear is applied to South Bay by the afternoon sea breeze. About one half the variance of SSC is caused by the spring-neap cycle, and SSC lags the spring-neap cycle by about 2 days. Relatively short duration of slack water limits the duration of deposition of suspended solids and consolidation of newly deposited bed sediment during the tidal cycle, so suspended solids accumulate in the water column as a spring tide is approached and slowly deposit as a neap tide is approached. Perturbations in SSC caused by wind and local runoff from winter storms during the study period were usually much smaller than SSC variations caused by the spring-neap cycle. Variations of SSC at the study sites at tidal timescales are tidally forced, and nonlinear physical processes are significant. Advective transport dominates during spring tides when water with higher SSC due to wind wave resuspension is advected to the main channel from shallow water, but during neap tides, advective transport is less significant. The findings of this and other studies indicate that the tidally averaged transport of suspended solids responds to seasonal variations of wind shear in South Bay.

  3. Photohadronic scenario in interpreting the February-March 2014 flare of 1ES 1011+496

    NASA Astrophysics Data System (ADS)

    Sahu, Sarira; de León, Alberto Rosales; Miranda, Luis Salvador

    2017-11-01

    The extraordinary multi-TeV flare from 1ES 1011+496 during February-March 2014 was observed by the MAGIC telescopes for 17 nights and the average spectrum of the whole period has a non-trivial shape. We have used the photohadronic model and a template extragalactic background light model to explain the average spectrum which fits the flare data well. The spectral index α is the only free parameter in our model. We have also shown that the non-trivial nature of the spectrum is due to the change in the behavior of the optical depth above ˜ 600 GeV γ -ray energy accompanied with the high SSC flux. This corresponds to an almost flat intrinsic flux for the multi-TeV γ -rays. Our model prediction can constrain the SSC flux of the leptonic models in the quiescent state.

  4. Sedimentary constraints on the development of a narrow deep strait (São Sebastião Channel, SE Brazil)

    NASA Astrophysics Data System (ADS)

    Alcántara-Carrió, Javier; Sasaki, Dalton Kei; Mahiques, Michel Michaelovitch de; Taborda, Rui; de Souza, Luiz Antonio Pereira

    2017-10-01

    The São Sebastião Channel (SSC), which separates São Sebastião Island from the continent, is a deep elongated strait on the inner shelf of the São Paulo Bight (SE Brazil). The aim of this study is to explain why it is presently sediment starved, instead of forming a tombolo. Wave data were obtained from both a WW3 model database and buoy records, and wave propagation patterns from the SWAN numerical model. Grain size trend analysis of 579 surficial sediment samples from the strait and the surrounding region served to estimate the residual transport directions. Bedload sediment transport was computed considering in situ currents and bottom sediment grain size. Moreover, six seismic profiles and one gravity core were obtained in the strait in order to evaluate the hickness of the sedimentary deposits. The geometry of the SSC (X/B=0.3, where B is the breakwater or island diameter and X is its cross-shore distance to the mainland) predicts that a tombolo should be formed, and wave patterns confirm that it is a zone sheltered from both S and NE waves. Previous studies have shown that the hydrodynamics of the SSC is controlled by wind-driven currents, which are more intense in the eastern and central sectors of the strait. The western sector is currently covered by sandy mud, whereas very coarse to fine sand prevails in the deeper eastern sector. Sediment patterns show a trend to deposition of fine sediment in the western sector of the SSC and two main depocentres located at the northern limit of the study area and at the southern mouth of the strait. Sandy mud in the western sector forms a 40-m-thick deposit close to the outer limit of Araçá Bay, whereas the remainder of the SSC is covered by a very thin layer of sandy sediments. Dominance of mud in the depositional western sector suggests low availability of sand in the area. Therefore, despite the geometry and wave patterns of the SSC favouring the formation of a tombolo, the dominance of wind-driven currents and the low availability of sand determine that such a sedimentary feature cannot be formed, resulting in a deep strait.

  5. Self-Consistent Field Lattice Model for Polymer Networks.

    PubMed

    Tito, Nicholas B; Storm, Cornelis; Ellenbroek, Wouter G

    2017-12-26

    A lattice model based on polymer self-consistent field theory is developed to predict the equilibrium statistics of arbitrary polymer networks. For a given network topology, our approach uses moment propagators on a lattice to self-consistently construct the ensemble of polymer conformations and cross-link spatial probability distributions. Remarkably, the calculation can be performed "in the dark", without any prior knowledge on preferred chain conformations or cross-link positions. Numerical results from the model for a test network exhibit close agreement with molecular dynamics simulations, including when the network is strongly sheared. Our model captures nonaffine deformation, mean-field monomer interactions, cross-link fluctuations, and finite extensibility of chains, yielding predictions that differ markedly from classical rubber elasticity theory for polymer networks. By examining polymer networks with different degrees of interconnectivity, we gain insight into cross-link entropy, an important quantity in the macroscopic behavior of gels and self-healing materials as they are deformed.

  6. Effect of EMIC Wave Normal Angle Distribution on Relativistic Electron Scattering Based on the Newly Developed Self-consistent RC/EMIC Waves Model by Khazanov et al. [2006

    NASA Technical Reports Server (NTRS)

    Khazanov, G. V.; Gallagher, D. L.; Gamayunov, K.

    2007-01-01

    It is well known that the effects of EMIC waves on RC ion and RB electron dynamics strongly depend on such particle/wave characteristics as the phase-space distribution function, frequency, wave-normal angle, wave energy, and the form of wave spectral energy density. Therefore, realistic characteristics of EMIC waves should be properly determined by modeling the RC-EMIC waves evolution self-consistently. Such a selfconsistent model progressively has been developing by Khaznnov et al. [2002-2006]. It solves a system of two coupled kinetic equations: one equation describes the RC ion dynamics and another equation describes the energy density evolution of EMIC waves. Using this model, we present the effectiveness of relativistic electron scattering and compare our results with previous work in this area of research.

  7. THE ENVIRONMENT AND DISTRIBUTION OF EMITTING ELECTRONS AS A FUNCTION OF SOURCE ACTIVITY IN MARKARIAN 421

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

    Mankuzhiyil, Nijil; Ansoldi, Stefano; Persic, Massimo

    2011-05-20

    For the high-frequency-peaked BL Lac object Mrk 421, we study the variation of the spectral energy distribution (SED) as a function of source activity, from quiescent to active. We use a fully automatized {chi}{sup 2}-minimization procedure, instead of the 'eyeball' procedure more commonly used in the literature, to model nine SED data sets with a one-zone synchrotron self-Compton (SSC) model and examine how the model parameters vary with source activity. The latter issue can finally be addressed now, because simultaneous broadband SEDs (spanning from optical to very high energy photon) have finally become available. Our results suggest that in Mrkmore » 421 the magnetic field (B) decreases with source activity, whereas the electron spectrum's break energy ({gamma}{sub br}) and the Doppler factor ({delta}) increase-the other SSC parameters turn out to be uncorrelated with source activity. In the SSC framework, these results are interpreted in a picture where the synchrotron power and peak frequency remain constant with varying source activity, through a combination of decreasing magnetic field and increasing number density of {gamma} {<=} {gamma}{sub br} electrons: since this leads to an increased electron-photon scattering efficiency, the resulting Compton power increases, and so does the total (= synchrotron plus Compton) emission.« less

  8. Cardiac mechanics and heart rate variability in patients with systemic sclerosis: the association that we should not miss.

    PubMed

    Zlatanovic, Maja; Tadic, Marijana; Celic, Vera; Ivanovic, Branislava; Stevanovic, Ana; Damjanov, Nemanja

    2017-01-01

    We aimed to determine left ventricular (LV) and right ventricular (RV) structure, function and mechanics, as well as heart rate variability (HRV), and their relationship, in patients with systemic sclerosis (SSc). The study included 41 SSc patients and 30 age-matched healthy volunteers. All the patients underwent clinical examination, serological tests, pulmonary function testing, 24-h Holter monitoring and complete two-dimensional echocardiography including strain analysis. The parameters of LV structure (interventricular septum thickness and LV mass index) and RV structure (RV wall thickness) were significantly higher in SSc patients. LV and RV diastolic function (estimated by mitral and tricuspid E/e' ratio) was significantly impaired in SSc group comparing with the healthy controls. LV and RV longitudinal function was significantly deteriorated in SSc patients. LV circumferential strain was also significantly lower in SSc group, whereas LV radial strain was similar between the observed groups. All parameters of time and frequency domain of HRV were decreased in SSc patients. LV and RV cardiac remodeling parameters, particularly diastolic function and longitudinal strain, were associated with HRV indices without regard to the main demographic or the clinical and echocardiographic characteristics. Rodnan Skin Score was also independently associated with biventricular cardiac remodeling in SSc patients. LV and RV structure, function and mechanics, as well as autonomic nervous function, were significantly impaired in SSc patients. There is the significant association between biventricular cardiac remodeling and autonomic function in these patients, which could be useful for their everyday clinical assessment.

  9. Correlation between bone quality and microvascular damage in systemic sclerosis patients.

    PubMed

    Ruaro, Barbara; Casabella, Andrea; Paolino, Sabrina; Pizzorni, Carmen; Alessandri, Elisa; Seriolo, Chiara; Botticella, Giulia; Molfetta, Luigi; Odetti, Patrizio; Smith, Vanessa; Cutolo, Maurizio

    2018-05-18

    SSc patients are recognized as presenting an increased risk of altered bone mass. The aim of this study was to assess the bone quality, by trabecular bone score (TBS), in SSc patients in correlation with different levels of microvascular damage, as evaluated by nailfold videocapillaroscopy (NVC), and to compare the results regarding bone quality with RA patients and healthy subjects (CNT). Eighty-four SSc patients, 98 RA patients and 60 CNT, were studied. BMD (g/cm2) of the lumbar spine (L1-L4) was analysed by DXA scan. Lumbar spine bone quality was derived from each spine DXA examination using the TBS analysis. NVC patterns were analysed. A total of 56/84 SSc patients (66%) as well as 78/98 RA patients (80%) showed bone loss at DXA and BMD was found to be significantly lower than in the CNT (P < 0.001). Similarly, lumbar spine TBS was found to be significantly lower in SSc and RA patients than in CNT (P < 0.001). TBS values were found to be lower in SSc with a late NVC pattern, compared with the active or early pattern (late vs active and early pattern, P < 0.001). There was no statistically significant difference in the mean lumbar spine TBS between SSc and RA patients (P = 0.238). The data obtained showed significantly lower bone quality (lower TBS and BMD) in SSc and RA patients compared with CNT. The bone quality seemed lower in SSc patients with more altered microvasculature (late NVC pattern).

  10. Pharmacotherapy of Systemic Sclerosis

    PubMed Central

    Postlethwaite, Arnold E.; Harris, L. Jeff; Raza, Syed H.; Kodura, Swapna; Akhigbe, Titilola

    2010-01-01

    Importance of the field Systemic-sclerosis (SSc) is an uncommon autoimmune disease with variable degrees of fibroproliferation in blood vessels and certain organs of the body. Presently, there is no cure for SSc. The purpose of this article is to review the current literature regarding pathogenesis and treatment of complications of SSc. Areas covered in this review All available articles regarding research related to SSc pathogenesis and treatment listed in the PubMed.gov database were searched, relevant articles were then reviewed and used as sources of information for this review. What the reader will gain This review attempts for the reader to highlight some current thought regarding mechanisms of SSc pathogenesis and how autoimmunity relates to vascular changes and fibrogenesis of the disease plus provide a review of results of completed clinical trials and current on-going clinical trials that address organ specific or global therapies for this disease which can aid physicians who provide medical care for patients with SSc. Take home message SSc is a complex autoimmune disease, the pathogenesis of which although not completely understood is under active study, and new insights into pathogenesis are continuously being discovered. Although there is no effective disease modifying treatment for patients with SSc, quality of life, morbidity and mortality can be improved by using targeted therapy directed at affecting the consequences of damage to lungs, blood vessels, kidneys and the gastrointestinal tract. Innovative approaches to treating SSc are under intense investigation. PMID:20210685

  11. Attitudes and beliefs about the surgical safety checklist: Just another tick box?

    PubMed

    Dharampal, Navjit; Cameron, Christopher; Dixon, Elijah; Ghali, William; Quan, May Lynn

    2016-08-01

    Following a landmark study showing decreased morbidity and mortality after implementation of the surgical safety checklist (SSC), it has been widely adopted into perioperative policy. We explored the impact of attitudes and beliefs surrounding the SSC on its uptake in Calgary. We used qualitative methodology to examine factors influencing SSC use. We performed semistructured interviews based on Rogers' theory of diffusion of innovation. Purposive and snowball sampling were used to identify surgeons, anesthesiologists and operating room nurses from hospitals in Calgary. Data collection and analysis were based on grounded theory. Two individuals jointly analyzed data and achieved consensus on emerging themes. Generated themes included 1) the SSC has brought organization to previous informal perioperative checks, 2) the SSC is most helpful when it is simple, and 3) the 3 current components of the checklist are redundant. The briefing was considered the most important aspect and the debriefing the least important. Initially the SSC was difficult to implement owing to a shift in time management and perioperative culture; however, it has now assimilated into perioperative routine. Finally, though most participants agreed that the SSC might avoid some delays and complications, only a few believe there have been observable improvements to morbidity and mortality. Although the SSC has been integrated into perioperative practice in Calgary, participants believe that previous informal checkpoints were able to circumvent most perioperative issues. Although the SSC may help with flow and equipment, participants believe it fails to show a subjective, clinically important improvement.

  12. A case study of infant physiologic response to skin-to-skin contact following surgery for complex congenital heart disease

    PubMed Central

    Harrison, Tondi M.; Ludington-Hoe, Susan

    2014-01-01

    Background Infants with complex congenital heart disease requiring surgical intervention within the first days or weeks of life may be the most seriously ill infants needing intensive nursing and medical care immediately after birth. Skin to skin contact (SSC) is well-accepted and practiced as a positive therapeutic intervention in premature infants, but is not routinely offered to infants in cardiac intensive care units. Physiologic effects of SSC in the congenital heart disease population must be examined before recommending incorporation of SSC into standard care routines. Objective The purpose of this case study was to describe the physiologic response to a single session of SSC in an 18-day-old infant with hypoplastic left heart syndrome. Methods Repeated measures of heart rate, respiratory rate, oxygen saturation, blood pressure, and temperature were recorded 30 minutes prior to SSC, during SSC (including interruptions for bottle and breast feedings), and 10 minutes after SSC was completed. Results All physiologic parameters were clinically acceptable throughout the 135-minute observation. Conclusion This case study provides beginning evidence that SSC is safe in full-term infants following surgery for complex congenital heart disease. Further research with a larger sample is needed to examine effects of SSC on infant physiology before surgery and earlier in the postoperative time period as well as on additional outcomes such as length of stay, maternal-infant interaction, and neurodevelopment. PMID:25325374

  13. Self-consistent assessment of Englert-Schwinger model on atomic properties

    NASA Astrophysics Data System (ADS)

    Lehtomäki, Jouko; Lopez-Acevedo, Olga

    2017-12-01

    Our manuscript investigates a self-consistent solution of the statistical atom model proposed by Berthold-Georg Englert and Julian Schwinger (the ES model) and benchmarks it against atomic Kohn-Sham and two orbital-free models of the Thomas-Fermi-Dirac (TFD)-λvW family. Results show that the ES model generally offers the same accuracy as the well-known TFD-1/5 vW model; however, the ES model corrects the failure in the Pauli potential near-nucleus region. We also point to the inability of describing low-Z atoms as the foremost concern in improving the present model.

  14. Self-consistent assessment of Englert-Schwinger model on atomic properties.

    PubMed

    Lehtomäki, Jouko; Lopez-Acevedo, Olga

    2017-12-21

    Our manuscript investigates a self-consistent solution of the statistical atom model proposed by Berthold-Georg Englert and Julian Schwinger (the ES model) and benchmarks it against atomic Kohn-Sham and two orbital-free models of the Thomas-Fermi-Dirac (TFD)-λvW family. Results show that the ES model generally offers the same accuracy as the well-known TFD-15vW model; however, the ES model corrects the failure in the Pauli potential near-nucleus region. We also point to the inability of describing low-Z atoms as the foremost concern in improving the present model.

  15. Speech Situation Checklist-Revised: Investigation With Adults Who Do Not Stutter and Treatment-Seeking Adults Who Stutter.

    PubMed

    Vanryckeghem, Martine; Matthews, Michael; Xu, Peixin

    2017-11-08

    The aim of this study was to evaluate the usefulness of the Speech Situation Checklist for adults who stutter (SSC) in differentiating people who stutter (PWS) from speakers with no stutter based on self-reports of anxiety and speech disruption in communicative settings. The SSC's psychometric properties were examined, norms were established, and suggestions for treatment were formulated. The SSC was administered to 88 PWS seeking treatment and 209 speakers with no stutter between the ages of 18 and 62. The SSC consists of 2 sections investigating negative emotional reaction and speech disruption in 38 speech situations that are identical in both sections. The SSC-Emotional Reaction and SSC-Speech Disruption data show that these self-report tests differentiate PWS from speakers with no stutter to a statistically significant extent and have great discriminative value. The tests have good internal reliability, content, and construct validity. Age and gender do not affect the scores of the PWS. The SSC-Emotional Reaction and SSC-Speech Disruption seem to be powerful measures to investigate negative emotion and speech breakdown in an array of speech situations. The item scores give direction to treatment by suggesting speech situations that need a clinician's attention in terms of generalization and carry-over of within-clinic therapeutic gains into in vivo settings.

  16. Quantitative nanohistological investigation of scleroderma: an atomic force microscopy-based approach to disease characterization

    PubMed Central

    Strange, Adam P; Aguayo, Sebastian; Ahmed, Tarek; Mordan, Nicola; Stratton, Richard; Porter, Stephen R; Parekh, Susan; Bozec, Laurent

    2017-01-01

    Scleroderma (or systemic sclerosis, SSc) is a disease caused by excess crosslinking of collagen. The skin stiffens and becomes painful, while internally, organ function can be compromised by the less elastic collagen. Diagnosis of SSc is often only possible in advanced cases by which treatment time is limited. A more detailed analysis of SSc may provide better future treatment options and information of disease progression. Recently, the histological stain picrosirius red showing collagen register has been combined with atomic force microscopy (AFM) to study SSc. Skin from healthy individuals and SSc patients was biopsied, stained and studied using AFM. By investigating the crosslinking of collagen at a smaller hierarchical stage, the effects of SSc were more pronounced. Changes in morphology and Young’s elastic modulus were observed and quantified; giving rise to a novel technique, we have termed “quantitative nanohistology”. An increase in nanoscale stiffness in the collagen for SSc compared with healthy individuals was seen by a significant increase in the Young’s modulus profile for the collagen. These markers of stiffer collagen in SSc are similar to the symptoms experienced by patients, giving additional hope that in the future, nanohistology using AFM can be readily applied as a clinical tool, providing detailed information of the state of collagen. PMID:28138238

  17. Serum osteopontin and vitronectin levels in systemic sclerosis.

    PubMed

    Gundogdu, Baris; Yolbas, Servet; Yilmaz, Musa; Aydin, Suleyman; Koca, Sulayman Serdar

    2017-11-01

    Osteopontin a matricellular protein has pro-fibrotic effects and binds integrin such as αvβ1 and αvβ3. Vitronectin is one of the integrin αvβ3 ligands and is a multifunctional glycoprotein. The aim of the present study was to evaluate serum osteopontin and vitronectin levels in a cohort of patients with systemic sclerosis (SSc). Eighty-six patients with SSc, 46 patients with systemic lupus erythematosus (SLE), and 38 healthy controls (HC) were enrolled in the study. Serum osteopontin, vitronectin, IL-6, and TGF-β levels were analyzed. Serum osteopontin levels were higher in the SSc and SLE groups compared to the HC group (p < 0.01 and p < 0.001, respectively). However, it was not correlated with disease activity and severity scores in the SSc group. On the other hand, serum vitronectin levels were lower in the SSc group than in the SLE and HC groups (p < 0.001 for both). These results may suggest that osteopontin levels may be increased due to the inflammatory process and osteopontin has not a specific role on fibrosis in SSc. On the other hand, serum vitronectin levels decrease in SSc in contrast to SLE. It may be concluded that the one cause of decreased serum vitronectin levels in SSc may be its accumulation in fibrotic area.

  18. Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL)

    PubMed Central

    Preston, Ioana R.; Roberts, Kari E.; Miller, Dave P.; Sen, Ginny P.; Selej, Mona; Benton, Wade W.; Hill, Nicholas S.

    2015-01-01

    Background— Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Methods and Results— Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. Conclusions— No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. PMID:26510696

  19. Effect of Warfarin Treatment on Survival of Patients With Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL).

    PubMed

    Preston, Ioana R; Roberts, Kari E; Miller, Dave P; Sen, Ginny P; Selej, Mona; Benton, Wade W; Hill, Nicholas S; Farber, Harrison W

    2015-12-22

    Long-term anticoagulation is recommended in idiopathic pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH. Patients who initiated warfarin on study (n=187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from the time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison with warfarin-naïve patients. No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214. © 2015 The Authors.

  20. D-penicillamine in systemic sclerosis? Yes!

    PubMed

    Medsger, T A; Lucas, M; Wildy, K S; Baker, C

    2001-01-01

    The use of D-penicillamine in systemic sclerosis (SSc) has been controversial. We have reviewed the major published studies on this drug in SSc with diffuse cutaneous (dc) involvement and summarized our own recent experience in dcSSc patients treated with and without D-penicillamine. We conclude that D-penicillamine favourably alters the natural history of skin involvement in dcSSc, even when used in low dose. Furthermore, recurrence of diffuse skin change after discontinuation of D-penicillamine and improvement in skin thickening after reinitiation of the drug support its effectiveness. We believe that the rheumatologic community should use D-penicillamine in patients with early dcSSc.

  1. Handling Input and Output for COAMPS

    NASA Technical Reports Server (NTRS)

    Fitzpatrick, Patrick; Tran, Nam; Li, Yongzuo; Anantharaj, Valentine

    2007-01-01

    Two suites of software have been developed to handle the input and output of the Coupled Ocean Atmosphere Prediction System (COAMPS), which is a regional atmospheric model developed by the Navy for simulating and predicting weather. Typically, the initial and boundary conditions for COAMPS are provided by a flat-file representation of the Navy s global model. Additional algorithms are needed for running the COAMPS software using global models. One of the present suites satisfies this need for running COAMPS using the Global Forecast System (GFS) model of the National Oceanic and Atmospheric Administration. The first step in running COAMPS downloading of GFS data from an Internet file-transfer-protocol (FTP) server computer of the National Centers for Environmental Prediction (NCEP) is performed by one of the programs (SSC-00273) in this suite. The GFS data, which are in gridded binary (GRIB) format, are then changed to a COAMPS-compatible format by another program in the suite (SSC-00278). Once a forecast is complete, still another program in the suite (SSC-00274) sends the output data to a different server computer. The second suite of software (SSC- 00275) addresses the need to ingest up-to-date land-use-and-land-cover (LULC) data into COAMPS for use in specifying typical climatological values of such surface parameters as albedo, aerodynamic roughness, and ground wetness. This suite includes (1) a program to process LULC data derived from observations by the Moderate Resolution Imaging Spectroradiometer (MODIS) instruments aboard NASA s Terra and Aqua satellites, (2) programs to derive new climatological parameters for the 17-land-use-category MODIS data; and (3) a modified version of a FORTRAN subroutine to be used by COAMPS. The MODIS data files are processed to reformat them into a compressed American Standard Code for Information Interchange (ASCII) format used by COAMPS for efficient processing.

  2. Suspended-sediment transport from the Green-Duwamish River to the Lower Duwamish Waterway, Seattle, Washington, 2013–17

    USGS Publications Warehouse

    Senter, Craig A.; Conn, Kathleen E.; Black, Robert W.; Peterson, Norman; Vanderpool-Kimura, Ann M.; Foreman, James R.

    2018-02-28

    The Green-Duwamish River transports watershed-derived sediment to the Lower Duwamish Waterway Superfund site near Seattle, Washington. Understanding the amount of sediment transported by the river is essential to the bed sediment cleanup process. Turbidity, discharge, suspended-sediment concentration (SSC), and particle-size data were collected by the U.S. Geological Survey (USGS) from February 2013 to January 2017 at the Duwamish River, Washington, within the tidal influence at river kilometer 16.7 (USGS streamgage 12113390; Duwamish River at Golf Course at Tukwila, WA). This report quantifies the timing and magnitude of suspended-sediment transported in the Duwamish River. Regression models were developed between SSC and turbidity and SSC and discharge to estimate 15- minute SSC. Suspended-sediment loads were calculated from the computed SSC and time-series discharge data for every 15-minute interval during the study period. The 2014–16 average annual suspended-sediment load computed was 117,246 tons (106,364 metric tons), of which 73.5 percent or (86,191 tons; 78,191 metric tons) was fine particle (less than 0.0625 millimeter in diameter) suspended sediment. The seasonality of this site is apparent when you divide the year into "wet" (October 16– April 15) and "dry" (April 16–October 15) seasons. Most (97 percent) of the annual suspended sediment was transported during the wet season, when brief periods of intense precipitation from storms, large releases from the Howard Hanson Dam, or a combination of both were much more frequent.

  3. Self-Consistent Chaotic Transport in a High-Dimensional Mean-Field Hamiltonian Map Model

    DOE PAGES

    Martínez-del-Río, D.; del-Castillo-Negrete, D.; Olvera, A.; ...

    2015-10-30

    We studied the self-consistent chaotic transport in a Hamiltonian mean-field model. This model provides a simplified description of transport in marginally stable systems including vorticity mixing in strong shear flows and electron dynamics in plasmas. Self-consistency is incorporated through a mean-field that couples all the degrees-of-freedom. The model is formulated as a large set of N coupled standard-like area-preserving twist maps in which the amplitude and phase of the perturbation, rather than being constant like in the standard map, are dynamical variables. Of particular interest is the study of the impact of periodic orbits on the chaotic transport and coherentmore » structures. Furthermore, numerical simulations show that self-consistency leads to the formation of a coherent macro-particle trapped around the elliptic fixed point of the system that appears together with an asymptotic periodic behavior of the mean field. To model this asymptotic state, we introduced a non-autonomous map that allows a detailed study of the onset of global transport. A turnstile-type transport mechanism that allows transport across instantaneous KAM invariant circles in non-autonomous systems is discussed. As a first step to understand transport, we study a special type of orbits referred to as sequential periodic orbits. Using symmetry properties we show that, through replication, high-dimensional sequential periodic orbits can be generated starting from low-dimensional periodic orbits. We show that sequential periodic orbits in the self-consistent map can be continued from trivial (uncoupled) periodic orbits of standard-like maps using numerical and asymptotic methods. Normal forms are used to describe these orbits and to find the values of the map parameters that guarantee their existence. Numerical simulations are used to verify the prediction from the asymptotic methods.« less

  4. Self-Consistent Chaotic Transport in a High-Dimensional Mean-Field Hamiltonian Map Model

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

    Martínez-del-Río, D.; del-Castillo-Negrete, D.; Olvera, A.

    We studied the self-consistent chaotic transport in a Hamiltonian mean-field model. This model provides a simplified description of transport in marginally stable systems including vorticity mixing in strong shear flows and electron dynamics in plasmas. Self-consistency is incorporated through a mean-field that couples all the degrees-of-freedom. The model is formulated as a large set of N coupled standard-like area-preserving twist maps in which the amplitude and phase of the perturbation, rather than being constant like in the standard map, are dynamical variables. Of particular interest is the study of the impact of periodic orbits on the chaotic transport and coherentmore » structures. Furthermore, numerical simulations show that self-consistency leads to the formation of a coherent macro-particle trapped around the elliptic fixed point of the system that appears together with an asymptotic periodic behavior of the mean field. To model this asymptotic state, we introduced a non-autonomous map that allows a detailed study of the onset of global transport. A turnstile-type transport mechanism that allows transport across instantaneous KAM invariant circles in non-autonomous systems is discussed. As a first step to understand transport, we study a special type of orbits referred to as sequential periodic orbits. Using symmetry properties we show that, through replication, high-dimensional sequential periodic orbits can be generated starting from low-dimensional periodic orbits. We show that sequential periodic orbits in the self-consistent map can be continued from trivial (uncoupled) periodic orbits of standard-like maps using numerical and asymptotic methods. Normal forms are used to describe these orbits and to find the values of the map parameters that guarantee their existence. Numerical simulations are used to verify the prediction from the asymptotic methods.« less

  5. Storm time plasma transport in a unified and inter-coupled global magnetosphere model

    NASA Astrophysics Data System (ADS)

    Ilie, R.; Liemohn, M. W.; Toth, G.

    2014-12-01

    We present results from the two-way self-consistent coupling between the kinetic Hot Electron and Ion Drift Integrator (HEIDI) model and the Space Weather Modeling Framework (SWMF). HEIDI solves the time dependent, gyration and bounced averaged kinetic equation for the phase space density of different ring current species and computes full pitch angle distributions for all local times and radial distances. During geomagnetic times the dipole approximation becomes unsuitable even in the inner magnetosphere. Therefore the HEIDI model was generalized to accommodate an arbitrary magnetic field and through the coupling with SWMF it obtains a magnetic field description throughout the HEIDI domain along with a plasma distribution at the model outer boundary from the Block Adaptive Tree Solar Wind Roe Upwind Scheme (BATS-R-US) magnetohydrodynamics (MHD) model within SWMF. Electric field self-consistency is assured by the passing of convection potentials from the Ridley Ionosphere Model (RIM) within SWMF. In this study we test the various levels of coupling between the 3 physics based models, highlighting the role that the magnetic field, plasma sheet conditions and the cross polar cap potential play in the formation and evolution of the ring current. We show that the dynamically changing geospace environment itself plays a key role in determining the geoeffectiveness of the driver. The results of the self-consistent coupling between HEIDI, BATS-R-US and RIM during disturbed conditions emphasize the importance of a kinetic self-consistent approach to the description of geospace.

  6. Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal

    PubMed Central

    Kanatsu-Shinohara, Mito; Tanaka, Takashi; Ogonuki, Narumi; Ogura, Atsuo; Morimoto, Hiroko; Cheng, Pei Feng; Eisenman, Robert N.; Trumpp, Andreas; Shinohara, Takashi

    2016-01-01

    Myc plays critical roles in the self-renewal division of various stem cell types. In spermatogonial stem cells (SSCs), Myc controls SSC fate decisions because Myc overexpression induces enhanced self-renewal division, while depletion of Max, a Myc-binding partner, leads to meiotic induction. However, the mechanism by which Myc acts on SSC fate is unclear. Here we demonstrate a critical link between Myc/Mycn gene activity and glycolysis in SSC self-renewal. In SSCs, Myc/Mycn are regulated by Foxo1, whose deficiency impairs SSC self-renewal. Myc/Mycn-deficient SSCs not only undergo limited self-renewal division but also display diminished glycolytic activity. While inhibition of glycolysis decreased SSC activity, chemical stimulation of glycolysis or transfection of active Akt1 or Pdpk1 (phosphoinositide-dependent protein kinase 1 ) augmented self-renewal division, and long-term SSC cultures were derived from a nonpermissive strain that showed limited self-renewal division. These results suggested that Myc-mediated glycolysis is an important factor that increases the frequency of SSC self-renewal division. PMID:28007786

  7. Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal.

    PubMed

    Kanatsu-Shinohara, Mito; Tanaka, Takashi; Ogonuki, Narumi; Ogura, Atsuo; Morimoto, Hiroko; Cheng, Pei Feng; Eisenman, Robert N; Trumpp, Andreas; Shinohara, Takashi

    2016-12-01

    Myc plays critical roles in the self-renewal division of various stem cell types. In spermatogonial stem cells (SSCs), Myc controls SSC fate decisions because Myc overexpression induces enhanced self-renewal division, while depletion of Max, a Myc-binding partner, leads to meiotic induction. However, the mechanism by which Myc acts on SSC fate is unclear. Here we demonstrate a critical link between Myc/Mycn gene activity and glycolysis in SSC self-renewal. In SSCs, Myc/Mycn are regulated by Foxo1, whose deficiency impairs SSC self-renewal. Myc/Mycn-deficient SSCs not only undergo limited self-renewal division but also display diminished glycolytic activity. While inhibition of glycolysis decreased SSC activity, chemical stimulation of glycolysis or transfection of active Akt1 or Pdpk1 (phosphoinositide-dependent protein kinase 1 ) augmented self-renewal division, and long-term SSC cultures were derived from a nonpermissive strain that showed limited self-renewal division. These results suggested that Myc-mediated glycolysis is an important factor that increases the frequency of SSC self-renewal division. © 2016 Kanatsu-Shinohara et al.; Published by Cold Spring Harbor Laboratory Press.

  8. Characteristics of nitrogen removal and microbial distribution by application of spent sulfidic caustic in pilot scale wastewater treatment plant.

    PubMed

    Park, S; Lee, J; Park, J; Byun, I; Park, T; Lee, T

    2010-01-01

    Since spent sulfidic caustic (SSC) produced from petrochemical industry contains a high concentration of alkalinity and sulfide, it was expected that SSC could be used as an electron donor for autotrophic denitrification. To investigate the nitrogen removal performance, a pilot scale Bardenpho process was operated. The total nitrogen removal efficiency increased as SSC dosage increased, and the highest efficiency was observed as 77.5% when SSC was injected into both anoxic tank (1) and (2). FISH analysis was also performed to shed light on the effect of SSC dosage on the distribution ratio of nitrifying bacteria and Thiobacillus denitrificans. FISH results indicated that the relative distribution ratio of ammonia-oxidizing bacteria, Nitrobacter spp., Nitrospira genus and Thiobacillus denitrificans to eubacteria varied little with the pH of the tanks, and SSC injection did not give harmful effect on nitrification efficiency. These results show that SSC can be applied as an electron donor of autotrophic denitrification to biological nitrogen removal process effectively, without any inhibitory effects to nitrifying bacteria and sulfur-utilizing denitrifying bacteria.

  9. Diagnostic criteria, severity classification and guidelines of systemic sclerosis.

    PubMed

    Asano, Yoshihide; Jinnin, Masatoshi; Kawaguchi, Yasushi; Kuwana, Masataka; Goto, Daisuke; Sato, Shinichi; Takehara, Kazuhiko; Hatano, Masaru; Fujimoto, Manabu; Mugii, Naoki; Ihn, Hironobu

    2018-06-01

    Several effective drugs have been identified for the treatment of systemic sclerosis (SSc). However, in advanced cases, not only their effectiveness is reduced but they may be also harmful due to their side-effects. Therefore, early diagnosis and early treatment is most important for the treatment of SSc. We established diagnostic criteria for SSc in 2003 and early diagnostic criteria for SSc in 2011, for the purpose of developing evaluation of each organ in SSc. Moreover, in November 2013, the American College of Rheumatology and the European Rheumatology Association jointly developed new diagnostic criteria for increasing their sensitivity and specificity, so we revised our diagnostic criteria and severity classification of SSc. Furthermore, we have revised the clinical guideline based on the newest evidence. In particular, the clinical guideline was established by clinical questions based on evidence-based medicine according to the New Minds Clinical Practice Guideline Creation Manual (version 1.0). We aimed to make the guideline easy to use and reliable based on the newest evidence, and to present guidance as specific as possible for various clinical problems in treatment of SSc. © 2018 Japanese Dermatological Association.

  10. Alteration of Th17 and Treg cell subpopulations co-exist in patients affected with systemic sclerosis.

    PubMed

    Fenoglio, Daniela; Battaglia, Florinda; Parodi, Alessia; Stringara, Silvia; Negrini, Simone; Panico, Nicoletta; Rizzi, Marta; Kalli, Francesca; Conteduca, Giuseppina; Ghio, Massimo; De Palma, Raffaele; Indiveri, Francesco; Filaci, Gilberto

    2011-06-01

    Aim of the study has been to understand the relationship between TH17 and Treg cell subsets in patients affected with systemic sclerosis (SSc). Phenotypes and functions of Th17 and Treg cell subsets were analyzed in a series of 36 SSc patients. Th17 cell concentration in the peripheral blood was found to be increased in SSc patients with respect to healthy controls independently from type or stage of disease. After PBMC stimulation with a polyclonal stimulus or Candida albicans antigens the frequency of Th17 T cell clones was significantly higher in SSc patients with respect to controls suggesting the skewing of immune response in SSc patients toward Th17 cell generation/expansion. Concerning the Treg compartment, both CD4+CD25+ and CD8+CD28- Treg subsets showed quantitative and qualitative alteration in the peripheral blood of SSc patients. Collectively, these data highlight the existence of an imbalanced ratio between Th17 and Treg cell subsets in SSc patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. CFD Modeling Activities at the NASA Stennis Space Center

    NASA Technical Reports Server (NTRS)

    Allgood, Daniel

    2007-01-01

    A viewgraph presentation on NASA Stennis Space Center's Computational Fluid Dynamics (CFD) Modeling activities is shown. The topics include: 1) Overview of NASA Stennis Space Center; 2) Role of Computational Modeling at NASA-SSC; 3) Computational Modeling Tools and Resources; and 4) CFD Modeling Applications.

  12. Self-consistent core-pedestal transport simulations with neural network accelerated models

    DOE PAGES

    Meneghini, Orso; Smith, Sterling P.; Snyder, Philip B.; ...

    2017-07-12

    Fusion whole device modeling simulations require comprehensive models that are simultaneously physically accurate, fast, robust, and predictive. In this paper we describe the development of two neural-network (NN) based models as a means to perform a snon-linear multivariate regression of theory-based models for the core turbulent transport fluxes, and the pedestal structure. Specifically, we find that a NN-based approach can be used to consistently reproduce the results of the TGLF and EPED1 theory-based models over a broad range of plasma regimes, and with a computational speedup of several orders of magnitudes. These models are then integrated into a predictive workflowmore » that allows prediction with self-consistent core-pedestal coupling of the kinetic profiles within the last closed flux surface of the plasma. Finally, the NN paradigm is capable of breaking the speed-accuracy trade-off that is expected of traditional numerical physics models, and can provide the missing link towards self-consistent coupled core-pedestal whole device modeling simulations that are physically accurate and yet take only seconds to run.« less

  13. Self-consistent core-pedestal transport simulations with neural network accelerated models

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

    Meneghini, Orso; Smith, Sterling P.; Snyder, Philip B.

    Fusion whole device modeling simulations require comprehensive models that are simultaneously physically accurate, fast, robust, and predictive. In this paper we describe the development of two neural-network (NN) based models as a means to perform a snon-linear multivariate regression of theory-based models for the core turbulent transport fluxes, and the pedestal structure. Specifically, we find that a NN-based approach can be used to consistently reproduce the results of the TGLF and EPED1 theory-based models over a broad range of plasma regimes, and with a computational speedup of several orders of magnitudes. These models are then integrated into a predictive workflowmore » that allows prediction with self-consistent core-pedestal coupling of the kinetic profiles within the last closed flux surface of the plasma. Finally, the NN paradigm is capable of breaking the speed-accuracy trade-off that is expected of traditional numerical physics models, and can provide the missing link towards self-consistent coupled core-pedestal whole device modeling simulations that are physically accurate and yet take only seconds to run.« less

  14. Self-consistent core-pedestal transport simulations with neural network accelerated models

    NASA Astrophysics Data System (ADS)

    Meneghini, O.; Smith, S. P.; Snyder, P. B.; Staebler, G. M.; Candy, J.; Belli, E.; Lao, L.; Kostuk, M.; Luce, T.; Luda, T.; Park, J. M.; Poli, F.

    2017-08-01

    Fusion whole device modeling simulations require comprehensive models that are simultaneously physically accurate, fast, robust, and predictive. In this paper we describe the development of two neural-network (NN) based models as a means to perform a snon-linear multivariate regression of theory-based models for the core turbulent transport fluxes, and the pedestal structure. Specifically, we find that a NN-based approach can be used to consistently reproduce the results of the TGLF and EPED1 theory-based models over a broad range of plasma regimes, and with a computational speedup of several orders of magnitudes. These models are then integrated into a predictive workflow that allows prediction with self-consistent core-pedestal coupling of the kinetic profiles within the last closed flux surface of the plasma. The NN paradigm is capable of breaking the speed-accuracy trade-off that is expected of traditional numerical physics models, and can provide the missing link towards self-consistent coupled core-pedestal whole device modeling simulations that are physically accurate and yet take only seconds to run.

  15. Remote Sensing of Suspended Sediment Dynamics in the Mississippi Sound

    NASA Astrophysics Data System (ADS)

    Merritt, D. N.; Skarke, A. D.; Silwal, S.; Dash, P.

    2016-02-01

    The Mississippi Sound is a semi-enclosed estuary between the coast of Mississippi and a chain of offshore barrier islands with relatively shallow water depths and high marine biodiversity that is wildly utilized for commercial fishing and public recreation. The discharge of sediment-laden rivers into the Mississippi Sound and the adjacent Northern Gulf of Mexico creates turbid plumes that can extend hundreds of square kilometers along the coast and persist for multiple days. The concentration of suspended sediment in these coastal waters is an important parameter in the calculation of regional sediment budgets as well as analysis of water-quality factors such as primary productivity, nutrient dynamics, and the transport of pollutants as well as pathogens. The spectral resolution, sampling frequency, and regional scale spatial domain associated with satellite based sensors makes remote sensing an ideal tool to monitor suspended sediment dynamics in the Northern Gulf of Mexico. Accordingly, the presented research evaluates the validity of published models that relate remote sensing reflectance with suspended sediment concentrations (SSC), for similar environmental settings, with 51 in situ observations of SSC from the Mississippi Sound. Additionally, regression analysis is used to correlate additional in situ observations of SSC in Mississippi Sound with coincident observations of visible and near-infrared band reflectance collected by the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor aboard the Aqua satellite, in order to develop a site-specific empirical predictive model for SSC. Finally, specific parameters of the sampled suspended sediment such as grain size and mineralogy are analyzed in order to quantify their respective contributions to total remotely sensed reflectance.

  16. Environmental Mycobiome Modifiers of Inflammation and Fibrosis in Systemic Sclerosis

    DTIC Science & Technology

    2016-09-01

    TUBB), and ribosomal proteins), while others are considered specific to SSc despite trace level detection in controls. For ex- ample, multiple SSc...Strong re- activity was seen against all five proteins in SSc with only trace levels detected in controls (Fig. 3a), indicating widespread immune...sequences in SSc RNA-seq data was used to detect microbial sequences in human tissues in an unbiased, quantitative manner. Our studies suggest that

  17. Sustainable supply chain design: a configurational approach.

    PubMed

    Masoumik, S Maryam; Abdul-Rashid, Salwa Hanim; Olugu, Ezutah Udoncy; Raja Ghazilla, Raja Ariffin

    2014-01-01

    Designing the right supply chain that meets the requirements of sustainable development is a significant challenge. Although there are a considerable number of studies on issues relating to sustainable supply chain design (SSCD) in terms of designing the practices, processes, and structures, they have rarely demonstrated how these components can be aligned to form an effective sustainable supply chain (SSC). Considering this gap in the literature, this study adopts the configurational approach to develop a conceptual framework that could configure the components of a SSC. In this respect, a process-oriented approach is utilized to classify and harmonize the design components. A natural-resource-based view (NRBV) is adopted to determine the central theme to align the design components around. The proposed framework presents three types of SSC, namely, efficient SSC, innovative SSC, and reputed SSC. The study culminates with recommendations concerning the direction for future research.

  18. Sulfide Stress Cracking Behavior of a Martensitic Steel Controlled by Tempering Temperature

    PubMed Central

    Sun, Yu; Wang, Qian; Gu, Shunjie; He, Zaoneng; Wang, Qingfeng; Zhang, Fucheng

    2018-01-01

    A medium-carbon Cr–Mo–V martensitic steel was thermally processed by quenching (Q) at 890 °C and tempering (T) at increasing temperatures from 650 °C to 720 °C and the effect of tempering temperature, Tt, on sulfide stress cracking (SSC) behaviors was estimated mainly via double cantilever beam (DCB) and electrochemical hydrogen permeation (EHP) tests and microstructure characterization. The results indicate that the threshold stress intensity factor for SSC, KISSC, increased with increasing Tt. The overall and local H concentration around the inclusions decreased with increasing Tt, due to reductions in the amounts of solute atoms, grain boundaries and dislocations, which effectively prevented SSC initiation. Also, increasing Tt caused an increased fraction of high-angle boundaries, which evidently lowered the SSC propagation rate by more frequently diverting the propagating direction and accordingly restricted SSC propagation. The overall SSC resistance of this Q&T–treated steel was therefore significantly enhanced. PMID:29522494

  19. Potential use of TNF-α inhibitors in systemic sclerosis.

    PubMed

    Murdaca, Giuseppe; Spanò, Francesca; Contatore, Miriam; Guastalla, Andrea; Puppo, Francesco

    2014-01-01

    Systemic sclerosis (SSc) is a rare connective tissue disease characterized by chronic inflammation and fibrosis of the skin, vascular abnormalities and variable involvement of organs. TNF-α has a central role in initial host response to infections and in the pathogenesis of various systemic immune-mediated diseases. Serum levels of TNF-α are elevated in patients with SSc and favor the development of pulmonary fibrosis and pulmonary arterial hypertension. Inflammatory arthritis can occur in patients with SSc. Infliximab and etanercept may improve the inflammatory arthritis and disability in SSc. TNF-α inhibitors reduce the systemic inflammation, improve the endothelial function decreasing the risk of pulmonary arterial hypertension progression and of acute cardiovascular and/or cerebrovascular events. Physicians need to be aware of the potential risks of tuberculosis reactivation and opportunistic infections. Randomized controlled trials with TNF-α inhibitors in patients with SSc are needed to confirm the potential role of these agents in the treatment of SSc.

  20. Systemic sclerosis and infections.

    PubMed

    Randone, Silvia Bellando; Guiducci, Serena; Cerinic, Marco Matucci

    2008-10-01

    Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular obliteration, excessive extracellular matrix deposition and fibrosis of the connective tissues of the skin, lungs, gastrointestinal tract, heart, and kidneys. Numerous infectious agents (bacterial and viral) have been proposed as possible triggering factors (Parvovirus B19, Cytomegalovirus, Epstein-Barr virus, Retroviruses). Homology between viruses and autoantibody targets suggests that molecular mimicry may have a role in initiating antibody response in different disorders characterized by diffuse vascular disease, including SSc. Endothelial cell may be infected bacteria or viruses that play a particular role in inducing vasculitis. The pathogenic hypothesis include: a mechanism of molecular mimicry, the role played by endothelial cell damage, the presence of superantigens and the role of microchimeric cells. Although several studies provide important information linking infectious agents to SSc, a direct casual association between infections and SSc is still missing. In SSc viral products could synergize with other factors in the microenvironment predisposing to SSc development.

  1. Sustainable Supply Chain Design: A Configurational Approach

    PubMed Central

    Masoumik, S. Maryam; Raja Ghazilla, Raja Ariffin

    2014-01-01

    Designing the right supply chain that meets the requirements of sustainable development is a significant challenge. Although there are a considerable number of studies on issues relating to sustainable supply chain design (SSCD) in terms of designing the practices, processes, and structures, they have rarely demonstrated how these components can be aligned to form an effective sustainable supply chain (SSC). Considering this gap in the literature, this study adopts the configurational approach to develop a conceptual framework that could configure the components of a SSC. In this respect, a process-oriented approach is utilized to classify and harmonize the design components. A natural-resource-based view (NRBV) is adopted to determine the central theme to align the design components around. The proposed framework presents three types of SSC, namely, efficient SSC, innovative SSC, and reputed SSC. The study culminates with recommendations concerning the direction for future research. PMID:24523652

  2. Modeling and Predicting the Electrical Conductivity of Composite Cathode for Solid Oxide Fuel Cell by Using Support Vector Regression

    NASA Astrophysics Data System (ADS)

    Tang, J. L.; Cai, C. Z.; Xiao, T. T.; Huang, S. J.

    2012-07-01

    The electrical conductivity of solid oxide fuel cell (SOFC) cathode is one of the most important indices affecting the efficiency of SOFC. In order to improve the performance of fuel cell system, it is advantageous to have accurate model with which one can predict the electrical conductivity. In this paper, a model utilizing support vector regression (SVR) approach combined with particle swarm optimization (PSO) algorithm for its parameter optimization was established to modeling and predicting the electrical conductivity of Ba0.5Sr0.5Co0.8Fe0.2 O3-δ-xSm0.5Sr0.5CoO3-δ (BSCF-xSSC) composite cathode under two influence factors, including operating temperature (T) and SSC content (x) in BSCF-xSSC composite cathode. The leave-one-out cross validation (LOOCV) test result by SVR strongly supports that the generalization ability of SVR model is high enough. The absolute percentage error (APE) of 27 samples does not exceed 0.05%. The mean absolute percentage error (MAPE) of all 30 samples is only 0.09% and the correlation coefficient (R2) as high as 0.999. This investigation suggests that the hybrid PSO-SVR approach may be not only a promising and practical methodology to simulate the properties of fuel cell system, but also a powerful tool to be used for optimal designing or controlling the operating process of a SOFC system.

  3. Key issues and challenges in developing a pedagogical intervention in the simulation skills center--an action research study.

    PubMed

    Reierson, Inger Åse; Hvidsten, Anne; Wighus, Marianne; Brungot, Solvor; Bjørk, Ida Torunn

    2013-07-01

    Simulation skills centers (SSC) are considered important learning arenas for preparing and qualifying nursing students. Limited clinical placements and claims of diminished learning opportunities raise concerns that newly educated nurses lack proficiency in many psychomotor skills. Accordingly, there is an increased focus on learning in the SSC. However, it has been questioned if the pedagogical underpinning of teaching and learning in the SSC is missing or unclear. At a bachelor nursing education in Norway, there was a desire to change practice and enhance learning in the SSC by systematic use of The Model of Practical Skill Performance (Bjørk and Kirkevold, 2000). A participatory action research design was chosen. A pedagogical intervention was developed and implemented in 2010 in a cohort of eighty-seven first year bachelor nursing students during their basic nursing skill course. The intervention is shortly described. This article reports key issues and challenges that emerged during development of the new intervention. Data to inform the study were collected via thorough meeting minutes and the project leader's logbook, and analyzed using fieldnotes analysis. Six key issues and challenges were identified. These are presented and discussed consecutively in light of their importance for development and implementation of the new intervention. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma

    PubMed Central

    2014-01-01

    Introduction We assessed the profile and frequency of malignancy subtypes in a large single-centre UK cohort for patients with scleroderma (systemic sclerosis; SSc). We evaluated the cancer risk among SSc patients with different antibody reactivities and explored the temporal association of cancer with the duration between SSc onset and cancer diagnosis. Methods We conducted a retrospective study of a well-characterised cohort of SSc patients attending a large tertiary referral centre, with clinical data collected from our clinical database and by review of patient records. We evaluated development of all cancers in this cohort, and comparison was assessed with the SSc cohort without cancer. The effect of demographics and clinical details, including antibody reactivities, were explored to find associations relevant to the risk for development of cancer in SSc patients. Results Among 2,177 patients with SSc, 7.1% had a history of cancer, 26% were positive for anticentromere antibodies (ACAs), 18.2% were positive for anti-Scl-70 antibodies and 26.6% were positive for anti-RNA polymerase III (anti-RNAP) antibody. The major malignancy cancer subtypes were breast (42.2%), haematological (12.3%), gastrointestinal (11.0%) and gynaecological (11.0%). The frequency of cancers among patients with RNAP (14.2%) was significantly increased compared with those with anti-Scl-70 antibodies (6.3%) and ACAs (6.8%) (P < 0.0001 and P < 0.001, respectively). Among the patients, who were diagnosed with cancer within 36 months of the clinical onset of SSc, there were more patients with RNAP (55.3%) than those with other autoantibody specificities (ACA = 23.5%, P < 0.008; and anti-Scl-70 antibodies = 13.6%, P < 0.002, respectively). Breast cancers were temporally associated with onset of SSc among patients with anti-RNAP, and SSc patients with anti-RNAP had a twofold increased hazard ratio for cancers compared to patients with ACAs (P < 0.0001). Conclusions Our study independently confirms, in what is to the best of our knowledge the largest population examined to date, that there is an association with cancer among SSc patients with anti-RNAP antibodies in close temporal relationship to onset of SSc, which supports the paraneoplastic phenomenon in this subset of SSc cases. An index of cautious suspicion should be maintained in these cases, and investigations for underlying malignancy should be considered when clinically appropriate. PMID:24524733

  5. Self-Consistent Ring Current Modeling with Propagating Electromagnetic Ion Cyclotron Waves in the Presence of Heavy Ions

    NASA Technical Reports Server (NTRS)

    Khazanov, G. V.; Gamayunov, K. V.; Gallagher, D. L.; Kozyra, J. U.; Liemohn, M. W.

    2006-01-01

    The self-consistent treatment of the RC ion dynamics and EMlC waves, which are thought to exert important influences on the ion dynamical evolution, is an important missing element in our understanding of the storm-and recovery-time ring current evolution. Under certain conditions, relativistic electrons, with energies greater than or equal to 1 MeV, can be removed from the outer radiation belt by EMlC wave scattering during a magnetic storm (Summers and Thorne, 2003; Albert, 2003). That is why the modeling of EMlC waves is critical and timely issue in magnetospheric physics. This study will generalize the self-consistent theoretical description of RC ions and EMlC waves that has been developed by Khazanov et al. [2002, 2003] and include the heavy ions and propagation effects of EMlC waves in the global dynamic of self-consistent RC - EMlC waves coupling. The results of our newly developed model that will be presented at Huntsville 2006 meeting, focusing mainly on the dynamic of EMlC waves and comparison of these results with the previous global RC modeling studies devoted to EMlC waves formation. We also discuss RC ion precipitations and wave induced thermal electron fluxes into the ionosphere.

  6. Subspace Compressive GLRT Detector for MIMO Radar in the Presence of Clutter.

    PubMed

    Bolisetti, Siva Karteek; Patwary, Mohammad; Ahmed, Khawza; Soliman, Abdel-Hamid; Abdel-Maguid, Mohamed

    2015-01-01

    The problem of optimising the target detection performance of MIMO radar in the presence of clutter is considered. The increased false alarm rate which is a consequence of the presence of clutter returns is known to seriously degrade the target detection performance of the radar target detector, especially under low SNR conditions. In this paper, a mathematical model is proposed to optimise the target detection performance of a MIMO radar detector in the presence of clutter. The number of samples that are required to be processed by a radar target detector regulates the amount of processing burden while achieving a given detection reliability. While Subspace Compressive GLRT (SSC-GLRT) detector is known to give optimised radar target detection performance with reduced computational complexity, it however suffers a significant deterioration in target detection performance in the presence of clutter. In this paper we provide evidence that the proposed mathematical model for SSC-GLRT detector outperforms the existing detectors in the presence of clutter. The performance analysis of the existing detectors and the proposed SSC-GLRT detector for MIMO radar in the presence of clutter are provided in this paper.

  7. Behavioral Adjustment of Toddler and Preschool-Aged Children with Single-Suture Craniosynostosis*

    PubMed Central

    Kapp-Simon, Kathleen A; Collett, Brent R; Barr-Schinzel, Michael A; Cradock, Mary M; Buono, Lauren A; Pietila, Kristen E; Speltz, Matthew L

    2012-01-01

    Background The purpose of this study was to confirm initial reports of elevated behavior problems in children with single-suture craniosynostosis (SSC), using multiple informants, longitudinal analyses and a control group. We hypothesized higher levels of maladjustment for children with SSC than comparison children, particularly at the older age and in selected areas of previously observed vulnerability: attention and social adjustment. Method A Child Behavior Checklist (CBCL) was completed when children were ~19 months by 436 mothers (219 with SSC) and 371 fathers (177 with SSC); and at ~37 months by 361 mothers (175 with SSC) and 303 fathers (142 with SSC). A minimum of one caregiver/teacher report was available for 169 of these children (74 with SSC) using the Caregiver-Teacher Report Form (CTRF). Results Average CBCL/CTRF externalizing, internalizing and total scores for all informants were consistently higher (worse) for children with SSC than control group children, but most differences were small and statistically non-significant. No differences associated with suture site were found. At the oldest age point, both mothers and fathers (but not teachers) generated higher average scores for patients than for controls on scales measuring attention and social problems, with small to medium effects sizes (0.20 to 0.32). Conclusion On average toddlers/preschoolers with SSC show behavioral development that is largely indistinguishable from same-aged peers of similar socioeconomic background. The predictive significance of small group differences in attention and social adjustment will be assessed in a follow-up of this cohort at age 7. PMID:22929249

  8. Circulating miR-142-3p levels in patients with systemic sclerosis.

    PubMed

    Makino, K; Jinnin, M; Kajihara, I; Honda, N; Sakai, K; Masuguchi, S; Fukushima, S; Inoue, Y; Ihn, H

    2012-01-01

    Recently, increased evidence has shown that serum micro (mi)RNA levels are a useful biomarker for the diagnosis, prognosis and therapeutic value of various diseases. However, serum miRNA has not been investigated in patients with systemic sclerosis (SSc), to our knowledge. To investigate the possibility that serum levels of Homo sapiens miR-142 stem-loop (hsa-miR-142-3p), one of the miRNAs regulating the expression of integrin αV, could be a specific disease marker for SSc. Serum samples were obtained from 61 patients with SSc and 20 healthy controls. Patients with systemic lupus erythematosus (SLE), dermatomyositis (DM) and scleroderma spectrum disorder (SSD), who did not fulfil American College of Rheumatology criteria for SSc but might develop SSc in the future, were included as disease controls in this study. miRNAs were purified from serum, and miR-142-3p levels were measured with a quantitative real-time PCR assay. Serum miR-142-3p levels in patients with SSc were significantly higher than in patients with SSD, SLE or DM, and healthy control groups. Patients with increased miR-142-3p levels tended to have a short sublingual frenulum. Our data indicate that serum levels of miR-142-3p may be elevated specifically in patients with SSc, correlating with the severity of this disease, and may be useful diagnostic markers for the presence of SSc and for the differentiation of SSc from SSD. © The Author(s). CED © 2011 British Association of Dermatologists.

  9. [Compliance with the surgical safety checklist and surgical events detected by the Global Trigger Tool].

    PubMed

    Menéndez Fraga, M D; Cueva Álvarez, M A; Franco Castellanos, M R; Fernández Moral, V; Castro Del Río, M P; Arias Pérez, J I; Fernández León, A; Vázquez Valdés, F

    2016-06-01

    The implementing of the WHO Surgical Safety Checklist (SSC) has helped to improve patient safety. The aim of this study was to assess the level of compliance of the SSC, and incorporating the non-compliances as «triggers» in the Global Trigger Tool (GTT). Acute Geriatric Hospital (200 beds). Retrospective study, study period: 2011-2014. The SSC formulary and the methodology of the GTT were used for the analysis of electronic medical records and the compliance with the SSC. The NCCP MERP categories were used to assess the severity of the harm. Out of all the electronic medical records (EMR), a total of 227 (23.6%) discharged patients (1.7% of interventions in the four year study period) were analysed. All (100%) of the EMR included the SSC, with 94.4% of the items being completed, and 28.2% of SSC had all items completed in the 3 phases of the process. Surgical adverse events decreased from 16.3% in 2011 to 9.4% in 2014 (P=.2838, not significant), and compliance with all items of SSC was increased from 18.6% to 39.1% (P=.0246, significant). The GTT systematises and evaluates, at low cost, the triggers and incidents/ AEs found in the EMR in order to assess the compliance with the SSC and consider non-compliance of SSC as «triggers» for further analysis. This strategy has never been referred to in the GTT or in the SCC formulary. Copyright © 2016 SECA. Published by Elsevier Espana. All rights reserved.

  10. Implementation of a Surgical Safety Checklist: Interventions to Optimize the Process and Hints to Increase Compliance

    PubMed Central

    Sendlhofer, Gerald; Mosbacher, Nina; Karina, Leitgeb; Kober, Brigitte; Jantscher, Lydia; Berghold, Andrea; Pregartner, Gudrun; Brunner, Gernot; Kamolz, Lars Peter

    2015-01-01

    Background A surgical safety checklist (SSC) was implemented and routinely evaluated within our hospital. The purpose of this study was to analyze compliance, knowledge of and satisfaction with the SSC to determine further improvements. Methods The implementation of the SSC was observed in a pilot unit. After roll-out into each operating theater, compliance with the SSC was routinely measured. To assess subjective and objective knowledge, as well as satisfaction with the SSC implementation, an online survey (N = 891) was performed. Results During two test runs in a piloting unit, 305 operations were observed, 175 in test run 1 and 130 in test run 2. The SSC was used in 77.1% of all operations in test run 1 and in 99.2% in test run 2. Within used SSCs, completion rates were 36.3% in test run 1 and 1.6% in test run 2. After roll-out, three unannounced audits took place and showed that the SSC was used in 95.3%, 91.9% and 89.9%. Within used SSCs, completion rates decreased from 81.7% to 60.6% and 53.2%. In 2014, 164 (18.4%) operating team members responded to the online survey, 160 of which were included in the analysis. 146 (91.3%) consultants and nursing staff reported to use the SSC regularly in daily routine. Conclusion These data show that the implementation of new tools such as the adapted WHO SSC needs constant supervision and instruction until it becomes self-evident and accepted. Further efforts, consisting mainly of hands-on leadership and training are necessary. PMID:25658317

  11. Correlations between skin blood perfusion values and nailfold capillaroscopy scores in systemic sclerosis patients.

    PubMed

    Ruaro, B; Sulli, A; Pizzorni, C; Paolino, S; Smith, V; Cutolo, M

    2016-05-01

    To correlate blood perfusion (BP) values assessed by laser speckle contrast analysis (LASCA) in selected skin areas of hands and face with nailfold capillary damage scores in systemic sclerosis (SSc) patients. Seventy SSc patients (mean SSc duration 6 ± 5 years) and 70 volunteer healthy subjects were enrolled after informed consent. LASCA was performed at different areas of the face (forehead, tip of nose, zygomas and perioral region) and at dorsal and volar regions of hands. Microvascular damage was assessed and scored by nailfold videocapillaroscopy (NVC) and the microangiopathy evolution score (MES) was calculated. SSc patients showed a significantly lower BP than healthy subjects at fingertips, periungual areas and palm of hands (p<0.0001), but not at the level of face and dorsum of hands. A gradual decrease of BP at fingertips, periungual and palm areas, was found in SSc patients with progressive severity of NVC patterns of microangiopathy ("early", "active", or "late") (p<0.01). A negative correlation was observed between MES and BP values, as well as between loss of capillaries and BP, at the same areas (p<0.001 and p<0.01, respectively). Patients with diffuse cutaneous SSc (dcSSc) showed lower BP than those with limited cutaneous SSc (p<0.04). LASCA detects a significant reduction of BP only in those areas usually affected by Raynaud's phenomenon (fingertips, periungual and palm areas), especially in dcSSc patients, and BP values significantly correlate with the nailfold capillaroscopy scores of microangiopathy. Copyright © 2016. Published by Elsevier Inc.

  12. Self-consistent study of local and nonlocal magnetoresistance in a YIG/Pt bilayer

    NASA Astrophysics Data System (ADS)

    Wang, Xi-guang; Zhou, Zhen-wei; Nie, Yao-zhuang; Xia, Qing-lin; Guo, Guang-hua

    2018-03-01

    We present a self-consistent study of the local spin Hall magnetoresistance (SMR) and nonlocal magnon-mediated magnetoresistance (MMR) in a heavy-metal/magnetic-insulator heterostructure at finite temperature. We find that the thermal fluctuation of magnetization significantly affects the SMR. It appears unidirectional with respect to the direction of electrical current (or magnetization). The unidirectionality of SMR originates from the asymmetry of creation or annihilation of thermal magnons induced by the spin Hall torque. Also, a self-consistent model can well describe the features of MMR.

  13. Self-consistent one dimension in space and three dimension in velocity kinetic trajectory simulation model of magnetized plasma-wall transition

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

    Chalise, Roshan, E-mail: plasma.roshan@gmail.com; Khanal, Raju

    2015-11-15

    We have developed a self-consistent 1d3v (one dimension in space and three dimension in velocity) Kinetic Trajectory Simulation (KTS) model, which can be used for modeling various situations of interest and yields results of high accuracy. Exact ion trajectories are followed, to calculate along them the ion distribution function, assuming an arbitrary injection ion distribution. The electrons, on the other hand, are assumed to have a cut-off Maxwellian velocity distribution at injection and their density distribution is obtained analytically. Starting from an initial guess, the potential profile is iterated towards the final time-independent self-consistent state. We have used it tomore » study plasma sheath region formed in presence of an oblique magnetic field. Our results agree well with previous works from other models, and hence, we expect our 1d3v KTS model to provide a basis for the studying of all types of magnetized plasmas, yielding more accurate results.« less

  14. Environmental Geographic Information Systems (EGIS) at Stennis Space Center (SSC)

    NASA Technical Reports Server (NTRS)

    Carr, Hugh; Smoot, James; Parikh, Joy

    2004-01-01

    This viewgraph presentation includes: 1) Background of SSC Environmental GIS (EGIS); 2) Principal Center Activities; 3) SSC's GIS Applications: a) Environmental Emergency Response Tool, b) CERCLA, c) Facilities Master Planning, d) Natural Resource Management and Site Assessment.

  15. 78 FR 6810 - Western Pacific Fishery Management Council; Public Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-31

    ... Scientific and Statistical Committee (SSC). DATES: The SSC will meet on February 26-28, 2013, between 8:30 a.... Introductions. 2. Approval of Draft Agenda and Assignment of Rapporteurs. 3. Status of the 111th SSC Meeting...

  16. Gene Profiling in Patients with Systemic Sclerosis Reveals the Presence of Oncogenic Gene Signatures

    PubMed Central

    Dolcino, Marzia; Pelosi, Andrea; Fiore, Piera Filomena; Patuzzo, Giuseppe; Tinazzi, Elisa; Lunardi, Claudio; Puccetti, Antonio

    2018-01-01

    Systemic sclerosis (SSc) is a rare connective tissue disease characterized by three pathogenetic hallmarks: vasculopathy, dysregulation of the immune system, and fibrosis. A particular feature of SSc is the increased frequency of some types of malignancies, namely breast, lung, and hematological malignancies. Moreover, SSc may also be a paraneoplastic disease, again indicating a strong link between cancer and scleroderma. The reason of this association is still unknown; therefore, we aimed at investigating whether particular genetic or epigenetic factors may play a role in promoting cancer development in patients with SSc and whether some features are shared by the two conditions. We therefore performed a gene expression profiling of peripheral blood mononuclear cells (PBMCs) derived from patients with limited and diffuse SSc, showing that the various classes of genes potentially linked to the pathogenesis of SSc (such as apoptosis, endothelial cell activation, extracellular matrix remodeling, immune response, and inflammation) include genes that directly participate in the development of malignancies or that are involved in pathways known to be associated with carcinogenesis. The transcriptional analysis was then complemented by a complex network analysis of modulated genes which further confirmed the presence of signaling pathways associated with carcinogenesis. Since epigenetic mechanisms, such as microRNAs (miRNAs), are believed to play a central role in the pathogenesis of SSc, we also evaluated whether specific cancer-related miRNAs could be deregulated in the serum of SSc patients. We focused our attention on miRNAs already found upregulated in SSc such as miR-21-5p, miR-92a-3p, and on miR-155-5p, miR 126-3p and miR-16-5p known to be deregulated in malignancies associated to SSc, i.e., breast, lung, and hematological malignancies. miR-21-5p, miR-92a-3p, miR-155-5p, and miR-16-5p expression was significantly higher in SSc sera compared to healthy controls. Our findings indicate the presence of modulated genes and miRNAs that can play a predisposing role in the development of malignancies in SSc and are important for a better risk stratification of patients and for the identification of a better individualized precision medicine strategy. PMID:29559981

  17. [Cognitive function in patients with systemic sclerosis].

    PubMed

    Straszecka, J; Jonderko, G; Kucharz, E J; Brzezińska-Wcisło, L; Kotulska, A; Bogdanowski, T

    1997-09-01

    Central nervous system involvement is seldom reported in patients with systemic sclerosis (SSc). Cognitive functions were determined in 21 patients with definite SSc and 42 healthy controls. Thyroid function was also measured in order to eliminate the effect of hypothyroidism on cognitive functioning. It was found that the SSc patients with normal thyroid function showed defective long-term and recent memory, learning ability, criticism, perception and visuo-perceptual skills, their simple reaction time was prolonged. Similar but less advanced cognitive defects were shown in the SSc patients with overt or latent hypothyroidism. The obtained results indicate that the central nervous system involvement is more common in patients with SSc than it has been reported earlier.

  18. Seismic source characterization for the 2014 update of the U.S. National Seismic Hazard Model

    USGS Publications Warehouse

    Moschetti, Morgan P.; Powers, Peter; Petersen, Mark D.; Boyd, Oliver; Chen, Rui; Field, Edward H.; Frankel, Arthur; Haller, Kathleen; Harmsen, Stephen; Mueller, Charles S.; Wheeler, Russell; Zeng, Yuehua

    2015-01-01

    We present the updated seismic source characterization (SSC) for the 2014 update of the National Seismic Hazard Model (NSHM) for the conterminous United States. Construction of the seismic source models employs the methodology that was developed for the 1996 NSHM but includes new and updated data, data types, source models, and source parameters that reflect the current state of knowledge of earthquake occurrence and state of practice for seismic hazard analyses. We review the SSC parameterization and describe the methods used to estimate earthquake rates, magnitudes, locations, and geometries for all seismic source models, with an emphasis on new source model components. We highlight the effects that two new model components—incorporation of slip rates from combined geodetic-geologic inversions and the incorporation of adaptively smoothed seismicity models—have on probabilistic ground motions, because these sources span multiple regions of the conterminous United States and provide important additional epistemic uncertainty for the 2014 NSHM.

  19. Self-consistency in the phonon space of the particle-phonon coupling model

    NASA Astrophysics Data System (ADS)

    Tselyaev, V.; Lyutorovich, N.; Speth, J.; Reinhard, P.-G.

    2018-04-01

    In the paper the nonlinear generalization of the time blocking approximation (TBA) is presented. The TBA is one of the versions of the extended random-phase approximation (RPA) developed within the Green-function method and the particle-phonon coupling model. In the generalized version of the TBA the self-consistency principle is extended onto the phonon space of the model. The numerical examples show that this nonlinear version of the TBA leads to the convergence of results with respect to enlarging the phonon space of the model.

  20. Self-consistent computation of the electric field near ICRH antennas. Application to the Tore Supra antenna

    NASA Astrophysics Data System (ADS)

    Pécoul, S.; Heuraux, S.; Koch, R.; Leclert, G.; Bécoulet, A.; Colas, L.

    1999-09-01

    Self-consistent calculations of the 3D electric field patterns between the screen and the plasma have been made with the ICANT code for realistic antennas. Here we explain how the ICRH antennas of the Tore Supra tokamak are modelled.

  1. Self-consistent computation of the electric field near ICRH antennas. Application to the Tore Supra antenna

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

    Pecoul, S.; Heuraux, S.; Koch, R.

    1999-09-20

    Self-consistent calculations of the 3D electric field patterns between the screen and the plasma have been made with the ICANT code for realistic antennas. Here we explain how the ICRH antennas of the Tore Supra tokamak are modelled.

  2. Direct brain recordings reveal impaired neural function in infants with single-suture craniosynostosis: a future modality for guiding management?

    PubMed

    Hashim, Peter W; Brooks, Eric D; Persing, John A; Reuman, Hannah; Naples, Adam; Travieso, Roberto; Terner, Jordan; Steinbacher, Derek; Landi, Nicole; Mayes, Linda; McPartland, James C

    2015-01-01

    Patients with single-suture craniosynostosis (SSC) are at an elevated risk for long-term learning disabilities. Such adverse outcomes indicate that the early development of neural processing in SSC may be abnormal. At present, however, the precise functional derangements of the developing brain remain largely unknown. Event-related potentials (ERPs) are a form of noninvasive neuroimaging that provide direct measurements of cortical activity and have shown value in predicting long-term cognitive functioning. The current study used ERPs to examine auditory processing in infants with SSC to help clarify the developmental onset of delays in this population. Fifteen infants with untreated SSC and 23 typically developing controls were evaluated. ERPs were recorded during the presentation of speech sounds. Analyses focused on the P150 and N450 components of auditory processing. Infants with SSC demonstrated attenuated P150 amplitudes relative to typically developing controls. No differences in the N450 component were identified between untreated SSC and controls. Infants with untreated SSC demonstrate abnormal speech sound processing. Atypicalities are detectable as early as 6 months of age and may represent precursors to long-term language delay. Electrophysiological assessments provide a precise examination of neural processing in SSC and hold potential as a future modality to examine the effects of surgical treatment on brain development.

  3. Association of Interleukin 23 Receptor Polymorphisms with Anti-Topoisomerase-I Positivity and Pulmonary Hypertension in Systemic Sclerosis

    PubMed Central

    AGARWAL, SANDEEP K.; GOURH, PRAVITT; SHETE, SANJAY; PAZ, GENE; DIVECHA, DIPAL; REVEILLE, JOHN D.; ASSASSI, SHERVIN; TAN, FILEMON K.; MAYES, MAUREEN D.; ARNETT, FRANK C.

    2010-01-01

    Objective IL23R has been identified as a susceptibility gene for development of multiple autoimmune diseases. We investigated the possible association of IL23R with systemic sclerosis (SSc), an autoimmune disease that leads to the development of cutaneous and visceral fibrosis. Methods We tested 9 single-nucleotide polymorphisms (SNP) in IL23R for association with SSc in a cohort of 1402 SSc cases and 1038 controls. IL23R SNP tested were previously identified as SNP showing associations with inflammatory bowel disease. Results Case-control comparisons revealed no statistically significant differences between patients and healthy controls with any of the IL23R polymorphisms. Analyses of subsets of SSc patients showed that rs11209026 (Arg381Gln variant) was associated with anti-topoisomerase I antibody (ATA)-positive SSc (p = 0.001)) and rs11465804 SNP was associated with diffuse and ATA-positive SSc (p = 0.0001, p = 0.0026, respectively). These associations remained significant after accounting for multiple comparisons using the false discovery rate method. Wild-type genotype at both rs11209026 and rs11465804 showed significant protection against the presence of pulmonary hypertension (PHT). (p = 3×10−5, p = 1×10−5, respectively). Conclusion Polymorphisms in IL23R are associated with susceptibility to ATA-positive SSc and protective against development of PHT in patients with SSc. PMID:19918037

  4. [Hashimoto thyroiditis may be associated with a subset of patients with systemic sclerosis with pulmonary hypertension].

    PubMed

    Costa, Ciliana Cardoso B; Medeiros, Morgana; Watanabe, Karen; Martin, Patricia; Skare, Thelma L

    2014-01-01

    Recent studies show an association between autoimmune thyroiditis and systemic sclerosis (SSc) and suggest that this condition may interfere with the ES phenotype. However these studies evaluate the autoimmune thyroiditis as a whole and none of them specifically addresses Hashimoto's thyroiditis (HT) in SSc. To investigate the presence of HT in SSc patients and its possible association with disease manifestations. Clinical manifestations of hypothyroidism, TSH and anti-thyroid auto antibodies (anti-TPO. anti TBG and TRAb) were studied in 56 patients with SSc. SSc patients with HT were compared with SSc patients without thyroiditis. HT was observed in 19.64% of patients with SSc. No association was observed between HT and the different forms of disease or profile of autoantibodies. Likewise, there was no difference between the mean modified Rodnan score and presence of Raynaud's phenomenon, scars, digital necrosis, myositis, arthritis, sicca symptoms, esophageal dysmotility and scleroderma renal crisis when the groups were compared. On the other hand, patients with HT had higher frequency of pulmonary hypertension in relation to patients without HT (66.6% vs 22.5%, p=0.016). In the studied sample patients with ES and HT had higher prevalence of pulmonary hypertension. Long-term follow-up studies with a larger number of TH and SSc patients are needed to confirm these data. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  5. KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor

    PubMed Central

    2012-01-01

    Introduction Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort. Methods The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay. Results Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients. Conclusions Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients. PMID:23270786

  6. Unfolding the pathogenesis of scleroderma through genomics and epigenomics.

    PubMed

    Tsou, Pei-Suen; Sawalha, Amr H

    2017-09-01

    With unknown etiology, scleroderma (SSc) is a multifaceted disease characterized by immune activation, vascular complications, and excessive fibrosis in internal organs. Genetic studies, including candidate gene association studies, genome-wide association studies, and whole-exome sequencing have supported the notion that while genetic susceptibility to SSc appears to be modest, SSc patients are genetically predisposed to this disease. The strongest genetic association for SSc lies within the MHC region, with loci in HLA-DRB1, HLA-DQB1, HLA-DPB1, and HLA-DOA1 being the most replicated. The non-HLA genes associated with SSc are involved in various functions, with the most robust associations including genes for B and T cell activation and innate immunity. Other pathways include genes involved in extracellular matrix deposition, cytokines, and autophagy. Among these genes, IRF5, STAT4, and CD247 were replicated most frequently while SNPs rs35677470 in DNASE1L3, rs5029939 in TNFAIP3, and rs7574685 in STAT4 have the strongest associations with SSc. In addition to genetic predisposition, it became clear that environmental factors and epigenetic influences also contribute to the development of SSc. Epigenetics, which refers to studies that focus on heritable phenotypes resulting from changes in chromatin structure without affecting the DNA sequence, is one of the most rapidly expanding fields in biomedical research. Indeed extensive epigenetic changes have been described in SSc. Alteration in enzymes and mediators involved in DNA methylation and histone modification, as well as dysregulated non-coding RNA levels all contribute to fibrosis, immune dysregulation, and impaired angiogenesis in this disease. Genes that are affected by epigenetic dysregulation include ones involved in autoimmunity, T cell function and regulation, TGFβ pathway, Wnt pathway, extracellular matrix, and transcription factors governing fibrosis and angiogenesis. In this review, we provide a comprehensive overview of the current findings of SSc genetic susceptibility, followed by an extensive description and a systematic review of epigenetic research that has been carried out to date in SSc. We also summarize the therapeutic potential of drugs that affect epigenetic mechanisms, and outline the future prospective of genomics and epigenomics research in SSc. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Platelet-derived growth factor receptor-β and epidermal growth factor receptor in pulmonary vasculature of systemic sclerosis-associated pulmonary arterial hypertension versus idiopathic pulmonary arterial hypertension and pulmonary veno-occlusive disease: a case-control study.

    PubMed

    Overbeek, Maria J; Boonstra, Anco; Voskuyl, Alexandre E; Vonk, Madelon C; Vonk-Noordegraaf, Anton; van Berkel, Maria P A; Mooi, Wolter J; Dijkmans, Ben A C; Hondema, Laurens S; Smit, Egbert F; Grünberg, Katrien

    2011-04-14

    Systemic sclerosis (SSc) complicated by pulmonary arterial hypertension (PAH) carries a poor prognosis, despite pulmonary vascular dilating therapy. Platelet-derived growth factor receptor-β (PDGFR-β) and epidermal growth factor receptor (EGFR) are potential therapeutic targets for PAH because of their proliferative effects on vessel remodelling. To explore their role in SScPAH, we compared PDGFR- and EGFR-mmunoreactivity in lung tissue specimens from SScPAH. We compared staining patterns with idiopathic PAH (IPAH) and pulmonary veno-occlusive disease (PVOD), as SScPAH vasculopathy differs from IPAH and sometimes displays features of PVOD. Immunoreactivity patterns of phosphorylated PDGFR-β (pPDGFR-β) and the ligand PDGF-B were evaluated to provide more insight into the patterns of PDGFR-b activation. Lung tissue specimens from five SScPAH, nine IPAH, six PVOD patients and five controls were examined. Immunoreactivity was scored for presence, distribution and intensity. All SScPAH and three of nine IPAH cases (P = 0.03) showed PDGFR-β-immunoreactivity in small vessels (arterioles/venules); of five SScPAH vs. two of nine IPAH cases (P = 0.02) showed venous immunoreactivity. In small vessels, intensity was stronger in SScPAH vs. IPAH. No differences were found between SScPAH and PVOD. One of five normal controls demonstrated focally mild immunoreactivity. There were no differences in PDGF-ligand and pPDGFR-b-immunoreactivity between patient groups; however, pPDGFR-b-immunoreactivity tended to be more prevalent in SScPAH small vasculature compared to IPAH. Vascular EGFR-immunoreactivity was limited to arterial and arteriolar walls, without differences between groups. No immunoreactivity was observed in vasculature of normals. PDGFR-β-immunoreactivity in SScPAH is more common and intense in small- and post-capillary vessels than in IPAH and does not differ from PVOD, fitting in with histomorphological distribution of vasculopathy. PDGFR-β immunoreactivity pattern is not paralleled by pPDGFR-β or PDGF-B patterns. PDGFR-β- and EGFR-immunoreactivity of pulmonary vessels distinguishes PAH patients from controls.

  8. Informatics can identify systemic sclerosis (SSc) patients at risk for scleroderma renal crisis

    PubMed Central

    Redd, Doug; Frech, Tracy M.; Murtaugh, Maureen A.; Rhiannon, Julia; Zeng, Qing T.

    2016-01-01

    Background Electronic medical records (EMR) provide an ideal opportunity for the detection, diagnosis, and management of systemic sclerosis (SSc) patients within the Veterans Health Administration (VHA). The objective of this project was to use informatics to identify potential SSc patients in the VHA that were on prednisone, in order to inform an outreach project to prevent scleroderma renal crisis (SRC). Methods The electronic medical data for this study came from Veterans Informatics and Computing Infrastructure (VINCI). For natural language processing (NLP) analysis, a set of retrieval criteria was developed for documents expected to have a high correlation to SSc. The two annotators reviewed the ratings to assemble a single adjudicated set of ratings, from which a support vector machine (SVM) based document classifier was trained. Any patient having at least one document positively classified for SSc was considered positive for SSc and the use of prednisone ≥ 10 mg in the clinical document was reviewed to determine whether it was an active medication on the prescription list. Results In the VHA, there were 4,272 patients that have a diagnosis of SSc determined by the presence of an ICD-9 code. From these patients, 1,118 patients (21%) had the use of prednisone ≥_10 mg. Of these patients, 26 had a concurrent diagnosis of hypertension, thus these patients should not be on prednisone. By the use of natural language processing (NLP) an additional 16,522 patients were identified as possible SSc, highlighting that cases of SSc in the VHA may exist that are unidentified by ICD-9. A 10-fold cross validation of the classifier resulted in a precision (positive predictive value) of 0.814, recall (sensitivity) of 0.973, and f-measure of 0.873. Conclusions Our study demonstrated that current clinical practice in the VHA includes the potentially dangerous use of prednisone for veterans with SSc. This present study also suggests there may be many undetected cases of SSc and NLP can successfully identify these patients. PMID:25168254

  9. Epstein-Barr virus lytic infection promotes activation of Toll-like receptor 8 innate immune response in systemic sclerosis monocytes.

    PubMed

    Farina, Antonella; Peruzzi, Giovanna; Lacconi, Valentina; Lenna, Stefania; Quarta, Silvia; Rosato, Edoardo; Vestri, Anna Rita; York, Michael; Dreyfus, David H; Faggioni, Alberto; Morrone, Stefania; Trojanowska, Maria; Farina, G Alessandra

    2017-02-28

    Monocytes/macrophages are activated in several autoimmune diseases, including systemic sclerosis (scleroderma; SSc), with increased expression of interferon (IFN)-regulatory genes and inflammatory cytokines, suggesting dysregulation of the innate immune response in autoimmunity. In this study, we investigated whether the lytic form of Epstein-Barr virus (EBV) infection (infectious EBV) is present in scleroderma monocytes and contributes to their activation in SSc. Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) depleted of the CD19+ cell fraction, using CD14/CD16 negative-depletion. Circulating monocytes from SSc and healthy donors (HDs) were infected with EBV. Gene expression of innate immune mediators were evaluated in EBV-infected monocytes from SSc and HDs. Involvement of Toll-like receptor (TLR)8 in viral-mediated TLR8 response was investigated by comparing the TLR8 expression induced by infectious EBV to the expression stimulated by CL075/TLR8/agonist-ligand in the presence of TLR8 inhibitor in THP-1 cells. Infectious EBV strongly induced TLR8 expression in infected SSc and HD monocytes in vitro. Markers of activated monocytes, such as IFN-regulated genes and chemokines, were upregulated in SSc- and HD-EBV-infected monocytes. Inhibiting TLR8 expression reduced virally induced TLR8 in THP-1 infected cells, demonstrating that innate immune activation by infectious EBV is partially dependent on TLR8. Viral mRNA and proteins were detected in freshly isolated SSc monocytes. Microarray analysis substantiated the evidence of an increased IFN signature and altered level of TLR8 expression in SSc monocytes carrying infectious EBV compared to HD monocytes. This study provides the first evidence of infectious EBV in monocytes from patients with SSc and links EBV to the activation of TLR8 and IFN innate immune response in freshly isolated SSc monocytes. This study provides the first evidence of EBV replication activating the TLR8 molecular pathway in primary monocytes. Immunogenicity of infectious EBV suggests a novel mechanism mediating monocyte inflammation in SSc, by which EBV triggers the innate immune response in infected cells.

  10. Direct detection of WIMPs: implications of a self-consistent truncated isothermal model of the Milky Way's dark matter halo

    NASA Astrophysics Data System (ADS)

    Chaudhury, Soumini; Bhattacharjee, Pijushpani; Cowsik, Ramanath

    2010-09-01

    Direct detection of Weakly Interacting Massive Particle (WIMP) candidates of Dark Matter (DM) is studied within the context of a self-consistent truncated isothermal model of the finite-size dark halo of the Galaxy. The halo model, based on the ``King model'' of the phase space distribution function of collisionless DM particles, takes into account the modifications of the phase-space structure of the halo due to the gravitational influence of the observed visible matter in a self-consistent manner. The parameters of the halo model are determined by a fit to a recently determined circular rotation curve of the Galaxy that extends up to ~ 60 kpc. Unlike in the Standard Halo Model (SHM) customarily used in the analysis of the results of WIMP direct detection experiments, the velocity distribution of the WIMPs in our model is non-Maxwellian with a cut-off at a maximum velocity that is self-consistently determined by the model itself. For our halo model that provides the best fit to the rotation curve data, the 90% C.L. upper limit on the WIMP-nucleon spin-independent cross section from the recent results of the CDMS-II experiment, for example, is ~ 5.3 × 10-8 pb at a WIMP mass of ~ 71 GeV. We also find, using the original 2-bin annual modulation amplitude data on the nuclear recoil event rate seen in the DAMA experiment, that there exists a range of small WIMP masses, typically ~ 2-16 GeV, within which DAMA collaboration's claimed annual modulation signal purportedly due to WIMPs is compatible with the null results of other experiments. These results, based as they are on a self-consistent model of the dark matter halo of the Galaxy, strengthen the possibility of low-mass (lsim10 GeV) WIMPs as a candidate for dark matter as indicated by several earlier studies performed within the context of the SHM. A more rigorous analysis using DAMA bins over smaller intervals should be able to better constrain the ``DAMA regions'' in the WIMP parameter space within the context of our model.

  11. 2013 ACR/EULAR systemic sclerosis classification criteria in patients with associated pulmonary arterial hypertension.

    PubMed

    Joven, Beatriz E; Escribano, Pilar; Andreu, Jose Luis; Loza, Estibaliz; Jimenez, Carmen; de Yebenes, M Jesus Garcia; Ruiz-Cano, M Jose; Carmona, Loreto; Carreira, Patricia E

    2018-06-01

    To analyze the performance of the 1980 ACR and new 2013 ACR/EULAR criteria for systemic sclerosis (SSc) in cutaneous SSc (lcSSc) patients, especially those affected by lcSSc and pulmonary arterial hypertension (PAH). All patients with a clinical lcSSc diagnosis from a prospective observational SSc cohort were included. Sociodemographic and disease-related variables were collected, and PAH confirmed by right heart catheterization (RHC). Performance of the 2013 and 1980 SSc criteria was analyzed in terms of clinical diagnosis. Descriptive and between-group analyses were performed as to the fulfillment of criterion sets, including comparison of survival. Overall, 321 patients were included, 63% of whom fulfilled the 1980 ACR and 93% the 2013 ACR/EULAR criteria. Agreement between both criteria sets proved poor (κ = 0.23). LcSSC patients fulfilling both criterion sets were significantly younger at diagnosis, whilst presenting organ involvement, calcinosis, fingertip digital ulcers, and pitting scars more frequently than those who met the 2013 criteria only. Patients who fulfilled the 2013 but not the 1980 criteria presented a higher degree of ACA positivity and PAH. Nearly 12% of patients developed PAH. Patients who did not meet the 1980 criteria were affected by a milder disease from but demonstrated higher pulmonary vascular resistance and lower cardiac index than those fulfilling both criterion sets. Whereas patients with PAH met the 2013 criteria, only 47% fulfilled the 1980 criteria. Regardless of criterion set fulfillment, high mortality was observed in PAH patients, with no significant between-patient difference based on criterion set. The new 2013 ARC/EULAR criteria prove more accurate than the former 1980 ACR criteria in identifying and differentiating patients with lcSSc, especially those with associated PAH. Since PAH exhibits a better prognosis if treated early, all SSc patients should undergo PAH screening. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Improving the quality of adult mortality data collected in demographic surveys: validation study of a new siblings' survival questionnaire in Niakhar, Senegal.

    PubMed

    Helleringer, Stéphane; Pison, Gilles; Masquelier, Bruno; Kanté, Almamy Malick; Douillot, Laetitia; Duthé, Géraldine; Sokhna, Cheikh; Delaunay, Valérie

    2014-05-01

    In countries with limited vital registration, adult mortality is frequently estimated using siblings' survival histories (SSHs) collected during Demographic and Health Surveys (DHS). These data are affected by reporting errors. We developed a new SSH questionnaire, the siblings' survival calendar (SSC). It incorporates supplementary interviewing techniques to limit omissions of siblings and uses an event history calendar to improve reports of dates and ages. We hypothesized that the SSC would improve the quality of adult mortality data. We conducted a retrospective validation study among the population of the Niakhar Health and Demographic Surveillance System in Senegal. We randomly assigned men and women aged 15-59 y to an interview with either the DHS questionnaire or the SSC. We compared SSHs collected in each group to prospective data on adult mortality collected in Niakhar. The SSC reduced respondents' tendency to round reports of dates and ages to the nearest multiple of five or ten ("heaping"). The SSC also had higher sensitivity in recording adult female deaths: among respondents whose sister(s) had died at an adult age in the past 15 y, 89.6% reported an adult female death during SSC interviews versus 75.6% in DHS interviews (p = 0.027). The specificity of the SSC was similar to that of the DHS questionnaire, i.e., it did not increase the number of false reports of deaths. However, the SSC did not improve the reporting of adult deaths among the brothers of respondents. Study limitations include sample selectivity, limited external validity, and multiple testing. The SSC has the potential to collect more accurate SSHs than the questionnaire used in DHS. Further research is needed to assess the effects of the SSC on estimates of adult mortality rates. Additional validation studies should be conducted in different social and epidemiological settings. Controlled-Trials.com ISRCTN06849961

  13. Simplex-stochastic collocation method with improved scalability

    NASA Astrophysics Data System (ADS)

    Edeling, W. N.; Dwight, R. P.; Cinnella, P.

    2016-04-01

    The Simplex-Stochastic Collocation (SSC) method is a robust tool used to propagate uncertain input distributions through a computer code. However, it becomes prohibitively expensive for problems with dimensions higher than 5. The main purpose of this paper is to identify bottlenecks, and to improve upon this bad scalability. In order to do so, we propose an alternative interpolation stencil technique based upon the Set-Covering problem, and we integrate the SSC method in the High-Dimensional Model-Reduction framework. In addition, we address the issue of ill-conditioned sample matrices, and we present an analytical map to facilitate uniformly-distributed simplex sampling.

  14. Molecular stratification and precision medicine in systemic sclerosis from genomic and proteomic data.

    PubMed

    Martyanov, Viktor; Whitfield, Michael L

    2016-01-01

    The goal of this review is to summarize recent advances into the pathogenesis and treatment of systemic sclerosis (SSc) from genomic and proteomic studies. Intrinsic gene expression-driven molecular subtypes of SSc are reproducible across three independent datasets. These subsets are a consistent feature of SSc and are found in multiple end-target tissues, such as skin and esophagus. Intrinsic subsets as well as baseline levels of molecular target pathways are potentially predictive of clinical response to specific therapeutics, based on three recent clinical trials. A gene expression-based biomarker of modified Rodnan skin score, a measure of SSc skin severity, can be used as a surrogate outcome metric and has been validated in a recent trial. Proteome analyses have identified novel biomarkers of SSc that correlate with SSc clinical phenotypes. Integrating intrinsic gene expression subset data, baseline molecular pathway information, and serum biomarkers along with surrogate measures of modified Rodnan skin score provides molecular context in SSc clinical trials. With validation, these approaches could be used to match patients with the therapies from which they are most likely to benefit and thus increase the likelihood of clinical improvement.

  15. Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

    PubMed Central

    Chaisson, Neal F.

    2013-01-01

    Pulmonary arterial hypertension (PAH) is the leading cause of death in systemic sclerosis (SSc) and affects up to 12% of all patients with SSc, with a 50% mortality rate within 3 years of PAH diagnosis. Compared with the idiopathic form of PAH (IPAH), patients with SSc-associated PAH (SSc-PAH) have a threefold increased risk of death and may receive a diagnosis late in the course of disease because of insidious onset and the high prevalence of cardiac, musculoskeletal, and pulmonary parenchymal comorbidities. Treatment with conventional forms of PAH therapy often yield poor results compared with IPAH cohorts; unfortunately, the exact reasons behind this remain poorly understood but likely include variations in the pathologic mechanisms, differences in cardiovascular response to increasing afterload, and inadequate strategies to detect and treat SSc-PAH early in its course. Current methods for screening and longitudinal evaluation of SSc-PAH, such as the 6-min walk test, transthoracic echocardiography, and MRI, each have notable advantages and disadvantages. We provide an up-to-date, focused review of SSc-PAH and how it differs from IPAH, including pathogenesis, appropriate screening for disease onset, and new approaches to treatment and longitudinal assessment of this disease. PMID:24081346

  16. Controls on sublithospheric small-scale convection on Curie depths

    NASA Astrophysics Data System (ADS)

    Likerman, Jeremias; Zlotnik, Sergio; Chun-Feng, Li

    2017-04-01

    As the ocean lithosphere cools and thickens, its bottom layer goes unstable leading to sub-lithospheric small-scale convection (SSC). Since SSC was originally proposed, there have been considerable efforts regarding the understanding of the physics that rules the thermal instabilities of the SSC (e.g. Dumoulin et al, 1999; Solomatov and Moresi, 2000). Over the last several years, it is understood that the interaction between the plate movement and the SSC tends to form longitudinal (LRs or also called 'Richter rolls') and transverse rolls (TRs), of which the axis is parallel and perpendicular to the plate motion, respectively. The geometry of these rolls have been been recently inferred by Li et al (2013) using Curie depths from the North Atlantic as proxies for plates temperatures. They showed that Curie depths have a large oscillating and heterogeneous patterns that could be related to SSC. In the North Atlantic transverse rolls seem predominant. In this work we analyze, by means of 3D dynamical numerical simulations, the influence of SSC on the Curie depths patterns observed in the North Atlantic and Pacific plates. We investigate the behaviour of the Curie isotherms trying to determine if SSC is able to reproduce the observed data, and the influence of several poorly constrained rheological parameters. Our numerical simulations show that: a) using realistic laboratory-constrained rheologies and temperature it is possible to modify temperatures as low as those at Curie depths; b) transverse rolls are generated as well as longitudinal rolls on those isotherms; c) the spreading rate is a first order control on the developing of transverse rolls. References Dumoulin, C., Doin, M. P., & Fleitout, L. (1999). Heat transport in stagnant lid convection with temperature-and pressure-dependent Newtonian or non-Newtonian rheology. Journal of Geophysical Research: Solid Earth, 104(B6), 12759-12777. Li, C. F., Wang, J., Lin, J., & Wang, T. (2013). Thermal evolution of the North Atlantic lithosphere: new constraints from magnetic anomaly inversion with a fractal magnetization model. Geochemistry, Geophysics, Geosystems, 14(12), 5078-5105. Solomatov, V. S., & Moresi, L. N. (2000). Scaling of time-dependent stagnant lid convection: Application to small-scale convection on Earth and other terrestrial planets. Journal of Geophysical Research: Solid Earth, 105(B9), 21795-21817.

  17. Sacroiliac joint involvement in systemic sclerosis.

    PubMed

    Arslan Tas, Didem; Yıldız, Fatih; Sakallı, Hakan; Kelle, Bayram; Ballı, Tuğsan; Erken, Eren

    2015-01-01

    One of the major problems for systemic sclerosis (SSc) patients is suggested to be articular involvement. Mostly involved joints in SSc were reported as wrist, carpometacarpal-interphalangeal, foot, knee, hip and shoulder; however, there has been little knowledge on the sacroiliac joint. Our aim was to evaluate sacroiliac joint involvement in SSc. Fifty-seven SSc patients, 54 rheumatoid arthritis patients and 64 healthy subjects were included. Anteroposterior pelvic radiographs were obtained and graded twice by three blinded rheumatologists. One competent radiologist has re-evaluated the X-ray results. The ASAS (Assessment of Spondylo Arthritis International Society) scoring method was applied for grading sacroiliac involvement. Inflammatory back pain was also evaluated. Other clinical and laboratory data were collected as proposed by the European Study Group. In the SSc group sacroiliitis was found in 13 patients (23%) and was significantly different from RA patients (two patients, 4%), P = 0.003; and the healthy control group (one participant, 2%), P < 0.001. The frequency of inflammatory back pain in SSc patients with sacroiliitis (8/13 patients, 62%) was significantly higher in SSc patients without sacroiliitis (4/44 patients, 9%), P < 0.001. The SSc patients with sacroiliitis and with inflammatory back pain (8/57 patients, 14%) were regarded as axial spondyloarthritis overlap. Male gender, diffuse subtype, inflammatory back pain and high C-reactive protein levels (odds ratio: 1.069, 1.059, 1.059 and 3.698, respectively) were found to be the significant risk factors for sacroiliitis. We suggest that, sacroiliitis may be a concern to be considered in SSc practice. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  18. Unique Abnormalities in Right Ventricular Longitudinal Strain in Systemic Sclerosis Patients.

    PubMed

    Mukherjee, Monica; Chung, Shang-En; Ton, Von Khue; Tedford, Ryan J; Hummers, Laura K; Wigley, Fredrick M; Abraham, Theodore P; Shah, Ami A

    2016-06-01

    Cardiac involvement in systemic sclerosis (scleroderma [SSc]) adversely affects long-term prognosis, often remaining undetectable despite close clinical examination and 2-dimensional echocardiographic monitoring. Speckle-derived strain of the right ventricle (RV) was utilized to detect occult abnormalities in regional and global contractility in SSc patients. A total of 138 SSc patients with technically adequate echocardiograms was studied and compared with 40 age- and sex-matched healthy non-SSc controls. Standard assessment of RV chamber function included tricuspid annular plane systolic excursion and fractional area change. RV longitudinal systolic speckle-derived strain was assessed in the basal, mid, and apical free wall. Tricuspid annular plane systolic excursion was not different between groups (P=0.307). Although fractional area change was lower in SSc patients than in controls (mean, 48.9 versus 55; P=0.002), the mean fractional area change was still within the normal range (>35). In contrast, RV longitudinal systolic speckle-derived strain measures were significantly different between groups, both globally (-20.4% versus -17.7%; P=0.005) and regionally: they were decreased in the apex (-8.5% versus -17.1%; P<0.0001) and mid segments (-12.4% versus -20.9%; P<0.0001), and increased in the base (-32.2% versus -23.3%; P=0.0001) for the SSc group. The regional difference in the base compared with the apex was significantly greater for SSc than for controls (P<0.0001 for interaction). The differences observed in regional strain between SSc and control were unchanged after adjusting for RV systolic pressure. Speckle-derived strain reveals a heterogenous pattern of regional heart strain in SSc that is not detected by conventional measures of function, suggestive of occult RV myocardial disease. © 2016 American Heart Association, Inc.

  19. Screening of thermophilic anaerobic bacteria for solid substrate cultivation on lignocellulosic substrates.

    PubMed

    Chinn, Mari S; Nokes, Sue E; Strobel, Herbert J

    2006-01-01

    Interest in solid substrate cultivation (SSC) techniques is gaining for biochemical production from renewable resources; however, heat and mass transfer problems may limit application of this technique. The use of anaerobic thermophiles in SSC offers a unique solution to overcoming these challenges. The production potential of nine thermophilic anaerobic bacteria was examined on corn stover, sugar cane bagasse, paper pulp sludge, and wheat bran in submerged liquid cultivation (SmC) and SSC. Production of acetate, ethanol, and lactate was measured over a 10 day period, and total product concentrations were used to compare the performance of different organism-substrate combinations using the two cultivation methods. Overall microbial activity in SmC and SSC was dependent on the organism and growth substrate. Clostridium thermocellum strains JW20, LQRI, and 27405 performed significantly better in SSC when grown on sugar cane bagasse and paper pulp sludge, producing at least 70 and 170 mM of total products, respectively. Growth of C. thermocellum strains in SSC on paper pulp sludge proved to be most favorable, generating at least twice the concentration of total products produced in SmC (p-value < 0.05). Clostridium thermolacticum TC21 demonstrated growth on all substrates producing 30-80 and 60-116 mM of total product in SmC and SSC, respectively. Bacterial species with optimal growth temperatures of 70 degrees C grew best on wheat bran in SmC, producing total product concentrations of 45-75 mM. For some of the organism-substrate combinations total end product concentrations in SSC exceeded those in SmC, indicating that SSC may be a promising alternative for microbial activity and value-added biochemical production.

  20. Cross-disease Meta-analysis of Genome-wide Association Studies for Systemic Sclerosis and Rheumatoid Arthritis Reveals IRF4 as a New Common Susceptibility Locus

    PubMed Central

    López-Isac, Elena; Martín, Jose-Ezequiel; Assassi, Shervin; Simeón, Carmen P; Carreira, Patricia; Ortego-Centeno, Norberto; Freire, Mayka; Beltrán, Emma; Narváez, Javier; Alegre-Sancho, Juan J; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; Ortiz, Ana M; González-Gay, Miguel A; Beretta, Lorenzo; Santaniello, Alessandro; Bellocchi, Chiara; Lunardi, Claudio; Moroncini, Gianluca; Gabrielli, Armando; Witte, Torsten; Hunzelmann, Nicolas; Distler, Jörg HW; Riekemasten, Gabriella; van der Helm-van Mil, Annete H; de Vries-Bouwstra, Jeska; Magro-Checa, Cesar; Voskuyl, Alexandre E; Vonk, Madelon C; Molberg, Øyvind; Merriman, Tony; Hesselstrand, Roger; Nordin, Annika; Padyukov, Leonid; Herrick, Ariane; Eyre, Steve; Koeleman, Bobby PC; Denton, Christopher P; Fonseca, Carmen; Radstake, Timothy RDJ; Worthington, Jane; Mayes, Maureen D; Martín, Javier

    2017-01-01

    Objectives Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that share clinical and immunological characteristics. To date, several shared SSc-RA loci have been identified independently. In this study, we aimed to systematically search for new common SSc-RA loci through an inter-disease meta-GWAS strategy. Methods We performed a meta-analysis combining GWAS datasets of SSc and RA using a strategy that allowed identification of loci with both same-direction and opposing-direction allelic effects. The top single-nucleotide polymorphisms (SNPs) were followed-up in independent SSc and RA case-control cohorts. This allowed us to increase the sample size to a total of 8,830 SSc patients, 16,870 RA patients and 43,393 controls. Results The cross-disease meta-analysis of the GWAS datasets identified several loci with nominal association signals (P-value < 5 × 10-6), which also showed evidence of association in the disease-specific GWAS scan. These loci included several genomic regions not previously reported as shared loci, besides risk factors associated with both diseases in previous studies. The follow-up of the putatively new SSc-RA loci identified IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 × 10-12). In addition, the analysis of the biological relevance of the known SSc-RA shared loci pointed to the type I interferon and the interleukin 12 signaling pathways as the main common etiopathogenic factors. Conclusions Our study has identified a novel shared locus, IRF4, for SSc and RA and highlighted the usefulness of cross-disease GWAS meta-analysis in the identification of common risk loci. PMID:27111665

  1. Systems Level Analysis of Systemic Sclerosis Shows a Network of Immune and Profibrotic Pathways Connected with Genetic Polymorphisms

    PubMed Central

    Mahoney, J. Matthew; Taroni, Jaclyn; Martyanov, Viktor; Wood, Tammara A.; Greene, Casey S.; Pioli, Patricia A.; Hinchcliff, Monique E.; Whitfield, Michael L.

    2015-01-01

    Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited) are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6–12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes using a gene-gene interaction network, and place the genetic risk loci in the context of the intrinsic subsets. To identify gene expression modules common to three independent datasets from three different clinical centers, we developed a consensus clustering procedure based on mutual information of partitions, an information theory concept, and performed a meta-analysis of these genome-wide gene expression datasets. We created a gene-gene interaction network of the conserved molecular features across the intrinsic subsets and analyzed their connections with SSc-associated genetic polymorphisms. The network is composed of distinct, but interconnected, components related to interferon activation, M2 macrophages, adaptive immunity, extracellular matrix remodeling, and cell proliferation. The network shows extensive connections between the inflammatory- and fibroproliferative-specific genes. The network also shows connections between these subset-specific genes and 30 SSc-associated polymorphic genes including STAT4, BLK, IRF7, NOTCH4, PLAUR, CSK, IRAK1, and several human leukocyte antigen (HLA) genes. Our analyses suggest that the gene expression changes underlying the SSc subsets may be long-lived, but mechanistically interconnected and related to a patients underlying genetic risk. PMID:25569146

  2. A loss of telocytes accompanies fibrosis of multiple organs in systemic sclerosis

    PubMed Central

    Manetti, Mirko; Rosa, Irene; Messerini, Luca; Guiducci, Serena; Matucci-Cerinic, Marco; Ibba-Manneschi, Lidia

    2014-01-01

    Systemic sclerosis (SSc) is a complex connective tissue disease characterized by fibrosis of the skin and various internal organs. In SSc, telocytes, a peculiar type of stromal (interstitial) cells, display severe ultrastructural damages and are progressively lost from the clinically affected skin. The aim of the present work was to investigate the presence and distribution of telocytes in the internal organs of SSc patients. Archival paraffin-embedded samples of gastric wall, myocardium and lung from SSc patients and controls were collected. Tissue sections were stained with Masson's trichrome to detect fibrosis. Telocytes were studied on tissue sections subjected to CD34 immunostaining. CD34/CD31 double immunofluorescence was performed to unequivocally differentiate telocytes (CD34-positive/CD31-negative) from vascular endothelial cells (CD34-positive/CD31-positive). Few telocytes entrapped in the fibrotic extracellular matrix were found in the muscularis mucosae and submucosa of SSc gastric wall. In the muscle layers and myenteric plexus, the network of telocytes was discontinuous or even completely absent around smooth muscle cells and ganglia. Telocytes were almost completely absent in fibrotic areas of SSc myocardium. In SSc fibrotic lung, few or no telocytes were observed in the thickened alveolar septa, around blood vessels and in the interstitial space surrounding terminal and respiratory bronchioles. In SSc, the loss of telocytes is not restricted to the skin, but it is a widespread process affecting multiple organs targeted by the fibrotic process. As telocytes are believed to be key players in the regulation of tissue/organ homoeostasis, our data suggest that telocyte loss might have important pathophysiological implications in SSc. PMID:24467430

  3. DNA methylation similarities in genes of black South Africans with systemic lupus erythematosus and systemic sclerosis.

    PubMed

    Matatiele, Puleng; Tikly, Mohamed; Tarr, Gareth; Gulumian, Mary

    2015-05-20

    Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are systemic autoimmune connective tissue diseases that share overlapping clinico-pathological features. It is highly probable that there is an overlap in epigenetic landscapes of both diseases. This study aimed to identify similarities in DNA methylation changes in genes involved in SLE and SSc. Global DNA methylation and twelve genes selected on the basis of their involvement in inflammation, autoimmunity and/or fibrosis were analyzed using PCR arrays in three groups, each of 30 Black South Africans with SLE and SSc, plus 40 healthy control subjects. Global methylation in both diseases was significantly lower (<25 %) than in healthy subjects (>30 %, p = 0.0000001). In comparison to healthy controls, a similar gene-specific methylation pattern was observed in both SLE and SSc. Three genes, namely; PRF1, ITGAL and FOXP3 were consistently hypermethylated while CDKN2A and CD70 were hypomethylated in both diseases. The other genes (SOCS1, CTGF, THY1, CXCR4, MT1-G, FLI1, and DNMT1) were generally hypomethylated in SLE whereas they were neither hyper- nor hypo-methylated in SSc. SSc and SLE patients have a higher global hypomethylation than healthy subjects with specific genes being hypomethylated and others hypermethylated. The majority of genes studied were hypomethylated in SLE compared to SSc. In addition to the commonly known hypomethylated genes in SLE and SSc, there are other hypomethylated genes (such as MT-1G and THY-1) that have not previously been investigated in SLE and SSc though are known to be hypermethylated in cancer.

  4. Impairment of endothelial cell differentiation from bone marrow-derived mesenchymal stem cells: new insight into the pathogenesis of systemic sclerosis.

    PubMed

    Cipriani, P; Guiducci, S; Miniati, I; Cinelli, M; Urbani, S; Marrelli, A; Dolo, V; Pavan, A; Saccardi, R; Tyndall, A; Giacomelli, R; Cerinic, M Matucci

    2007-06-01

    Systemic sclerosis (SSc) is a disorder characterized by vascular damage and fibrosis of the skin and internal organs. Despite marked tissue hypoxia, there is no evidence of compensatory angiogenesis. The ability of mesenchymal stem cells (MSCs) to differentiate into endothelial cells was recently demonstrated. The aim of this study was to determine whether impaired differentiation of MSCs into endothelial cells in SSc might contribute to disease pathogenesis by decreasing endothelial repair. MSCs obtained from 7 SSc patients and 15 healthy controls were characterized. The number of colony-forming unit-fibroblastoid colonies was determined. After culture in endothelial-specific medium, the endothelial-like MSC (EL-MSC) phenotype was assessed according to the surface expression of vascular endothelial growth factor receptors (VEGFRs). Senescence, chemoinvasion, and capillary morphogenesis studies were also performed. MSCs from SSc patients displayed the same phenotype and clonogenic activity as those from controls. In SSc MSCs, a decreased percentage of VEGFR-2+, CXCR4+, VEGFR-2+/CXCR4+ cells and early senescence was detected. After culturing, SSc EL-MSCs showed increased expression of VEGFR-1, VEGFR-2, and CXCR4, did not express CD31 or annexin V, and showed significantly decreased migration after specific stimuli. Moreover, the addition of VEGF and stromal cell-derived factor 1 to cultured SSc EL-MSCs increased their angiogenic potential less than that in controls. Our data strongly suggest that endothelial repair may be affected in SSc. The possibility that endothelial progenitor cells could be used to increase vessel growth in chronic ischemic tissues may open up new avenues in the treatment of vascular damage caused by SSc.

  5. Inspiring the Next Generation of Naval Scientists and Engineers in Mississippi and Louisiana

    NASA Astrophysics Data System (ADS)

    Breland-Mensi, S.; Calantoni, J.

    2012-12-01

    In 2011, the American Institute of Physics ranked Mississippi 50th out of 50 states in preparing students for science, technology, engineering and math (STEM) careers. Louisiana placed 48th on the list. [1] The Naval Research Laboratory - Stennis Space Center detachment (NRL-SSC) is located on the Mississippi Gulf Coast, approximately 2 miles from the Louisiana state line. In response to a growing need for NRL-SSC to sustain recruitment and retention of the best and brightest scientists and engineers (S&Es), NRL-SSC became a National Defense Education Program (NDEP) site in August 2009. NDEP's mission is to support a new generation of S&Es who will apply their talents in U.S. Defense laboratories. As an NDEP site, NRL-SSC receives funding to promote STEM at K-12 institutions geographically local to NRL-SSC. NDEP funding allows present Department of Defense civilian S&Es to collaborate with teachers to enrich student learning in the classroom environment through various programs, events, training and activities. Since NRL-SSC's STEM program's inception, more than 30 S&Es have supported an array of STEM outreach activities in over 30 different local schools. An important part of the K-12 outreach from NRL-SSC is to provide professional development opportunities for local teachers. During the summer of 2012, in collaboration with STEM programs sponsored by the Office of Naval Research (ONR), we provided a series of professional development opportunities for 120 local science and mathematics teachers across K-12. The foundation of NRL-SSC STEM programs includes MATHCOUNTS, FIRST and SeaPerch—all nationally recognized, results-driven programs. We will discuss the breadth of participation in these programs and how these programs will support NRL-SSC future recruitment goals.

  6. Self-Consistent Ring Current Modeling with Propagating Electromagnetic Ion Cyclotron Waves in the Presence of Heavy Ions

    NASA Technical Reports Server (NTRS)

    Khazanov, George V.

    2006-01-01

    The self-consistent treatment of the RC ion dynamics and EMIC waves, which are thought to exert important influences on the ion dynamical evolution, is an important missing element in our understanding of the storm-and recovery-time ring current evolution. Under certain conditions, relativistic electrons, with energies 21 MeV, can be removed from the outer radiation belt by EMIC wave scattering during a magnetic storm. That is why the modeling of EMIC waves is critical and timely issue in magnetospheric physics. To describe the RC evolution itself this study uses the ring current-atmosphere interaction model (RAM). RAM solves the gyration and bounce-averaged Boltzmann-Landau equation inside of geosynchronous orbit. Originally developed at the University of Michigan, there are now several branches of this model currently in use as describe by Liemohn namely those at NASA Goddard Space Flight Center This study will generalize the self-consistent theoretical description of RC ions and EMIC waves that has been developed by Khazanov and include the heavy ions and propagation effects of EMIC waves in the global dynamic of self-consistent RC - EMIC waves coupling. The results of our newly developed model that will be presented at GEM meeting, focusing mainly on the dynamic of EMIC waves and comparison of these results with the previous global RC modeling studies devoted to EMIC waves formation. We also discuss RC ion precipitations and wave induced thermal electron fluxes into the ionosphere.

  7. Large Eddy Simulation of jets laden with evaporating drops

    NASA Technical Reports Server (NTRS)

    Leboissetier, A.; Okong'o, N.; Bellan, J.

    2004-01-01

    LES of a circular jet laden with evaporating liquid drops are conducted to assess computational-drop modeling and three different SGS-flux models: the Scale Similarity model (SSC), using a constant coefficient calibrated on a temporal mixing layer DNS database, and dynamic-coefficient Gradient and Smagorinsky models.

  8. Shared services centers and work sustainability: which contributions from ergonomics?

    PubMed

    Arnoud, Justine; Falzon, Pierre

    2012-01-01

    This study examines the way in which Shared Services Centers (SSCs) were implemented in a French multinational company. It aims to characterize the change according to the capabilities model developed by Amartya Sen: what are the effects of SSCs in terms of capabilities development and developmental quality of work, i.e. in the enabling potential of work? A 3-step methodology has been used: first, an investigation was conducted in a pay service of a local entity moving into SSC in 2013; second, two investigations were conducted in another pay service of a SSC: first, a few months after the change, and then, one year after the change (the same operators were interviewed). Results show a tendency to the decrease of the enabling potential. Additionally, it was noted that administrators are kept away from the design process and have to struggle with inappropriate rules. The efficiency and sustainability of the SSC are questioned; in this context, the human factor specialist has an important role to play.

  9. Temporal variation of floc size and settling velocity in the Dollard estuary

    NASA Astrophysics Data System (ADS)

    Van der Lee, Willem T. B.

    2000-09-01

    Temporal changes in floc size and settling velocity were measured in the Dollard estuary with an under water video camera. The results show that the flocs in the Dollard are very heterogeneous and that larger flocs have much lower effective densities than smaller flocs. Due to this density decrease, floc settling velocities show only a minor increase with increasing floc size. Floc sizes and settling velocities correlate with the suspended sediment concentration (SSC) on a tidal time scale, but not on a seasonal time scale. On a seasonal time scale floc sizes depend on the binding properties of the sediment, while floc settling velocities show hardly any variation, as an increase in floc size is mainly counterbalanced by a decrease in floc density. Tidal variations in settling velocity occur but cannot be modeled solely as a function of SSC, as the relation between floc size/settling velocity and SSC constantly changes in time and space. Settling velocity variations throughout the tide can however be expressed as a function of tidal phase.

  10. An Ultrasound Surface Wave Technique for Assessing Skin and Lung Diseases.

    PubMed

    Zhang, Xiaoming; Zhou, Boran; Kalra, Sanjay; Bartholmai, Brian; Greenleaf, James; Osborn, Thomas

    2018-02-01

    Systemic sclerosis (SSc) is a multi-organ connective tissue disease characterized by immune dysregulation and organ fibrosis. Severe organ involvement, especially of the skin and lung, is the cause of morbidity and mortality in SSc. Interstitial lung disease (ILD) includes multiple lung disorders in which the lung tissue is fibrotic and stiffened. The purpose of this study was to translate ultrasound surface wave elastography (USWE) for assessing patients with SSc and/or ILD via measuring surface wave speeds of both skin and superficial lung tissue. Forty-one patients with both SSc and ILD and 30 healthy patients were enrolled in this study. An external harmonic vibration was used to generate the wave propagation on the skin or lung. Three excitation frequencies of 100, 150 and 200 Hz were used. An ultrasound probe was used to measure the wave propagation in the tissue non-invasively. Surface wave speeds were measured on the forearm and upper arm of both left and right arm, as well as the upper and lower lungs, through six intercostal spaces of patients and healthy patients. Viscoelasticity of the skin was calculated by the wave speed dispersion with frequency using the Voigt model. The magnitudes of surface wave speed and viscoelasticity of patients' skin were significantly higher than those of healthy patients (p <0.0001) for each location and each frequency. The surface wave speeds of patients' lung were significantly higher than those of healthy patients (p <0.0001) for each location and each frequency. USWE is a non-invasive and non-ionizing technique for measuring both skin and lung surface wave speed and may be useful for quantitative assessment of SSc and/or ILD. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

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

    Dahl, P.F.

    The magnet system for the Superconducting Super Collider will likely remain the most ambitions-and challenging-application of superconducting technology for the foreseeable future. The centerpiece of the system is the behemoth collider dipole magnet. Its design, still evolving in its detailed features, dates from the mid-1980's when it emerged as the winter in an early technical showdown that occupied the fledgling SSC project. In the present report we chronicle the origins and chief milestones in the development of certain SSC dipole design concepts. Unfortunately, the chronicle must remain incomplete, with the design not yet frozen as we go to press andmore » still subject to important modifications as the SSC Laboratory settles in near its future home in Ellis County, Texas, hard on the heels of a wide-ranging design review in the closing days of the SSC Central Design Group in (CDG) Berkeley. Be that as it may, in what follows we concentrate on the early years in an attempt to recapitulate the birth of the dipole, taking as our point of departure the SSC Reference Designs Study (RDS) of 1984. In Section 3 we touch on the background for the various RDS options, including ISABELLE/CBA and the Tevatron. In Section 4 the narrative focuses on the two final protagonists, a high-field cosine theta (cos {theta}) magnet and a low-field superferric magnet. Section 5 recounts the circumstances surrounding the selection of a particular magnet style'' for further development, and the ups and downs of the first model magnets. We conclude with a smattering of progress highlights in refining the design during the final push under the reign of the CDG. Beyond that, the ongoing chronicle must be left for others to amplify and complete.« less

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

    Dahl, P.F.

    The magnet system for the Superconducting Super Collider will likely remain the most ambitions-and challenging-application of superconducting technology for the foreseeable future. The centerpiece of the system is the behemoth collider dipole magnet. Its design, still evolving in its detailed features, dates from the mid-1980`s when it emerged as the winter in an early technical showdown that occupied the fledgling SSC project. In the present report we chronicle the origins and chief milestones in the development of certain SSC dipole design concepts. Unfortunately, the chronicle must remain incomplete, with the design not yet frozen as we go to press andmore » still subject to important modifications as the SSC Laboratory settles in near its future home in Ellis County, Texas, hard on the heels of a wide-ranging design review in the closing days of the SSC Central Design Group in (CDG) Berkeley. Be that as it may, in what follows we concentrate on the early years in an attempt to recapitulate the birth of the dipole, taking as our point of departure the SSC Reference Designs Study (RDS) of 1984. In Section 3 we touch on the background for the various RDS options, including ISABELLE/CBA and the Tevatron. In Section 4 the narrative focuses on the two final protagonists, a high-field cosine theta (cos {theta}) magnet and a low-field superferric magnet. Section 5 recounts the circumstances surrounding the selection of a particular magnet ``style`` for further development, and the ups and downs of the first model magnets. We conclude with a smattering of progress highlights in refining the design during the final push under the reign of the CDG. Beyond that, the ongoing chronicle must be left for others to amplify and complete.« less

  13. Activity-dependent decrease in contact areas between subsurface cisterns and plasma membrane of hippocampal neurons.

    PubMed

    Tao-Cheng, Jung-Hwa

    2018-04-16

    Subsurface cistern (SSC) in neuronal soma and primary dendrites is a specialized compartment of endoplasmic reticulum (ER) that is in close apposition (10 nm) with the plasma membrane (PM). ER-PM contact areas are thought to be involved in intracellular calcium regulation. Here, structural changes of SSC in hippocampal neurons were examined by electron microscopy upon depolarization with high K + (90 mM) or application of NMDA (50 μM) in rat dissociated cultures as well as organotypic slice cultures. The number and average length of SSC-PM contact areas in neuronal somas significantly decreased within 30 s under excitatory condition. This decrease in SSC-PM contact area progressed with time and was reversible. These results demonstrate a structural decoupling between the SSC and the PM upon stimulation, suggesting that there may be a functional decoupling of the calcium regulation. Because SSC-PM contact areas may mediate calcium influx, the decrease in contact area may protect neurons from calcium overload upon heightened stimulation.

  14. Self-consistent large- N analytical solutions of inhomogeneous condensates in quantum ℂP N - 1 model

    NASA Astrophysics Data System (ADS)

    Nitta, Muneto; Yoshii, Ryosuke

    2017-12-01

    We give, for the first time, self-consistent large- N analytical solutions of inhomogeneous condensates in the quantum ℂP N - 1 model in the large- N limit. We find a map from a set of gap equations of the ℂP N - 1 model to those of the Gross-Neveu (GN) model (or the gap equation and the Bogoliubov-de Gennes equation), which enables us to find the self-consistent solutions. We find that the Higgs field of the ℂP N - 1 model is given as a zero mode of solutions of the GN model, and consequently only topologically non-trivial solutions of the GN model yield nontrivial solutions of the ℂP N - 1 model. A stable single soliton is constructed from an anti-kink of the GN model and has a broken (Higgs) phase inside its core, in which ℂP N - 1 modes are localized, with a symmetric (confining) phase outside. We further find a stable periodic soliton lattice constructed from a real kink crystal in the GN model, while the Ablowitz-Kaup-Newell-Segur hierarchy yields multiple solitons at arbitrary separations.

  15. Lopsidedness of Self-consistent Galaxies Caused by the External Field Effect of Clusters

    NASA Astrophysics Data System (ADS)

    Wu, Xufen; Wang, Yougang; Feix, Martin; Zhao, HongSheng

    2017-08-01

    Adopting Schwarzschild’s orbit-superposition technique, we construct a series of self-consistent galaxy models, embedded in the external field of galaxy clusters in the framework of Milgrom’s MOdified Newtonian Dynamics (MOND). These models represent relatively massive ellipticals with a Hernquist radial profile at various distances from the cluster center. Using N-body simulations, we perform a first analysis of these models and their evolution. We find that self-gravitating axisymmetric density models, even under a weak external field, lose their symmetry by instability and generally evolve to triaxial configurations. A kinematic analysis suggests that the instability originates from both box and nonclassified orbits with low angular momentum. We also consider a self-consistent isolated system that is then placed in a strong external field and allowed to evolve freely. This model, just like the corresponding equilibrium model in the same external field, eventually settles to a triaxial equilibrium as well, but has a higher velocity radial anisotropy and is rounder. The presence of an external field in the MOND universe generically predicts some lopsidedness of galaxy shapes.

  16. Lopsidedness of Self-consistent Galaxies Caused by the External Field Effect of Clusters

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

    Wu, Xufen; Wang, Yougang; Feix, Martin

    2017-08-01

    Adopting Schwarzschild’s orbit-superposition technique, we construct a series of self-consistent galaxy models, embedded in the external field of galaxy clusters in the framework of Milgrom’s MOdified Newtonian Dynamics (MOND). These models represent relatively massive ellipticals with a Hernquist radial profile at various distances from the cluster center. Using N -body simulations, we perform a first analysis of these models and their evolution. We find that self-gravitating axisymmetric density models, even under a weak external field, lose their symmetry by instability and generally evolve to triaxial configurations. A kinematic analysis suggests that the instability originates from both box and nonclassified orbitsmore » with low angular momentum. We also consider a self-consistent isolated system that is then placed in a strong external field and allowed to evolve freely. This model, just like the corresponding equilibrium model in the same external field, eventually settles to a triaxial equilibrium as well, but has a higher velocity radial anisotropy and is rounder. The presence of an external field in the MOND universe generically predicts some lopsidedness of galaxy shapes.« less

  17. Systemic sclerosis, birth order and parity.

    PubMed

    Russo, Paul A J; Lester, Susan; Roberts-Thomson, Peter J

    2014-06-01

    A recent study identified increasing birth order to be a risk factor for the development of systemic sclerosis (SSc). This finding supports the theory that transplacental microchimerism may be a key pathological event in the initiation of SSc. We investigated the relationship between birth order and parity and the age of onset of SSc in South Australia. A retrospective analysis of patient data in the South Australian Scleroderma Register was performed. Data were obtained from a mailed questionnaire. Control data was collected prospectively using a similar questionnaire. The relationship between birth order, family size or parity and risk of subsequent development of SSc was analyzed by mixed effects logistic regression analysis. Three hundred and eighty-seven index probands were identified and compared with 457 controls. Controls were well matched for gender, but not for age. No statistically significant relationship was identified between SSc and birth order, parity in females, family size, age at first pregnancy in females or gender of first child in parous females. Our data suggests that parity, age at first pregnancy and the gender of the first child are not relevant factors in our understanding of the epidemiology and pathogenesis of SSc. Birth order and family size in both genders also appears irrelevant. These results argue against microchimerism as being relevant in the pathogenesis of SSc and add further support to the theory that stochastic events may be important in the etiopathogenesis of SSc. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  18. Pharyngoesophageal dysphagia: an under recognised, potentially fatal, but very treatable feature of systemic sclerosis.

    PubMed

    Rajapakse, C

    2016-11-01

    Dysfunction of upper pharyngoesophageal region in systemic sclerosis (SSc) is infrequent, poorly recognised and poorly documented in the literature. Yet, it can have very distressing and even fatal consequences that may yet be very responsive to appropriate management. This paper documents the findings and outcome of management of a series of five patients with SSc who had pharyngoesophageal dysphagia to demonstrate the above. Following the documentation of a patient with SSc that had severe pharyngoesophageal dysphagia in 1981, this paper reports the findings in five patients with SSc presenting thereafter, having the same manifestations. Patients 1-4 who had barium swallow and fluoroscopy, demonstrated pharyngoesophageal dysfunction as basis of their symptoms. Patient 1 had fatal outcome from pulmonary haemorrhage following repeated bouts of aspiration pneumonia. Patients 2 and 3 had a long history of SSc and were on appropriate medical treatment. They developed a short history of dysphagia that resolved with additional improvements in swallowing techniques. Patient 4 had a short history of scleroderma, but severe and very distressing dysphagia that failed to respond to improved swallowing techniques alone, but responded well to the addition of medical treatment for SSc, over a 14-24 months period. Patient 5 had a short history of SSc and dysphagia that responded well to medical treatment over 6-12months. We conclude that pharyngoesophageal dysphagia in SSc, is a rare, very distressing and potentially fatal manifestation that can have a very favourable outcome with appropriate management. © 2016 Royal Australasian College of Physicians.

  19. Muscle power output properties using the stretch-shortening cycle of the upper limb and their relationships with a one-repetition maximum bench press.

    PubMed

    Miyaguchi, Kazuyoshi; Demura, Shinichi

    2006-05-01

    The purpose of this study was to examine the output properties of muscle power by the dominant upper limb using SSC, and the relationships between the power output by SSC and a one-repetition maximum bench press (1 RM BP) used as a strength indicator of the upper body. Sixteen male athletes (21.4+/-0.9 yr) participated in this study. They pulled a load of 40% of maximum voluntary contraction (MVC) at a stretch by elbow flexion of the dominant upper limb in the following three preliminary conditions: static relaxed muscle state (SR condition), isometric muscle contraction state (ISO condition), and using SSC (SSC condition). The velocity with a wire load via a pulley during elbow flexion was measured accurately using a power instrument with a rotary encoder, and the muscle power curve was drawn from the product of the velocity and load. Significant differences were found among all evaluation parameters of muscle power exerted from the above three conditions and the parameters regarding early power output during concentric contraction were larger in the SSC condition than the SR and ISO conditions. The parameters on initial muscle contraction velocity when only using SSC significantly correlated with 1 RM BP (r=0.60-0.62). The use of SSC before powerful elbow flexion may contribute largely to early explosive power output during concentric contraction. Bench press capacity relates to a development of the above early power output when using SSC.

  20. Supernatants from culture of type I collagen-stimulated PBMC from patients with cutaneous systemic sclerosis versus localized scleroderma demonstrate suppression of MMP-1 by fibroblasts.

    PubMed

    Brown, Monica; Postlethwaite, Arnold E; Myers, Linda K; Hasty, Karen A

    2012-06-01

    Systemic sclerosis (SSc) is a chronic fibrosing disease characterized by vasculopathy, autoimmunity, and an accumulation of collagen in tissues. Numerous studies have shown that compared to healthy or diseased controls, the peripheral blood mononuclear cells (PBMC) from patients with SSc produce a variety of cytokines or proliferate when cultured with solubilized type I collagen (CI) or constituent α1(II) and α2(I) polypeptide chains. The purpose of this study was to determine whether PBMC isolated from patients with SSc and cultured in vitro with soluble CI elaborated soluble mediators that inhibit the production of collagenase (i.e., matrix metalloproteinase, MMP-1) by fibroblasts. Supernatants of CI-stimulated PBMC from juvenile and adult diffuse cutaneous (dc)SSc patients significantly reduced MMP-1 production by SSc dermal fibroblasts, while supernatants of CI-stimulated PBMC from patients with localized scleroderma (LS) did not. CI-stimulated PBMC culture supernatants from patients with dcSSc in contrast to patients with LS exhibited increased levels of platelet-derived growth factor (PDGF)-AA, PDGF-BB, TNF-α, IL-13, and EGF. Prolonged culture of SSc dermal fibroblasts with recombinant PDGF-BB or IL-13 inhibited the induction of MMP-1 in response to subsequent TNF-α stimulation. These data suggest that therapies aimed at reducing these cytokines may decrease collagen accumulation in SSc, preventing the development of chronic fibrosis.

  1. 50 CFR 600.133 - Scientific and Statistical Committee (SSC).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Scientific and Statistical Committee (SSC). 600.133 Section 600.133 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC... Fishery Management Councils § 600.133 Scientific and Statistical Committee (SSC). (a) Each Council shall...

  2. 40 CFR 35.6820 - Conclusion of the SSC.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... STATE AND LOCAL ASSISTANCE Cooperative Agreements and Superfund State Contracts for Superfund Response Actions Requirements for Administering A Superfund State Contract (ssc) § 35.6820 Conclusion of the SSC... (See § 35.6805(i)(4)). (b) After the administrative conclusion of the Superfund State Contract, EPA may...

  3. 40 CFR 35.6820 - Conclusion of the SSC.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... STATE AND LOCAL ASSISTANCE Cooperative Agreements and Superfund State Contracts for Superfund Response Actions Requirements for Administering A Superfund State Contract (ssc) § 35.6820 Conclusion of the SSC... (See § 35.6805(i)(4)). (b) After the administrative conclusion of the Superfund State Contract, EPA may...

  4. 40 CFR 35.6820 - Conclusion of the SSC.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... STATE AND LOCAL ASSISTANCE Cooperative Agreements and Superfund State Contracts for Superfund Response Actions Requirements for Administering A Superfund State Contract (ssc) § 35.6820 Conclusion of the SSC... (See § 35.6805(i)(4)). (b) After the administrative conclusion of the Superfund State Contract, EPA may...

  5. 40 CFR 35.6820 - Conclusion of the SSC.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... STATE AND LOCAL ASSISTANCE Cooperative Agreements and Superfund State Contracts for Superfund Response Actions Requirements for Administering A Superfund State Contract (ssc) § 35.6820 Conclusion of the SSC... (See § 35.6805(i)(4)). (b) After the administrative conclusion of the Superfund State Contract, EPA may...

  6. 40 CFR 35.6820 - Conclusion of the SSC.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... STATE AND LOCAL ASSISTANCE Cooperative Agreements and Superfund State Contracts for Superfund Response Actions Requirements for Administering A Superfund State Contract (ssc) § 35.6820 Conclusion of the SSC... (See § 35.6805(i)(4)). (b) After the administrative conclusion of the Superfund State Contract, EPA may...

  7. 75 FR 2488 - Mid-Atlantic Fishery Management Council; Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-15

    ... Mid-Atlantic Fishery Management Council's (MAFMC) Scientific and Statistical Committee (SSC) will hold... include new member orientation (overview of Council process and role of the SSC), review and adoption of SSC Standard Operating Practices and Procedures, ABC Control Rule Framework and Council Risk Policy...

  8. 50 CFR 600.133 - Scientific and Statistical Committee (SSC).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Scientific and Statistical Committee (SSC... Fishery Management Councils § 600.133 Scientific and Statistical Committee (SSC). (a) Each Council shall..., evaluation, and peer review of such statistical, biological, economic, social, and other scientific...

  9. Genome Wide Screening of Candidate Genes for Improving Piglet Birth Weight Using High and Low Estimated Breeding Value Populations

    PubMed Central

    Zhang, Lifan; Zhou, Xiang; Michal, Jennifer J.; Ding, Bo; Li, Rui; Jiang, Zhihua

    2014-01-01

    Birth weight is an economically important trait in pig production because it directly impacts piglet growth and survival rate. In the present study, we performed a genome wide survey of candidate genes and pathways associated with individual birth weight (IBW) using the Illumina PorcineSNP60 BeadChip on 24 high (HEBV) and 24 low estimated breeding value (LEBV) animals. These animals were selected from a reference population of 522 individuals produced by three sires and six dam lines, which were crossbreds with multiple breeds. After quality-control, 43,257 SNPs (single nucleotide polymorphisms), including 42,243 autosomal SNPs and 1,014 SNPs on chromosome X, were used in the data analysis. A total of 27 differentially selected regions (DSRs), including 1 on Sus scrofa chromosome 1 (SSC1), 1 on SSC4, 2 on SSC5, 4 on SSC6, 2 on SSC7, 5 on SSC8, 3 on SSC9, 1 on SSC14, 3 on SSC18, and 5 on SSCX, were identified to show the genome wide separations between the HEBV and LEBV groups for IBW in piglets. A DSR with the most number of significant SNPs (including 7 top 0.1% and 31 top 5% SNPs) was located on SSC6, while another DSR with the largest genetic differences in FST was found on SSC18. These regions harbor known functionally important genes involved in growth and development, such as TNFRSF9 (tumor necrosis factor receptor superfamily member 9), CA6 (carbonic anhydrase VI) and MDFIC (MyoD family inhibitor domain containing). A DSR rich in imprinting genes appeared on SSC9, which included PEG10 (paternally expressed 10), SGCE (sarcoglycan, epsilon), PPP1R9A (protein phosphatase 1, regulatory subunit 9A) and ASB4 (ankyrin repeat and SOCS box containing 4). More importantly, our present study provided evidence to support six quantitative trait loci (QTL) regions for pig birth weight, six QTL regions for average birth weight (ABW) and three QTL regions for litter birth weight (LBW) reported previously by other groups. Furthermore, gene ontology analysis with 183 genes harbored in these 27 DSRs suggested that protein, metal, ion and ATP binding, viral process and innate immune response present important pathways for deciphering their roles in fetal growth or development. Overall, our study provides useful information on candidate genes and pathways for regulating birth weight in piglets, thus improving our understanding of the genetic mechanisms involved in porcine embryonic or fetal development. PMID:24644423

  10. Constraining the location of gamma-ray flares in luminous blazars

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

    Nalewajko, Krzysztof; Begelman, Mitchell C.; Sikora, Marek, E-mail: knalew@jila.colorado.edu

    2014-07-10

    Locating the gamma-ray emission sites in blazar jets is a long standing and highly controversial issue. We jointly investigate several constraints on the distance scale r and Lorentz factor Γ of the gamma-ray emitting regions in luminous blazars (primarily flat spectrum radio quasars). Working in the framework of one-zone external radiation Comptonization models, we perform a parameter space study for several representative cases of actual gamma-ray flares in their multiwavelength context. We find a particularly useful combination of three constraints: from an upper limit on the collimation parameter Γθ ≲ 1, from an upper limit on the synchrotron self-Compton (SSC)more » luminosity L{sub SSC} ≲ L{sub X}, and from an upper limit on the efficient cooling photon energy E{sub cool,obs} ≲ 100 MeV. These three constraints are particularly strong for sources with low accretion disk luminosity L{sub d}. The commonly used intrinsic pair-production opacity constraint on Γ is usually much weaker than the SSC constraint. The SSC and cooling constraints provide a robust lower limit on the collimation parameter Γθ ≳ 0.1-0.7. Typical values of r corresponding to moderate values of Γ ∼ 20 are in the range 0.1-1 pc, and are determined primarily by the observed variability timescale t{sub var,obs}. Alternative scenarios motivated by the observed gamma-ray/millimeter connection, in which gamma-ray flares of t{sub var,obs} ∼ a few days are located at r ∼ 10 pc, are in conflict with both the SSC and cooling constraints. Moreover, we use a simple light travel time argument to point out that the gamma-ray/millimeter connection does not provide a significant constraint on the location of gamma-ray flares. We argue that spine-sheath models of the jet structure do not offer a plausible alternative to external radiation fields at large distances; however, an extended broad-line region is an idea worth exploring. We propose that the most definite additional constraint could be provided by determination of the synchrotron self-absorption frequency for correlated synchrotron and gamma-ray flares.« less

  11. Unprecedented study of the broadband emission of Mrk 421 during flaring activity in March 2010

    NASA Astrophysics Data System (ADS)

    Aleksić, J.; Ansoldi, S.; Antonelli, L. A.; Antoranz, P.; Babic, A.; Bangale, P.; Barres de Almeida, U.; Barrio, J. A.; Becerra González, J.; Bednarek, W.; Bernardini, E.; Biasuzzi, B.; Biland, A.; Blanch, O.; Boller, A.; Bonnefoy, S.; Bonnoli, G.; Borracci, F.; Bretz, T.; Carmona, E.; Carosi, A.; Colin, P.; Colombo, E.; Contreras, J. L.; Cortina, J.; Covino, S.; Da Vela, P.; Dazzi, F.; De Angelis, A.; De Caneva, G.; De Lotto, B.; de Oña Wilhelmi, E.; Delgado Mendez, C.; Dominis Prester, D.; Dorner, D.; Doro, M.; Einecke, S.; Eisenacher, D.; Elsaesser, D.; Fonseca, M. V.; Font, L.; Frantzen, K.; Fruck, C.; Galindo, D.; García López, R. J.; Garczarczyk, M.; Garrido Terrats, D.; Gaug, M.; Godinović, N.; González Muñoz, A.; Gozzini, S. R.; Hadasch, D.; Hanabata, Y.; Hayashida, M.; Herrera, J.; Hildebrand, D.; Hose, J.; Hrupec, D.; Hughes, G.; Idec, W.; Kadenius, V.; Kellermann, H.; Knoetig, M. L.; Kodani, K.; Konno, Y.; Krause, J.; Kubo, H.; Kushida, J.; La Barbera, A.; Lelas, D.; Lewandowska, N.; Lindfors, E.; Lombardi, S.; López, M.; López-Coto, R.; López-Oramas, A.; Lorenz, E.; Lozano, I.; Makariev, M.; Mallot, K.; Maneva, G.; Mankuzhiyil, N.; Mannheim, K.; Maraschi, L.; Marcote, B.; Mariotti, M.; Martínez, M.; Mazin, D.; Menzel, U.; Miranda, J. M.; Mirzoyan, R.; Moralejo, A.; Munar-Adrover, P.; Nakajima, D.; Niedzwiecki, A.; Nilsson, K.; Nishijima, K.; Noda, K.; Orito, R.; Overkemping, A.; Paiano, S.; Palatiello, M.; Paneque, D.; Paoletti, R.; Paredes, J. M.; Paredes-Fortuny, X.; Persic, M.; Prada Moroni, P. G.; Prandini, E.; Puljak, I.; Reinthal, R.; Rhode, W.; Ribó, M.; Rico, J.; Rodriguez Garcia, J.; Rügamer, S.; Saito, T.; Saito, K.; Satalecka, K.; Scalzotto, V.; Scapin, V.; Schultz, C.; Schweizer, T.; Sun, S.; Shore, S. N.; Sillanpää, A.; Sitarek, J.; Snidaric, I.; Sobczynska, D.; Spanier, F.; Stamatescu, V.; Stamerra, A.; Steinbring, T.; Steinke, B.; Storz, J.; Strzys, M.; Takalo, L.; Takami, H.; Tavecchio, F.; Temnikov, P.; Terzić, T.; Tescaro, D.; Teshima, M.; Thaele, J.; Tibolla, O.; Torres, D. F.; Toyama, T.; Treves, A.; Uellenbeck, M.; Vogler, P.; Zanin, R.; MAGIC Collaboration; Archambault, S.; Archer, A.; Beilicke, M.; Benbow, W.; Berger, K.; Bird, R.; Biteau, J.; Buckley, J. H.; Bugaev, V.; Cerruti, M.; Chen, X.; Ciupik, L.; Collins-Hughes, E.; Cui, W.; Eisch, J. D.; Falcone, A.; Feng, Q.; Finley, J. P.; Fortin, P.; Fortson, L.; Furniss, A.; Galante, N.; Gillanders, G. H.; Griffin, S.; Gyuk, G.; Håkansson, N.; Holder, J.; Johnson, C. A.; Kaaret, P.; Kar, P.; Kertzman, M.; Kieda, D.; Lang, M. J.; McArthur, S.; McCann, A.; Meagher, K.; Millis, J.; Moriarty, P.; Ong, R. A.; Otte, A. N.; Perkins, J. S.; Pichel, A.; Pohl, M.; Popkow, A.; Prokoph, H.; Pueschel, E.; Ragan, K.; Reyes, L. C.; Reynolds, P. T.; Richards, G. T.; Roache, E.; Rovero, A. C.; Sembroski, G. H.; Shahinyan, K.; Staszak, D.; Telezhinsky, I.; Tucci, J. V.; Tyler, J.; Varlotta, A.; Wakely, S. P.; Welsing, R.; Wilhelm, A.; Williams, D. A.; VERITAS Collaboration; Buson, S.; Finke, J.; Villata, M.; Raiteri, C.; Aller, H. D.; Aller, M. F.; Cesarini, A.; Chen, W. P.; Gurwell, M. A.; Jorstad, S. G.; Kimeridze, G. N.; Koptelova, E.; Kurtanidze, O. M.; Kurtanidze, S. O.; Lähteenmäki, A.; Larionov, V. M.; Larionova, E. G.; Lin, H. C.; McBreen, B.; Moody, J. W.; Morozova, D. A.; Marscher, A. P.; Max-Moerbeck, W.; Nikolashvili, M. G.; Perri, M.; Readhead, A. C. S.; Richards, J. L.; Ros, J. A.; Sadun, A. C.; Sakamoto, T.; Sigua, L. A.; Smith, P. S.; Tornikoski, M.; Troitsky, I. S.; Wehrle, A. E.; Jordan, B.

    2015-06-01

    Context. Because of its proximity, Mrk 421 is one of the best sources on which to study the nature of BL Lac objects. Its proximity allows us to characterize its broadband spectral energy distribution (SED). Aims: The goal is to better understand the mechanisms responsible for the broadband emission and the temporal evolution of Mrk 421. These mechanisms may also apply to more distant blazars that cannot be studied with the same level of detail. Methods: A flare occurring in March 2010 was observed for 13 consecutive days (from MJD 55 265 to MJD 55 277) with unprecedented wavelength coverage from radio to very high energy (VHE; E> 100 GeV) γ-rays with MAGIC, VERITAS, Whipple, Fermi-LAT, MAXI, RXTE, Swift, GASP-WEBT, and several optical and radio telescopes. We modeled the day-scale SEDs with one-zone and two-zone synchrotron self-Compton (SSC) models, investigated the physical parameters, and evaluated whether the observed broadband SED variability can be associated with variations in the relativistic particle population. Results: The activity of Mrk 421 initially was high and then slowly decreased during the 13-day period. The flux variability was remarkable at the X-ray and VHE bands, but it was minor or not significant at the other bands. The variability in optical polarization was also minor. These observations revealed an almost linear correlation between the X-ray flux at the 2-10 keV band and the VHE γ-ray flux above 200 GeV, consistent with the γ-rays being produced by inverse-Compton scattering in the Klein-Nishina regime in the framework of SSC models. The one-zone SSC model can describe the SED of each day for the 13 consecutive days reasonably well, which once more shows the success of this standard theoretical scenario to describe the SEDs of VHE BL Lacs such as Mrk 421. This flaring activity is also very well described by a two-zone SSC model, where one zone is responsible for the quiescent emission, while the other smaller zone, which is spatially separated from the first, contributes to the daily variable emission occurring at X-rays and VHE γ-rays. The second blob is assumed to have a smaller volume and a narrow electron energy distribution with 3 × 104<γ< 6 × 105, where γ is the Lorentz factor of the electrons. Such a two-zone scenario would naturally lead to the correlated variability at the X-ray and VHE bands without variability at the optical/UV band, as well as to shorter timescales for the variability at the X-ray and VHE bands with respect to the variability at the other bands. Conclusions: Both the one-zone and the two-zone SSC models can describe the daily SEDs via the variation of only four or five model parameters, under the hypothesis that the variability is associated mostly with the underlying particle population. This shows that the particle acceleration and cooling mechanism that produces the radiating particles might be the main mechanism responsible for the broadband SED variations during the flaring episodes in blazars. The two-zone SSC model provides a better agreement with the observed SED at the narrow peaks of the low- and high-energy bumps during the highest activity, although the reported one-zone SSC model could be further improved by varying the parameters related to the emitting region itself (δ, B and R), in addition to the parameters related to the particle population. Appendices are available in electronic form at http://www.aanda.orgMulti-wavelength light curves (data in Fig. 1) and broadband spectral energy distributions (the data in Figs. 7, 8a-9f, 12a-13f) are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/578/A22

  12. The phonon-coupling model for Skyrme forces

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

    Lyutorovich, N.; Tselyaev, V.; Speth, J., E-mail: J.Speth@fz-juelich.de

    2016-11-15

    A short review on the self-consistent RPA based on the energy-density functional of the Skyrme type is given. We also present an extension of the RPA where the coupling of phonons to the single-particle states is considered. Within this approach we present numerical results which are compared with data. The self-consistent approach is compared with the Landau–Migdal theory. Here we derive from the self-consistent ph interaction, the Landau–Migdal parameters as well as their density dependence. In the Appendix a new derivation of the reduced matrix elements of the ph interaction is presented.

  13. Developing the Polish Educational Needs Assessment Tool (Pol-ENAT) in rheumatoid arthritis and systemic sclerosis: a cross-cultural validation study using Rasch analysis.

    PubMed

    Sierakowska, Matylda; Sierakowski, Stanisław; Sierakowska, Justyna; Horton, Mike; Ndosi, Mwidimi

    2015-03-01

    To undertake cross-cultural adaptation and validation of the educational needs assessment tool (ENAT) for use with people with rheumatoid arthritis (RA) and systemic sclerosis (SSc) in Poland. The study involved two main phases: (1) cross-cultural adaptation of the ENAT from English into Polish and (2) Cross-cultural validation of Polish Educational Needs Assessment Tool (Pol-ENAT). The first phase followed an established process of cross-cultural adaptation of self-report measures. The second phase involved completion of the Pol-ENAT by patients and subjecting the data to Rasch analysis to assess the construct validity, unidimensionality, internal consistency and cross-cultural invariance. An adequate conceptual equivalence was achieved following the adaptation process. The dataset for validation comprised a total of 278 patients, 237 (85.3 %) of which were female. In each disease group (145, RA and 133, SSc), the 7 domains of the Pol-ENAT were found to fit the Rasch model, X (2)(df) = 16.953(14), p = 0.259 and 8.132(14), p = 0.882 for RA and SSc, respectively. Internal consistency of the Pol-ENAT was high (patient separation index = 0.85 and 0.89 for SSc and RA, respectively), and unidimensionality was confirmed. Cross-cultural differential item functioning (DIF) was detected in some subscales, and DIF-adjusted conversion tables were calibrated to enable cross-cultural comparison of data between Poland and the UK. Using a standard process in cross-cultural adaptation, conceptual equivalence was achieved between the original (UK) ENAT and the adapted Pol-ENAT. Fit to the Rasch model, confirmed that the construct validity, unidimensionality and internal consistency of the ENAT have been preserved.

  14. Cross-Language Measurement Equivalence of the Center for Epidemiologic Studies Depression (CES-D) Scale in Systemic Sclerosis: A Comparison of Canadian and Dutch Patients

    PubMed Central

    Kwakkenbos, Linda; Arthurs, Erin; van den Hoogen, Frank H. J.; Hudson, Marie; van Lankveld, Wim G. J. M.; Baron, Murray; van den Ende, Cornelia H. M.; Thombs, Brett D.

    2013-01-01

    Objectives Increasingly, medical research involves patients who complete outcomes in different languages. This occurs in countries with more than one common language, such as Canada (French/English) or the United States (Spanish/English), as well as in international multi-centre collaborations, which are utilized frequently in rare diseases such as systemic sclerosis (SSc). In order to pool or compare outcomes, instruments should be measurement equivalent (invariant) across cultural or linguistic groups. This study provides an example of how to assess cross-language measurement equivalence by comparing the Center for Epidemiologic Studies Depression (CES-D) scale between English-speaking Canadian and Dutch SSc patients. Methods The CES-D was completed by 922 English-speaking Canadian and 213 Dutch SSc patients. Confirmatory factor analysis (CFA) was used to assess the factor structure in both samples. The Multiple-Indicator Multiple-Cause (MIMIC) model was utilized to assess the amount of differential item functioning (DIF). Results A two-factor model (positive and negative affect) showed excellent fit in both samples. Statistically significant, but small-magnitude, DIF was found for 3 of 20 items on the CES-D. The English-speaking Canadian sample endorsed more feeling-related symptoms, whereas the Dutch sample endorsed more somatic/retarded activity symptoms. The overall estimate in depression scores between English and Dutch was not influenced substantively by DIF. Conclusions CES-D scores from English-speaking Canadian and Dutch SSc patients can be compared and pooled without concern that measurement differences may substantively influence results. The importance of assessing cross-language measurement equivalence in rheumatology studies prior to pooling outcomes obtained in different languages should be emphasized. PMID:23326538

  15. Accuracy of the Generalized Self-Consistent Method in Modelling the Elastic Behaviour of Periodic Composites

    NASA Technical Reports Server (NTRS)

    Walker, Kevin P.; Freed, Alan D.; Jordan, Eric H.

    1993-01-01

    Local stress and strain fields in the unit cell of an infinite, two-dimensional, periodic fibrous lattice have been determined by an integral equation approach. The effect of the fibres is assimilated to an infinite two-dimensional array of fictitious body forces in the matrix constituent phase of the unit cell. By subtracting a volume averaged strain polarization term from the integral equation we effectively embed a finite number of unit cells in a homogenized medium in which the overall stress and strain correspond to the volume averaged stress and strain of the constrained unit cell. This paper demonstrates that the zeroth term in the governing integral equation expansion, which embeds one unit cell in the homogenized medium, corresponds to the generalized self-consistent approximation. By comparing the zeroth term approximation with higher order approximations to the integral equation summation, both the accuracy of the generalized self-consistent composite model and the rate of convergence of the integral summation can be assessed. Two example composites are studied. For a tungsten/copper elastic fibrous composite the generalized self-consistent model is shown to provide accurate, effective, elastic moduli and local field representations. The local elastic transverse stress field within the representative volume element of the generalized self-consistent method is shown to be in error by much larger amounts for a composite with periodically distributed voids, but homogenization leads to a cancelling of errors, and the effective transverse Young's modulus of the voided composite is shown to be in error by only 23% at a void volume fraction of 75%.

  16. Turbidity - a Semi-Continuous Monitoring Option for Suspended Solids

    NASA Astrophysics Data System (ADS)

    Lendvay, J. M.; Rosasco, M. V.; David, K. E.

    2012-12-01

    Redwood Creek, a third order coastal stream flowing through Muir Woods National Monument and Golden Gate National Recreation Area in Marin County, California, was once the spawning grounds for a relatively large population of Coho Salmon (Oncorhynchus kisutch). In recent years less than 1% of historic populations have been returning to the stream. Redwood creek is currently undergoing extensive ecological restoration in an attempt to improve the spawning habitat for the salmon. The original stream path has been altered in the past to make way for development and the National Park Service has been working towards restoring much of the stream's natural functionality with the hope that the salmon population will increase. The restoration process has altered the surrounding riparian landscape in the Redwood Creek watershed. Riparian disturbance caused by vegetation and levee removal as a part of the restoration process followed by installation of seedlings raises concern about the concentration of sediments in the water. Throughout 2011-2012 three parameters for water quality were monitored at Redwood Creek. Suspended sediment concentration (SSC) and total suspended solids (TSS) measurements to determine the concentration of suspended particles in the water column at a given point in time. Turbidity, measured in Nephelometric Turbidity Units (NTU) is a measure of the water's cloudiness caused by suspended particles. Turbidity measurements are favored as they provide a semi-automated monitoring option. Therefore, development of a relationship between turbidity and SSC and TSS is desired. Water samples were analyzed for TSS and SSC using the EPA standard methods, and Turbidity was measured using a Hach 2100Q portable turbidimeter. Additional semi-continuous monitoring of turbidity was completed in situ using Hydrolab DS5X datasondes (with self-cleaning turbidity sensor). The relationship between TSS, SSC and turbidity was determined using a linear regression model for two separate sites within Redwood creek. The linear correlation coefficient values for the two sites were high for both TSS vs. Turbidity (R2=0.929) and SSC vs. Turbidity (R2=0.929). Measures of suspended particle concentrations in the water column are important indicators of water quality, as sediments can be transporters of both nutrients and contaminants alike, particularly those with high binding affinities for soils. Moreover, the relationships between TSS, SSC and turbidity may serve as an important predictor when developing a model for nutrient and contaminant dynamics in coastal California streams. Determining the best way to measure suspended solids in the water column will help elucidate the most practicable in-stream monitoring methods.

  17. Modeling of ground-water flow in subsurface Austin Chalk and Taylor marl in Ellis County, Texas, near the superconducting super collider site

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

    Mace, R.E.

    1993-02-01

    Numerical models are useful tools for developing an understanding of ground-water flow in sparsely characterized low-permeability aquifers. Finite-difference, cross-sectional models of Cretaceous chalk and marl formations near the Superconducting Super Collider (SSC) were constructed using MODFLOW to evaluate ground-water circulation paths and travel times. Weathered and fractured zones with enhanced permeability were included to assess the effect these features had on flow paths and times. Pump tests, slug tests, packer tests, core tests, and estimates were used to define hydraulic properties for model input. The model was calibrated with water-level data from monitor wells and from wire-line piezometers near amore » test shaft excavated by the SSC project. A ratio of vertical-to-horizontal permeability of 0.0085 was estimated through model calibration. A chalk-to-marl permeability ratio of 18 was needed to reproduce artesian head in a well completed in chalk beneath marl. Hydraulic head distributions and ground-water flow paths reflected local, intermediate, and regional flow systems with recharge beneath upland surface-water divides and discharge in valleys. Most of the flow (99%) occurred in the weathered zone, with average residence times of 5 to 10 years. Residence time in unweathered chalk bedrock was substantially longer, at an average of 1.7 Ma. As expected, the model demonstrated that deep and rapid ground-water circulation might occur in fracture zones. Particle paths calculated using MODPATH showed that ground-water travel times from recharge areas to the SSC subsurface facilities might be 20 to 60 years where flow is through fracture zones.« less

  18. GENESIS: new self-consistent models of exoplanetary spectra

    NASA Astrophysics Data System (ADS)

    Gandhi, Siddharth; Madhusudhan, Nikku

    2017-12-01

    We are entering the era of high-precision and high-resolution spectroscopy of exoplanets. Such observations herald the need for robust self-consistent spectral models of exoplanetary atmospheres to investigate intricate atmospheric processes and to make observable predictions. Spectral models of plane-parallel exoplanetary atmospheres exist, mostly adapted from other astrophysical applications, with different levels of sophistication and accuracy. There is a growing need for a new generation of models custom-built for exoplanets and incorporating state-of-the-art numerical methods and opacities. The present work is a step in this direction. Here we introduce GENESIS, a plane-parallel, self-consistent, line-by-line exoplanetary atmospheric modelling code that includes (a) formal solution of radiative transfer using the Feautrier method, (b) radiative-convective equilibrium with temperature correction based on the Rybicki linearization scheme, (c) latest absorption cross-sections, and (d) internal flux and external irradiation, under the assumptions of hydrostatic equilibrium, local thermodynamic equilibrium and thermochemical equilibrium. We demonstrate the code here with cloud-free models of giant exoplanetary atmospheres over a range of equilibrium temperatures, metallicities, C/O ratios and spanning non-irradiated and irradiated planets, with and without thermal inversions. We provide the community with theoretical emergent spectra and pressure-temperature profiles over this range, along with those for several known hot Jupiters. The code can generate self-consistent spectra at high resolution and has the potential to be integrated into general circulation and non-equilibrium chemistry models as it is optimized for efficiency and convergence. GENESIS paves the way for high-fidelity remote sensing of exoplanetary atmospheres at high resolution with current and upcoming observations.

  19. Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease.

    PubMed

    Volkmann, Elizabeth R; Tashkin, Donald P; Roth, Michael D; Clements, Philip J; Khanna, Dinesh; Furst, Daniel E; Mayes, Maureen; Charles, Julio; Tseng, Chi-Hong; Elashoff, Robert M; Assassi, Shervin

    2016-12-30

    Increased circulatory levels of the chemokine CXCL4 have been associated with the presence of interstitial lung disease (ILD) in an observational study of patients with systemic sclerosis (SSc). The purpose of the present study was to evaluate the relationship between baseline CXCL4 level and extent of ILD in the context of a randomized controlled trial and to determine whether changes in CXCL4 levels in response to immunosuppression are associated with future progression of SSc-ILD. A total of 142 SSc-ILD patients from Scleroderma Lung Study (SLS) II were randomized in a double-blind, parallel-arm trial, to receive mycophenolate (MMF) for 2 years or oral cyclophosphamide (CYC) for 1 year followed by 1 year of placebo. Plasma CXCL4 levels were measured at baseline, 12 months, and 24 months in SLS II participants (N = 136) and at a single time point in healthy controls (N = 67). A mixed-effects model evaluated the relationship between change in CXCL4 levels and SSc-ILD progression. The primary outcome was the course of the forced vital capacity. Baseline CXCL4 levels were significantly higher in SSc-ILD patients compared with healthy controls (2699 ± 1489 ng/ml vs 2233 ± 1351 ng/ml (mean ± SD); P = 0.019). However, no significant correlations were identified between CXCL4 levels and extent of ILD at baseline, as measured by the forced vital capacity, diffusing capacity of carbon monoxide, or radiographic extent of ILD. Plasma CXCL4 decreased significantly from baseline to 12 months in all patients (CYC: P < 0.001; MMF: P = 0.006) with no between-treatment differences (CYC vs MMF). Patients with the largest decline in CXCL4 levels during the first 12 months had an improved course of forced vital capacity %-predicted from 12 to 24 months (P = 0.040), even after adjusting for baseline disease severity and treatment arm assignment. Levels of CXCL4 were higher in patients with SSc-ILD compared with controls and decreased in all patients treated with immunosuppressive therapy. While CXCL4 levels were not correlated with extent of ILD at baseline, changes in CXCL4 at 12 months predicted future progression of SSc-ILD from 12 to 24 months. These findings suggest that intermediate-term changes in CXCL4 may have predictive significance for long-term progression of SSc-ILD in patients receiving immunosuppressive therapy. ClinicalTrials.gov NCT00883129 . Registered 16 April 2009.

  20. Software sensors for biomass concentration in a SSC process using artificial neural networks and support vector machine.

    PubMed

    Acuña, Gonzalo; Ramirez, Cristian; Curilem, Millaray

    2014-01-01

    The lack of sensors for some relevant state variables in fermentation processes can be coped by developing appropriate software sensors. In this work, NARX-ANN, NARMAX-ANN, NARX-SVM and NARMAX-SVM models are compared when acting as software sensors of biomass concentration for a solid substrate cultivation (SSC) process. Results show that NARMAX-SVM outperforms the other models with an SMAPE index under 9 for a 20 % amplitude noise. In addition, NARMAX models perform better than NARX models under the same noise conditions because of their better predictive capabilities as they include prediction errors as inputs. In the case of perturbation of initial conditions of the autoregressive variable, NARX models exhibited better convergence capabilities. This work also confirms that a difficult to measure variable, like biomass concentration, can be estimated on-line from easy to measure variables like CO₂ and O₂ using an adequate software sensor based on computational intelligence techniques.

  1. SSC San Diego Strategic Plan. Revision 2

    DTIC Science & Technology

    2000-05-01

    information dominance . This Strategic Plan is SSC San Diego’s blueprint to meet that challenge. The plan is both a vehicle for carrying us into the...provider of integrated C4ISR solutions for warrior information dominance is our enduring goal. Our plan specifies five long-range strategic objectives. SSC

  2. 78 FR 43146 - Gulf of Mexico Fishery Management Council; Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-19

    ... Mackerel and Special Reef Fish Scientific and Statistical Committees (SSC). DATES: The meeting will be held.... Introductions and Adoption of Mackerel SSC Agenda 2. Approval of May 29, 2013 Standing and Special Mackerel SSC... and Statistical Committees for discussion, in accordance with the Magnuson-Stevens Fishery...

  3. Long-term spectral and temporal behavior of the high-frequency peaked BL LAC object 1ES 1959+650

    NASA Astrophysics Data System (ADS)

    Backes, M.; Uellenbeck, M.; Hayashida, M.; Satalecka, K.; Tescaro, D.; Terzić, T.; MAGIC Collaboration; Fuhrmann, L.; Nestoras, I.; F-GAMMA project; Lähteenmäki, A.; Tornikoski, M.; Nieppola, E.; Metsähovi; Böttcher, M.; Collmar, W.; Weidinger, M.

    2012-12-01

    The high-frequency peaked BL Lac object 1ES 1959+650 is well-known for an exceptional outburst, which was observed at very high energy (VHE) γ-rays by the Whipple 10m and HEGRA telescopes in 2002. Remarkably, this outburst lacked associated X-ray emission (a socalled "orphan flare") and by this cannot easily be described by standard Synchrotron Self Compton (SSC) models. Models based on hadronic emission processes have also been proposed to explain the observed behavior. Subsequent multi-wavelength observations during a low flux state at TeV energies in 2006 can, instead, be explained by a standard single-zone SSC model. In this context, 1ES 1959+650 has been regularly monitored by the MAGIC telescope since 2005. During these years, no significant variation in the VHE γ-ray flux has been observed. The low energy part of this is in very good agreement with the high-energy part of the time-integrated energy spectrum as measured by Fermi-LAT. Based on this constant flux level in VHE γ-rays, we assembled the time-integrated spectral energy distribution (SED) of 1ES 1959+650 from radio to VHE γ-rays. Despite the non-variability at very high energies, significant flux and spectral variations have been observed at optical and X-ray frequencies in the meanwhile. Furthermore, the shape of the SED at high energy γ-rays as measured by Fermi-LAT is essentially flat which cannot be explained by either conventional single-zone SSC models, or models invoking external radiation fields (EC).

  4. Microbiological analysis of bile and its impact in critically ill patients with secondary sclerosing cholangitis.

    PubMed

    Voigtländer, Torsten; Leuchs, Ensieh; Vonberg, Ralf-Peter; Solbach, Philipp; Manns, Michael P; Suerbaum, Sebastian; Lankisch, Tim O

    2015-05-01

    Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is an emerging disease entity with unfavourable outcome. Our aim was to analyze the microbial spectrum in bile of patients with SSC-CIP and to evaluate the potential impact on the empiric antibiotic treatment in these patients. 169 patients (72 patients with SSC-CIP and 97 patients with primary sclerosing cholangitis (PSC)) were included in a prospective observational study between 2010 and 2013. Bile was obtained during endoscopic retrograde cholangiography (ERC) and microbiologically analyzed. Patients with SSC displayed a significantly different microbiological profile in bile. Enterococcus faecium, Pseudomonas aeruginosa and non-albicans species of Candida were more frequent in SSC compared to patients with PSC (p < 0.05). Patients with SSC showed a higher incidence of drug or multi-drug resistant organisms in bile (p = 0.001). The antimicrobial therapy was adjusted in 64% of patients due to resistance or presence of microorganisms not covered by the initial therapy regimen. Patients with SSC-CIP have a distinct microbial profile in bile. Difficult to treat organisms are frequent and an ERC with bile fluid collection for microbiological analysis should be considered in case of insufficient antimicrobial treatment. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  5. Systemic sclerosis in Argentina: evaluation of a large cohort from a single centre and comparison with other international series.

    PubMed

    Scolnik, M; Lancioni, E; Saucedo, C; Marin, J; Sabelli, M; Bedran, Z; Soriano, E R; Catoggio, L J

    2014-01-01

    Prevalence of systemic sclerosis (SSc) and different clinical subsets varies across the world. Few data have been published on SSc patients in Latin America. Our objective was to describe a SSc cohort in Argentina and to compare clinical findings, disease subsets and antibodies with other international SSc populations. Patients with SSc (n=234) seen at the Rheumatology section of the Hospital Italiano de Buenos Aires between 2000-2011 were retrospectively analysed. Data on clinical manifestations, disease subsets and antibodies were obtained. Patients were classified into diffuse cutaneous (dc) and limited cutaneous (lc) subsets. Comparison with other cohorts (France, United States, Germany, Italy, Mexico, EUSTAR and Brazil) was made based on published information. A higher female:male ratio (12:1) and a higher limited subset prevalence (76.1%) was found in this Argentine cohort comparing with others. We also found a lower prevalence of diffuse disease, anti Scl-70 (antitopoisomerase) and nucleolar pattern antinuclear antibodies. Within each subset, clinical findings were similar with other SSc populations except for a very low prevalence in renal crisis (0.02% of dc SS). With slight variations perhaps due to genetic, environmental or referral factors, SSc in this cohort appears to be similar to that described in other parts of the world.

  6. High Rhodotorula sequences in skin transcriptome of patients with diffuse systemic sclerosis

    PubMed Central

    Arron, Sarah T.; Dimon, Michelle T.; Li, Zhenghui; Johnson, Michael E.; Wood, Tammara; Feeney, Luzviminda; Angeles, Jorge Gil; Lafyatis, Robert; Whitfield, Michael L.

    2014-01-01

    Previous studies have suggested a role for pathogens as a trigger of systemic sclerosis (SSc), though neither a pathogen nor a mechanism of pathogenesis is known. Here we show enrichment of Rhodotorula sequences in the skin of patients with early, diffuse SSc compared to normal controls. RNA-seq was performed on four SSc and four controls, to a depth of 200 million reads per patient. Data were analyzed to quantify the non-human sequence reads in each sample. We found little difference between bacterial microbiome and viral read counts, but found a significant difference between the read counts for a mycobiome component, R. glutinis. Normal samples contained almost no detected R. glutinis or other Rhodotorula sequence reads (mean score 0.021 for R. glutinis, 0.024 for all Rhodotorula). In contrast, SSc samples had a mean score of 5.039 for R. glutinis (5.232 for Rhodotorula). We were able to assemble the D1–D2 hypervariable region of the 28S rRNA of R. glutinis from each of the SSc samples. Taken together, these results suggest R. glutinis may be present in the skin of early SSc patients at higher levels than normal skin, raising the possibility that it may be triggering the inflammatory response found in SSc. PMID:24608988

  7. High Rhodotorula sequences in skin transcriptome of patients with diffuse systemic sclerosis.

    PubMed

    Arron, Sarah T; Dimon, Michelle T; Li, Zhenghui; Johnson, Michael E; Wood, Tammara A; Feeney, Luzviminda; Angeles, Jorge G; Lafyatis, Robert; Whitfield, Michael L

    2014-08-01

    Previous studies have suggested a role for pathogens as a trigger of systemic sclerosis (SSc), although neither a pathogen nor a mechanism of pathogenesis is known. Here we show enrichment of Rhodotorula sequences in the skin of patients with early, diffuse SSc compared with that in normal controls. RNA-seq was performed on four SSc patients and four controls, to a depth of 200 million reads per patient. Data were analyzed to quantify the nonhuman sequence reads in each sample. We found little difference between bacterial microbiome and viral read counts, but found a significant difference between the read counts for a mycobiome component, R. glutinis. Normal samples contained almost no detected R. glutinis or other Rhodotorula sequence reads (mean score 0.021 for R. glutinis, 0.024 for all Rhodotorula). In contrast, SSc samples had a mean score of 5.039 for R. glutinis (5.232 for Rhodotorula). We were able to assemble the D1-D2 hypervariable region of the 28S ribosomal RNA (rRNA) of R. glutinis from each of the SSc samples. Taken together, these results suggest that R. glutinis may be present in the skin of early SSc patients at higher levels than in normal skin, raising the possibility that it may be triggering the inflammatory response found in SSc.

  8. Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

    PubMed

    Distler, Oliver; Cozzio, Antonio

    2016-01-01

    Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their preclinical characterization. Soluble guanylate cyclase (sGC) stimulators such as riociguat might target both vascular remodeling and tissue fibrosis. Blockade of interleukin-6 might be particularly promising for early inflammatory stages of SSc. Inhibition of serotonin receptor 2b signaling links platelet activation to tissue fibrosis. Targeting simultaneously multiple key molecules with the multityrosine kinase-inhibitor nintedanib might be a promising approach in complex fibrotic diseases such as SSc, in which many partially independent pathways are activated. Herein, we also give a state of the art overview of the current classification, clinical presentation, diagnostic approach, and treatment options of localized scleroderma. Finally, we discuss whether the novel targeted therapies currently tested in SSc could be used for localized scleroderma.

  9. Estimation of suspended sediment concentration from Acoustic Doppler Current Profiler (ADCP) instrument: A case study of Lembeh Strait, North Sulawesi

    NASA Astrophysics Data System (ADS)

    Dwinovantyo, Angga; Manik, Henry M.; Prartono, Tri; Susilohadi; Ilahude, Delyuzar

    2017-01-01

    Measurement of suspended sediment concentration (SSC) is one of the parameters needed to determine the characteristics of sediment transport. However, the measurement of SSC nowadays still uses conventional technique and it has limitations; especially in temporal resolution. With advanced technology, the measurement can use hydroacoustic technology such as Acoustic Doppler Current Profiler (ADCP). ADCP measures the intensity of backscatter as echo intensity unit from sediment particles. The frequency of ADCP used in this study was 400 kHz. The samples were measured and collected from Lembeh Strait, North Sulawesi. The highest concentration of suspended sediment was 98.89 mg L-1 and the lowest was 45.20 mg L-1. Time series data showed the tidal condition affected the SSC. From the research, we also made correction from sound signal losses effect such as spherical spreading and sound absorption to get more accurate results by eliminating these parameters in echo intensity data. Simple linear regression analysis at echo intensity measured from ADCP to direct measurement of SSC was performed to obtain the estimation of the SSC. The comparison result of estimation of SSC from ADCP measurements and SSC from laboratory analyses was insignificantly different based on t-test statistical analysis with 95% confidence interval percentage.

  10. Effectiveness of skin-to-skin contact versus care-as-usual in mothers and their full-term infants: study protocol for a parallel-group randomized controlled trial.

    PubMed

    Cooijmans, Kelly H M; Beijers, Roseriet; Rovers, Anne C; de Weerth, Carolina

    2017-07-06

    Twenty-to-forty percent of women experience postpartum depressive symptoms, which can affect both the mother and infant. In preterm infants, daily skin-to-skin contact (SSC) between the mother and her infant has been shown to decrease maternal postpartum depressive symptoms. In full-term infants, only two studies investigated SSC effects on maternal depressive symptoms and found similar results. Research in preterm infants also showed that SSC improves other mental and physical health outcomes of the mother and the infant, and improves the quality of mother-infant relationship. This randomized controlled trial will investigate the effects of a SSC intervention on maternal postpartum depressive symptoms and additional outcomes in mothers and their full-term infants. Moreover, two potential underlying mechanisms for the relation between SSC and the maternal and infant outcomes will be examined, namely maternal oxytocin concentrations and infant intestinal microbiota. Design: A parallel-group randomized controlled trial. 116 mothers and their full-term infants. Mothers in the SSC condition will be requested to provide daily at least one continuous hour of SSC to their infant. The intervention starts immediately after birth and lasts for 5 weeks. Mothers in the control condition will not be requested to provide SSC. Maternal and infant outcomes will be measured at 2 weeks, 5 weeks, 12 weeks and 1 year after birth. maternal postpartum depressive symptoms. Secondary maternal outcomes: mental health (anxiety, stress, traumatic stress following child birth, sleep quality), physical health (physical recovery from the delivery, health, breastfeeding, physiological stress), mother-infant relationship (mother-infant bond, quality of maternal caregiving behavior). Secondary infant outcomes: behavior (fussing and crying, sleep quality), physical health (growth and health, physiological stress), general development (regulation capacities, social-emotional capacities, language, cognitive and motor capacities). Secondary underlying mechanisms: maternal oxytocin concentrations, infant intestinal microbiota. As a simple and cost-effective intervention, SSC may benefit both the mother and her full-term infant in the short-and long-term. Additionally, if SSC is shown to be effective in low-risk mother-infant dyads, then thought could be given to developing programs in high-risk samples and using SSC in a preventive manner. NTR5697 ; Registered on March 13, 2016.

  11. Self-consistent electrostatic potential due to trapped plasma in the magnetosphere

    NASA Technical Reports Server (NTRS)

    Miller, Ronald H.; Khazanov, George V.

    1993-01-01

    A steady state solution for the self-consistent electrostatic potential due to a plasma confined in a magnetic flux tube is considered. A steady state distribution function is constructed for the trapped particles from the constants of the motion, in the absence of waves and collisions. Using Liouville's theorem, the particle density along the geomagnetic field is determined and found to depend on the local magnetic field, self-consistent electric potential, and the equatorial plasma distribution function. A hot anisotropic magnetospheric plasma in steady state is modeled by a bi-Maxwellian at the equator. The self-consistent electric potential along the magnetic field is calculated assuming quasineutrality, and the potential drop is found to be approximately equal to the average kinetic energy of the equatorially trapped plasma. The potential is compared with that obtained by Alfven and Faelthammar (1963).

  12. EMITTING ELECTRONS AND SOURCE ACTIVITY IN MARKARIAN 501

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

    Mankuzhiyil, Nijil; Ansoldi, Stefano; Persic, Massimo

    2012-07-10

    We study the variation of the broadband spectral energy distribution (SED) of the BL Lac object Mrk 501 as a function of source activity, from quiescent to flaring. Through {chi}{sup 2}-minimization we model eight simultaneous SED data sets with a one-zone synchrotron self-Compton (SSC) model, and examine how model parameters vary with source activity. The emerging variability pattern of Mrk 501 is complex, with the Compton component arising from {gamma}-e scatterings that sometimes are (mostly) Thomson and sometimes (mostly) extreme Klein-Nishina. This can be seen from the variation of the Compton to synchrotron peak distance according to source state. Themore » underlying electron spectra are faint/soft in quiescent states and bright/hard in flaring states. A comparison with Mrk 421 suggests that the typical values of the SSC parameters are different in the two sources: however, in both jets the energy density is particle-dominated in all states.« less

  13. SAM Photovoltaic Model Technical Reference

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

    Gilman, P.

    2015-05-27

    This manual describes the photovoltaic performance model in the System Advisor Model (SAM). The U.S. Department of Energy’s National Renewable Energy Laboratory maintains and distributes SAM, which is available as a free download from https://sam.nrel.gov. These descriptions are based on SAM 2015.1.30 (SSC 41).

  14. Autoantibodies to the Rpp25 component of the Th/To complex are the most common antibodies in patients with systemic sclerosis without antibodies detectable by widely available commercial tests.

    PubMed

    Mahler, Michael; Satoh, Minoru; Hudson, Marie; Baron, Murray; Chan, Jason Y F; Chan, Edward K L; Wick, James; Fritzler, Marvin J

    2014-07-01

    Antinuclear antibodies (ANA) occur in up to 95% of patients with systemic sclerosis (SSc). In most, SSc-associated antibodies are detected (i.e., centromere, topoisomerase I, RNA polymerase III, PM/Scl, Ro52/TRIM21, and U1RNP). Ribonuclease P protein subunit p25, (Rpp25) is an autoantigenic component of the Th/To complex. The contribution of anti-Th/To and anti-Rpp25 antibodies to ANA positivity in patients with SSc remains unknown. Sera from 873 patients with SSc were tested for ANA, and SSc-associated antibodies were measured. Samples without antibodies to extractable nuclear antigens (ENA; n = 53, ANA+/ENA-), were analyzed by immunoprecipitation (IP) and metabolically labeled proteins and for anti-Rpp25 antibodies (n = 50) by a chemiluminescent immunoassay (CLIA) and Rpp25 ELISA. Anti-Th/To antibodies occurred in 19/53 (36%), as determined by IP, and were the most common autoantibody in ANA+/ENA- SSc. Of those samples, 50/53 were available for additional testing by CLIA and ELISA. Anti-Rpp25 antibodies were detected in 12 (24% CLIA) or 10 (20% ELISA) of 50 patients. Receiver-operating characteristic curve analysis showed similar discrimination between Th/To IP-positive (n = 19) and -negative samples (n = 31) by CLIA and ELISA (area under the curve 0.90 vs 0.87; p = 0.6691). The positive percent agreement between IP and CLIA or ELISA was 12/19 (63.2%, 95% CI 38.4-83.7%) or 10/19 (52.6%, 95% CI 73.3-94.2%), respectively. Negative percent agreement was 100% for both assays. Autoantibodies to the Th/To autoantigen are important in patients with SSc who have been considered negative for SSc-specific or SSc-associated antibodies by widely available commercial assays. Rpp25 can be considered a major target of anti-Th/To antibodies. Assays detecting anti-Th/To and anti-Rpp25 antibodies may be important in SSc.

  15. Improving the Quality of Adult Mortality Data Collected in Demographic Surveys: Validation Study of a New Siblings' Survival Questionnaire in Niakhar, Senegal

    PubMed Central

    Helleringer, Stéphane; Pison, Gilles; Masquelier, Bruno; Kanté, Almamy Malick; Douillot, Laetitia; Duthé, Géraldine; Sokhna, Cheikh; Delaunay, Valérie

    2014-01-01

    Background In countries with limited vital registration, adult mortality is frequently estimated using siblings' survival histories (SSHs) collected during Demographic and Health Surveys (DHS). These data are affected by reporting errors. We developed a new SSH questionnaire, the siblings' survival calendar (SSC). It incorporates supplementary interviewing techniques to limit omissions of siblings and uses an event history calendar to improve reports of dates and ages. We hypothesized that the SSC would improve the quality of adult mortality data. Methods and Findings We conducted a retrospective validation study among the population of the Niakhar Health and Demographic Surveillance System in Senegal. We randomly assigned men and women aged 15–59 y to an interview with either the DHS questionnaire or the SSC. We compared SSHs collected in each group to prospective data on adult mortality collected in Niakhar. The SSC reduced respondents' tendency to round reports of dates and ages to the nearest multiple of five or ten (“heaping”). The SSC also had higher sensitivity in recording adult female deaths: among respondents whose sister(s) had died at an adult age in the past 15 y, 89.6% reported an adult female death during SSC interviews versus 75.6% in DHS interviews (p = 0.027). The specificity of the SSC was similar to that of the DHS questionnaire, i.e., it did not increase the number of false reports of deaths. However, the SSC did not improve the reporting of adult deaths among the brothers of respondents. Study limitations include sample selectivity, limited external validity, and multiple testing. Conclusions The SSC has the potential to collect more accurate SSHs than the questionnaire used in DHS. Further research is needed to assess the effects of the SSC on estimates of adult mortality rates. Additional validation studies should be conducted in different social and epidemiological settings. Trial Registration Controlled-Trials.com ISRCTN06849961 Please see later in the article for the Editors' Summary PMID:24866715

  16. Increasing compliance with the World Health Organization Surgical Safety Checklist-A regional health system's experience.

    PubMed

    Gitelis, Matthew E; Kaczynski, Adelaide; Shear, Torin; Deshur, Mark; Beig, Mohammad; Sefa, Meredith; Silverstein, Jonathan; Ujiki, Michael

    2017-07-01

    In 2009, NorthShore University HealthSystem adapted the World Health Organization Surgical Safety Checklist (SSC) at each of its 4 hospitals. Despite evidence that SSC reduces intraoperative mistakes and increase patient safety, compliance was found to be low with the paper form. In November 2013, NorthShore integrated the SSC into the electronic health record (EHR). The aim was to increase communication between operating room (OR) personnel and to encourage best practices during the natural workflow of surgeons, anesthesiologists, and nurses. The purpose of this study was to examine the impact of an electronic SSC on compliance and patient safety. An anonymous OR observer selected cases at random and evaluated the compliance rate before the rollout of the electronic SSC. In June 2014, an electronic audit was performed to assess the compliance rate. Random OR observations were also performed throughout the summer in 2014. Perioperative risk events, such as consent issues, incorrect counts, wrong site, and wrong procedure were compared before and after the electronic SSC rollout. A perception survey was also administered to NorthShore OR personnel. Compliance increased from 48% (n = 167) to 92% (n = 1,037; P < .001) after the SSC was integrated into the electronic health record. Surgeons (91% vs 97%; P < .001), anesthesiologists (89% vs 100%; P < .001), and nurses (55% vs 93%; P < .001) demonstrated an increase in compliance. A comparison between risk events in the pre- and post-rollout period showed a 32% decrease (P < .01). Hospital-wide indicators including length of stay and 30-day readmissions were lower. In a survey to assess the OR personnel's perceptions of the new checklist, 76% of surgeons, 86% of anesthesiologists, and 88% of nurses believed the electronic SSC will have a positive impact on patient safety. The World Health Organization SSC is a validated tool to increase patient safety and reduce intraoperative complications. The electronic SSC has demonstrated an increased compliance rate, a reduced number of risk events, and most OR personnel believe it will have a positive impact on patient safety. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Self-consistent Non-LTE Model of Infrared Molecular Emissions and Oxygen Dayglows in the Mesosphere and Lower Thermosphere

    NASA Technical Reports Server (NTRS)

    Feofilov, Artem G.; Yankovsky, Valentine A.; Pesnell, William D.; Kutepov, Alexander A.; Goldberg, Richard A.; Mauilova, Rada O.

    2007-01-01

    We present the new version of the ALI-ARMS (for Accelerated Lambda Iterations for Atmospheric Radiation and Molecular Spectra) model. The model allows simultaneous self-consistent calculating the non-LTE populations of the electronic-vibrational levels of the O3 and O2 photolysis products and vibrational level populations of CO2, N2,O2, O3, H2O, CO and other molecules with detailed accounting for the variety of the electronic-vibrational, vibrational-vibrational and vibrational-translational energy exchange processes. The model was used as the reference one for modeling the O2 dayglows and infrared molecular emissions for self-consistent diagnostics of the multi-channel space observations of MLT in the SABER experiment It also allows reevaluating the thermalization efficiency of the absorbed solar ultraviolet energy and infrared radiative cooling/heating of MLT by detailed accounting of the electronic-vibrational relaxation of excited photolysis products via the complex chain of collisional energy conversion processes down to the vibrational energy of optically active trace gas molecules.

  18. Detection of dermal systemic sclerosis using noncontact optical coherence elastography

    NASA Astrophysics Data System (ADS)

    Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Li, Jiasong; Wu, Chen; Han, Zhaolong; Raghunathan, Raksha; Hsu, Thomas; Noorani, Shezaan; Hicks, M. John; Mohan, Chandra; Larin, Kirill V.

    2016-03-01

    Systemic sclerosis (SSc) is a connective tissue disease that results in excessive accumulation of collagen in the skin and internal organs. Overall, SSc is a rare disorder, but has a high mortality, particularly in last decade of life. To improve the survival rate, an accurate and early diagnosis is crucial. Currently, the modified Rodnan skin score (mRSS) is the gold standard for evaluating SSc progression based on clinical palpation at 17 sites on the body. However, this procedure can be time consuming, and the assessed score may be biased by the experience of the clinician, causing inter- and intraobserver variabilities. Moreover, the instrinsic elasticity of skin may further bias the mRSS assessment in the early stages of SSc, such as oedematous. To overcome these limitations, there is a need for a rapid, accurate, and objective assessment technique. Optical coherence elastography (OCE) is a novel, rapidly emerging technique, which can assess mechanical contrast in tissues with micrometer spatial resolution. In this work, we demonstrate the first use of OCE to assess the mechanical properties of control and SSc-like diseased skin non-invasively. A focused air-pulse induced an elastic wave in the skin, which was detected by a home-built OCE system. The elastic wave propagated significantly faster in SSc skin compared to healthy skin. The Young's modulus of the SSc skin was significantly higher than that of normal skin (P<0.05). Thus, OCE was able to objectively differentiate healthy and fibrotic skin completely noninvasively and is a promising and potentially useful new technology for quantifying skin involvement in SSc.

  19. Association Study of ITGAM, ITGAX, and CD58 Autoimmune Risk Loci in Systemic Sclerosis: Results from 2 Large European Caucasian Cohorts

    PubMed Central

    COUSTET, BAPTISTE; AGARWAL, SANDEEP K.; GOURH, PRAVITT; GUEDJ, MICKAEL; MAYES, MAUREEN D.; DIEUDE, PHILIPPE; WIPFF, JULIEN; AVOUAC, JEROME; HACHULLA, ERIC; DIOT, ELISABETH; CRACOWSKI, JEAN LUC; TIEV, KIET; SIBILIA, JEAN; MOUTHON, LUC; FRANCES, CAMILLE; AMOURA, ZAHIR; CARPENTIER, PATRICK; MEYER, OLIVIER; KAHAN, ANDRE; BOILEAU, CATHERINE; ARNETT, FRANK C.; ALLANORE, YANNICK

    2012-01-01

    Objective Accumulating evidence shows that shared autoimmunity is critical for the pathogenesis of many autoimmune diseases. Systemic sclerosis (SSc) belongs to the connective tissue disorders, and recent data have highlighted strong associations with autoimmunity genes shared with other autoimmune diseases. To determine whether novel risk loci associated with systemic lupus erythematosus or multiple sclerosis may confer susceptibility to SSc, we tested single-nucleotide polymorphisms (SNP) from ITGAM, ITGAX, and CD58 for associations. Methods SNP harboring associations with autoimmune diseases, ITGAM rs9937837, ITGAX rs11574637, and CD58 rs12044852, were genotyped in 2 independent cohorts of European Caucasian ancestry: 1031 SSc patients and 1014 controls from France and 1038 SSc patients and 691 controls from the USA, providing a combined study population of 3774 individuals. ITGAM rs1143679 was additionally genotyped in the French cohort. Results The 4 polymorphisms were in Hardy-Weinberg equilibrium in the 2 control populations, and allelic frequencies were similar to those expected in European Caucasian populations. Allelic and genotypic frequencies for these 3 SNP were found to be statistically similar in SSc patients and controls. Subphenotype analyses for subgroups having diffuse cutaneous subtype disease, specific autoantibodies, or fibrosing alveolitis did not reveal any difference between SSc patients and controls. Conclusion These results obtained through 2 large cohorts of SSc patients of European Caucasian ancestry do not support the implication of ITGAM, ITGAX, and CD58 genes in the genetic susceptibility of SSc, although they were recently identified as autoimmune disease risk genes. PMID:21362770

  20. Genomic regions associated with kyphosis in swine

    PubMed Central

    2010-01-01

    Background A back curvature defect similar to kyphosis in humans has been observed in swine herds. The defect ranges from mild to severe curvature of the thoracic vertebrate in split carcasses and has an estimated heritability of 0.3. The objective of this study was to identify genomic regions that affect this trait. Results Single nucleotide polymorphism (SNP) associations performed with 198 SNPs and microsatellite markers in a Duroc-Landrace-Yorkshire resource population (U.S. Meat Animal Research Center, USMARC resource population) of swine provided regions of association with this trait on 15 chromosomes. Positional candidate genes, especially those involved in human skeletal development pathways, were selected for SNP identification. SNPs in 16 candidate genes were genotyped in an F2 population (n = 371) and the USMARC resource herd (n = 1,257) with kyphosis scores. SNPs in KCNN2 on SSC2, RYR1 and PLOD1 on SSC6 and MYST4 on SSC14 were significantly associated with kyphosis in the resource population of swine (P ≤ 0.05). SNPs in CER1 and CDH7 on SSC1, PSMA5 on SSC4, HOXC6 and HOXC8 on SSC5, ADAMTS18 on SSC6 and SOX9 on SSC12 were significantly associated with the kyphosis trait in the F2 population of swine (P ≤ 0.05). Conclusions These data suggest that this kyphosis trait may be affected by several loci and that these may differ by population. Carcass value could be improved by effectively removing this undesirable trait from pig populations. PMID:21176156

  1. Using genome wide association studies to identify common QTL regions in three different genetic backgrounds based on Iberian pig breed.

    PubMed

    Martínez-Montes, Ángel M; Fernández, Almudena; Muñoz, María; Noguera, Jose Luis; Folch, Josep M; Fernández, Ana I

    2018-01-01

    One of the major limitation for the application of QTL results in pig breeding and QTN identification has been the limited number of QTL effects validated in different animal material. The aim of the current work was to validate QTL regions through joint and specific genome wide association and haplotype analyses for growth, fatness and premier cut weights in three different genetic backgrounds, backcrosses based on Iberian pigs, which has a major role in the analysis due to its high productive relevance. The results revealed nine common QTL regions, three segregating in all three backcrosses on SSC1, 0-3 Mb, for body weight, on SSC2, 3-9 Mb, for loin bone-in weight, and on SSC7, 3 Mb, for shoulder weight, and six segregating in two of the three backcrosses, on SSC2, SSC4, SSC6 and SSC10 for backfat thickness, shoulder and ham weights. Besides, 18 QTL regions were specifically identified in one of the three backcrosses, five identified only in BC_LD, seven in BC_DU and six in BC_PI. Beyond identifying and validating QTL, candidate genes and gene variants within the most interesting regions have been explored using functional annotation, gene expression data and SNP identification from RNA-Seq data. The results allowed us to propose a promising list of candidate mutations, those identified in PDE10A, DHCR7, MFN2 and CCNY genes located within the common QTL regions and those identified near ssc-mir-103-1 considered PANK3 regulators to be further analysed.

  2. Association between an endoglin gene polymorphism and systemic sclerosis-related pulmonary arterial hypertension.

    PubMed

    Wipff, J; Kahan, A; Hachulla, E; Sibilia, J; Cabane, J; Meyer, O; Mouthon, L; Guillevin, L; Junien, C; Boileau, C; Allanore, Y

    2007-04-01

    Systemic sclerosis (SSc) is a connective tissue disorder characterized by early generalized microangiopathy with disturbed angiogenesis. Endoglin gene (ENG) encodes a transmembrane glycoprotein which acts as an accessory receptor for the transforming growth factor-beta (TGF-beta) superfamily, and is crucial for maintaining vascular integrity. A 6-base insertion in intron 7 (6bINS) of ENG has been reported to be associated with microvascular disturbance. Our objective was to investigate the relationship between 6bINS and the vascular complication pulmonary arterial hypertension (PAH) in SSc in a French Caucasian population. Two hundred eighty SSc cases containing 29/280 having PAH diagnosed by catheterism were compared with 140 patients with osteoarthritis. Genotyping was performed by polymerase-chain-reaction-based fluorescence and direct sequencing of genomic DNA. The polymorphism was in Hardy-Weinberg equilibrium. We observed a significant lower frequency of 6bINS allele in SSc patients with associated PAH compared with controls [10.3 vs 23.9%, P = 0.01; odds ratio (OR) 0.37, 95% confidence interval (CI) 0.15-0.89], and a trend in comparison with SSc patients without PAH (10.3 vs 20.3%, P = 0.05; OR: 0.45, 95% CI: 0.19-1.08). Genotypes carrying allele 6bINS were also less frequent in SSc patients with PAH than in controls (20.7 vs 42.9%, P = 0.02). Thus the frequency of 6bINS differs between SSc patients with or without PAH, suggesting the implication of ENG in this devastating vascular complication of SSc.

  3. Testicular Cancer and Cryptorchidism

    PubMed Central

    Ferguson, Lydia; Agoulnik, Alexander I.

    2013-01-01

    The failure of testicular descent or cryptorchidism is the most common defect in newborn boys. The descent of the testes during development is controlled by insulin-like 3 peptide and steroid hormones produced in testicular Leydig cells, as well as by various genetic and developmental factors. While in some cases the association with genetic abnormalities and environmental causes has been shown, the etiology of cryptorchidism remains uncertain. Cryptorchidism is an established risk factor for infertility and testicular germ cell tumors (TGCT). Experimental animal models suggest a causative role for an abnormal testicular position on the disruption of spermatogenesis however the link between cryptorchidism and TGCT is less clear. The most common type of TGCT in cryptorchid testes is seminoma, believed to be derived from pluripotent prenatal germ cells. Recent studies have shown that seminoma cells and their precursor carcinoma in situ cells express a number of spermatogonial stem cell (SSC) markers suggesting that TGCTs might originate from adult stem cells. We review here the data on changes in the SSC somatic cell niche observed in cryptorchid testes of mouse models and in human patients. We propose that the misregulation of growth factors’ expression may alter the balance between SSC self-renewal and differentiation and shift stem cells toward neoplastic transformation. PMID:23519268

  4. 40 CFR 35.6805 - Contents of an SSC.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... to approve modifications to the project so long as such changes are within the scope of the contract... compel cleanup, or for cost recovery under section 107 of CERCLA. (o) Sanctions for failure to comply with SSC terms, which states that if the signatories fail to comply with the terms of the SSC, EPA may...

  5. The involvement of immunoglobulin E isotype switch in scleroderma skin tissue.

    PubMed

    Ohtsuka, Tsutomu; Yamazaki, Soji

    2005-08-01

    The involvement of mast cell, which is activated by immunoglobulin E (IgE), has been reported in the formation of systemic sclerosis (SSc) abnormality. IgE is generated with isotype switch. During isotype switch, switch circles resulting from direct mu to epsilon, or from sequential mu to gamma via epsilon switching will be created. We studied whether switching occurs in SSc. We used nested polymerase chain reaction to analyze the S fragments from switch circles. Fifty-two patients with SSc, and 62 healthy women were studied. Neither of 62 normal skin tissues showed direct switch, nor sequential switch. Neither of seven normal whole blood cells showed direct switch, nor sequential switch. In 52SSc skin tissues, three (5.8%) showed direct switch, and two (3.8%) showed sequential switch. As a result, five (9.6%) of SSc skin tissue showed immunogobulin E class switch. These results were confirmed by DNA sequencing. These results demonstrated that isotype switch to the epsilon locus achieved by direct and/or sequential switch are involved in SSc skin.

  6. Productivity Losses and Costs in the Less-Common Systemic Autoimmune Rheumatic Diseases.

    PubMed

    McCormick, Natalie; Marra, Carlo A; Aviña-Zubieta, J Antonio

    2017-10-30

    We synthesised the literature on productivity losses and costs in the less-common systemic autoimmune rheumatic diseases: Sjogren's syndrome (SjS), systemic sclerosis (SSc), poly/dermatomyositis (PM/DM), and systemic vasculitides (SV). Of 29 studies located, 12 were published 2012 onwards (SSc = 6, SjS = 2, PM/DM = 2, SV = 2). In these, 25% of PM/DM, and 21-26% of SV, were work disabled, 22% of SSc stopped work within 3 years of diagnosis, and annual costs of absenteeism in SSc averaged $12,024 2017 USD. Very few studies reported on costs, presenteeism (working at reduced levels), or unpaid productivity loss. Across multiple systemic autoimmune rheumatic diseases (SARDs), major drivers of lost productivity were generalised items like pain, depression, and fatigue, rather than disease-specific factors. Evidence suggests that work disability is common in SSc and strikes quickly. However, in SSc and other SARDs, more comprehensive estimates are needed, which include absenteeism and presenteeism from paid and unpaid work, costs, and drivers of productivity loss.

  7. Analysis of the association between CD40 and CD40 ligand polymorphisms and systemic sclerosis.

    PubMed

    Teruel, María; Simeon, Carmen P; Broen, Jasper; Vonk, Madelon C; Carreira, Patricia; Camps, Maria Teresa; García-Portales, Rosa; Delgado-Frías, Esmeralda; Gallego, Maria; Espinosa, Gerard; Beretta, Lorenzo; Airó, Paolo; Lunardi, Claudio; Riemekasten, Gabriela; Witte, Torsten; Krieg, Thomas; Kreuter, Alexander; Distler, Jörg H W; Hunzelmann, Nicolas; Koeleman, Bobby P; Voskuyl, Alexandre E; Schuerwegh, Annemie J; González-Gay, Miguel Angel; Radstake, Timothy R D J; Martin, Javier

    2012-06-25

    The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc). In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genotyped by using a predesigned TaqMan allele-discrimination assay technology. Meta-analysis was assessed to determine whether an association exists between the genetic variants and SSc or its main clinical subtypes. No evidence of association between CD40 and CD40LG genes variants and susceptibility to SSc was observed. Similarly, no significant statistical differences were observed when SSc patients were stratified by the clinical subtypes, the serologic features, and pulmonary fibrosis. Our results do not suggest an important role of CD40 and CD40LG gene polymorphisms in the susceptibility to or clinical expression of SSc.

  8. Clinical significance of serum decoy receptor 3 levels in patients with systemic sclerosis.

    PubMed

    Yamada, Daisuke; Asano, Yoshihide; Takahashi, Takehiro; Masui, Yuri; Aozasa, Naohiko; Akamata, Kaname; Noda, Shinji; Tamaki, Zenshiro; Tada, Yayoi; Sugaya, Makoto; Sato, Shinichi; Kadono, Takafumi

    2012-01-01

    Decoy receptor 3 (DcR3) is associated with autoimmunity and altered angiogenesis in certain pathological conditions. We herein measured serum DcR3 levels in 51 patients with systemic sclerosis (SSc) and 19 healthy controls and evaluated their clinical significance in this disorder. Serum DcR3 levels were significantly higher in diffuse cutaneous SSc (dcSSc) patients than in limited cutaneous SSc patients and in healthy controls. In dcSSc, serum DcR3 levels were significantly elevated in patients with disease duration of ≤6 years compared with healthy controls, but not in those with disease duration of >6 years. Serum DcR3 levels correlated negatively with the percentage of predicted diffusion lung capacity for carbon monoxide and positively with right ventricular systolic pressure. Furthermore, serum DcR3 levels positively correlated with C-reactive protein, erythrocyte sedimentation rate and immunoglobulin G. Collectively, the elevation of serum DcR3 levels is associated with the development of pulmonary arterial hypertension and systemic inflammation in SSc.

  9. A3 Subscale Diffuser Test Article Design

    NASA Technical Reports Server (NTRS)

    Saunders, G. P.

    2009-01-01

    This paper gives a detailed description of the design of the A3 Subscale Diffuser Test (SDT) Article Design. The subscale diffuser is a geometrically accurate scale model of the A3 altitude rocket facility. It was designed and built to support the SDT risk mitigation project located at the E3 facility at Stennis Space Center, MS (SSC) supporting the design and construction of the A3 facility at SSC. The subscale test article is outfitted with a large array of instrumentation to support the design verification of the A3 facility. The mechanical design of the subscale diffuser and test instrumentation are described here

  10. Stretching Reduces Skin Thickness and Improves Subcutaneous Tissue Mobility in a Murine Model of Systemic Sclerosis.

    PubMed

    Xiong, Ying; Berrueta, Lisbeth; Urso, Katia; Olenich, Sara; Muskaj, Igla; Badger, Gary J; Aliprantis, Antonios; Lafyatis, Robert; Langevin, Helene M

    2017-01-01

    Although physical therapy can help preserve mobility in patients with systemic sclerosis (SSc), stretching has not been used systematically as a treatment to prevent or reverse the disease process. We previously showed in rodent models that stretching promotes the resolution of connective tissue inflammation and reduces new collagen formation after injury. Here, we tested the hypothesis that stretching would impact scleroderma development using a mouse sclerodermatous graft-versus-host disease (sclGvHD) model. The model consists in the adoptive transfer (allogeneic) of splenocytes from B10.D2 mice (graft) into Rag2 -/- BALB/c hosts (sclGvHD), resulting in skin inflammation followed by fibrosis over 4 weeks. SclGvHD mice and controls were randomized to stretching in vivo for 10 min daily versus no stretching. Weekly ultrasound measurements of skin thickness and subcutaneous tissue mobility in the back (relative tissue displacement during passive trunk motion) successfully captured the different phases of the sclGvHD model. Stretching reduced skin thickness and increased subcutaneous tissue mobility compared to no stretching at week 3. Stretching also reduced the expression of CCL2 and ADAM8 in the skin at week 4, which are two genes known to be upregulated in both murine sclGvHD and the inflammatory subset of human SSc. However, there was no evidence that stretching attenuated inflammation at week 2. Daily stretching for 10 min can improve skin thickness and mobility in the absence of any other treatment in the sclGvHD murine model. These pre-clinical results suggest that a systematic investigation of stretching as a therapeutic modality is warranted in patients with SSc.

  11. Altered expression of CD63 and exosomes in scleroderma dermal fibroblasts.

    PubMed

    Nakamura, Kayo; Jinnin, Masatoshi; Harada, Miho; Kudo, Hideo; Nakayama, Wakana; Inoue, Kuniko; Ogata, Aki; Kajihara, Ikko; Fukushima, Satoshi; Ihn, Hironobu

    2016-10-01

    Exosomes are small vesicles shed from various cells. They contain proteins, lipids, and nucleic acids, and are regarded as a tool of cell-cell communication. To reveal the putative role of exosomes in systemic sclerosis (SSc), and to elucidate the effect of exosomes on wound healing. The expression of common markers for exosomes (CD63, CD9, and CD81) and type I collagen were examined with real-time PCR, immunohistochemical analysis, ELISA, immunoblotting, and flow cytometry. The effect of serum-derived exosomes on wound healing was tested on full-thickness wounds in the mid-dorsal skin of BALB/c mice. The expression levels of CD63 as well as CD9 and CD81 tended to be increased in SSc dermal fibroblasts compared to normal fibroblasts. Increased exosomes in a cultured media of SSc fibroblasts stimulated the expression levels of type I collagen in normal fibroblasts. As the mechanism, collagen-related microRNA levels in SSc fibroblast-derived exosomes were dysregulated, indicating that both the amount and the content of exosomes were altered in SSc. On the other hand, SSc sera showed significantly decreased exosome levels compared to normal sera. The frequencies of vascular involvements, including skin ulcers or pitting scars, were significantly increased in patients with decreased serum exosome levels. The healing of mice wounds was accelerated by treatment with serum-derived exosomes. Vascular abnormalities in SSc may account for the decreased serum exosome levels by the disturbed transfer of exosomes from the skin tissue to the blood stream. Our study suggests the possibility that SSc patients with vascular involvements have decreased serum exosome levels, which causes the delay of wound healing due to down-regulation of collagen, resulting in higher susceptibility to pitting scars and/or ulcers. Exosome research will lead to a detailed understanding of SSc pathogenesis and new therapeutic approaches. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  12. Identification of differentially expressed small RNAs and prediction of target genes in Italian Large White pigs with divergent backfat deposition.

    PubMed

    Davoli, R; Gaffo, E; Zappaterra, M; Bortoluzzi, S; Zambonelli, P

    2018-06-01

    The identification of the molecular mechanisms regulating pathways associated with the potential for fat deposition in pigs can lead to the detection of key genes and markers for the genetic improvement of fat traits. Interactions of microRNAs (miRNAs) with target RNAs regulate gene expression and modulate pathway activation in cells and tissues. In pigs, miRNA discovery is far from saturation, and the knowledge of miRNA expression in backfat tissue and particularly of the impact of miRNA variations is still fragmentary. Using RNA-seq, we characterized the small RNA (sRNA) expression profiles in Italian Large White pig backfat tissue. Comparing two groups of pigs divergent for backfat deposition, we detected 31 significant differentially expressed (DE) sRNAs: 14 up-regulated (including ssc-miR-132, ssc-miR-146b, ssc-miR-221-5p, ssc-miR-365-5p and the moRNA ssc-moR-21-5p) and 17 down-regulated (including ssc-miR-136, ssc-miR-195, ssc-miR-199a-5p and ssc-miR-335). To understand the biological impact of the observed miRNA expression variations, we used the expression correlation of DE miRNA target transcripts expressed in the same samples to define a regulatory network of 193 interactions between DE miRNAs and 40 DE target transcripts showing opposite expression profiles and being involved in specific pathways. Several miRNAs and mRNAs in the network were found to be expressed from backfat-related pig QTL. These results are informative for the complex mechanisms influencing fat traits, shed light on a new aspect of the genetic regulation of fat deposition in pigs and facilitate the prospective implementation of innovative strategies of pig genetic improvement based on genomic markers. © 2018 Stichting International Foundation for Animal Genetics.

  13. Association of the FAM167A-BLK region with systemic sclerosis.

    PubMed

    Ito, Ikue; Kawaguchi, Yasushi; Kawasaki, Aya; Hasegawa, Minoru; Ohashi, Jun; Kawamoto, Manabu; Fujimoto, Manabu; Takehara, Kazuhiko; Sato, Shinichi; Hara, Masako; Tsuchiya, Naoyuki

    2010-03-01

    An association of single-nucleotide polymorphisms (SNPs) in the FAM167A (previously referred to as C8orf13)-BLK region with systemic lupus erythematosus (SLE) has been demonstrated in Caucasians and in Asians. Recent studies have shown that many genes, including IRF5, STAT4, and PTPN22, are shared susceptibility genes in multiple autoimmune diseases. We undertook the current study to examine whether the FAM167A-BLK region is also associated with susceptibility to systemic sclerosis (SSc). Japanese patients with SSc (n = 309) and healthy controls (n = 769) were enrolled in a 2-tiered case-control association study. In tier 1, 124 patients and 412 controls were tested to determine association of 16 tag SNPs encompassing the FAM167A-BLK region with SSc. In tier 2, an additional 185 patients and 357 controls were analyzed for SNP rs13277113. Two haplotype blocks that correspond approximately to FAM167A and BLK were observed. In tier 1 of the study, the rs13277113A allele in the BLK block exhibited the most significant association with SSc after correction for multiple testing (permutated P = 0.024). Two SNP haplotypes formed by rs13277113 and the most significant SNP in the FAM167A block did not exhibit stronger association. When samples from tier 1 and tier 2 were combined, the rs13277113A allele was significantly associated with SSc (odds ratio 1.45 [95% confidence interval 1.17-1.79], P = 6.1 x 10(-4)). Association or a tendency toward association of rs13277113A with SSc was observed regardless of a patient's autoantibody profile or whether a patient had diffuse cutaneous or limited cutaneous SSc. Our findings indicate that the rs13277113A allele is associated not only with SLE but also with SSc and that the FAM167A-BLK region is a common genetic risk factor for both SLE and SSc.

  14. Skin-to-skin contact with an umbilical venous catheter: prospective evaluation in a level 3 unit.

    PubMed

    Catherine, Zaoui-Grattepanche; Béatrice, Pindi; Fabrice, Lapeyre; Claire, Huart; Alain, Duhamel

    2016-04-01

    The aim was to assess the incidence of complications related to skin-to-skin contact (SSC) in newborns with an umbilical venous catheter (UVC). We carried out a prospective follow-up study of all UVCs in a level 3 unit where SSC is systematic. A total of 333 babies were included (mean gestational age of 31.3 weeks (24-41), mean birth weight of 1618 g (454-4900). Two hundred sixty-three babies (78.9 %) had SSC, at a mean postnatal age of 24 h (3-144 h). Two babies presented with a significant umbilical bleeding, all in the first 3 h, before SSC. In 17 cases of UVC leaking, this necessitated an unwanted withdrawal of the UVC; of these, 14 UVCs (82 %) were in sub-hepatic position. In five cases of UVC displacement, babies had no SSC. The overall incidence (3 % [95 % CI = 1.4-5.4]) and incidence density (6.2/1000 UVC-day [95 % CI = 3-11.4]) of catheter-associated infections are similar to those identified by the French multicenter network NEOCAT in 2012 (5 % [95 % CI = 4.1-5.9] and 11.3/1000 UVC-day [95 % CI = 9.3-13.2]). In this prospective, non-randomized study in a level unit, routine practice of SSC with a UVC does not seem to influence the incidence of mechanical and infectious complications. What is known? • SSC is beneficial for pretem infants. • Fear of mechanical problems and/or infections with a UVC is an obstacle to early use of SSC. What is New: • In this study, SSC for preterm infants with a UVC is associated with low risks of mechanical complications, and does not seem to be associated with any higher risk of catheter-related infections.

  15. Early skin-to-skin contact after cesarean section: A randomized clinical pilot study

    PubMed Central

    Kollmann, Martina; Aldrian, Lisa; Scheuchenegger, Anna; Mautner, Eva; Herzog, Sereina A.; Urlesberger, Berndt; Raggam, Reinhard B.; Lang, Uwe; Obermayer-Pietsch, Barbara; Klaritsch, Philipp

    2017-01-01

    Objective Early bonding by skin-to-skin contact (SSC) has been demonstrated to be beneficial for mothers and newborns following vaginal delivery. The aim of this study was to investigate the impact of intraoperative bonding (early SSC) after cesarean section on neonatal adaptation, maternal pain and stress response. Study design This prospective, randomized-controlled pilot study was performed at a single academic tertiary hospital (Department of Obstetrics and Gynecology, Medical University of Graz, Austria) between September 2013 and January 2014. Women were randomly assigned to intraoperative (“early”) SCC (n = 17) versus postoperative (“late”) SCC (n = 18). Main variables investigated were neonatal transition (Apgar score, arterial oxygen saturation, heart rate and temperature), maternal pain perception and both maternal and neonatal stress response by measuring the stress biomarkers salivary free cortisol and salivary alpha amylase. Results There was no evidence for differences in parameters reflecting neonatal transition or stress response between the ‘Early SSC Group’ and the ‘Late SSC Group’. Maternal salivary cortisol and alpha-amylase levels as well as maternal wellbeing and pain did not differ between the groups. However, the rise of maternal salivary alpha-amylase directly after delivery was higher in the ‘Early SSC Group’ compared to the ‘Late SSC Group’ (p = 0.004). Conclusions This study did not reveal significant risks for the newborn in terms of neonatal transition when early SSC is applied in the operating room. Maternal condition and stress marker levels did not differ either, although the rise of maternal salivary alpha-amylase directly after delivery was higher in the ‘Early SSC Group’ compared to the ‘Late SSC Group’, which may indicate a stressor sign due to intensive activation of the sympathetic-adreno-medullary-system. This needs to be further evaluated in a larger prospective randomized trial. Trial registration ClinicalTrials.gov NCT01894880 PMID:28231274

  16. Deficient Adipogenesis of Scleroderma Patient and Healthy African American Monocytes

    PubMed Central

    Lee, Rebecca; Reese, Charles; Carmen-Lopez, Gustavo; Perry, Beth; Bonner, Michael; Zemskova, Marina; Wilson, Carole L.; Helke, Kristi L.; Silver, Richard M.; Hoffman, Stanley; Tourkina, Elena

    2017-01-01

    Monocytes from systemic sclerosis (SSc, scleroderma) patients and healthy African Americans (AA) are deficient in the regulatory protein caveolin-1 leading to enhanced migration toward chemokines and fibrogenic differentiation. While dermal fibrosis is the hallmark of SSc, loss of subcutaneous adipose tissue is a lesser-known feature. To better understand the etiology of SSc and the predisposition of AA to SSc, we studied the adipogenic potential of SSc and healthy AA monocytes. The ability of SSc and healthy AA monocytes to differentiate into adipocyte-like cells (ALC) is inhibited compared to healthy Caucasian (C) monocytes. We validated that monocyte-derived ALCs are distinct from macrophages by flow cytometry and immunocytochemistry. Like their enhanced fibrogenic differentiation, their inhibited adipogenic differentiation is reversed by the caveolin-1 scaffolding domain peptide (CSD, a surrogate for caveolin-1). The altered differentiation of SSc and healthy AA monocytes is additionally regulated by peroxisome proliferator-activated receptor γ (PPARγ) which is also present at reduced levels in these cells. In vivo studies further support the importance of caveolin-1 and PPARγ in fibrogenesis and adipogenesis. In SSc patients, healthy AA, and mice treated systemically with bleomycin, adipocytes lose caveolin-1 and PPARγ and the subcutaneous adipose layer is diminished. CSD treatment of these mice leads to a reappearance of the caveolin-1+/PPARγ+/FABP4+ subcutaneous adipose layer. Moreover, many of these adipocytes are CD45+, suggesting they are monocyte derived. Tracing experiments with injected EGFP+ monocytes confirm that monocytes contribute to the repair of the adipose layer when it is damaged by bleomycin treatment. Our observations strongly suggest that caveolin-1 and PPARγ work together to maintain a balance between the fibrogenic and adipogenic differentiation of monocytes, that this balance is altered in SSc and in healthy AA, and that monocytes make a major contribution to the repair of the adipose layer. PMID:28420992

  17. Bone marrow-derived mesenchymal stem cells from early diffuse systemic sclerosis exhibit a paracrine machinery and stimulate angiogenesis in vitro.

    PubMed

    Guiducci, Serena; Manetti, Mirko; Romano, Eloisa; Mazzanti, Benedetta; Ceccarelli, Claudia; Dal Pozzo, Simone; Milia, Anna Franca; Bellando-Randone, Silvia; Fiori, Ginevra; Conforti, Maria Letizia; Saccardi, Riccardo; Ibba-Manneschi, Lidia; Matucci-Cerinic, Marco

    2011-11-01

    To characterise bone marrow-derived mesenchymal stem cells (MSCs) from patients with systemic sclerosis (SSc) for the expression of factors implicated in MSC recruitment at sites of injury, angiogenesis and fibrosis. The study also analysed whether the production/release of bioactive mediators by MSCs were affected by stimulation with cytokines found upregulated in SSc serum and tissues, and whether MSCs could modulate dermal microvascular endothelial cell (MVEC) angiogenesis. MSCs obtained from five patients with early severe diffuse SSc (SSc-MSCs) and five healthy donors (H-MSCs) were stimulated with vascular endothelial growth factor (VEGF), transforming growth factor β (TGFβ) or stromal cell-derived factor-1 (SDF-1). Transcript and protein levels of SDF-1 and its receptor CXCR4, VEGF, TGFβ(1) and receptors TβRI and TβRII were evaluated by quantitative real-time PCR, western blotting and confocal microscopy. VEGF, SDF-1 and TGFβ(1) secretion in culture supernatant was measured by ELISA. MVEC capillary morphogenesis was performed on Matrigel with the addition of MSC-conditioned medium. In SSc-MSCs the basal expression of proangiogenic SDF-1/CXCR4 and VEGF was significantly increased compared with H-MSCs. SSc-MSCs constitutively released higher levels of SDF-1 and VEGF. SDF-1/CXCR4 were upregulated after VEGF stimulation and CXCR4 redistributed from the cytoplasm to the cell surface. VEGF was increased by SDF-1 challenge. VEGF, TGFβ and SDF-1 stimulation upregulated TGFβ(1), TβRI and TβRII in SSc-MSCs. TβRII redistributed from the cytoplasm to focal adhesion contacts. SSc-MSC-conditioned medium showed a greater proangiogenic effect on MVECs than H-MSCs. Experiments with blocking antibodies showed that MSC-derived cytokines were responsible for this potent proangiogenic effect. SSc-MSCs constitutively overexpress and release bioactive mediators/proangiogenic factors and potentiate dermal MVEC angiogenesis.

  18. Caveolin-1 deficiency may predispose African Americans to systemic sclerosis-related interstitial lung disease.

    PubMed

    Reese, Charles; Perry, Beth; Heywood, Jonathan; Bonner, Michael; Visconti, Richard P; Lee, Rebecca; Hatfield, Corey M; Silver, Richard M; Hoffman, Stanley; Tourkina, Elena

    2014-07-01

    Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis (SSc; scleroderma). Although SSc-related ILD is more common and severe in African Americans than in Caucasians, little is known about factors underlying this significant health disparity. The aim of this study was to examine the role that low expression of caveolin-1 might play in susceptibility to ILD among African Americans. Assays of monocyte migration toward stromal cell-derived factor 1 (SDF-1) were performed using monocytes from Caucasian and African American healthy donors and patients with SSc. For fibrocyte differentiation studies, total peripheral blood mononuclear cells were incubated on fibronectin-coated plates. Protein expression was evaluated by immunohistochemistry and Western blotting. Monocytes from healthy African American donors and those from patients with SSc had low caveolin-1 levels, enhanced migration toward the CXCR4 ligand SDF-1, and enhanced differentiation to fibrocytes. Enhanced migration and differentiation of monocytes from African Americans and patients with SSc appeared to be attributable to the lack of caveolin-1, because restoring caveolin-1 function using a caveolin-1 scaffolding domain peptide inhibited these processes. Although they differed from monocytes from Caucasians, monocytes from both African Americans and patients with SSc were not identical, because SSc monocytes showed major increases from baseline in ERK, JNK, p38, and Smad2/3 activation, while monocytes from African Americans showed only limited ERK activation and no activation of JNK, p38, or Smad2/3. In contrast, SDF-1 exposure caused no additional ERK activation in SSc monocytes but did cause significant additional activation in monocytes from African Americans. African Americans may be predisposed to SSc-related ILD due to low baseline caveolin-1 levels in their monocytes, potentially affecting signaling, migration, and fibrocyte differentiation. The monocytes of African Americans may lack caveolin-1 due to high levels of transforming growth factor β in their blood. Copyright © 2014 by the American College of Rheumatology.

  19. Caveolin-1 Deficiency May Predispose African Americans to Systemic Sclerosis–Related Interstitial Lung Disease

    PubMed Central

    Reese, Charles; Perry, Beth; Heywood, Jonathan; Bonner, Michael; Visconti, Richard P.; Lee, Rebecca; Hatfield, Corey M.; Silver, Richard M.; Hoffman, Stanley; Tourkina, Elena

    2014-01-01

    Objective Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis (SSc; scleroderma). Although SSc-related ILD is more common and severe in African Americans than in Caucasians, little is known about factors underlying this significant health disparity. The aim of this study was to examine the role that low expression of caveolin-1 might play in susceptibility to ILD among African Americans. Methods Assays of monocyte migration toward stromal cell–derived factor 1 (SDF-1) were performed using monocytes from Caucasian and African American healthy donors and patients with SSc. For fibrocyte differentiation studies, total peripheral blood mono-nuclear cells were incubated on fibronectin-coated plates. Protein expression was evaluated by immuno-histochemistry and Western blotting. Results Monocytes from healthy African American donors and those from patients with SSc had low caveolin-1 levels, enhanced migration toward the CXCR4 ligand SDF-1, and enhanced differentiation to fibrocytes. Enhanced migration and differentiation of monocytes from African Americans and patients with SSc appeared to be attributable to the lack of caveolin-1, because restoring caveolin-1 function using a caveolin-1 scaffolding domain peptide inhibited these processes. Although they differed from monocytes from Caucasians, monocytes from both African Americans and patients with SSc were not identical, because SSc monocytes showed major increases from baseline in ERK, JNK, p38, and Smad2/3 activation, while monocytes from African Americans showed only limited ERK activation and no activation of JNK, p38, or Smad2/3. In contrast, SDF-1 exposure caused no additional ERK activation in SSc monocytes but did cause significant additional activation in monocytes from African Americans. Conclusion African Americans may be predisposed to SSc-related ILD due to low baseline caveolin-1 levels in their monocytes, potentially affecting signaling, migration, and fibrocyte differentiation. The monocytes of African Americans may lack caveolin-1 due to high levels of transforming growth factor β in their blood. PMID:24578173

  20. Advances in the Evaluation and Management of Esophageal Disease of Systemic Sclerosis

    PubMed Central

    Carlson, Dustin A.; Hinchcliff, Monique; Pandolfino, John E.

    2015-01-01

    Symptoms of heartburn and dysphagia, as well as objective findings of abnormal esophageal acid exposure and esophageal dysmotility are common in patients with systemic sclerosis (SSc). Treatments for SSc esophageal disease are generally limited to gastroesophageal reflux disease (GERD) treatment with proton pump inhibitors. Progresses made in esophageal diagnostic testing offer the potential for improved clinical characterization of esophageal disease in SSc that may help direct management decisions. In addition to reviewing GERD management in patients with SSc, present and potential uses of endoscopy, reflux monitoring, manometry, impedance planimetry, and endoscopic ultrasound are discussed. PMID:25475597

  1. Thermal issues at the SSC

    NASA Technical Reports Server (NTRS)

    Ranganathan, Raj P.; Dao, Bui V.

    1992-01-01

    A variety of heat transfer problems arise in the design of the Superconducting Super Collider (SSC). One class of problems is to minimize heat leak from the ambient to the SSC rings, since the rings contain superconducting magnets maintained at a temperature of 4 K. Another arises from the need to dump the beam of protrons (traveling around the SSC rings) on to absorbers during an abort of the collider. Yet another category of problems is the cooling of equipment to dissipate the heat generated during operation. An overview of these problems and sample heat transfer results are given in this paper.

  2. The use of modeling and suspended sediment concentration measurements for quantifying net suspended sediment transport through a large tidally dominated inlet

    USGS Publications Warehouse

    Erikson, Li H.; Wright, Scott A.; Elias, Edwin; Hanes, Daniel M.; Schoellhamer, David H.; Largier, John; Barnard, P.L.; Jaffee, B.E.; Schoellhamer, D.H.

    2013-01-01

    Sediment exchange at large energetic inlets is often difficult to quantify due complex flows, massive amounts of water and sediment exchange, and environmental conditions limiting long-term data collection. In an effort to better quantify such exchange this study investigated the use of suspended sediment concentrations (SSC) measured at an offsite location as a surrogate for sediment exchange at the tidally dominated Golden Gate inlet in San Francisco, CA. A numerical model was calibrated and validated against water and suspended sediment flux measured during a spring–neap tide cycle across the Golden Gate. The model was then run for five months and net exchange was calculated on a tidal time-scale and compared to SSC measurements at the Alcatraz monitoring site located in Central San Francisco Bay ~ 5 km from the Golden Gate. Numerically modeled tide averaged flux across the Golden Gate compared well (r2 = 0.86, p-value

  3. Decadal-scale Evolution of Sediment Flux in the Aulne Estuary

    NASA Astrophysics Data System (ADS)

    Moskalski, S. M.; Deschamps, A.; Floc'h, F.; Verney, R.; Piete, H.; Fromant, G.; Delacourt, C.

    2013-12-01

    Estuarine sediment transport processes have the potential to evolve over time in response to alterations in various factors both internal and external to the estuary, such as sediment supply, river discharge, tidal forcing, or changes to bathymetry. Changes in sediment transport can affect many estuarine processes (e.g. budgets of sediment-adsorbed contaminants or nutrients) and ecosystem services, such as aquaculture, primary production and the need to dredge shipping channels. Most studies of decadal-scale changes in estuaries focus on geomorphology or bathymetry, or are performed using models calibrated by a limited set of observational studies. Because of the potential for sediment flux to both affect and be affected by geomorphology and bathymetry, observational studies oriented to sediment flux evolution are needed. This study focuses on two intensive observational studies separated by 30 years to quantify change in suspended sediment concentration (SSC) in the Aulne river, a shallow macrotidal estuary in western Brittany. Moored and vessel-mounted acoustic Doppler current profilers and YSIs were deployed over a three-week period in the winter of 2013 to examine hydrodynamic and sediment transport processes. The results of the modern study were compared to a 1977 investigation of currents, suspended sediment concentration, and erosion/deposition. The 1977 study found that SSC during spring tide and average river discharge was less than 30 mg/L near the mouth and above 300 mg/L landward, with near-bottom concentrations in the turbidity maximum zone occasionally greater than 1000 mg/L. SSC was highest during low tide and remained elevated throughout, in the upstream part of the estuary. Sediment deposition was stronger after flood tide due to a longer slack period, which implies landward sediment transport in the estuary. In the 2013 study, near-bottom SSC during spring tide and average river discharge was also highest during low tide, but SSC was above 1000 mg/L for a longer duration than in 1977 and SSC decreased during low tide slack before increasing again during maximum flooding velocity. Despite strong similarities in SSC, suspended sediment fluxes near the turbidity maximum zone were stronger in the seaward direction in 2013, due to stronger and longer-duration ebbing velocities. Furthermore, fluxes were higher at the upstream observational site and lower near the mouth, indicating a high likelihood of sediment deposition in the lower estuary. The results of this study indicate that decadal-scale changes in observed sediment transport in the Aulne estuary are significant, but this conclusion will be discussed by analyzing discrepancies between data sources and quality between 1977 and 2013.

  4. The Integrative Studies of Genetic and Environmental Factors in Systemic Sclerosis

    DTIC Science & Technology

    2008-05-01

    15. SUBJECT TERMS Scleroderma (SSc), fibroblasts, fibrosis, silica, environmental particles, susceptibility. 16. SECURITY CLASSIFICATION OF...factors in a viable system - human fibroblasts. Fibroblasts with a scleroderma (SSc) susceptible genetic background may be more vulnerable to...for understanding environmental contributions to fibrosing diseases such as scleroderma (SSc). Third, in the studies of specific biological

  5. Laboratory Inquiry for Determining the Chemical Composition of a Component in a Daily Use Detergent: Sodium Sesquicarbonate

    ERIC Educational Resources Information Center

    Koga, Nobuyoshi; Kimura, Tomoyasu; Shigedomi, Kana

    2011-01-01

    An inquiry-based laboratory activity to determine the chemical composition of a component in alkaline detergents, sodium sesquicarbonate (SSC), is proposed. On the basis of introductory demonstrations by the instructor on the chemical properties and reactions of SSC, students propose the hypothetical composition of SSC and possible quantitative…

  6. Defining Munition Constituent (MC) Source Terms in Aquatic Environments on DoD Ranges

    DTIC Science & Technology

    2013-01-01

    Civil Engineering and Mechanics 5622 Hull Street University of Wisconsin-Milwaukee San Diego, CA 92152–5001...release. SSC Pacific San Diego, CA 92152-5001 Technical Report 1999 January 2013 Defining Munition Constituent (MC) Source...Wisconsin-Milwaukee Approved for public release. SSC Pacific San Diego, CA 92152-5001 SB SSC Pacific San Diego

  7. Validation of a coupled core-transport, pedestal-structure, current-profile and equilibrium model

    NASA Astrophysics Data System (ADS)

    Meneghini, O.

    2015-11-01

    The first workflow capable of predicting the self-consistent solution to the coupled core-transport, pedestal structure, and equilibrium problems from first-principles and its experimental tests are presented. Validation with DIII-D discharges in high confinement regimes shows that the workflow is capable of robustly predicting the kinetic profiles from on axis to the separatrix and matching the experimental measurements to within their uncertainty, with no prior knowledge of the pedestal height nor of any measurement of the temperature or pressure. Self-consistent coupling has proven to be essential to match the experimental results, and capture the non-linear physics that governs the core and pedestal solutions. In particular, clear stabilization of the pedestal peeling ballooning instabilities by the global Shafranov shift and destabilization by additional edge bootstrap current, and subsequent effect on the core plasma profiles, have been clearly observed and documented. In our model, self-consistency is achieved by iterating between the TGYRO core transport solver (with NEO and TGLF for neoclassical and turbulent flux), and the pedestal structure predicted by the EPED model. A self-consistent equilibrium is calculated by EFIT, while the ONETWO transport package evolves the current profile and calculates the particle and energy sources. The capabilities of such workflow are shown to be critical for the design of future experiments such as ITER and FNSF, which operate in a regime where the equilibrium, the pedestal, and the core transport problems are strongly coupled, and for which none of these quantities can be assumed to be known. Self-consistent core-pedestal predictions for ITER, as well as initial optimizations, will be presented. Supported by the US Department of Energy under DE-FC02-04ER54698, DE-SC0012652.

  8. On the Relationship Between Transit Velocity of Interplanetary Shocks and Solar Active Processes

    NASA Technical Reports Server (NTRS)

    Wilson, Robert M.

    1996-01-01

    Recently, it was reported that preferential relationships exist between the transit velocity V(sub T) of earthward-directed interplanetary shocks and solar active processes, in particular, eruptive filaments outside active regions (the size of the erupting filament L(sub f)) and solar flares (the value of the X-ray characteristic J). Unfortunately, statistical testing of the proposed associations was not accomplished, nor was the 'geo-effectiveness' of the events adequately described. Reported here are the results of a re-examination of the 21 eruptive filaments (SSC-EF events) and 26 X-ray flares (SSC-F events) that have been associated with storm sudden commencements (SSCs) at Earth. Simple statistical testing refutes the claim that a preferential relationship exists between V(sub T) and L(sub F), while it supports the claim that one exists between V(sub T) and J. More importantly, the inferred relationship between V(sub T) and J is found to be more complicated than previously thought. In particular, it now appears that SSC-F events may be separable into two groups, based on the value of J: a low-J group (J less than 56), in which V(sub T) varies directly with J, and a high-J group (J greater than 56), in which V(sub T) varies inversely with J. As a whole, high-J events are associated with shocks of higher average transit velocity than those of low-J events, and SSC-F events with shocks of higher average transit velocity than those of SSC-EF events. Further, high-J events tend to be of greater X-ray class ( greater than M3), longer duration (greater then 80 min), and are more likely to be associated with type II/IV radio emission (9 of 12) than low-J events. They also tend to occur in magnetically complex (gamma/delta configuration) active regions (10 of 12) that are large in area extent (area greater than 445 millionths of a solar hemisphere) on the day of flaring (9 of 12). Of the 9 solar proton events that affected the Earth's environment that were found to be associated with SSC-F events, six were high-J events. Concerning 'geo-effectiveness', there appears to be no preferential relationship between the value of the J-parameter and the most negative value of the Dst geomagnetic index Dst(min) following the SSC, which is found to usually occur at 6-14 h after SSC onset (18 of 26) and which ranged in value from -1 to -249 (having a median value of about -75). Of the 26 SSC-F events, only 14 can be associated with a Dst(min) less than or equal to -75, and of these only 7 were high-J events. Of the 14 storm-related events (i.e. Dst(min) less than or equal to -75), three have previously been identified as being either 'magnetic clouds' or 'bidirectional flows', both manifestations of earthward-directed coronal mass ejections (CMEs). Superposed epoch analyses of selected solar wind parameters and Dst during the interval of storm-related SSC-F events demonstrate that geoeffective SSC-F events tend to be associated with solar wind flows that are faster, greater in magnetic field strength, and have a rotating field which has a strong southward component shortly after SSC onset, in comparison to SSC-F events that do not have Dst(min) less than or equal to 75. Therefore, it is inferred that geoeffective SSC-F events are probably fast earthward-directed CMEs. Although no single parameter is found that can serve as a predictor of high-skill level for determining the geoeffectiveness of an SSC-F event prior to its occurrence at Earth, one finds that knowledge of the flare's hemispheric location and appearance or lack of appearance of a two-ribbon structure is sufficient to correctly predict the geoeffectiveness of 20 out of 25 of the SSC-F events (80%). Surprisingly, the association or lack of association of metric type II/IV radio emission as a characteristic for determining the geoeffectiveness of the SSC-F events proved unfruitful, as did, to a lesser extent, the duration of the X-ray emission.

  9. Suspended-sediment concentrations, loads, total suspended solids, turbidity, and particle-size fractions for selected rivers in Minnesota, 2007 through 2011

    USGS Publications Warehouse

    Ellison, Christopher A.; Savage, Brett E.; Johnson, Gregory D.

    2014-01-01

    Sediment-laden rivers and streams pose substantial environmental and economic challenges. Excessive sediment transport in rivers causes problems for flood control, soil conservation, irrigation, aquatic health, and navigation, and transports harmful contaminants like organic chemicals and eutrophication-causing nutrients. In Minnesota, more than 5,800 miles of streams are identified as impaired by the Minnesota Pollution Control Agency (MPCA) due to elevated levels of suspended sediment. The U.S. Geological Survey, in cooperation with the MPCA, established a sediment monitoring network in 2007 and began systematic sampling of suspended-sediment concentrations (SSC), total suspended solids (TSS), and turbidity in rivers across Minnesota to improve the understanding of fluvial sediment transport relations. Suspended-sediment samples collected from 14 sites from 2007 through 2011 indicated that the Zumbro River at Kellogg in the driftless region of southeast Minnesota had the highest mean SSC of 226 milligrams per liter (mg/L) followed by the Minnesota River at Mankato with a mean SSC of 193 mg/L. During the 2011 spring runoff, the single highest SSC of 1,250 mg/L was measured at the Zumbro River. The lowest mean SSC of 21 mg/L was measured at Rice Creek in the northern Minneapolis- St. Paul metropolitan area. Total suspended solids (TSS) have been used as a measure of fluvial sediment by the MPCA since the early 1970s; however, TSS concentrations have been determined to underrepresent the amount of suspended sediment. Because of this, the MPCA was interested in quantifying the differences between SSC and TSS in different parts of the State. Comparisons between concurrently sampled SSC and TSS indicated significant differences at every site, with SSC on average two times larger than TSS concentrations. The largest percent difference between SSC and TSS was measured at the South Branch Buffalo River at Sabin, and the smallest difference was observed at the Des Moines River at Jackson. Regression analysis indicated that 7 out of 14 sites had poor or no relation between SSC and streamflow. Only two sites, the Knife River and the Wild Rice River at Twin Valley, had strong correlations between SSC and streamflow, with coefficient of determination (R2) values of 0.82 and 0.80, respectively. In contrast, turbidity had moderate to strong relations with SSC at 10 of 14 sites and was superior to streamflow for estimating SSC at all sites. These results indicate that turbidity may be beneficial as a surrogate for SSC in many of Minnesota’s rivers. Suspended-sediment loads and annual basin yields indicated that the Minnesota River had the largest average annual sediment load of 1.8 million tons per year and the largest mean annual sediment basin yield of 120 tons of sediment per year per square mile. Annual TSS loads were considerably lower than suspended-sediment loads. Overall, the largest suspended-sediment and TSS loads were transported during spring snowmelt runoff, although loads during the fall and summer seasons occasionally exceeded spring runoff at some sites. This study provided data from which to characterize suspended sediment across Minnesota’s diverse geographical settings. The data analysis improves understanding of sediment transport relations, provides information for improving sediment budgets, and documents baseline data to aid in understanding the effects of future land use/land cover on water quality. Additionally, the data provides insight from which to evaluate the effectiveness and efficiency of best management practices at the watershed scale.

  10. Impaired quality of life in patients with systemic sclerosis compared to the general population and chronic dermatoses.

    PubMed

    Bretterklieber, Agnes; Painsi, Clemens; Avian, Alexander; Wutte, Nora; Aberer, Elisabeth

    2014-09-02

    Systemic sclerosis (SSc) is a rare and potentially life threatening autoimmune disorder. The burden of disease compared to other dermatoses is unknown. The purpose of this study was to assess both the quality of life in patients with SSc and the variables that are associated with poor quality of life. Forty-one patients with systemic sclerosis (29 limited, 2 diffuse, 10 undifferentiated forms) were assessed with respect to their health status and compared to published data for the normal population, SSc patients from other studies, and patients with chronic skin diseases. For the most part, our SSc patients had better outcomes in all 8 dimensions of the SF-36 than SSc patients from other studies, and poorer scores than the healthy population and those with occupational contact dermatitis, ichthyosis, non-melanoma skin cancer, contact dermatitis, atopic eczema, chronic nail disease, vitiligo, health care workers with work-related disease, and those with other chronic skin diseases, but significantly better scores for mental health than those with nail disease, vitiligo, and health-care workers. Patients with atopic dermatitis, psoriasis and pemphigus had significantly poorer mean scores in social function and mental health than SSc patients. Patients with pemphigus were also significantly impaired in their physical and emotional roles. Patients with systemic lupus erythematosus (SLE) had the significantly poorest mean scores for QoL in all 8 domains except bodily pain and emotional role. Besides SLE, SSc is one of the most severe chronic dermatologic diseases in terms of reduced QoL. Since SSc cannot be cured, treatment strategies should include therapeutic interventions such as psychotherapy, social support, physiotherapy, and spiritual care. Their beneficial effects could be studied in future.

  11. Longitudinal Evaluation of Central Corneal Thickness in Patients With Systemic Sclerosis.

    PubMed

    Gomes, Beatriz F; Santhiago, Marcony R; Gomes, Silvia Fiuza; Kara-Junior, Newton; Moraes, Haroldo V

    2016-12-01

    To investigate the longitudinal change of central corneal thickness (CCT) in patients with systemic sclerosis (SSc) and to elucidate whether it contributes to misinterpretation of intraocular pressure (IOP) in this group of patients. Twenty patients with SSc and 20 sex- and age-matched controls were examined at 2 visits 5 years apart. Age, sex, race, subtype of SSc, disease duration, autoantibody profile, use of disease-modifying antirheumatic drugs (DMARDs), best-corrected visual acuity, spherical equivalent refraction, IOP, and CCT were recorded. IOP was assessed by applanation tonometry and CCT by ultrasonic pachymetry. CCT decreased by 7.2 μm [95% confidence interval (CI), -2.1 to -12.2 μm] between the first and second measurements (P = 0.008) in patients with SSc and by 2.4 μm (P = 0.39, 95% CI, -8.0 to 3.3 μm) in the control group. Considering patients with SSc, CCT decreased by a mean of 11.6 μm [95% CI, -4.3 to -19.0 μm (P = 0.007)] among those taking DMARDs at the second visit and by 4.2 μm [95% CI, -3.0 to -11.5 μm (P = 0.2)] in patients not taking any DMARDs. There was no statistically significant change in IOP between the 2 visits for either the SSc group (P = 0.84) or the control group (P = 0.29). Mean change in CCT was not associated with either IOP at first visit or with change in IOP in SSc patients. CCT decreased with time in SSc. However, the slight rates of thinning observed are unlikely to considerably influence applanation tonometry or clinical decision-making over the short to intermediate term.

  12. The association of illness perceptions with physical and mental health in systemic sclerosis patients: an exploratory study.

    PubMed

    Arat, Seher; Verschueren, Patrick; De Langhe, Ellen; Smith, Vanessa; Vanthuyne, Marie; Diya, Luwis; Van den Heede, Koen; Blockmans, Daniel; De Keyser, Filip; Houssiau, Frédéric A; Westhovens, René

    2012-03-01

    The aim of the present study was to evaluate the association between illness perceptions and the ability to cope with physical and mental health problems in a large cohort of systemic sclerosis (SSc) patients. This was a cross-sectional study in 217 systemic sclerosis patients from the Belgian Systemic Sclerosis Cohort. Illness perception and coping were measured by the Revised Illness Perception Questionnaire and a coping questionnaire--the Coping Orientation of Problem Experience inventory (COPE). Physical and mental health-related quality of life was measured by the 36-item short-form health survey (SF-36), as were disease activity and several severity parameters. The relationship between illness perceptions and the ability to cope with physical/mental health problems was examined using multiple linear regression analysis. According to LeRoy's classification, 49 patients had limited SSc (lSSc), 129 had limited cutaneous SSc (lcSSc) and 39 had diffuse cutaneous SSc (dcSSc). Median disease duration was five years and the modified Rodnan skin score was 4. Good physical health was significantly associated with the lcSSc subtype and low disease activity (p < 0.01 and p < 0.05, respectively). The perception of 'serious consequences' and strong 'illness identity' correlated with poor physical health (p < 0.001). Good mental health was associated with low illness identity scores and low 'emotional response' scores (p < 0.001). Coping variables were less significantly correlated with physical and mental health compared with the illness perception items. Illness representations contribute more than classical disease characteristics to physical and mental health. Copyright © 2011 John Wiley & Sons, Ltd.

  13. Clinical, Functional and Health-Related Quality of Life Correlates of Clinically Significant Symptoms of Anxiety and Depression in Patients with Systemic Sclerosis: A Cross-Sectional Survey

    PubMed Central

    Nguyen, Christelle; Ranque, Brigitte; Baubet, Thierry; Bérezné, Alice; Mestre-Stanislas, Caroline; Rannou, François; Papelard, Agathe; Morell-Dubois, Sandrine; Revel, Michel; Moro, Marie-Rose; Guillevin, Loïc; Poiraudeau, Serge; Mouthon, Luc

    2014-01-01

    Objectives To identify clinical, functional and health-related quality of life (HRQoL) correlates of clinically significant symptoms of anxiety and depression in patients with systemic sclerosis (SSc). Methods Three-hundred-and-eighty-one patients fulfilling the American College of Rheumatology and/or the Leroy and Medsger criteria for SSc were assessed for visceral involvement, disability and HRQoL (assessed by SF-36). Clinically significant symptoms of anxiety and depression were evaluated with the Hospital Anxiety Depression Scale (HAD) (defined cut-off≥8). Results 9.2% the patients had limited SSc, 50.5% limited cutaneous SSc (lcSSc), and 40.3% diffuse cutaneous SSc (dcSSc). Overall, 40.4% and 58.8% of the patients had clinically significant symptoms of depression and anxiety, respectively. Compared to patients without clinically significant symptoms of depression, patients with clinically significant symptoms of depression had poorer health status, HRQoL mental and physical component, and greater global disability, hand disability and aesthetic impairment. Compared to patients without clinically significant symptoms of anxiety, patients with clinically significant symptoms of anxiety had poorer SF-36 mental and physical component scores. On multivariable analysis, excluding mental component score of SF-36, variables independently associated with clinically significant symptoms of depression and anxiety were global disability and physical component of SF-36, plus female gender for clinically significant symptoms of anxiety only. Remarkably, patients with and without clinically significant psychiatric symptoms were comparable for all disease-related clinical features assessed. Conclusion High levels of clinically significant symptoms of anxiety and depression are observed among SSc patients. Clinically significant psychiatric symptoms are rather associated with increased disability and altered HRQoL, than with disease-specific organ manifestations. PMID:24587375

  14. Trends in Maternity Care Practice Skin-to-Skin Contact Indicators: United States, 2007-2015.

    PubMed

    Boundy, Ellen O; Perrine, Cria G; Barrera, Chloe M; Li, Ruowei; Hamner, Heather C

    2018-05-21

    Mother-infant skin-to-skin contact (SSC) immediately after birth helps transition infants to the post-uterine environment and increases the likelihood of breastfeeding initiation and duration. This study examines trends in U.S. maternity practices related to SSC, and variations by facility demographics. Data were from the Maternity Practices in Infant Nutrition and Care (mPINC) surveys (2007-2015), a biennial assessment of all U.S. maternity facilities. Facilities reported how often patients were encouraged to practice mother-infant SSC for ≥30 minutes within 1 hour of uncomplicated vaginal birth and 2 hours of uncomplicated cesarean birth, and how often routine infant procedures are performed while in SSC. We calculated the percentage of maternity facilities reporting these indicators for ≥90% of patients across the United States for each survey year. Estimates by facility characteristics (size, type, and state) were calculated for 2015 only. The percentage of facilities reporting "Most (≥90%)" women, which were encouraged to practice early SSC, increased from 2007 to 2015 following both vaginal (40.4% to 83.0%) and cesarean (29.3% to 69.9%) births. The percentage of facilities reporting routine infant procedures were performed "Almost always (≥90%)," while mother and infant were SSC increased from 16.6% to 49.5% (2007 to 2015) for vaginal births and from 2.2% to 10.7% (2009 to 2015) for cesarean births. Variations in SSC practice by facility type, size, and state were noted. Significant progress has been made in increasing hospital encouragement of early SSC for both vaginal and cesarean births. Continued efforts to support evidence-based maternity practices are needed.

  15. Separate Influences of Birth Order and Gravidity/Parity on the Development of Systemic Sclerosis

    PubMed Central

    COCKRILL, TONYA; del JUNCO, DEBORAH J.; ARNETT, FRANK C.; ASSASSI, SHERVIN; TAN, FILEMON K.; McNEARNEY, TERRY; FISCHBACH, MICHAEL; PERRY, MARILYN; MAYES, MAUREEN D.

    2010-01-01

    Objective Birth order has been valuable in revealing the role of environmental influences on the risk of developing certain diseases such as allergy and atopy. In addition, pregnancy has profound effects on the immune system such as short-term effects that permit fetal survival as well as longer-term effects that could influence late-onset diseases. In order to better evaluate these influences, we studied the association of birth order and gravidity/parity as risk factors for systemic sclerosis (SSc; scleroderma). Methods Data regarding SSc cases and their unaffected sibling controls were obtained from the Scleroderma Family Registry and DNA Repository. The case-sibling design was used to minimize confounding due to differences in age, race, ethnicity, or calendar time. The gravidity/parity analysis was based on sibships with at least one SSc-affected and one unaffected sister. Results Birth order was examined in 974 sibships, comparing SSc cases (n = 987) with their unaffected siblings (n = 3,088). The risk of scleroderma increased with increasing birth order (odds ratio [OR] 1.25, 95% confidence interval [95% CI] 1.06–1.50 for birth order 2–5; OR 2.22, 95% CI 1.57–3.15 for birth order 6–9; and OR 3.53, 95% CI 1.68–7.45 for birth order 10–15). Gravidity/parity was analyzed in 168 sibships (256 unaffected sisters, 172 SSc cases). We found an association between a history of one or more pregnancies and SSc (OR 2.8). Conclusion Birth order and pregnancy were independently associated with a higher risk of developing SSc. These findings suggest that immune development in early childhood and/or pregnancy-associated events, including but not limited to microchimerism, plays a role in SSc susceptibility. PMID:20391489

  16. Valuing Scleroderma Health States: A Picture is Worth a Thousand Words, and Quite a Few Utiles – A Randomized Study

    PubMed Central

    Khanna, Dinesh; Kaplan, Robert M.; Eckman, Mark H.; Hays, Ron D.; Leonard, Anthony C.; Ginsburg, Shaari S.; Tsevat, Joel

    2009-01-01

    Objective Assigning utilities to hypothetical health states requires that the health states be described in adequate detail, but there is no agreement on exactly how health states should be described. We assessed utilities from the general public for health states common in scleroderma (SSc) by describing the health states in writing alone vs. with photographs of patients with SSc. Methods Subjects rated several SSc health states on a 0-100 rating scale (RS) and completed computer-assisted time tradeoff (TTO, range: 0.0-1.0) and standard gamble (SG, range: 0.0-1.0) utility assessments. Half of the subjects were assigned to be shown photographs of patients with SSc health states in addition to written health state descriptions whereas the other half were given only the written descriptions. Results Of the 213 subjects, 133 (62%) were female, 138 (65%) were Caucasian, and 62 (29%) were African-Americans. Median RS, TTO, and SG scores for the 5 SSc health states ranged from 20-70; 0.28-0.94; and 0.50-0.90, respectively. In bivariate analyses, showing pictures was associated with lower RS scores for 2 of 5 health states and lower SG values for all 5 health states (P<0.05 for comparison of pictures vs. no pictures), but with no difference in TTO values. Multivariable analyses revealed negative associations between pictures and SG valuations for the 3 most severe SSc health states (R2 range: 0.04-0.08). Conclusion Adding pictures of people with SSc to written health state descriptions can affect valuations of SSc health states, although the effect differs by valuation measurement method and by health state severity. PMID:19015284

  17. Clinical motivation and the surgical safety checklist.

    PubMed

    Yu, X; Huang, Y; Guo, Q; Wang, Y; Ma, H; Zhao, Y

    2017-03-01

    Although the surgical safety checklist (SSC) has been adopted worldwide, its efficacy can be diminished by poor clinical motivation. Systematic methods for improving implementation are lacking. A multicentre prospective study was conducted in 2015 in four academic/teaching hospitals to investigate changes during revision of the SSC for content, staffing and workflow. All modifications were based on feedback from medical staff. Questionnaires were used to monitor dynamic changes in surgeons', nurses' and anaesthetists' perceptions. Complete information was obtained from 30 654 operations in which the newly developed SSC system was used. Implementation quality was evaluated in 1852 operations before, and 1822 after the changes. The revised SSC content was simplified from 34 to 22 items. Anaesthetists achieved widespread recommendation as SSC coordinators. Completion rates of all stages reached over 80·0 per cent at all sites (compared with 10·2-59·5 per cent at the sign-out stage in the baseline survey). There was a significant change in doctors who participated (for example, surgeon: from 24·6 to 64·5 per cent at one site). The rates of hasty (15·1-33·7 per cent) or casual (0·4-4·4 per cent) checking decreased to less than 6·0 per cent overall. Perceptions about the SSC were studied from 2211 forms. They improved, with a converging trend among the three different professions, to a uniform 80·0 per cent agreeing on the need for its regular use. Medical staff members are both the users and owners of the SSC. High-quality SSC implementation can be achieved by clinically motivated adaptation. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  18. Assessment of tissue fibrosis in skin biopsies from patients with systemic sclerosis employing confocal laser scanning microscopy: an objective outcome measure for clinical trials?

    PubMed Central

    Busquets, Joanna; Del Galdo, Francesco; Kissin, Eugene Y.

    2010-01-01

    Objectives. To obtain an objective, unbiased assessment of skin fibrosis in patients with SSc for use in clinical trials of SSc disease-modifying therapeutics. Methods. Skin biopsies from the dorsal forearm of six patients with diffuse SSc and six healthy controls, and skin biopsies from the forearm of one patient with diffuse SSc before and following 1 year treatment with mycophenolate mofetil were analysed by confocal laser scanning microscopy (CLSM) with specific antibodies against collagen types I and III or fibronectin. The integrated density of fluorescence (IDF) was calculated employing National Institutes of Health-ImageJ software in at least four different fields per biopsy spanning the full dermal thickness. Results. The intensities of collagen types I and III and fibronectin IDF were 174, 147 and 139% higher in SSc skin than in normal skin, respectively. All differences were statistically significant. The sum of the IDF values obtained for the three proteins yielded a comprehensive fibrosis score. The average fibrosis score for the six SSc samples was 28.3 × 106 compared with 18.6 × 106 for the six normal skin samples (P < 0.0001). Comparison of skin biopsies obtained from the same SSc patient before treatment and after 12 months of treatment with mycophenolate mofetil showed a reduction of 39% in total fibrosis score after treatment. Conclusions. CLSM followed by quantitative image analysis provides an objective and unbiased assessment of skin fibrosis in SSc and could be a useful end-point for clinical trials with disease-modifying agents to monitor the response or progression of the disease. PMID:20202926

  19. Autoantibody-mediated regulation of B cell responses by functional anti-CD22 autoantibodies in patients with systemic sclerosis.

    PubMed

    Odaka, M; Hasegawa, M; Hamaguchi, Y; Ishiura, N; Kumada, S; Matsushita, T; Komura, K; Sato, S; Takehara, K; Fujimoto, M

    2010-02-01

    Studies have demonstrated that B cells play important roles in systemic sclerosis (SSc), especially through the CD19/CD22 autoimmune loop. CD22 is a B cell-specific inhibitory receptor that dampens B cell antigen receptor (BCR) signalling via tyrosine phosphorylation-dependent mechanism. In this study, we examined the presence and functional property of circulating autoantibodies reacting with CD22 in systemic sclerosis. Serum samples from 10 tight skin (TSK/+) mice and 50 SSc patients were assessed for anti-CD22 autoantibodies by enzyme-linked immunosorbent assays using recombinant mouse or human CD22. The association between anti-CD22 antibodies and clinical features was also investigated in SSc patients. Furthermore, the influence of SSc serum including anti-CD22 autoantibodies for CD22 tyrosine phosphorylation was examined by Western blotting using phosphotyrosine-specific antibodies reacting with four major tyrosine motifs of CD22 cytoplasmic domain. Anti-CD22 autoantibodies were positive in 80% of TSK/+ mice and in 22% of SSc patients. Patients positive for anti-CD22 antibodies showed significantly higher modified Rodnan skin thickness score compared with patients negative for anti-CD22 antibodies. Furthermore, anti-CD22 antibodies from patients' sera were capable of reducing phosphorylation of all four CD22 tyrosine motifs, while sera negative for anti-CD22 antibodies did not affect CD22 phosphorylation. Thus, a subset of SSc patients possessed autoantibodies reacting with a major inhibitory B cell response regulator, CD22. Because these antibodies can interfere CD22-mediated suppression onto B cell activation in vitro, SSc B cells produce functional autoantibodies that can enhance their own activation. This unique regulation may contribute to the autoimmune aspect of SSc.

  20. Evidence-based management of systemic sclerosis: Navigating recommendations and guidelines.

    PubMed

    Pellar, Russell Edward; Pope, Janet Elizabeth

    2017-06-01

    Systemic sclerosis (SSc) is a rare heterogeneous connective tissue disease. Recommendations addressing the major issues in the management of SSc including screening and treatment of organ complications are needed. The updated European League Against Rheumatism/European Scleroderma Trial and Research (EULAR/EUSTAR) and the British Society of Rheumatology (BSR) and British Health Professionals in Rheumatology (BHPR) guidelines were compared and contrasted. The updated EULAR/EUSTAR guidelines focus specifically on the management of SSc features and include data on newer therapeutic modalities and mention a research agenda. These recommendations are pharmacologic, with few guidelines regarding investigations and non-pharmacologic management. Recommendations from BSR/BHPR are similar to the organ manifestations mentioned in the EULAR/EUSTAR recommendations, and expand on several domains of treatment, including general measures, non-pharmacologic treatment, cardiac involvement, calcinosis, and musculoskeletal features. The guidelines usually agree with one another. Limitations include the lack of guidance for combination or second-line therapy, algorithmic suggestions, the absence of evidence-based recommendations regarding the treatment of specific complications (i.e., gastric antral ectasia and erectile dysfunction). Consensus for when to treat interstitial lung disease in SSc is lacking. There are differences between Europe and North American experts due to access and indications for certain therapies. Care gaps in SSc have been demonstrated so the EULAR/EUSTAR and BSR/BHP guidelines can promote best practices. Certain complications warrant active investigation to further improve outcomes in SSc and future updates of these recommendations. Care gaps in SSc have been demonstrated so the EULAR/EUSTAR and BSR/BHP guidelines can promote best practices. Certain complications warrant active investigation to further improve outcomes in SSc. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Influence of antiphospholipid antibody positivity on glomerular filtration rate markers in a group of systemic sclerosis patients - a 24-month observation.

    PubMed

    Wielosz, Ewa; Majdan, Maria; Koszarny, Arkadiusz; Dryglewska, Magdalena; Tabarkiewicz, Jacek

    2017-01-01

    The aim of the study was the assessment of changes in the glomerular filtration rate (GFR) during long-term observation in a group of systemic sclerosis (SSc) patients with and without chronic antiphospholipid (aPL) antibody positivity. The observation comprised 50 patients - 23 with diffuse cutaneous SSc - dcSSc and 27 limited cutaneous SSc - lcSSc. After 24 months we assessed 27 patients (9 died, 14 lost follow up); 24 patients (88%) were treated chronically with angiotensin-converting-enzyme inhibitors (ACEIs). Patients were investigated for the presence of aPL: to cardiolipin and to β2 glycoprotein I in IgM and IgG classes. Serum levels of creatinine (S-Cr), cystatin C and creatinine clearance values were determined in all patients. According to the presence of a significant level of at least one of aPL antibodies, pts were divided into groups: group I aPL positive: 14 patients, group II aPL negative - 13 patients. We did not find significant differences in S-Cr, cystatin C levels and creatinine clearance before and after 24 months of observation between both groups. In follow up observations, the presence of anti-centromere antibodies was significantly more frequent in the aPL positive, as compared to the aPL negative group (p = 0.01). In follow up observations, the level of anticardiolipin antibodies in IgG class was significantly higher in dcSSc compared to lcSSc patients (p = 0.02). In long-term observation chronic positivity for aPL antibodies does not significantly decrease the GFR in patients with SSc treated with ACEIs.

  2. Reduction of regulatory T cells in skin lesions but not in peripheral blood of patients with systemic scleroderma.

    PubMed

    Klein, S; Kretz, C C; Ruland, V; Stumpf, C; Haust, M; Hartschuh, W; Hartmann, M; Enk, A; Suri-Payer, E; Oberle, N; Krammer, P H; Kuhn, A

    2011-08-01

    To determine the frequency and suppressive capacity of regulatory T cells (T(reg)) and their association with clinical parameters in patients with systemic scleroderma (SSc). Peripheral blood from 25 patients with SSc, 15 patients with localised scleroderma (LS) and 29 healthy controls (HC) was studied. Analysis of CD4(+) forkhead box P3 (Foxp3)(+) and CD4(+)CD25(++)Foxp3(+) T(reg) subpopulations was carried out by flow cytometry and cell proliferation was quantified by (3)H-thymidine incorporation. Quantitative analysis of T(reg) was further performed in skin biopsies from 17 patients with SSc and 21 patients with LS using anti-CD4 and anti-Foxp3 monoclonal antibodies for immunohistochemistry. The frequency of CD4(+)Foxp3(+) and CD4(+)CD25(++)Foxp3(+) T(reg) in peripheral blood from patients with SSc was not significantly different from that of patients with LS or HC. The suppressive capacity of CD4(+)CD25(++) T(reg) in SSc was also found to be similar to that of HC. Phenotypic and functional data revealed no significant difference between the limited or diffuse form of SSc. Moreover, therapy with bosentan showed no significant effect on the frequency of T(reg) during the course of the disease. However, the frequency of T(reg) in skin lesions from patients with SSc or LS, determined as the percentage of CD4(+) cells expressing Foxp3 in the inflammatory infiltrate, was significantly reduced compared with other inflammatory skin diseases. These results indicate that although the authors found no defect in the frequency or function of peripheral T(reg) subpopulations, the reduction of CD4(+)Foxp3(+) T(reg) in the skin of patients with SSc may be important in the pathogenesis of the disease.

  3. Quantification of Fine-grained Sediment Concentration in the Aquatic Environment Using Optical and Acoustic Sensors: Insight from Lab Experiments

    NASA Astrophysics Data System (ADS)

    Xu, K.; Champagne, B. N.

    2017-12-01

    The transport of sediment in the coastal zone and continental shelf is highly impacted by fluvial and oceanographic dynamics. In Louisiana, the Mississippi River delivers a bulk of water, sediment, and nutrients to the coast. However, coastal land loss highlights the importance of the sediment deposited at the mouth of the river. Sediment is the foundation to build land and suspended sediment concentration (SSC) tracks the delivery, deposition, and erosion of sediment. On a more applicable scale, variables such as SSC can be used to calculate sediment transport flux, an important parameter for projects such as sediment diversions and barrier island restoration. In order to rely on suspended sediment concentration (SSC) as continuous data, lab experiments are needed to establish the relationship between turbidity and SSC. Factors such as sensor type (optical or acoustic) and grain size (coarse or fine) can greatly impact the estimated SSC. In this study, fine-grained sediment was collected from multiple sites in coastal Louisiana and used to calibrate both optical backscatter (OBS) and acoustic backscatter (ABS) sensors to establish the relationship between sensor type and accuracy of the SSC estimation. Multiple grain-size analyses using a Laser Diffraction Particle Size Analyzer helped determine the effects of sensor accuracy regarding grain size. The results of these experiments were combined in order to establish the calibration curves of SSC. Our results indicated that the OBS-3A sensor's turbidity data were more correlated with the SSC than the OBS-5+'s data. Possible explanations for this could be due to differences between the instruments' measuring ranges and their sensitivity to various grain sizes. This technology development has a broad impact to the studies of sediment delivery, transport, and deposition in multiple types of coastal protection and restoration projects.

  4. Suspended sediment and turbidity after road construction/improvement and forest harvest in streams of the Trask River Watershed Study, Oregon

    NASA Astrophysics Data System (ADS)

    Arismendi, Ivan; Groom, Jeremiah D.; Reiter, Maryanne; Johnson, Sherri L.; Dent, Liz; Meleason, Mark; Argerich, Alba; Skaugset, Arne E.

    2017-08-01

    Transport of fine-grained sediment from unpaved forest roads into streams is a concern due to the potential negative effects of additional suspended sediment on aquatic ecosystems. Here we compared turbidity and suspended sediment concentration (SSC) dynamics in five nonfish bearing coastal Oregon streams above and below road crossings, during three consecutive time periods ("before", "after road construction/improvement", and "after forest harvest and hauling"). We hypothesized that the combined effects of road construction/improvement and the hauling following forest harvest would increase turbidity and SSC in these streams. We tested whether the differences between paired samples from above and below road crossing exceeded various biological thresholds, using literature values of biological responses to increases in SSC and turbidity. Overall, we found minimal increases of both turbidity and SSC after road improvement, forest harvest, and hauling. Because flow is often used as a surrogate for turbidity or SSC we examined these relationships using data from locations above road crossings that were unaffected by roads or forest harvest and hauling. In addition, we examined the association between turbidity and SSC for these background locations. We found a positive, but in some cases weak association between flow and turbidity, and between flow and SSC; the relationship between turbidity and SSC was more robust, but also inconsistent among sites over time. In these low order streams, the concentrations and transport of suspended sediment seems to be highly influenced by the variability of local conditions. Our study provides an expanded understanding of current forest road management practice effects on fine-grained sediment in streams and introduces alternative metrics using multiple thresholds to evaluate potential indicators of biological relevance.

  5. The association of sociodemographic and objectively-assessed disease variables with fatigue in systemic sclerosis: an analysis of 785 Canadian Scleroderma Research Group Registry patients.

    PubMed

    Levis, Brooke; Kwakkenbos, Linda; Hudson, Marie; Baron, Murray; Thombs, Brett D

    2017-02-01

    Fatigue is prevalent among patients with systemic sclerosis (SSc). To date, studies investigating fatigue in SSc have been hampered by the instruments used to measure fatigue in SSc and have included patient-reported rather than objectively-rated measures of disease. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale is a validated measure for assessing fatigue in SSc that, compared to other instruments, provides good coverage of the full range of the fatigue spectrum. The objective of this study was to assess sociodemographic and objectively-rated disease-related associates of fatigue, as measured by the FACIT-F, in a large sample of patients with SSc. Fatigue was assessed using the FACIT-F scale. Disease severity was assessed using Medsger's severity scale. Multivariable linear regression was performed to assess the independent associations between sociodemographic and medical variables and fatigue. Among 785 patients, the mean FACIT-F score was 32.2 (SD = 12.1). Being age 40-49 (reference = 60+; standardized regression coefficient (β) = -0.11), less than post-secondary education (β = 0.07), having more medical comorbidities (β = -0.11) and more severe muscle (β = -0.10), gastrointestinal (β = -0.15), lung (β = -0.13), and general system disease severity (β = -0.13) were independently associated with more fatigue (p < 0.05). Fatigue in SSc was independently associated with more severe disease. These data contribute to a better understanding of fatigue in SSc and help inform patient-centered research in SSc.

  6. Significance of palpable tendon friction rubs in early diffuse cutaneous systemic sclerosis.

    PubMed

    Doré, Adam; Lucas, Mary; Ivanco, Dana; Medsger, Thomas A; Domsic, Robyn T

    2013-08-01

    Palpable tendon friction rubs (TFRs) in systemic sclerosis (SSc; scleroderma) have been associated with diffuse skin thickening, increased disability, and poor survival. Our objective was to quantify the prognostic implications of palpable TFRs on the development of disease complications and longer-term mortality in an incident cohort of early diffuse cutaneous SSc (dcSSc) patients. We identified early dcSSc patients (disease duration <2 years from the first SSc symptom) first evaluated at the University of Pittsburgh Scleroderma Center between 1980 and 2006 and found to have palpable TFRs. These patients were matched 1:1 with the next consecutive early dcSSc patient without TFRs as a control. All had ≥2 clinic visits and 5 years of followup from the first visit. A total of 287 early dcSSc patients with TFR were identified and matched to 287 controls. The median disease duration was 0.83 years in TFR patients and 1.04 years in controls. The median followup was 10.1 years in TFR patients and 7.9 years in controls. Over the course of their illness, patients with TFRs had a >2-fold risk of developing renal crisis and cardiac and gastrointestinal disease complications, even after adjustment for other known risk factors. Patients with TFRs had poorer 5- and 10-year survival rates. Patients with early dcSSc having ≥1 TFRs are at an increased risk of developing renal, cardiac, and gastrointestinal involvement before and after their first Scleroderma Center visit and have reduced survival. Patients presenting with TFRs should be carefully monitored for serious internal organ involvement. Copyright © 2013 by the American College of Rheumatology.

  7. Using genome wide association studies to identify common QTL regions in three different genetic backgrounds based on Iberian pig breed

    PubMed Central

    Martínez-Montes, Ángel M.; Fernández, Almudena; Muñoz, María; Noguera, Jose Luis; Folch, Josep M.

    2018-01-01

    One of the major limitation for the application of QTL results in pig breeding and QTN identification has been the limited number of QTL effects validated in different animal material. The aim of the current work was to validate QTL regions through joint and specific genome wide association and haplotype analyses for growth, fatness and premier cut weights in three different genetic backgrounds, backcrosses based on Iberian pigs, which has a major role in the analysis due to its high productive relevance. The results revealed nine common QTL regions, three segregating in all three backcrosses on SSC1, 0–3 Mb, for body weight, on SSC2, 3–9 Mb, for loin bone-in weight, and on SSC7, 3 Mb, for shoulder weight, and six segregating in two of the three backcrosses, on SSC2, SSC4, SSC6 and SSC10 for backfat thickness, shoulder and ham weights. Besides, 18 QTL regions were specifically identified in one of the three backcrosses, five identified only in BC_LD, seven in BC_DU and six in BC_PI. Beyond identifying and validating QTL, candidate genes and gene variants within the most interesting regions have been explored using functional annotation, gene expression data and SNP identification from RNA-Seq data. The results allowed us to propose a promising list of candidate mutations, those identified in PDE10A, DHCR7, MFN2 and CCNY genes located within the common QTL regions and those identified near ssc-mir-103-1 considered PANK3 regulators to be further analysed. PMID:29522525

  8. Mechanisms in the loss of capillaries in systemic sclerosis: angiogenesis versus vasculogenesis

    PubMed Central

    Manetti, Mirko; Guiducci, Serena; Ibba-Manneschi, Lidia; Matucci-Cerinic, Marco

    2010-01-01

    Abstract Systemic sclerosis (SSc, scleroderma) is a chronic, multisystem connective tissue disorder affecting the skin and various internal organs. Although the disease is characterized by a triad of widespread microangiopathy, fibrosis and autoimmunity, increasing evidence indicates that vascular damage is a primary event in the pathogenesis of SSc. The progressive vascular injury includes persistent endothelial cell activation/damage and apoptosis, intimal thickening, delamination, vessel narrowing and obliteration. These profound vascular changes lead to vascular tone dysfunction and reduced capillary blood flow, with consequent tissue ischemia and severe clinical manifestations, such as digital ulceration or amputation, pulmonary arterial hypertension and scleroderma renal crisis. The resulting tissue hypoxia induces complex cellular and molecular mechanisms in the attempt to recover endothelial cell function and tissue perfusion. Nevertheless, in SSc patients there is no evidence of significant angiogenesis and the disease evolves towards chronic tissue ischemia, with progressive and irreversible structural changes in multiple vascular beds culminating in the loss of capillaries. A severe imbalance between pro-angiogenic and angiostatic factors may also lead to impaired angiogenic response during SSc. Besides insufficient angiogenesis, defective vasculogenesis with altered numbers and functional defects of bone marrow-derived endothelial progenitor cells may contribute to the vascular pathogenesis of SSc. The purpose of this article is to review the contribution of recent studies to the understanding of the complex mechanisms of impaired vascular repair in SSc. Indeed, understanding the pathophysiology of SSc-associated vascular disease may be the key in dissecting the disease pathogenesis and developing novel therapies. Either angiogenic or vasculogenic mechanisms may potentially become in the future the target of therapeutic strategies to promote capillary regeneration in SSc. PMID:20132409

  9. Separate influences of birth order and gravidity/parity on the development of systemic sclerosis.

    PubMed

    Cockrill, Tonya; del Junco, Deborah J; Arnett, Frank C; Assassi, Shervin; Tan, Filemon K; McNearney, Terry; Fischbach, Michael; Perry, Marilyn; Mayes, Maureen D

    2010-03-01

    Birth order has been valuable in revealing the role of environmental influences on the risk of developing certain diseases such as allergy and atopy. In addition, pregnancy has profound effects on the immune system such as short-term effects that permit fetal survival as well as longer-term effects that could influence late-onset diseases. In order to better evaluate these influences, we studied the association of birth order and gravidity/parity as risk factors for systemic sclerosis (SSc; scleroderma). Data regarding SSc cases and their unaffected sibling controls were obtained from the Scleroderma Family Registry and DNA Repository. The case-sibling design was used to minimize confounding due to differences in age, race, ethnicity, or calendar time. The gravidity/parity analysis was based on sibships with at least one SSc-affected and one unaffected sister. Birth order was examined in 974 sibships, comparing SSc cases (n = 987) with their unaffected siblings (n = 3,088). The risk of scleroderma increased with increasing birth order (odds ratio [OR] 1.25, 95% confidence interval [95% CI] 1.06-1.50 for birth order 2-5; OR 2.22, 95% CI 1.57-3.15 for birth order 6-9; and OR 3.53, 95% CI 1.68-7.45 for birth order 10-15). Gravidity/parity was analyzed in 168 sibships (256 unaffected sisters, 172 SSc cases). We found an association between a history of one or more pregnancies and SSc (OR 2.8). Birth order and pregnancy were independently associated with a higher risk of developing SSc. These findings suggest that immune development in early childhood and/or pregnancy-associated events, including but not limited to microchimerism, plays a role in SSc susceptibility.

  10. Patient phenotypes in fibromyalgia comorbid with systemic sclerosis or rheumatoid arthritis: influence of diagnostic and screening tests. Screening with the FiRST questionnaire, diagnosis with the ACR 1990 and revised ACR 2010 criteria.

    PubMed

    Perrot, Serge; Peixoto, Mariana; Dieudé, Philippe; Hachulla, Eric; Avouac, Jerome; Ottaviani, Sebastien; Allanore, Yannick

    2017-01-01

    Fibromyalgia (FM) may occur with rheumatoid arthritis (RA) and systemic sclerosis (SSc), and debate remains about its diagnosis. We aimed to use three FM tools (a screening tool (FiRST), diagnostic criteria (ACR 1990 and revised 2010), to compare FM prevalence between RA and SSc patients, to describe the phenotypes of patients with comorbid FM, and to analyze links between FM and secondary Sjögren's syndrome (SS). Consecutive adult patients with confirmed RA or SSc from four university hospitals were tested with the three FM tools. FiRST detected FM in 22.6% of the 172 RA patients, with confirmation in 22.1% (ACR1990) and 19.1% (ACR2010). ACR1990FM+ RA patients had more diffuse pain, whereas ACR2010FM+ RA patients had higher BMI and pain intensity, more diffuse pain, active disease, disability, and associated SS. FiRST detected FM in 27.8% of the 122 SSc patients, with confirmation in 30.3% (ACR1990) and 23.7% (ACR2010). ACR1990FM+ SSc patients had greater disability and pain intensity, and more diffuse pain, whereas ACR2010FM+ SSc patients had higher BMI, pain intensity, more disability and diffuse pain, and associated SS. Correlations between FM diagnostic and screening tool results were modest in both conditions. Secondary SS was associated with comorbid FM. The prevalence of FM is high in SSc and RA, whatever the FM diagnostic tool used. Secondary SS is associated with FM in both RA and SSc. The revised ACR 2010 FM criteria and FiRST screening tool reveal specific phenotypes potentially useful for improving disease management.

  11. Critical experiments of the self-consistent model for polycrystalline Hastelloy-X

    NASA Technical Reports Server (NTRS)

    Shi, Shixiang; Walker, Kevin P.; Jordan, Eric H.

    1991-01-01

    A viscoplastic constitutive model is presented for the estimation of the overall mechanical response of Hastelloy-X polycrystalline metals from a knowledge of single crystal behavior. The behavior of polycrystal is derived from that of single crystals using a self-consistent formulation. The single crystal behavior which has been used was developed by summing postulated slip on crystallographic slip systems. The plasticity and creep are treated coupledly using unified viscoplastic model which includes the interaction effects between rapid and slow deformation at elevated temperature. The validity of the model is directly tested by experiments on Hastelloy-X in both single crystal and polycrystalline versions.

  12. A new approach to modeling the effective thermal conductivity of ceramics porous media using a generalized self-consistent method

    NASA Astrophysics Data System (ADS)

    Edrisi, Siroos; Bidhendi, Norollah Kasiri; Haghighi, Maryam

    2017-01-01

    Effective thermal conductivity of the porous media was modeled based on a self-consistent method. This model estimates the heat transfer between insulator surface and air cavities accurately. In this method, the pore size and shape, the temperature gradient and other thermodynamic properties of the fluid was taken into consideration. The results are validated by experimental data for fire bricks used in cracking furnaces at the olefin plant of Maroon petrochemical complexes well as data published for polyurethane foam (synthetic polymers) IPTM and IPM. The model predictions present a good agreement against experimental data with thermal conductivity deviating <1 %.

  13. On the Role of Global Magnetic Field Configuration in Affecting Ring Current Dynamics

    NASA Technical Reports Server (NTRS)

    Zheng, Y.; Zaharia, S. G.; Fok, M. H.

    2010-01-01

    Plasma and field interaction is one important aspect of inner magnetospheric physics. The magnetic field controls particle motion through gradient, curvature drifts and E cross B drift. In this presentation, we show how the global magnetic field affects dynamics of the ring current through simulations of two moderate geomagnetic storms (20 November 2007 and 8-9 March 2008). Preliminary results of coupling the Comprehensive Ring Current Model (CRCM) with a three-dimensional plasma force balance code (to achieve self-consistency in both E and B fields) indicate that inclusion of self-consistency in B tends to mitigate the intensification of the ring current as other similar coupling efforts have shown. In our approach, self-consistency in the electric field is already an existing capability of the CRCM. The magnetic self-consistency is achieved by computing the three-dimensional magnetic field in force balance with anisotropic ring current ion distributions. We discuss the coupling methodology and its further improvement. In addition, comparative studies by using various magnetic field models will be shown. Simulation results will be put into a global context by analyzing the morphology of the ring current, its anisotropy and characteristics ofthe interconnected region 2 field-aligned currents.

  14. A Simulation Model for Drift Resistive Ballooning Turbulence Examining the Influence of Self-consistent Zonal Flows

    NASA Astrophysics Data System (ADS)

    Cohen, Bruce; Umansky, Maxim; Joseph, Ilon

    2015-11-01

    Progress is reported on including self-consistent zonal flows in simulations of drift-resistive ballooning turbulence using the BOUT + + framework. Previous published work addressed the simulation of L-mode edge turbulence in realistic single-null tokamak geometry using the BOUT three-dimensional fluid code that solves Braginskii-based fluid equations. The effects of imposed sheared ExB poloidal rotation were included, with a static radial electric field fitted to experimental data. In new work our goal is to include the self-consistent effects on the radial electric field driven by the microturbulence, which contributes to the sheared ExB poloidal rotation (zonal flow generation). We describe a model for including self-consistent zonal flows and an algorithm for maintaining underlying plasma profiles to enable the simulation of steady-state turbulence. We examine the role of Braginskii viscous forces in providing necessary dissipation when including axisymmetric perturbations. We also report on some of the numerical difficulties associated with including the axisymmetric component of the fluctuating fields. This work was performed under the auspices of the U.S. Department of Energy under contract DE-AC52-07NA27344 at the Lawrence Livermore National Laboratory (LLNL-ABS-674950).

  15. A system out of breath: how hypoxia possibly contributes to the pathogenesis of systemic sclerosis.

    PubMed

    van Hal, T W; van Bon, L; Radstake, T R D J

    2011-01-01

    Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially caused by a yet to be indentified circuitry involving the three features that typify SSc. In addition, once present, the hypoxia creates a vicious circle of ongoing pathology. In this paper, we provide an overview of the evidence that points towards the mechanisms causing hypoxia in SSc. In addition, data that suggest how hypoxia itself may orchestrate worsening of symptoms is presented. Altogether, it is clear that hypoxia is an important hallmark in SSc patients. By providing an overview of the mechanisms at play and the possible therapeutic avenues that have emerged, we hope to stimulate researchers to provide novel clues into the conundrum in SSc patients.

  16. Self-Consistent Ring Current/Electromagnetic Ion Cyclotron Waves Modeling

    NASA Technical Reports Server (NTRS)

    Khazanov, G. V.; Gamayunov, K. V.; Gallagher, D. L.

    2006-01-01

    The self-consistent treatment of the RC ion dynamics and EMIC waves, which are thought to exert important influences on the ion dynamical evolution, is an important missing element in our understanding of the storm-and recovery-time ring current evolution. For example, the EMlC waves cause the RC decay on a time scale of about one hour or less during the main phase of storms. The oblique EMIC waves damp due to Landau resonance with the thermal plasmaspheric electrons, and subsequent transport of the dissipating wave energy into the ionosphere below causes an ionosphere temperature enhancement. Under certain conditions, relativistic electrons, with energies 21 MeV, can be removed from the outer radiation belt by EMIC wave scattering during a magnetic storm. That is why the modeling of EMIC waves is critical and timely issue in magnetospheric physics. This study will generalize the self-consistent theoretical description of RC ions and EMIC waves that has been developed by Khazanov et al. [2002, 2003] and include the heavy ions and propagation effects of EMIC waves in the global dynamic of self-consistent RC - EMIC waves coupling. The results of our newly developed model that will be presented at the meeting, focusing mainly on the dynamic of EMIC waves and comparison of these results with the previous global RC modeling studies devoted to EMIC waves formation. We also discuss RC ion precipitations and wave induced thermal electron fluxes into the ionosphere.

  17. Gas-dynamic model and experimental study of the plasma properties in the Earth's magnetosheath

    NASA Astrophysics Data System (ADS)

    Dobreva, Polya; Zastenker, Georgy; Kartalev, Monio; Borodkova, Natalia

    2016-07-01

    This paper uses numerical self-consistent model to investigate the boundaries and structures in the Earth's magnetosheath. The model is developed to represent the interaction between the regions of the magnetosheath and magnetosphere. In the magnetosheath, the gas-dynamic approach is used for the description of the solar wind flow. The magnetosphere module is based on the modified Tsyganenko magnetic field model, where the magnetopause currents are calculated self-consistently. The magnetosheath boundaries are determined from the boundary conditions. WIND and ACE data are used as a solar wind monitor. The model calculations are compared with real satellite measurements of the boundary positions. The plasma parameters behavior in the magnetosheath is also discussed.

  18. A combined radio and GeV γ-ray view of the 2012 and 2013 flares of Mrk 421

    DOE PAGES

    Hovatta, Talvikki; Petropoulou, M.; Richards, J. L.; ...

    2015-03-09

    In 2012 Markarian 421 underwent the largest flare ever observed in this blazar at radio frequencies. In the present study, we start exploring this unique event and compare it to a less extreme event in 2013. We use 15 GHz radio data obtained with the Owens Valley Radio Observatory 40-m telescope, 95 GHz millimetre data from the Combined Array for Research in Millimeter-Wave Astronomy, and GeV γ-ray data from the Fermi Gamma-ray Space Telescope. Here, the radio light curves during the flaring periods in 2012 and 2013 have very different appearances, in both shape and peak flux density. Assuming thatmore » the radio and γ-ray flares are physically connected, we attempt to model the most prominent sub-flares of the 2012 and 2013 activity periods by using the simplest possible theoretical framework. We first fit a one-zone synchrotron self-Compton (SSC) model to the less extreme 2013 flare and estimate parameters describing the emission region. We then model the major γ-ray and radio flares of 2012 using the same framework. The 2012 γ-ray flare shows two distinct spikes of similar amplitude, so we examine scenarios associating the radio flare with each spike in turn. In the first scenario, we cannot explain the sharp radio flare with a simple SSC model, but we can accommodate this by adding plausible time variations to the Doppler beaming factor. In the second scenario, a varying Doppler factor is not needed, but the SSC model parameters require fine-tuning. Both alternatives indicate that the sharp radio flare, if physically connected to the preceding γ-ray flares, can be reproduced only for a very specific choice of parameters.« less

  19. 78 FR 48653 - Fisheries of the South Atlantic; South Atlantic Fishery Management Council; Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-09

    ...). SUMMARY: The SAFMC will hold a meeting of its SSC to discuss a proposal for peer review of a wreckfish... in accordance with the SAFMC Peer Review Guidelines. Although non-emergency issues not contained in... . SUPPLEMENTARY INFORMATION: The items of discussion in the SSC webinar are as follows: A proposal for an SSC peer...

  20. Software for Managing an Archive of Images

    NASA Technical Reports Server (NTRS)

    Hallai, Charles; Jones, Helene; Callac, Chris

    2003-01-01

    This is a revised draft by Innovators concerning the report on Software for Managing and Archive of Images.The SSC Multimedia Archive is an automated electronic system to manage images, acquired both by film and digital cameras, for the Public Affairs Office (PAO) at Stennis Space Center (SSC). Previously, the image archive was based on film photography and utilized a manual system that, by todays standards, had become inefficient and expensive. Now, the SSC Multimedia Archive, based on a server at SSC, contains both catalogs and images for pictures taken both digitally and with a traditional film-based camera, along with metadata about each image.

  1. Management of Systemic Sclerosis-Associated Interstitial Lung Disease (SSc-ILD)

    PubMed Central

    Silver, Katherine Culp

    2015-01-01

    Although scleroderma-associated interstitial lung disease (SSc-ILD) is a significant contributor to both morbidity and mortality, its pathogenesis is largely unclear. Pulmonary function tests (PFTs) and high resolution CT (HRCT) scanning continue to be the most effective tools to screen for lung involvement and to monitor for disease progression. More research and better biomarkers are needed to identify patients most at risk for developing SSc-ILD as well as to recognize which of these patients will progress to more severe disease. While immunosuppression remains the mainstay of treatment, anti-fibrotic agents may offer new avenues of treatment for patients with SSc-ILD in the future. PMID:26210128

  2. Parent-Infant Skin-to-Skin Contact Following Birth: History, Benefits, and Challenges.

    PubMed

    Hubbard, Jessie Marie; Gattman, Kindsey Rae

    2017-03-01

    It is a practice with strong roots in nature and has a significant influence on health outcomes, particularly for at-risk newborns in low-resource settings. In this comprehensive review, benefits of SSC for newborns, mothers, and fathers after vaginal and cesarean births are discussed as well as the benefits of SSC observed for infants in the NICU. Barriers to SSC practice implementation are discussed, and proposed solutions and recommendations are offered. By understanding the many benefits of SSC and strategies for implementation, health care providers can best support and promote this high-quality, evidence-based practice with mothers, newborns, and their families.

  3. Adjustment of total suspended solids data for use in sediment studies

    USGS Publications Warehouse

    Glysson, G. Douglas; Gray, John R.; Conge, L.M.; Hotchkiss, Rollin H.; Glade, Michael

    2000-01-01

    The U.S. Environmental Protection Agency identifies fluvial sediment as the single most widespread pollutant in the Nation's rivers and streams, affecting aquatic habitat, drinking water treatment processes, and recreational uses of rivers, lakes, and estuaries. A significant amount of suspended-sediment data has been produced using the total suspended solids (TSS) laboratory analysis method. An evaluation of data collected and analyzed by the U.S. Geological Survey and others has shown that the variation in TSS analytical results is considerably larger than that for traditional suspended-sediment concentration analyses (SSC) and that the TSS data show a negative bias when compared to SSC data. This paper presents the initial results of a continuing investigation into the differences between TSS and SSC results. It explores possible relations between these differences and other hydrologic data collected at the same stations. A general equation was developed to relate TSS data to SSC data. However, this general equation is not applicable for data from individual stations. Based on these analyses, there appears to be no simple, straightforward way to relate TSS and SSC data unless pairs of TSS and SSC results are available for a station.

  4. Evaluation and management of esophageal manifestations in systemic sclerosis.

    PubMed

    Denaxas, Konstantinos; Ladas, Spyros D; Karamanolis, George P

    2018-01-01

    Systemic sclerosis (SSc) is a multisystemic autoimmune connective tissue disorder; in the gastrointestinal tract, the esophagus is the most commonly affected organ. Symptoms of esophageal disease are due to gastroesophageal reflux disease (GERD) and esophageal motor dysfunction. Since the development of high-resolution manometry (HRM), this method has been preferred for the study of SSc patients with esophageal involvement. Using HRM, classic scleroderma esophagus, defined as absent or ineffective peristalsis of the distal esophagus in combination with a hypotensive lower esophageal sphincter, was found in as many as 55% of SSc patients. Endoscopy is the appropriate test for evaluating dysphagia and identifying evidence and possible complications of GERD. In the therapeutic area, treatment ranges from general supportive measures to the administration of drugs such as proton pump inhibitors and/or prokinetics. However, as many SSc patients do not respond to existing therapies, there is an urgent need for new therapeutic modalities. Buspirone, a 5-hydroxytryptamine 1A receptor agonist, could be a putative therapeutic option, as it was found to exert a significant beneficial effect in SSc patients with esophageal involvement. This review summarizes our knowledge concerning the evaluation and management of esophageal manifestations in SSc patients, including emerging therapeutic modalities.

  5. SSC OCIO, IT SUMMIT 2011

    NASA Technical Reports Server (NTRS)

    Cottrell, Dinna L.

    2011-01-01

    The Stennis Space Center (SSC) Records Retention Facility is a centralized location for all SSC records, Records Management staff, and the SSC History Office. The building is a storm resistant facility and provides a secure environment for records housing. The Records Retention Facility was constructed in accordance with The National Archives and Records Administration (NARA) requirements for records storage, making it the first NARA compliant facility in the agency. Stennis Space Center's Records Retention Facility became operational in May 2010. The SSC Records Retention Facility ensures that the required federal records are preserved, managed and accessible to all interested personnel. The facility provides 20,000 cubic feet of records storage capacity for the purpose of managing the centers consolidated records within a central, protected environment. Records housed in the facility are in the form of paper, optical, film and magnetic media. Located within the SSC Records Retention Facility, the Records Management Office provides comprehensive records management services in the form of: a) Storage and life-cycle management of inactive records of all media types; b) Digitizing/scanning of records and documents; c) Non-textual/digital electronic records media storage, migration and transfer; d) Records Remediation.

  6. Evaluation and management of esophageal manifestations in systemic sclerosis

    PubMed Central

    Denaxas, Konstantinos; Ladas, Spyros D.; Karamanolis, George P.

    2018-01-01

    Systemic sclerosis (SSc) is a multisystemic autoimmune connective tissue disorder; in the gastrointestinal tract, the esophagus is the most commonly affected organ. Symptoms of esophageal disease are due to gastroesophageal reflux disease (GERD) and esophageal motor dysfunction. Since the development of high-resolution manometry (HRM), this method has been preferred for the study of SSc patients with esophageal involvement. Using HRM, classic scleroderma esophagus, defined as absent or ineffective peristalsis of the distal esophagus in combination with a hypotensive lower esophageal sphincter, was found in as many as 55% of SSc patients. Endoscopy is the appropriate test for evaluating dysphagia and identifying evidence and possible complications of GERD. In the therapeutic area, treatment ranges from general supportive measures to the administration of drugs such as proton pump inhibitors and/or prokinetics. However, as many SSc patients do not respond to existing therapies, there is an urgent need for new therapeutic modalities. Buspirone, a 5-hydroxytryptamine 1A receptor agonist, could be a putative therapeutic option, as it was found to exert a significant beneficial effect in SSc patients with esophageal involvement. This review summarizes our knowledge concerning the evaluation and management of esophageal manifestations in SSc patients, including emerging therapeutic modalities. PMID:29507463

  7. Microbial community analysis in the autotrophic denitrification process using spent sulfidic caustic by denaturing gradient gel electrophoresis of PCR-amplified genes.

    PubMed

    Lee, J-H; Lee, S-M; Choi, G-C; Park, H-S; Kang, D-H; Park, J-J

    2011-01-01

    Spent sulfidic caustic (SSC) produced from petrochemical plants contains a high concentration of hydrogen sulfide and alkalinity, and some almost non-biodegradable organic compounds such as benzene, toluene, ethylbenzene and xylenes (BTEX). SSC is mainly incinerated with auxiliary fuel, leading to secondary pollution problems. The reuse of this waste is becoming increasingly important from economic and environmental viewpoints. To denitrify wastewater with low COD/N ratio, additional carbon sources are required. Thus, autotrophic denitrification has attracted increasing attention. In this study, SSC was injected as an electron donor for sulfur-based autotrophic denitrification in the modified Ludzack-Ettinger (MLE) process. The efficiencies of nitrification, COD, and total nitrogen (TN) removal were evaluated with varying SSC dosage. Adequate SSC injection exhibited stable autotrophic denitrification. No BTEX were detected in the monitored BTEX concentrations of the effluent. To analyse the microbial community of the MLE process, PCR-DGGE based on 16 S rDNA with EUB primers, TD primers and nirK gene with nirK primers was performed in order to elucidate the application of the MLE process to SSC.

  8. Methyl-CpG-binding protein 2 mediates antifibrotic effects in scleroderma fibroblasts.

    PubMed

    He, Ye; Tsou, Pei-Suen; Khanna, Dinesh; Sawalha, Amr H

    2018-05-14

    Emerging evidence supports a role for epigenetic regulation in the pathogenesis of scleroderma (SSc). We aimed to assess the role of methyl-CpG-binding protein 2 (MeCP2), a key epigenetic regulator, in fibroblast activation and fibrosis in SSc. Dermal fibroblasts were isolated from patients with diffuse cutaneous SSc (dcSSc) and from healthy controls. MeCP2 expression was measured by qPCR and western blot. Myofibroblast differentiation was evaluated by gel contraction assay in vitro. Fibroblast proliferation was analysed by ki67 immunofluorescence staining. A wound healing assay in vitro was used to determine fibroblast migration rates. RNA-seq was performed with and without MeCP2 knockdown in dcSSc to identify MeCP2-regulated genes. The expression of MeCP2 and its targets were modulated by siRNA or plasmid. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) using anti-MeCP2 antibody was performed to assess MeCP2 binding sites within MeCP2-regulated genes. Elevated expression of MeCP2 was detected in dcSSc fibroblasts compared with normal fibroblasts. Overexpressing MeCP2 in normal fibroblasts suppressed myofibroblast differentiation, fibroblast proliferation and fibroblast migration. RNA-seq in MeCP2-deficient dcSSc fibroblasts identified MeCP2-regulated genes involved in fibrosis, including PLAU , NID2 and ADA . Plasminogen activator urokinase (PLAU) overexpression in dcSSc fibroblasts reduced myofibroblast differentiation and fibroblast migration, while nidogen-2 (NID2) knockdown promoted myofibroblast differentiation and fibroblast migration. Adenosine deaminase (ADA) depletion in dcSSc fibroblasts inhibited cell migration rates. Taken together, antifibrotic effects of MeCP2 were mediated, at least partly, through modulating PLAU, NID2 and ADA. ChIP-seq further showed that MeCP2 directly binds regulatory sequences in NID2 and PLAU gene loci. This study demonstrates a novel role for MeCP2 in skin fibrosis and identifies MeCP2-regulated genes associated with fibroblast migration, myofibroblast differentiation and extracellular matrix degradation, which can be potentially targeted for therapy in SSc. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Assessment of esophageal involvement in systemic sclerosis and morphea (localized scleroderma) by clinical, endoscopic, manometric and pH metric features: a prospective comparative hospital based study.

    PubMed

    Arif, Tasleem; Masood, Qazi; Singh, Jaswinder; Hassan, Iffat

    2015-02-15

    Systemic sclerosis (SSc) is a generalized disorder of unknown etiology affecting the connective tissue of the body. It affects the skin and various internal organs. Gastrointestinal tract involvement is seen in almost 90% of the patients. Esophagus is the most frequently affected part of the gastrointestinal tract. Esophageal motility disturbance classically manifests as a reduced lower esophageal sphincter pressure (LESP) and loss of distal esophageal body peristalsis. Consequently, SSc patients may be complicated by erosive esophagitis and eventually by Barrett's esophagus and esophageal adenocarcinoma. Morphea, also known as localized scleroderma, is characterized by predominant skin involvement, with occasional involvement of subjacent muscles and usually sparing the internal organs. The involvement of esophagus in morphea has been studied very scarcely. The proposed study will investigate the esophageal involvement in the two forms of scleroderma (systemic and localized), compare the same and address any need of upper gastrointestinal evaluation in morphea (localized scleroderma) patients. 56 and 31 newly and already diagnosed cases of SSc and morphea respectively were taken up for the study. All the patients were inquired about the dyspeptic symptoms (heartburn and/or acid regurgitation and/or dysphagia). Upper gastrointestinal endoscopy, esophageal manometry and 24-hour pH monitoring were done in 52, 47 and 41 patients of SSc; and 28, 25 and 20 patients of morphea respectively. Esophageal symptoms were present in 39 cases (69.6%) of SSc which were mild in 22 (39.3%), moderate in 14 (25%), severe in three (5.3%); while only four cases (7.1%) of morphea had esophageal symptoms all of which were mild in severity. Reflux esophagitis was seen in 17 cases (32.7%) of SSc and only two cases (7.14%) of morphea. Manometric abnormalities were seen in 32 cases (68.1%) of SSc and none in morphea. Ambulatory 24-hour esophageal pH monitoring documented abnormal reflux in 33 cases (80.5%) of SSc and no such abnormality in morphea. While the esophageal involvement is frequent in SSc, no such motility disorder is seen in morphea. Meticulous upper gastrointestinal tract evaluation is justified only in SSc and not in morphea.

  10. Comparison of laser Doppler imaging, fingertip lacticemy test, and nailfold capillaroscopy for assessment of digital microcirculation in systemic sclerosis

    PubMed Central

    2010-01-01

    Introduction Laser Doppler imaging (LDI) is a relatively new method for assessing the functional aspect of superficial skin blood flow in systemic sclerosis (SSc) and Raynaud's phenomenon. The present study investigated the dynamic behavior of digital skin microvascular blood flow before and after cold stimulus (CS) in SSc patients and in healthy controls by means of a comprehensive approach of the functional (LDI), morphological (nailfold capillaroscopy (NFC)), and biochemical (fingertip lacticemy (FTL)) microcirculation components. Methods Forty-four SSc patients and 40 healthy controls were included. After acclimatization, all subjects underwent NFC followed by LDI and FTL measurement. NFC was performed with a stereomicroscope under 10× to 20× magnification in the 10 digits of the hands. Skin blood flow of the dorsum of four fingertips (excluding the thumb) of the left hand was measured using LDI at baseline and for 30 minutes after CS. The mean finger blood flow (FBF) of the four fingertips was expressed as arbitrary perfusion units. FTL was determined on the fourth left finger before (pre-CS-FTL) and 10 minutes after CS. Results LDI showed significantly lower mean baseline FBF in SSc patients as compared with controls (296.9 ± 208.8 vs. 503.6 ± 146.4 perfusion units; P < 0.001) and also at all time points after CS (P < 0.001). There was a significant decrease in mean FBF after CS as compared with baseline in SSc patients and in controls, followed by recovery of the blood flow 27 minutes after CS in healthy controls, but not in SSc patients. FBF tended to be lower in patients with digital scars and previous ulceration/amputation (P = 0.06). There was no correlation between mean baseline FBF and NFC parameters. Interestingly, there was a negative correlation between FTL and FBF measured by LDI in basal conditions and 10 minutes after CS in SSc patients. Conclusions LDI showed lower digital blood flow in SSc patients when compared with healthy controls and correlated well with FTL both at baseline and after CS, allowing objective measurement of blood perfusion in SSc patients. The lack of correlation between functional and morphological microvascular abnormalities, measured by LDI and NFC, suggests they are complementary tools for evaluation of independent microangiopathy aspects in SSc patients. PMID:20696074

  11. Comparison of laser Doppler imaging, fingertip lacticemy test, and nailfold capillaroscopy for assessment of digital microcirculation in systemic sclerosis.

    PubMed

    Correa, Marcelo Ju; Andrade, Luis Ec; Kayser, Cristiane

    2010-01-01

    Laser Doppler imaging (LDI) is a relatively new method for assessing the functional aspect of superficial skin blood flow in systemic sclerosis (SSc) and Raynaud's phenomenon. The present study investigated the dynamic behavior of digital skin microvascular blood flow before and after cold stimulus (CS) in SSc patients and in healthy controls by means of a comprehensive approach of the functional (LDI), morphological (nailfold capillaroscopy (NFC)), and biochemical (fingertip lacticemy (FTL)) microcirculation components. Forty-four SSc patients and 40 healthy controls were included. After acclimatization, all subjects underwent NFC followed by LDI and FTL measurement. NFC was performed with a stereomicroscope under 10× to 20× magnification in the 10 digits of the hands. Skin blood flow of the dorsum of four fingertips (excluding the thumb) of the left hand was measured using LDI at baseline and for 30 minutes after CS. The mean finger blood flow (FBF) of the four fingertips was expressed as arbitrary perfusion units. FTL was determined on the fourth left finger before (pre-CS-FTL) and 10 minutes after CS. LDI showed significantly lower mean baseline FBF in SSc patients as compared with controls (296.9 ± 208.8 vs. 503.6 ± 146.4 perfusion units; P < 0.001) and also at all time points after CS (P < 0.001). There was a significant decrease in mean FBF after CS as compared with baseline in SSc patients and in controls, followed by recovery of the blood flow 27 minutes after CS in healthy controls, but not in SSc patients. FBF tended to be lower in patients with digital scars and previous ulceration/amputation (P = 0.06). There was no correlation between mean baseline FBF and NFC parameters. Interestingly, there was a negative correlation between FTL and FBF measured by LDI in basal conditions and 10 minutes after CS in SSc patients. LDI showed lower digital blood flow in SSc patients when compared with healthy controls and correlated well with FTL both at baseline and after CS, allowing objective measurement of blood perfusion in SSc patients. The lack of correlation between functional and morphological microvascular abnormalities, measured by LDI and NFC, suggests they are complementary tools for evaluation of independent microangiopathy aspects in SSc patients.

  12. Post-decision biases reveal a self-consistency principle in perceptual inference.

    PubMed

    Luu, Long; Stocker, Alan A

    2018-05-15

    Making a categorical judgment can systematically bias our subsequent perception of the world. We show that these biases are well explained by a self-consistent Bayesian observer whose perceptual inference process is causally conditioned on the preceding choice. We quantitatively validated the model and its key assumptions with a targeted set of three psychophysical experiments, focusing on a task sequence where subjects first had to make a categorical orientation judgment before estimating the actual orientation of a visual stimulus. Subjects exhibited a high degree of consistency between categorical judgment and estimate, which is difficult to reconcile with alternative models in the face of late, memory related noise. The observed bias patterns resemble the well-known changes in subjective preferences associated with cognitive dissonance, which suggests that the brain's inference processes may be governed by a universal self-consistency constraint that avoids entertaining 'dissonant' interpretations of the evidence. © 2018, Luu et al.

  13. Numerical modeling of the coupling of an ICRH antenna with a plasma with self-consistent antenna currents

    NASA Astrophysics Data System (ADS)

    Pécoul, S.; Heuraux, S.; Koch, R.; Leclert, G.

    2002-07-01

    A realistic modeling of ICRH antennas requires the knowledge of the antenna currents. The code ICANT determines self-consistently these currents and, as a byproduct, the electrical characteristics of the antenna (radiated power, propagation constants on straps, frequency response, … ). The formalism allows for the description of three-dimensional antenna elements (for instance, finite size thick screen blades). The results obtained for various cases where analytical results are available are discussed. The resonances appearing in the spectrum and the occurrence of unphysical resonant modes are discussed. The capability of this self-consistent method is illustrated by a number of examples, e.g., fully conducting thin or thick screen bars leading to magnetic shielding effects, frequency response and resonances of an end-tuned antenna, field distributions in front of a Tore-Supra type antenna with tilted screen blades.

  14. Many-body Green’s function theory for electron-phonon interactions: Ground state properties of the Holstein dimer

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

    Säkkinen, Niko; Leeuwen, Robert van; Peng, Yang

    2015-12-21

    We study ground-state properties of a two-site, two-electron Holstein model describing two molecules coupled indirectly via electron-phonon interaction by using both exact diagonalization and self-consistent diagrammatic many-body perturbation theory. The Hartree and self-consistent Born approximations used in the present work are studied at different levels of self-consistency. The governing equations are shown to exhibit multiple solutions when the electron-phonon interaction is sufficiently strong, whereas at smaller interactions, only a single solution is found. The additional solutions at larger electron-phonon couplings correspond to symmetry-broken states with inhomogeneous electron densities. A comparison to exact results indicates that this symmetry breaking is stronglymore » correlated with the formation of a bipolaron state in which the two electrons prefer to reside on the same molecule. The results further show that the Hartree and partially self-consistent Born solutions obtained by enforcing symmetry do not compare well with exact energetics, while the fully self-consistent Born approximation improves the qualitative and quantitative agreement with exact results in the same symmetric case. This together with a presented natural occupation number analysis supports the conclusion that the fully self-consistent approximation describes partially the bipolaron crossover. These results contribute to better understanding how these approximations cope with the strong localizing effect of the electron-phonon interaction.« less

  15. Parental desire and acceptability of spermatogonial stem cell cryopreservation in boys with cancer.

    PubMed

    van den Berg, H; Repping, S; van der Veen, F

    2007-02-01

    In the near future, a substantial proportion of adults will be childhood cancer survivors. The cryopreservation and transplantation of spermatogonial stem cells (SSCs) is currently successful in animals; application in humans seems likely in the near future. Cryopreserving SSCs might become an important issue in childhood cancer. Because this might require testicular biopsies or hemicastration, parental desire/acceptability for SSC collection was enquired for. Three hundred eighteen parents of boys surviving at least 2 years after the diagnosis of cancer were asked about collecting SSCs by biopsy or hemicastration and collecting sperm by masturbation or electrostimulation. Opinions were assessed as if at the time of diagnosis and at the present time. Sixty-three per cent of parents responded. At diagnosis, SSC collection by means of biopsy was approved by 61%, hemicastration by 33% and collecting sperm by 70% (P < 0.013). The acceptability of performing hemicastration was significantly lower than all other forms of SSC/sperm collection. No differences were observed between parents' present opinion and opinion at diagnosis. No differences related to treatment intensity, presumed negative fertility effects and pubertal state were found. Infertility is a major topic for parents. For prepubertal boys, the collection of SSCs might be a great relief in respect of the fertility issue. Collecting SSCs by biopsy is desired and accepted by the majority of parents; hemicastration is accepted by one-third of parents. The translation of SSC cryopreservation and transplantation from animal models to humans is eagerly awaited.

  16. Suspended sediment and sediment-associated contaminants in San Francisco Bay

    USGS Publications Warehouse

    Schoellhamer, D.H.; Mumley, T.E.; Leatherbarrow, J.E.

    2007-01-01

    Water-quality managers desire information on the temporal and spatial variability of contaminant concentrations and the magnitudes of watershed and bed-sediment loads in San Francisco Bay. To help provide this information, the Regional Monitoring Program for Trace Substances in the San Francisco Estuary (RMP) takes advantage of the association of many contaminants with sediment particles by continuously measuring suspended-sediment concentration (SSC), which is an accurate, less costly, and more easily measured surrogate for several trace metals and organic contaminants. Continuous time series of SSC are collected at several sites in the Bay. Although semidiurnal and diurnal tidal fluctuations are present, most of the variability of SSC occurs at fortnightly, monthly, and semiannual tidal time scales. A seasonal cycle of sediment inflow, wind-wave resuspension, and winnowing of fine sediment also is observed. SSC and, thus, sediment-associated contaminants tend to be greater in shallower water, at the landward ends of the Bay, and in several localized estuarine turbidity maxima. Although understanding of sediment transport has improved in the first 10 years of the RMP, determining a simple mass budget of sediment or associated contaminants is confounded by uncertainties regarding sediment flux at boundaries, change in bed-sediment storage, and appropriate modeling techniques. Nevertheless, management of sediment-associated contaminants has improved greatly. Better understanding of sediment and sediment-associated contaminants in the Bay is of great interest to evaluate the value of control actions taken and the need for additional controls. ?? 2007 Elsevier Inc. All rights reserved.

  17. Suspended sediment and sediment-associated contaminants in San Francisco Bay.

    PubMed

    Schoellhamer, David H; Mumley, Thomas E; Leatherbarrow, Jon E

    2007-09-01

    Water-quality managers desire information on the temporal and spatial variability of contaminant concentrations and the magnitudes of watershed and bed-sediment loads in San Francisco Bay. To help provide this information, the Regional Monitoring Program for Trace Substances in the San Francisco Estuary (RMP) takes advantage of the association of many contaminants with sediment particles by continuously measuring suspended-sediment concentration (SSC), which is an accurate, less costly, and more easily measured surrogate for several trace metals and organic contaminants. Continuous time series of SSC are collected at several sites in the Bay. Although semidiurnal and diurnal tidal fluctuations are present, most of the variability of SSC occurs at fortnightly, monthly, and semiannual tidal time scales. A seasonal cycle of sediment inflow, wind-wave resuspension, and winnowing of fine sediment also is observed. SSC and, thus, sediment-associated contaminants tend to be greater in shallower water, at the landward ends of the Bay, and in several localized estuarine turbidity maxima. Although understanding of sediment transport has improved in the first 10 years of the RMP, determining a simple mass budget of sediment or associated contaminants is confounded by uncertainties regarding sediment flux at boundaries, change in bed-sediment storage, and appropriate modeling techniques. Nevertheless, management of sediment-associated contaminants has improved greatly. Better understanding of sediment and sediment-associated contaminants in the Bay is of great interest to evaluate the value of control actions taken and the need for additional controls.

  18. Factors associated with oral hygiene practices among adults with systemic sclerosis

    PubMed Central

    Yuen, Hon K.; Hant, Faye N.; Hatfield, Corey; Summerlin, Lisa M.; Smith, Edwin A.; Silver, Richard M.

    2013-01-01

    OBJECTIVE To identify factors associated with oral hygiene practices in adults with systemic sclerosis (SSc) METHODS In this cross-sectional study, 178 dentate adults with SSc received an oral examination which included measurement of oral aperture, assessment of manual dexterity to perform oral hygiene, as well as completion of the Center of Epidemiological Studies Depression (CES-D) Scale, and an oral health-related questionnaire. RESULTS Multivariable logistic regression modeling showed male, minority and high CES-D scores (i.e., clinically significant symptoms of depression) were associated with less likelihood of participants brushing teeth at least twice daily, but the presence of self-reported dry mouth symptoms increased the likelihood of toothbrushing. Having a dental visit in the past 12 months, and use of an adapted flossing or interdental cleaning device were significantly associated with daily dental flossing; however, having difficulty flossing teeth reduced the likelihood of daily flossing. CONCLUSIONS Overall, demographic variables were strongly associated with toothbrushing frequency, whereas, flossing self-efficacy and barriers were strongly associated with dental flossing frequency in adults with SSc. The results suggest that dental health professionals should take mental health into consideration when educating patients with SSc to improve their oral hygiene, and consider making referrals for patients exhibiting suspected clinically significant depressive symptoms to mental health professionals for further evaluation and treatment. In addition, an appropriate adapted flossing or interdental cleaning device should be recommended to increase dental flossing practices in this patient population. PMID:24128049

  19. Unprecedented study of the broadband emission of Mrk 421 during flaring activity in March 2010

    DOE PAGES

    Aleksić, J.; Ansoldi, S.; Antonelli, L. A.; ...

    2015-05-27

    Because of its proximity, Mrk 421 is one of the best sources on which to study the nature of BL Lac objects. Its proximity allows us to characterize its broadband spectral energy distribution (SED). Here, the goal is to better understand the mechanisms responsible for the broadband emission and the temporal evolution of Mrk 421. These mechanisms may also apply to more distant blazars that cannot be studied with the same level of detail. A flare occurring in March 2010 was observed for 13 consecutive days (from MJD 55 265 to MJD 55 277) with unprecedented wavelength coverage from radiomore » to very high energy (VHE; E> 100 GeV) γ-rays with MAGIC, VERITAS, Whipple, Fermi-LAT, MAXI, RXTE, Swift, GASP-WEBT, and several optical and radio telescopes. We modeled the day-scale SEDs with one-zone and two-zone synchrotron self-Compton (SSC) models, investigated the physical parameters, and evaluated whether the observed broadband SED variability can be associated with variations in the relativistic particle population. As a result, the activity of Mrk 421 initially was high and then slowly decreased during the 13-day period. The flux variability was remarkable at the X-ray and VHE bands, but it was minor or not significant at the other bands. The variability in optical polarization was also minor. These observations revealed an almost linear correlation between the X-ray flux at the 2–10 keV band and the VHE γ-ray flux above 200 GeV, consistent with the γ-rays being produced by inverse-Compton scattering in the Klein-Nishina regime in the framework of SSC models. The one-zone SSC model can describe the SED of each day for the 13 consecutive days reasonably well, which once more shows the success of this standard theoretical scenario to describe the SEDs of VHE BL Lacs such as Mrk 421. This flaring activity is also very well described by a two-zone SSC model, where one zone is responsible for the quiescent emission, while the other smaller zone, which is spatially separated from the first, contributes to the daily variable emission occurring at X-rays and VHE γ-rays. The second blob is assumed to have a smaller volume and a narrow electron energy distribution with 3 × 104« less

  20. [Screening of pulmonary hypertension in a Spanish cohort of patients with systemic sclerosis].

    PubMed

    García Hernández, Francisco José; Castillo Palma, María Jesús; Montero Mateos, Enrique; González León, Rocío; López Haldón, José Eduardo; Sánchez Román, Julio

    2016-01-01

    Pulmonary arterial hypertension (PAH) is an important cause of morbimortality in systemic sclerosis (SSc). Evolution is worse than that of subjects with idiopathic PAH, but prognosis improves when PAH is diagnosed early. The aim of this research is to describe results of a screening program for diagnosis of pulmonary hypertension (PH) carried out in a cohort of Spanish patients with SSc. PH screening was performed by transthoracic doppler echocardiography (TTDE) in 184 patients with SSc. Patients with systolic pulmonary arterial pressure estimated by TTDE>35 mmHg were evaluated per protocol to confirm diagnosis and type of PH. PAH was diagnosed in 25 patients (13.6%). Patients with diffuse and limited SSc developed PAH in a similar degree, 9/60 (15%) vs. 16/100 (16%), with no cases among patients with SSc "sine scleroderma" or "pre-scleroderma" (P<.001). The only clinical or epidemiological data characterizing patients with PAH were older age (mean age 67 years for patients with PAH vs. 56 years for those without PAH, P=.007), limited SSc, a trend toward shorter evolution of the underlying disease (median 8 years for patients with PAH vs. 10 years for those without PAH, P=.73), and a higher frequency of positive anticentromere antibodies (16 patients [64%] with PAH vs. 70 (48,3%) without PAH, P=.19). Prevalence of PAH in SSc was high and supports the implementation of a regular screening program. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  1. Influence of the IL6 gene in susceptibility to systemic sclerosis.

    PubMed

    Cénit, Maria Carmen; Simeón, Carmen P; Vonk, Madelon C; Callejas-Rubio, Jose L; Espinosa, Gerard; Carreira, Patricia; Blanco, Francisco J; Narvaez, Javier; Tolosa, Carlos; Román-Ivorra, José A; Gómez-García, Inmaculada; García-Hernández, Francisco J; Gallego, María; García-Portales, Rosa; Egurbide, María Victoria; Fonollosa, Vicente; García de la Peña, Paloma; López-Longo, Francisco J; González-Gay, Miguel A; Hesselstrand, Roger; Riemekasten, Gabriela; Witte, Torsten; Voskuyl, Alexandre E; Schuerwegh, Annemie J; Madhok, Rajan; Fonseca, Carmen; Denton, Christopher; Nordin, Annika; Palm, Øyvind; van Laar, Jacob M; Hunzelmann, Nicolas; Distler, Jörg H W; Kreuter, Alexander; Herrick, Ariane; Worthington, Jane; Koeleman, Bobby P; Radstake, Timothy R D J; Martín, Javier

    2012-12-01

    Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc. We performed a large metaanalysis including a total of 2749 cases and 3189 controls from 6 white populations (Germany, The Netherlands, Norway, Spain, Sweden, and United Kingdom). Three IL6 single-nucleotide polymorphisms (SNP; rs2069827, rs1800795, and rs2069840) were selected by SNP tagging and genotyped using TaqMan(®) allele discrimination technology. Individual SNP metaanalysis showed no evidence of association of the 3 IL6 genetic variants with the global disease. Phenotype analyses revealed a significant association between the minor allele of rs2069840 and the limited cutaneous SSc clinical form (Bonferroni p = 0.036, OR 1.14, 95% CI 1.04-1.25). A trend of association between the minor allele of the rs1800795 and the diffuse cutaneous SSc clinical form was also evident (Bonferroni p = 0.072, OR 0.86, 95% CI 0.77-0.96). In the IL6 allelic combination analyses, the GGC allelic combination rs2069827-rs1800795-rs2069840 showed an association with overall SSc (Bonferroni p = 0.016, OR 1.13, 95% CI 1.04-1.23). Our results suggest that the IL6 gene may influence the development of SSc and its progression.

  2. Solvent oriented hobbies and the risk of systemic sclerosis.

    PubMed

    Nietert, P J; Sutherland, S E; Silver, R M; Pandey, J P; Dosemeci, M

    1999-11-01

    To examine whether those participating in solvent oriented hobbies (SOH) are at greater risk of developing systemic sclerosis (SSc), and if the association is modified by the presence of the anti-Scl70 antibody. Patients with SSc and controls were recruited from a university hospital rheumatology clinic. Recreational hobby and occupational histories were obtained along with blood samples. Cumulative scores were created for participation in SOH. Logistic regression was used to calculate odds ratios associated with SOH exposure after adjustment for sex, age at diagnosis, and occupational solvent exposure, and to examine the association between SOH exposure and the presence of anti-Scl70. Solvent exposure based on hobbies and occupations was determined for 178 cases (141 women, 37 men) and 200 controls (138 women, 62 men). Overall participation in SOH was not associated with SSc. However, odds of high cumulative SOH exposure was 3 times greater in those patients with SSc testing positive for the anti-Scl70 antibody compared to patients testing negative (OR 2.9, 95% CI 1.1, 7.9), and twice as great as controls (OR 2.5, 95% CI 1.1, 5.9). While patients with SSc did not participate more often in SOH than controls over all, odds of high cumulative SOH exposure was greater among patients with SSc testing positive for anti-Scl70 compared to those testing negative and compared to controls. These results provide further evidence that environmental agents may play a role in the development of Ssc.

  3. Practice of skin-to-skin contact, exclusive breastfeeding and other newborn care interventions in Ethiopia following promotion by facility and community health workers: results from a prospective outcome evaluation.

    PubMed

    Callaghan-Koru, Jennifer A; Estifanos, Abiy Seifu; Sheferaw, Ephrem Daniel; de Graft-Johnson, Joseph; Rosado, Carina; Patton-Molitors, Rachel; Worku, Bogale; Rawlins, Barbara; Baqui, Abdullah

    2016-12-01

    To assess the effects of a facility and community newborn intervention package on coverage of early skin-to-skin contact (SSC) and exclusive breastfeeding - the therapeutic components of kangaroo mother care. A multilevel community and facility intervention in Ethiopia trained health workers in 10 health centres and the surrounding communities to promote early SSC and exclusive breastfeeding for all babies born at home or in the facility. Changes in SSC and exclusive breastfeeding were assessed by comparing baseline and endline household surveys. Overall practice of SSC at any time following delivery increased significantly from 13.1 to 44.1% of mothers. Coverage of immediate SSC also increased significantly from 8.4 to 24.1%. Breastfeeding within the first hour increased from 51.4 to 67.9% and exclusive breastfeeding within the first three days increased from 86 to 95.8%. At endline, SSC was significantly higher among facility births than home births and community health workers had limited contact with mothers. While targeted behaviours improved overall, the programme did not achieve adequate increases in SSC and exclusive breastfeeding among home deliveries to expect a reduction in mortality for low birthweight babies. Newborn care programs in Ethiopia should continue to encourage facility delivery while strengthening coverage of community programmes. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  4. Astro Camp Counselors

    NASA Technical Reports Server (NTRS)

    2007-01-01

    Barbara Marino (left), Stennis Space Center education technology specialist, shows Astro Camp Counselor Beverly Fitzsimmons a LEGO model during a teambuilding exercise May 29 at SSC's North Gate computer lab as a part of the counselors' `new hire' orientation.

  5. Astro Camp Counselors

    NASA Image and Video Library

    2007-06-08

    Barbara Marino (left), Stennis Space Center education technology specialist, shows Astro Camp Counselor Beverly Fitzsimmons a LEGO model during a teambuilding exercise May 29 at SSC's North Gate computer lab as a part of the counselors' `new hire' orientation.

  6. Self-consistency tests of large-scale dynamics parameterizations for single-column modeling

    DOE PAGES

    Edman, Jacob P.; Romps, David M.

    2015-03-18

    Large-scale dynamics parameterizations are tested numerically in cloud-resolving simulations, including a new version of the weak-pressure-gradient approximation (WPG) introduced by Edman and Romps (2014), the weak-temperature-gradient approximation (WTG), and a prior implementation of WPG. We perform a series of self-consistency tests with each large-scale dynamics parameterization, in which we compare the result of a cloud-resolving simulation coupled to WTG or WPG with an otherwise identical simulation with prescribed large-scale convergence. In self-consistency tests based on radiative-convective equilibrium (RCE; i.e., no large-scale convergence), we find that simulations either weakly coupled or strongly coupled to either WPG or WTG are self-consistent, butmore » WPG-coupled simulations exhibit a nonmonotonic behavior as the strength of the coupling to WPG is varied. We also perform self-consistency tests based on observed forcings from two observational campaigns: the Tropical Warm Pool International Cloud Experiment (TWP-ICE) and the ARM Southern Great Plains (SGP) Summer 1995 IOP. In these tests, we show that the new version of WPG improves upon prior versions of WPG by eliminating a potentially troublesome gravity-wave resonance.« less

  7. Response of a tidal freshwater marsh to changes in sea level and suspended-sediment concentrations

    NASA Astrophysics Data System (ADS)

    Palinkas, C. M.

    2016-02-01

    Tidal marshes are among the world's most valuable ecosystems from a variety of perspectives, but they are also perhaps the most threatened by environmental changes, such as increased rates of sea-level rise and decreased concentrations of fluvial suspended sediments. In this study, time-series measurements of sedimentation over 5 years (2010-2014) at Dyke Marsh Preserve (Potomac River, VA, USA) are used to evaluate the influence of environmental drivers on sediment accretion within the marsh. To do so, bimonthly (deposition on ceramic tiles) and seasonal-scale (from 7Be (half-life 53.3 d) measurements) sedimentation rates are placed in the context of factors that can influence inorganic sediment availability and delivery to the marsh platform, specifically winds, river discharge, suspended-sediment concentrations (SSC; calculated from rating curves), and local sea level. Because of marsh geography and dominant storm patterns in this area, the influence of events is complex - wind speed and direction are negatively correlated with local sea level but positively correlated with SSC. This is, stronger winds from a more westerly direction drive water seaward of the marsh platform; increased precipitation results in higher river discharge and SSC from runoff and/or sediment resuspension. At the bimonthly scale, changes in sea level are correlated with both the rate and character (organic content) of sediments collected on tiles, but there was no relationship between sedimentation rates and SSC. Instead, bimonthly sedimentation rates are correlated with the fluvial sediment load (product of river discharge and SSC), which is not often included in models of marsh accretion. These trends are similar for seasonal-scale observations, though statistical tests are not as robust. These results suggest that, while events drive sedimentation within the marsh, their influence can be obscured over longer time scales that incorporate quiescent times of non-deposition.

  8. Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis: A Multicenter, Prospective Cohort Study.

    PubMed

    Cutolo, Maurizio; Herrick, Ariane L; Distler, Oliver; Becker, Mike O; Beltran, Emma; Carpentier, Patrick; Ferri, Clodoveo; Inanç, Murat; Vlachoyiannopoulos, Panayiotis; Chadha-Boreham, Harbajan; Cottreel, Emmanuelle; Pfister, Thomas; Rosenberg, Daniel; Torres, Juan V; Smith, Vanessa

    2016-10-01

    To identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6-month period in patients with systemic sclerosis (SSc). In this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses. Of the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow-up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681-0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510-0.756). This international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs. © 2016, American College of Rheumatology.

  9. Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis: A Multicenter, Prospective Cohort Study

    PubMed Central

    Herrick, Ariane L.; Distler, Oliver; Becker, Mike O.; Beltran, Emma; Carpentier, Patrick; Ferri, Clodoveo; Inanç, Murat; Vlachoyiannopoulos, Panayiotis; Chadha‐Boreham, Harbajan; Cottreel, Emmanuelle; Pfister, Thomas; Rosenberg, Daniel; Torres, Juan V.; Cutolo, Maurizio; Herrick, Ariane L.; Distler, Oliver; Becker, Mike; Beltran, Emma; Carpentier, Patrick; Ferri, Clodoveo; Inanç, Murat; Vlachoyiannopoulos, Panayiotis; Smith, Vanessa; Erlacher, L; Hirschl, M; Kiener, HP; Pilger, E; Smith, V; Blockmans, D; Wautrecht, J‐C; Becvár, R; Carpentier, P; Frances, C; Lok, C; Sparsa, A; Hachulla, E; Quere, I; Allanore, Y; Agard, C; Riemekasten, G; Hunzelmann, N; Stücker, M; Ahmadi‐Simab, K; Sunderkötter, C; Wohlrab, J; Müller‐Ladner, U; Schneider, M; Vlachoyianopoulos, P; Vassilopoulos, D; Drosos, A; Antonopoulos, A; Balbir‐Gurman, A; Langevitz, P; Rosner, I; Levy, Y; Cutolo, M; Bombardieri, S; Ferraccioli, G; Mazzuca, S; Grassi, W; Lunardi, C; Airó, P; Riccieri, V; Voskuyl, AE; Schuerwegh, A; Santos, L; Rodrigues, AC; Grilo, A; Amaral, MC; Román Ivorra, JA; Castellvi, I; Distler, O; Spertini, F; Müller, R; Inanç, M; Oksel, F; Turkcapar, N; Herrick, A; Denton, C; McHugh, N; Chattopadhyay, C; Hall, F; Buch, M

    2016-01-01

    Objective To identify nailfold videocapillaroscopic features and other clinical risk factors for new digital ulcers (DUs) during a 6‐month period in patients with systemic sclerosis (SSc). Methods In this multicenter, prospective, observational cohort study, the videoCAPillaroscopy (CAP) study, we evaluated 623 patients with SSc from 59 centers (14 countries). Patients were stratified into 2 groups: a DU history group and a no DU history group. At enrollment, patients underwent detailed nailfold videocapillaroscopic evaluation and assessment of demographic characteristics, DU status, and clinical and SSc characteristics. Risk factors for developing new DUs were assessed using univariable and multivariable logistic regression (MLR) analyses. Results Of the 468 patients in the DU history group (mean ± SD age 54.0 ± 13.7 years), 79.5% were female, 59.8% had limited cutaneous SSc, and 22% developed a new DU during follow‐up. The strongest risk factors for new DUs identified by MLR in the DU history group included the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs (categorized as 0, 1, 2, or ≥3), and the presence of critical digital ischemia. The receiver operating characteristic (ROC) of the area under the curve (AUC) of the final MLR model was 0.738 (95% confidence interval [95% CI] 0.681–0.795). Internal validation through bootstrap generated a ROC AUC of 0.633 (95% CI 0.510–0.756). Conclusion This international prospective study, which included detailed nailfold videocapillaroscopic evaluation and extensive clinical characterization of patients with SSc, identified the mean number of capillaries per millimeter in the middle finger of the dominant hand, the number of DUs at enrollment, and the presence of critical digital ischemia at enrollment as risk factors for the development of new DUs. PMID:27111549

  10. Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8.

    PubMed

    Ah Kioon, Marie Dominique; Tripodo, Claudio; Fernandez, David; Kirou, Kyriakos A; Spiera, Robert F; Crow, Mary K; Gordon, Jessica K; Barrat, Franck J

    2018-01-10

    Systemic sclerosis (SSc) is a multisystem life-threatening fibrosing disorder that lacks effective treatment. The link between the inflammation observed in organs such as the skin and profibrotic mechanisms is not well understood. The plasmacytoid dendritic cell (pDC) is a key cell type mediating Toll-like receptor (TLR)-induced inflammation in autoimmune disease patients, including lupus and skin diseases with interface dermatitis. However, the role of pDCs in fibrosis is less clear. We show that pDCs infiltrate the skin of SSc patients and are chronically activated, leading to secretion of interferon-α (IFN-α) and CXCL4, which are both hallmarks of the disease. We demonstrate that the secretion of CXCL4 is under the control of phosphatidylinositol 3-kinase δ and is due to the aberrant presence of TLR8 on pDCs of SSc patients, which is not seen in healthy donors or in lupus pDCs, and that CXCL4 primarily acts by potentiating TLR8- but also TLR9-induced IFN production by pDCs. Depleting pDCs prevented disease in a mouse model of scleroderma and could revert fibrosis in mice with established disease. In contrast, the disease was exacerbated in mice transgenic for TLR8 with recruitment of pDCs to the fibrotic skin, whereas TLR7 only partially contributed to the inflammatory response, indicating that TLR8 is the key RNA-sensing TLR involved in the establishment of fibrosis. We conclude that the pDC is an essential cell type involved in the pathogenesis of SSc and its removal using depleting antibodies or attenuating pDC function could be a novel approach to treat SSc patients. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  11. Spatio-temporal patterns of soil erosion and suspended sediment dynamics in the Mekong River Basin.

    PubMed

    Suif, Zuliziana; Fleifle, Amr; Yoshimura, Chihiro; Saavedra, Oliver

    2016-10-15

    Understanding of the distribution patterns of sediment erosion, concentration and transport in river basins is critically important as sediment plays a major role in river basin hydrophysical and ecological processes. In this study, we proposed an integrated framework for the assessment of sediment dynamics, including soil erosion (SE), suspended sediment load (SSL) and suspended sediment concentration (SSC), and applied this framework to the Mekong River Basin. The Revised Universal Soil Loss Equation (RUSLE) model was adopted with a geographic information system to assess SE and was coupled with a sediment accumulation and a routing scheme to simulate SSL. This framework also analyzed Landsat imagery captured between 1987 and 2000 together with ground observations to interpolate spatio-temporal patterns of SSC. The simulated SSL results from 1987 to 2000 showed the relative root mean square error of 41% and coefficient of determination (R(2)) of 0.89. The polynomial relationship of the near infrared exoatmospheric reflectance and the band 4 wavelength (760-900nm) to the observed SSC at 9 sites demonstrated the good agreement (overall relative RMSE=5.2%, R(2)=0.87). The result found that the severe SE occurs in the upper (China and Lao PDR) and lower (western part of Vietnam) regions. The SSC in the rainy season (June-November) showed increasing and decreasing trends longitudinally in the upper (China and Lao PDR) and lower regions (Cambodia), respectively, while the longitudinal profile of SSL showed a fluctuating trend along the river in the early rainy season. Overall, the results described the unique spatio-temporal patterns of SE, SSL and SSC in the Mekong River Basin. Thus, the proposed integrated framework is useful for elucidating complex process of sediment generation and transport in the land and river systems of large river basins. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Dahl, P.F.

    The magnet system for the Superconducting Super Collider will likely remain the most ambitious -- and challenging -- application of superconducting technology for the foreseeable future. The centerpiece of the system is the behemoth collider dipole magnet. Its design, still evolving in its detailed features, dates from the mid-1980's when it emerged as the winner in an early technical showdown that occupied the fledgling SSC project. However, some of its gross features can be traced back to three path-breaking superconducting accelerator initiatives under way a decade earlier -- on the East Coast, on the West Coast, and in the Midwest.more » Other features have a still earlier legacy. In the present report we chronicle the origins and chief milestones in the development of certain SSC dipole design concepts. Unfortunately, the chronicle must remain incomplete, with the design not yet frozen as we go to press and still subject to important modifications as the SSC Laboratory settles in near its future home in Ellis County, Texas, hard on the heels of a wide-ranging design review in the closing days of the SSC Central Design Group in (CDG) Berkeley. Be that as it may, in what follows we concentrate on the early years in an attempt to recapitulate the birth of the dipole, taking as our point of departure the SSC Reference Designs Study (RDS) of 1984. In Section 3 we touch on the background for the various RDS options, including ISABELLE/CBA and the Tevatron. In Section 4 the narrative focuses on the two final protagonists, a high-field cosine theta (cos {theta}) magnet and a low-field superferric magnet. Section 5 recounts the circumstances surrounding the selection of a particular magnet style'' for further development, and the ups and downs of the first model magnets. We conclude with a smattering of progress highlights in refining the design during the final push under the reign of the CDG.« less

  13. Supercritical/Solid Catalyst (SSC)

    ScienceCinema

    Ginosar, Daniel; Fox, Robert; Bright, Patricia

    2018-05-23

    INL's patented, continuous-flow Supercritical/Solid Catalyst (SSC) produces the highest ASTM-quality B-100 biodiesel from waste fats, oils, and greases at the site of waste generation. SSC delivers low-cost transportation fuel, avoids significant landfill costs for municipalities, and reduces potent methane and other emissions produced in landfills from these wastes. You can learn more about INL's energy research programs at http://www.facebook.com/idahonationallaboratory.

  14. Supercritical/Solid Catalyst (SSC)

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

    Ginosar, Daniel; Fox, Robert; Bright, Patricia

    2010-05-28

    INL's patented, continuous-flow Supercritical/Solid Catalyst (SSC) produces the highest ASTM-quality B-100 biodiesel from waste fats, oils, and greases at the site of waste generation. SSC delivers low-cost transportation fuel, avoids significant landfill costs for municipalities, and reduces potent methane and other emissions produced in landfills from these wastes. You can learn more about INL's energy research programs at http://www.facebook.com/idahonationallaboratory.

  15. Regulatory Issues and Challenges in Developing Seismic Source Characterizations for New Nuclear Power Plant Applications in the US

    NASA Astrophysics Data System (ADS)

    Fuller, C. W.; Unruh, J.; Lindvall, S.; Lettis, W.

    2009-05-01

    An integral component of the safety analysis for proposed nuclear power plants within the US is a probabilistic seismic hazard assessment (PSHA). Most applications currently under NRC review followed guidance provided within NRC Regulatory Guide 1.208 (RG 1.208) for developing seismic source characterizations (SSC) for their PSHA. Three key components of RG 1.208 guidance is that applicants should: (1) use existing PSHA models and SSCs accepted by the NRC as SSC as a starting point for their SSCs; (2) evaluate new information and data developed since acceptance of the starting model to determine if the model should be updated; and (3) follow guidelines set forth by the Senior Seismic Hazard Analysis Committee (SSHAC) (NUREG/CR-6372) in developing significant updates (i.e., updates should capture SSC uncertainty through representing the "center, body, and range of technical interpretations" of the informed technical community). Major motivations for following this guidance are to ensure accurate representations of hazard and regulatory stability in hazard estimates for nuclear power plants. All current applications with the NRC have used the EPRI-SOG source characterizations developed in the 1980s as their starting point model, and all applicants have followed RG 1.208 guidance in updating the EPRI- SOG model. However, there has been considerable variability in how applicants have interpreted the guidance, and thus there has been considerable variability in the methodology used in updating the SSCs. Much of the variability can be attributed to how different applicants have interpreted the implications of new data, new interpretations of new and/or old data, and new "opinions" of members of the informed technical community. For example, many applicants and the NRC have wrestled with the challenge of whether or not to update SSCs in light of new opinions or interpretations of older data put forth by one member of the technical community. This challenge has been further complicated by: (1) a given applicant's uncertainty in how to revise the EPRI-SOG model, which was developed using a process similar to that dictated by SSHAC for a level 3 or 4 study, without conducting a resource-intensive SSHAC level 3 or higher study for their respective application; and (2) a lack of guidance from the NRC on acceptable methods of demonstrating that new data, interpretations, and opinions are adequately represented within the EPRI-SOG model. Partly because of these issues, initiative was taken by the nuclear industry, NRC and DOE to develop a new base PSHA model for the central and eastern US. However, this new SSC model will not be completed for several years and does not resolve many of the fundamental regulatory and philosophical issues that have been raised during the current round of applications. To ensure regulatory stability and to provide accurate estimates of hazard for nuclear power plants, a dialog must be started between regulators and industry to resolve these issues. Two key issues that must be discussed are: (1) should new data and new interpretations or opinions of old data be treated differently in updated SSCs, and if so, how?; and (2) how can new data or interpretations developed by a small subset of the technical community be weighed against and potentially combined with a SSC model that was originally developed to capture the "center, body and range" of the technical community?

  16. Nondestructive evaluation of soluble solid content in strawberry by near infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Guo, Zhiming; Huang, Wenqian; Chen, Liping; Wang, Xiu; Peng, Yankun

    This paper indicates the feasibility to use near infrared (NIR) spectroscopy combined with synergy interval partial least squares (siPLS) algorithms as a rapid nondestructive method to estimate the soluble solid content (SSC) in strawberry. Spectral preprocessing methods were optimized selected by cross-validation in the model calibration. Partial least squares (PLS) algorithm was conducted on the calibration of regression model. The performance of the final model was back-evaluated according to root mean square error of calibration (RMSEC) and correlation coefficient (R2 c) in calibration set, and tested by mean square error of prediction (RMSEP) and correlation coefficient (R2 p) in prediction set. The optimal siPLS model was obtained with after first derivation spectra preprocessing. The measurement results of best model were achieved as follow: RMSEC = 0.2259, R2 c = 0.9590 in the calibration set; and RMSEP = 0.2892, R2 p = 0.9390 in the prediction set. This work demonstrated that NIR spectroscopy and siPLS with efficient spectral preprocessing is a useful tool for nondestructively evaluation SSC in strawberry.

  17. Best practices: Strategic stigma change (SSC): five principles for social marketing campaigns to reduce stigma.

    PubMed

    Corrigan, Patrick W

    2011-08-01

    This column describes strategic stigma change (SSC), which comprises five principles and corresponding practices developed as a best practice to erase prejudice and discrimination associated with mental illness and promote affirming behaviors and social inclusion. SSC principles represent more than ten years of insights from the National Consortium on Stigma and Empowerment. The principles, which are centered on consumer contact that is targeted, local, credible, and continuous, were developed to inform the growth of large-scale social marketing campaigns supported by governments and nongovernmental organizations. Future social marketing efforts to address stigma and the need for evidence to determine SSC's penetration and impact are also discussed.

  18. Fuel cell catalyst layers containing short-side-chain perfluorosulfonic acid ionomers

    NASA Astrophysics Data System (ADS)

    Peron, Jennifer; Edwards, Dave; Haldane, Mark; Luo, Xiaoyan; Zhang, Yongming; Holdcroft, Steven; Shi, Zhiqing

    Porous catalyst layers (CLs) containing short-side-chain (SSC) perfluorosulfonic acid (PFSA) ionomers of different ion exchange capacity (IEC: 1.3, 1.4 and 1.5 meq g -1) were deposited onto Nafion 211 to form catalyst-coated membranes. The porosity of SSC-PFSA-based CLs is larger than Nafion-CL analogues. CLs incorporating SSC ionomer extend the current density of fuel cell polarization curves at elevated temperature and lower relative humidity compared to those based on long-side chain PFSA (e.g., Nafion)-based CLs. Fuel cell polarization performance was greatly improved at 110 °C and 30% relative humidity (RH) when SSC PFSI was incorporated into the catalyst layer.

  19. On a self-consistent representation of earth models, with an application to the computing of internal flattening

    NASA Astrophysics Data System (ADS)

    Denis, C.; Ibrahim, A.

    Self-consistent parametric earth models are discussed in terms of a flexible numerical code. The density profile of each layer is represented as a polynomial, and figures of gravity, mass, mean density, hydrostatic pressure, and moment of inertia are derived. The polynomial representation also allows computation of the first order flattening of the internal strata of some models, using a Gauss-Legendre quadrature with a rapidly converging iteration technique. Agreement with measured geophysical data is obtained, and algorithm for estimation of the geometric flattening for any equidense surface identified by its fractional radius is developed. The program can also be applied in studies of planetary and stellar models.

  20. Solvent effects in time-dependent self-consistent field methods. I. Optical response calculations

    DOE PAGES

    Bjorgaard, J. A.; Kuzmenko, V.; Velizhanin, K. A.; ...

    2015-01-22

    In this study, we implement and examine three excited state solvent models in time-dependent self-consistent field methods using a consistent formalism which unambiguously shows their relationship. These are the linear response, state specific, and vertical excitation solvent models. Their effects on energies calculated with the equivalent of COSMO/CIS/AM1 are given for a set of test molecules with varying excited state charge transfer character. The resulting solvent effects are explained qualitatively using a dipole approximation. It is shown that the fundamental differences between these solvent models are reflected by the character of the calculated excitations.

  1. [Nutritional evaluation and physical functional ability in scleroderma patients].

    PubMed

    Azevedo, Valderilio Feijó; Müller, Carolina de Souza; Rinaldi, Luciane; Bredt, Murilo Cézar; Giovanni, Karizianni; Pereira, Marcela Abou Chami; Volaco, Fernanda Copabianco

    2009-01-01

    Systemic Sclerosis (SSc) is an inflammatory disease that decreases functional capacity through muscular atrophy, skin sclerosis and loss of joint function. Scleroderma patients suffer from movement's restriction. In addition, the disease affects the nutritional status, compromising the quality of life in varying degrees. The gastrointestinal involvement appears to be the main responsible for the nutritional impairment. To evaluate the physical and nutritional status of patients with SSc. We conducted a cross-sectional and descriptive study in 20 patients with SSc. All patients were evaluated in Physioteraphy Clinic of the Catholic University of Paraná, from July 2003 to April 2004. The evaluation was performed by Bioimpedance Body (BIA), the questionnaires Nutritional Risk Assessment (Determine), Mini Nutritional Assessment of Aging and Health Assessment Questionnaire (HAQ) and Visual Analogue Scale (VAS) for pain. The work muscle ability was assessed by measuring the peak torque of flexor and extensor muscles of the elbow in the isokinetic dynamometer Cybex Norm model 7000. We have calculated the mean and standard deviation for each variable analyzed, in addition to the percentage of peak torque deficit. The values of the VAS ranged from zero to 97.8 mm (mean: 48.9 +/- 32.9 mm). The HAQ scores ranged from zero to 2.75 (average: 0.95 +/- 0.8). The average BMI was 22.4 +/- 3.9 kg / m2. The average deficit of mass was: 1.3 +/- 2.1 kg. Ten patients had high nutritional risk. 1 patient was malnourished and 15 were at high risk for malnutrition. The average peak torque to the muscle groups of elbows was 19.2 +/- 5 N / m to the flexor and 21.9 +/-6.6 N/m for the extensors, with an average deficit of 17% and 13% for the both groups. We found that SSc patients were in poor nutritional status and had decreased functional and physical capacity by the weakening of the muscles of the elbow demonstrated by the isokinetic evaluation. We concluded that our SSc patients were at high risk for malnutrition and this may indicate that scleroderma patients need a better nutritional orientation. We do consider that SSc patients also must be included in physical activity programs in order to achieve better physical performance.

  2. [Fertility preservation in boys: spermatogonial stem cell transplantation and testicular grafting].

    PubMed

    Goossens, E; Tournaye, H

    2013-09-01

    Spermatogonial stem cells (SSC) are the founder cells of spermatogenesis and are responsible for the lifelong production of spermatozoa. The cryopreservation and transplantation of these cells has been proposed as a fertility preservation strategy for young boys at risk for stem cell loss, i.e. patients undergoing chemotherapy for cancer or as a conditioning treatment for bone marrow transplantation. To prevent lifelong sterility in boys, two fertility restoration strategies are being developed: the injection of SSC and the grafting of testicular tissue containing SSC. Depending on the disease of the patient one of these two approaches will be applicable. Grafting has the advantage that SSC can reside within their natural niche, preserving the interactions between germ cells and their supporting cells and may therefore be regarded as the first choice strategy. However, in cases where the risk for malignant contamination of the testicular tissue is real, e.g. leukemia, transplantation of SSC by injection is preferable over grafting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  3. The Primary Care Physician in the Early Diagnosis of Systemic Sclerosis: the Cornerstone of Recognition and Hope

    PubMed Central

    Saketkoo, Lesley Ann; Magnus, Jeanette H.; Doyle, Mittie K.

    2013-01-01

    Systemic sclerosis (SSc) is a disease of unknown etiology that manifests as a heterogeneous group of multi-organ system manifestations and is characterized by vasculopathy and fibrosis of the skin and internal organs, with mortality related to pulmonary, cardiac, renal or gastrointestinal involvement. The prevalence of SSc may be underestimated in the general population. Cases are often undiagnosed or misdiagnosed, particularly cases with mild or no skin manifestations. Due to late referrals to rheumatologic care, many moderate-to-severe cases progress to irreversible end-organ damage that might have been prevented by early diagnosis. Early diagnosis of SSc with initiation of appropriate treatment is essential, with great impact on morbidity and mortality. This review examines presenting features, ensuing complications and treatment providing a focus on SSc as a treatable disease. Primary care providers play a pivotal role in recognizing initial symptoms associated with SSc and securing early diagnosis through early referral to specialists. PMID:24366221

  4. Nondestructive quantification of the soluble-solids content and the available acidity of apples by Fourier-transform near-infrared spectroscopy

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

    Ying Yibin; Liu Yande; Tao Yang

    2005-09-01

    This research evaluated the feasibility of using Fourier-transform near-infrared (FT-NIR) spectroscopy to quantify the soluble-solids content (SSC) and the available acidity (VA) in intact apples. Partial least-squares calibration models, obtained from several preprocessing techniques (smoothing, derivative, etc.) in several wave-number ranges were compared. The best models were obtained with the high coefficient determination (r{sup 2}) 0.940 for the SSC and a moderate r{sup 2} of 0.801 for the VA, root-mean-square errors of prediction of 0.272% and 0.053%, and root-mean-square errors of calibration of 0.261% and 0.046%, respectively. The results indicate that the FT-NIR spectroscopy yields good predictions of the SSCmore » and also showed the feasibility of using it to predict the VA of apples.« less

  5. Standardized Verification, Validation, and Accreditation (VV&A) Documentation Schema Description Document

    DTIC Science & Technology

    2008-10-31

    SSC Charleston; Mr. David Broyles, SSC Charleston; Dr. Richard Daehler-Wilking, SSC Charleston; Ms. Marcy Stutzman, Northrop Grumman ; and Tammie...PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 hour per response, including...1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188) Washington DC 20503. 1 . AGENCY

  6. Ship to Shore Connector Amphibious Craft (SSC)

    DTIC Science & Technology

    2015-12-01

    M2 .50 Caliber (12.7mm) Machine Gun ...MK19 40mm Grenade Machine Gun and M60/M240 Series 7.62mm Light Machine Gun . TBD The SSC shall provide protection to the crew and internally... Machine Gun , MK19 40mm Grenade Machine Gun and M60/M240 Series 7.62mm Light Machine Gun . Survivability (Sea-Worthiness) T=O The SSC shall be

  7. Rapid, noninvasive quantitation of skin disease in systemic sclerosis using optical coherence elastography

    NASA Astrophysics Data System (ADS)

    Du, Yong; Liu, Chih-Hao; Lei, Ling; Singh, Manmohan; Li, Jiasong; Hicks, M. John; Larin, Kirill V.; Mohan, Chandra

    2016-04-01

    Systemic sclerosis (SSc) is a connective tissue disease that results in excessive accumulation of collagen in the skin and internal organs. Overall, SSc has a rare morbidity (276 cases per million adults in the United States), but has a 10-year survival rate of 55%. Currently, the modified Rodnan skin score (mRSS) is assessed by palpation on 17 sites on the body. However, the mRSS assessed score is subjective and may be influenced by the experience of the rheumatologists. In addition, the inherent elasticity of skin may bias the mRSS assessment in the early stage of SSc, such as oedematous. Optical coherence elastography (OCE) is a rapidly emerging technique, which can assess mechanical contrast in tissues with micrometer spatial resolution. In this work, the OCE technique is applied to assess the mechanical properties of skin in both control and bleomycin (BLM) induced SSc-like disease noninvasively. Young's modulus of the BLM-SSc skin was found be significantly higher than that of normal skin, in both the in vivo and in vitro studies (p<0.05). Thus, OCE is able to differentiate healthy and fibrotic skin using mechanical contrast. It is a promising new technology for quantifying skin involvement in SSc in a rapid, unbiased, and noninvasive manner.

  8. Spermatogonial stem cells: Current biotechnological advances in reproduction and regenerative medicine.

    PubMed

    Aponte, Pedro Manuel

    2015-05-26

    Spermatogonial stem cells (SSCs) are the germ stem cells of the seminiferous epithelium in the testis. Through the process of spermatogenesis, they produce sperm while concomitantly keeping their cellular pool constant through self-renewal. SSC biology offers important applications for animal reproduction and overcoming human disease through regenerative therapies. To this end, several techniques involving SSCs have been developed and will be covered in this article. SSCs convey genetic information to the next generation, a property that can be exploited for gene targeting. Additionally, SSCs can be induced to become embryonic stem cell-like pluripotent cells in vitro. Updates on SSC transplantation techniques with related applications, such as fertility restoration and preservation of endangered species, are also covered on this article. SSC suspensions can be transplanted to the testis of an animal and this has given the basis for SSC functional assays. This procedure has proven technically demanding in large animals and men. In parallel, testis tissue xenografting, another transplantation technique, was developed and resulted in sperm production in testis explants grafted into ectopical locations in foreign species. Since SSC culture holds a pivotal role in SSC biotechnologies, current advances are overviewed. Finally, spermatogenesis in vitro, already demonstrated in mice, offers great promises to cope with reproductive issues in the farm animal industry and human clinical applications.

  9. What tests should you use to assess small intestinal bacterial overgrowth in systemic sclerosis?

    PubMed

    Braun-Moscovici, Yolanda; Braun, Marius; Khanna, Dinesh; Balbir-Gurman, Alexandra; Furst, Daniel E

    2015-01-01

    Small intestinal bacterial overgrowth (SIBO) plays a major role in the pathogenesis of malabsorption in SSc patients and is a source of great morbidity and even mortality, in those patients. This manuscript reviews which tests are valid and should be used in SSc when evaluating SIBO. We performed systematic literature searches in PubMed, Embase and the Cochrane library from 1966 up to November 2014 for English language, published articles examining bacterial overgrowth in SSc (e.g. malabsorption tests, breath tests, xylose test, etc). Articles obtained from these searches were reviewed for additional references. The validity of the tests was evaluated according to the OMERACT principles of truth, discrimination and feasibility. From a total of 65 titles, 22 articles were reviewed and 20 were ultimately extracted to examine the validity of tests for GI morphology, bacterial overgrowth and malabsorption in SSc. Only 1 test (hydrogen and methane breath tests) is fully validated. Four tests are partially validated, including jejunal cultures, xylose, lactulose tests, and 72 hours fecal fat test. Only 1 of a total of 5 GI tests of bacterial overgrowth (see above) is fully validated in SSc. For clinical trials, fully validated tests are preferred, although some investigators use partially validated tests (4 tests). Further validation of GI tests in SSc is needed.

  10. Genome-wide scan reveals LEMD3 and WIF1 on SSC5 as the candidates for porcine ear size.

    PubMed

    Zhang, Longchao; Liang, Jing; Luo, Weizhen; Liu, Xin; Yan, Hua; Zhao, Kebin; Shi, Huibi; Zhang, Yuebo; Wang, Ligang; Wang, Lixian

    2014-01-01

    The quantitative trait loci (QTL) for porcine ear size was previously reported to mainly focus on SSC5 and SSC7. Recently, a missense mutation, G32E, in PPARD in the QTL interval on SSC7 was identified as the causative mutation for ear size. However, on account of the large interval of QTL, the responsible gene on SSC5 has not been identified. In this study, an intercross population was constructed from the large-eared Minzhu, an indigenous Chinese pig breed, and the Western commercial Large White pig to examine the genetic basis of ear size diversity. A GWAS was performed to detect SNPs significantly associated with ear size. Thirty-five significant SNPs defined a 10.78-Mb (30.14-40.92 Mb) region on SSC5. Further, combining linkage disequilibrium and haplotype sharing analysis, a reduced region of 3.07-Mb was obtained. Finally, by using a selective sweep analysis, a critical region of about 450-kb interval containing two annotated genes LEMD3 and WIF1 was refined in this work. Functional analysis indicated that both represent biological candidates for porcine ear size, with potential application in breeding programs. The two genes could also be used as novel references for further study of the mechanism underlying human microtia.

  11. Proinflammatory Effects of Diesel Exhaust Nanoparticles on Scleroderma Skin Cells

    PubMed Central

    Mastrofrancesco, A.; Alfè, M.; Rosato, E.; Gargiulo, V.; Beatrice, C.; Di Blasio, G.; Zhang, B.; Su, D. S.; Picardo, M.; Fiorito, S.

    2014-01-01

    Autoimmune diseases are complex disorders of unknown etiology thought to result from interactions between genetic and environmental factors. We aimed to verify whether environmental pollution from diesel engine exhaust nanoparticulate (DEP) of actually operating vehicles could play a role in the development of a rare immune-mediated disease, systemic sclerosis (SSc), in which the pathogenetic role of environment has been highlighted. The effects of carbon-based nanoparticulate collected at the exhaust of newer (Euro 5) and older (Euro 4) diesel engines on SSc skin keratinocytes and fibroblasts were evaluated in vitro by assessing the mRNA expression of inflammatory cytokines (IL-1α, IL-6, IL-8, and TNF-α) and fibroblast chemical mediators (metalloproteases 2, 3, 7, 9, and 12; collagen types I and III; VEGF). DEP was shown to stimulate cytokine gene expression at a higher extent in SSc keratinocytes versus normal cells. Moreover, the mRNA gene expression of all MMPs, collagen types, and VEGF genes was significantly higher in untreated SSc fibroblasts versus controls. Euro 5 particle exposure increased the mRNA expression of MMP-2, -7, and -9 in SSc fibroblasts in a dose dependent manner and only at the highest concentration in normal cells. We suggest that environmental DEP could trigger the development of SSc acting on genetically hyperreactive cell systems. PMID:24982919

  12. Role of the testis interstitial compartment in spermatogonial stem cell function

    PubMed Central

    Potter, Sarah J.; DeFalco, Tony

    2017-01-01

    Male fertility is maintained through intricate cellular and molecular interactions that ensure spermatogonial stem cells (SSCs) proceed in a step-wise differentiation process through spermatogenesis and spermiogenesis to produce sperm. SSCs lie within the seminiferous tubule compartment, which provides a nurturing environment for the development of sperm. Cells outside of the tubules, such as interstitial and peritubular cells, also help direct SSC activity. This review focuses on interstitial (interstitial macrophages, Leydig cells, and vasculature) and peritubular (peritubular macrophages, peritubular myoid cells) cells and their role in regulating SSC self-renewal and differentiation in mammals. Leydig cells, the major steroidogenic cells in the testis, influence SSCs through secreted factors, such as insulin growth factor 1 (IGF1) and colony stimulating factor 1 (CSF1). Macrophages interact with SSCs through various potential mechanisms, such as CSF1 and retinoic acid (RA), to induce proliferation or differentiation of SSCs, respectively. Vasculature influences SSC dynamics through CSF1, vascular endothelial growth factor (VEGF), and regulating oxygen levels. Lastly, peritubular myoid cells produce one of the most well-known factors that is required for SSC self-renewal, glial cell line derived neurotrophic factor (GDNF), as well as CSF1. Overall, SSC interactions with interstitial and peritubular cells are critical for SSC function and are an important underlying factor promoting male fertility. PMID:28115580

  13. A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

    PubMed Central

    Martin, Jose-Ezequiel; Assassi, Shervin; Diaz-Gallo, Lina-Marcela; Broen, Jasper C.; Simeon, Carmen P.; Castellvi, Ivan; Vicente-Rabaneda, Esther; Fonollosa, Vicente; Ortego-Centeno, Norberto; González-Gay, Miguel A.; Espinosa, Gerard; Carreira, Patricia; Camps, Mayte; Sabio, Jose M.; D'alfonso, Sandra; Vonk, Madelon C.; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Kreuter, Alexander; Witte, Torsten; Riemekasten, Gabriella; Hunzelmann, Nicolas; Airo, Paolo; Beretta, Lorenzo; Scorza, Raffaella; Lunardi, Claudio; Van Laar, Jacob; Chee, Meng May; Worthington, Jane; Herrick, Arianne; Denton, Christopher; Fonseca, Carmen; Tan, Filemon K.; Arnett, Frank; Zhou, Xiaodong; Reveille, John D.; Gorlova, Olga; Koeleman, Bobby P.C.; Radstake, Timothy R.D.J.; Vyse, Timothy; Mayes, Maureen D.; Alarcón-Riquelme, Marta E.; Martin, Javier

    2013-01-01

    Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10−11, OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10−11, OR = 1.20) and JAZF1 (P = 1.11 × 10−8, OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity. PMID:23740937

  14. Association between nailfold capillaroscopy findings and pulmonary function tests in patients with systemic sclerosis.

    PubMed

    Castellví, Ivan; Simeón-Aznar, Carmen Pilar; Sarmiento, Mónica; Fortuna, Ana; Mayos, Mercedes; Geli, Carme; Diaz-Torné, César; Moya, Patricia; De Llobet, Josep Maria; Casademont, Jordi

    2015-02-01

    To determine whether there is an association between different capillaroscopic findings and pulmonary function tests in systemic sclerosis (SSc). We did a retrospective observational study in a cohort of patients with SSc and early SSc. Patients with at least 1 nailfold videocapillaroscopy (NVC) magnified 120× were included. Pathological findings were giant capillaries, angiogenesis, and density loss. Findings were compared with lung function values: percent expected value of forced vital capacity (FVC), DLCO, and FVC/DLCO ratio. Other variables collected were sex and SSc type, and the presence of digital ulcers (DU), interstitial lung disease (ILD), scleroderma renal crisis, and/or pulmonary hypertension (PH). Of 136 patients with SSc, 85 had undergone an NVC. The frequency of ILD, DU, and PH was 24.1%, 28.7%, and 17.2%, respectively. Data analysis showed that patients with density loss had worse FVC% (86.91 ± 19.42 vs 101.13 ± 16.06, p < 0.01) and DLCO% (71.43 ± 21.19 vs 85.9 ± 19.81, p < 0.01) compared to those without. Patients with loss of density present worse FVC and DLCO values. Prospective studies are warranted to determine whether NVC is useful for studying pulmonary function in SSc.

  15. Improved compliance with the World Health Organization Surgical Safety Checklist is associated with reduced surgical specimen labelling errors.

    PubMed

    Martis, Walston R; Hannam, Jacqueline A; Lee, Tracey; Merry, Alan F; Mitchell, Simon J

    2016-09-09

    A new approach to administering the surgical safety checklist (SSC) at our institution using wall-mounted charts for each SSC domain coupled with migrated leadership among operating room (OR) sub-teams, led to improved compliance with the Sign Out domain. Since surgical specimens are reviewed at Sign Out, we aimed to quantify any related change in surgical specimen labelling errors. Prospectively maintained error logs for surgical specimens sent to pathology were examined for the six months before and after introduction of the new SSC administration paradigm. We recorded errors made in the labelling or completion of the specimen pot and on the specimen laboratory request form. Total error rates were calculated from the number of errors divided by total number of specimens. Rates from the two periods were compared using a chi square test. There were 19 errors in 4,760 specimens (rate 3.99/1,000) and eight errors in 5,065 specimens (rate 1.58/1,000) before and after the change in SSC administration paradigm (P=0.0225). Improved compliance with administering the Sign Out domain of the SSC can reduce surgical specimen errors. This finding provides further evidence that OR teams should optimise compliance with the SSC.

  16. A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.

    PubMed

    Martin, Jose-Ezequiel; Assassi, Shervin; Diaz-Gallo, Lina-Marcela; Broen, Jasper C; Simeon, Carmen P; Castellvi, Ivan; Vicente-Rabaneda, Esther; Fonollosa, Vicente; Ortego-Centeno, Norberto; González-Gay, Miguel A; Espinosa, Gerard; Carreira, Patricia; Camps, Mayte; Sabio, Jose M; D'alfonso, Sandra; Vonk, Madelon C; Voskuyl, Alexandre E; Schuerwegh, Annemie J; Kreuter, Alexander; Witte, Torsten; Riemekasten, Gabriella; Hunzelmann, Nicolas; Airo, Paolo; Beretta, Lorenzo; Scorza, Raffaella; Lunardi, Claudio; Van Laar, Jacob; Chee, Meng May; Worthington, Jane; Herrick, Arianne; Denton, Christopher; Fonseca, Carmen; Tan, Filemon K; Arnett, Frank; Zhou, Xiaodong; Reveille, John D; Gorlova, Olga; Koeleman, Bobby P C; Radstake, Timothy R D J; Vyse, Timothy; Mayes, Maureen D; Alarcón-Riquelme, Marta E; Martin, Javier

    2013-10-01

    Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21,109 (6835 cases and 14,274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10(-11), OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10(-11), OR = 1.20) and JAZF1 (P = 1.11 × 10(-8), OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.

  17. Early sign of microangiopathy in systemic sclerosis: The significance of cold stress test in dynamic laser Doppler flowmetry.

    PubMed

    Yu, Sebastian; Hu, Stephen Chu-Sung; Yu, Hsin-Su; Chin, Yi-Ying; Cheng, Yang-Chun; Lee, Chih-Hung

    2018-06-05

    Skin physiology measurement is receiving more attention for detecting vasculopathy in systemic sclerosis (SSc). Laser Doppler flowmetry (LDF) is a widely used physiological measurement to assess cutaneous microcirculation. However, findings of LDF may be normal during early stage of microangiopathy in SSc. We hypothesized that cold stress test combined with LDF could detect early-stage microangiopathy in patients with SSc. A 67-year-old male came with multiple ulcerations on his fingers for one year. After excluding diseases such as diabetes mellitus-related peripheral arterial occlusive disease and smoking-related Buerger's disease, the diagnosis of SSc was made according to the 2013 ACR/EULAR criteria. We performed LDF and angiography for a patient with SSc and compared the results. Although occlusions of right ulnar and digital arteries were obvious in angiography, the baseline skin temperature and perfusion unit on right fingers remained within normal limits. While the microcirculatory abnormalities measured by LDF alone are subtle, LDF combined with cold stress test detected a significant slow recovery of skin blood flow 40 minutes after cold immersion. In conclusion, there may be discordance between macrovasculopathy and baseline microcirculatory blood flow in SSc. In such a case, cold immersion test is essential to measure the dynamic change and slow recovery of blood flow.

  18. Phenotypic Alterations Involved in CD8+ Treg Impairment in Systemic Sclerosis

    PubMed Central

    Negrini, Simone; Fenoglio, Daniela; Parodi, Alessia; Kalli, Francesca; Battaglia, Florinda; Nasi, Giorgia; Curto, Monica; Tardito, Samuele; Ferrera, Francesca; Filaci, Gilberto

    2017-01-01

    Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis, vasculopathy, and autoimmunity. Although the exact pathogenetic mechanisms behind SSc remain to be fully elucidated, a great deal of evidence suggests the existence of an unbalanced ratio between the effector and regulatory arms of the immune system. With regard to the T regulatory (Treg) compartment, we observed that CD8+ Treg subsets display functional defects in SSc-affected patients. Since CD127 down-modulation and CD39 upregulation have been observed on Treg subsets, the phenotypic expression of these molecules was analyzed on the CD8+CD28− Treg precursors and on CD8+ Treg cells generated in vitro through interleukin-10 commitment. Immunophenotypic data from SSc patients were compared to those obtained from healthy subjects. The analyses performed on ex vivo-isolated CD8+CD28− Treg precursors did not show any significant differences in CD39 or CD127 expression as compared to values obtained from healthy donors. On the contrary, in vitro-generated CD8+ Tregs obtained from SSc patients displayed reduced expression of the CD39 molecule as compared to controls. Moreover, the percentage of CD127+ cells was significantly higher in in vitro-generated CD8+ Tregs from SSc patients compared to CD8+ Tregs obtained from healthy donors. Taken together, these findings may indicate an impairment of maturation processes affecting CD8+ Treg cells in SSc patients. This impairment of maturation involves phenotypic alterations that are mainly characterized by a deficient CD39 upregulation and a lack of down-modulation of the CD127 molecule. PMID:28154567

  19. There is a need for new systemic sclerosis subset criteria. A content analytic approach.

    PubMed

    Johnson, S R; Soowamber, M L; Fransen, J; Khanna, D; Van Den Hoogen, F; Baron, M; Matucci-Cerinic, M; Denton, C P; Medsger, T A; Carreira, P E; Riemekasten, G; Distler, J; Gabrielli, A; Steen, V; Chung, L; Silver, R; Varga, J; Müller-Ladner, U; Vonk, M C; Walker, U A; Wollheim, F A; Herrick, A; Furst, D E; Czirjak, L; Kowal-Bielecka, O; Del Galdo, F; Cutolo, M; Hunzelmann, N; Murray, C D; Foeldvari, I; Mouthon, L; Damjanov, N; Kahaleh, B; Frech, T; Assassi, S; Saketkoo, L A; Pope, J E

    2018-01-01

    Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets. We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed. Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly). We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies).

  20. Access to care for children and young people diagnosed with localized scleroderma or juvenile SSc in the UK.

    PubMed

    Hawley, Daniel P; Baildam, Eileen M; Amin, Tania S; Cruikshank, Mary K; Davidson, Joyce E; Dixon, Jennifer; Martin, Neil S; Ohlsson, Victoria; Pilkington, Clarissa; Rangaraj, Satyapal; Riley, Philip; Sundaramoorthy, Chitra; Walsh, Jo; Foster, Helen E

    2012-07-01

    To describe pathways of care and referral to paediatric rheumatology from onset of first symptom (noticed by the patient or their family) to diagnosis for children and young people diagnosed with localized scleroderma (LS) or juvenile SSc (jSSc). Retrospective case note audit of patients under paediatric rheumatology care who presented during January 2005-January 2010. Data included disease subtype, sex, age at key points in the referral pathway and health care professional (HCP) contact. All patient and HCP data were pseudo-anonymized in accordance with good clinical practice. Data were from eight UK centres that saw 89 cases: 62 females, 26 males; 73 LS, 16 jSSc. Median time from first symptom to first HCP review was 4 (range 0-72) months (LS) and 1 (range 0-50) month (jSSc). Median time from first symptom to paediatric rheumatology review was 15 (range 1-103) months (LS) and 7 (range 0-50) months (jSSc). Median time from first HCP review to first paediatric rheumatology review was 11 (range 0-103) months (LS) and 2 (range 0-10) months. First HCP seen (74%) was usually a general practitioner. The referring HCP to paediatric rheumatology was usually a dermatologist (56%) for LS. Median time from first symptom to diagnosis was 13 (range 1-102) months (LS) and 8 (range 1-50) months (jSSc). A prolonged interval occurs from first symptom to definitive diagnosis, which may adversely affect outcome. There is a need to raise awareness of this rare diagnosis and facilitate earlier recognition.

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