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.

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.

(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.

Fertility and pregnancy outcome in women with systemic sclerosis.

PubMed

Steen, V D; Medsger, T A

1999-04-01

To determine fertility and pregnancy outcome in women with systemic sclerosis (SSc; scleroderma) who had disease onset before age 45 years. All living women with scleroderma who had first been evaluated at the University of Pittsburgh Scleroderma Clinic after January 1, 1972 were sent a detailed self-administered questionnaire in 1986 specifically concerning pregnancy outcomes and infertility. This group was compared with 2 race- and age-matched control groups, one comprising women with rheumatoid arthritis (RA) and one comprising healthy neighborhood women identified by random-digit dialing. We determined the number, history, treatment, and outcome of women who either had never been pregnant or had attempted to become pregnant unsuccessfully for more than 1 year. We also obtained data regarding pregnancy outcomes, including the frequency of miscarriage, premature births, small full-term infants, perinatal deaths, and births of live healthy infants. The study group comprised 214 women with SSc, 167 with RA, and 105 neighborhood controls. There were no significant differences in the overall rates of miscarriage, premature births, small full-term births, or neonatal deaths between the 3 groups. Women with SSc were more likely than those without SSc to have adverse outcomes of pregnancy after the onset of their rheumatic disease, particularly premature births (also seen in RA women after disease onset) and small full-term infants. Although a significantly greater number of women with SSc had never been pregnant, there were no significant differences in the frequency of never having been pregnant or of infertility in the 3 groups after adjustment for contributing factors. This study indicates that women with SSc have acceptable pregnancy outcomes compared with those of women with other rheumatic disease and healthy neighborhood controls. Infertility was not a frequent problem. We believe that there are no excessive pregnancy risks to women with SSc or their infants. However, a well-timed pregnancy with careful obstetric monitoring will maximize the likelihood of a successful outcome.

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.

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.

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.

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

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.

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

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.

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.

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.

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.

Overview of Propellant Delivery Systems at the NASA John C. Stennis Space Center

NASA Technical Reports Server (NTRS)

Haselmaier, L. Haynes; Field, Robert E.; Ryan, Harry M.; Dickey, Jonathan C.

2006-01-01

A wide range of rocket propulsion test work occurs at he 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. One of the greatest challenges associated with operating a test facility is maintaining the health of the primary propellant system and test-critical support systems. The challenge emerges due to the fact that the operating conditions of the various system components are extreme (e.g., low temperatures, high pressures) and due to the fact that many of the components and systems are unique. The purpose of this paper is to briefly describe the experience and modeling techniques that are used to operate the unique test facilities at NASA SSC that continue to support successful propulsion testing.

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.

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.

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.

Super-sample covariance approximations and partial sky coverage

NASA Astrophysics Data System (ADS)

Lacasa, Fabien; Lima, Marcos; Aguena, Michel

2018-04-01

Super-sample covariance (SSC) is the dominant source of statistical error on large scale structure (LSS) observables for both current and future galaxy surveys. In this work, we concentrate on the SSC of cluster counts, also known as sample variance, which is particularly useful for the self-calibration of the cluster observable-mass relation; our approach can similarly be applied to other observables, such as galaxy clustering and lensing shear. We first examined the accuracy of two analytical approximations proposed in the literature for the flat sky limit, finding that they are accurate at the 15% and 30-35% level, respectively, for covariances of counts in the same redshift bin. We then developed a harmonic expansion formalism that allows for the prediction of SSC in an arbitrary survey mask geometry, such as large sky areas of current and future surveys. We show analytically and numerically that this formalism recovers the full sky and flat sky limits present in the literature. We then present an efficient numerical implementation of the formalism, which allows fast and easy runs of covariance predictions when the survey mask is modified. We applied our method to a mask that is broadly similar to the Dark Energy Survey footprint, finding a non-negligible negative cross-z covariance, i.e. redshift bins are anti-correlated. We also examined the case of data removal from holes due to, for example bright stars, quality cuts, or systematic removals, and find that this does not have noticeable effects on the structure of the SSC matrix, only rescaling its amplitude by the effective survey area. These advances enable analytical covariances of LSS observables to be computed for current and future galaxy surveys, which cover large areas of the sky where the flat sky approximation fails.

Does nailfold capillaroscopy help predict future outcomes in systemic sclerosis? A systematic literature review.

PubMed

Paxton, Dolcie; Pauling, John D

2018-02-14

Nailfold capillaroscopy (NC) is an important diagnostic tool in systemic sclerosis (SSc). Confirmation of NC as a prognostic factor could facilitate earlier intervention and slow disease progression in SSc. We undertook a systematic literature review to evaluate the prognostic value of NC in predicting SSc disease progression. Standardised searches of EMBASE and MEDLINE were undertaken to identify longitudinal studies of adult subjects with SSc reporting the prognostic value of NC for any aspect of disease progression and/or survival. Non-English, non-original research, animal studies, non-adult studies and non-full length reports were excluded from the analysis (PROSPERO 2017:CRD42017071719). Wide heterogeneity in study design, prognostic factor measurement and study outcomes necessitated a qualitative data synthesis. The "QUality In Prognosis Studies" (QUIPS) risk-of-bias tool was used to assess study quality. Study selection, data extraction and risk-of-bias assessment were each undertaken independently by 2 reviewers and consensus reached where necessary. Of 942 retrieved articles, 18 studies fulfilled the inclusion criteria. The majority of studies (17/18, 94%) reported positive associations between baseline NC appearances (using a variety of qualitative, semi-quantitative and quantitative NC endpoints) and clinical outcomes including digital ulcer (DU) occurrence/healing, survival, disease progression (using domains of Medsger disease severity scale), calcinosis, skin progression, pulmonary arterial hypertension (PAH), and/or a composite analysis of "cardiovascular events". Application of the QUIPS tool identified a moderate-high risk of potential bias in 6/18 studies for study participation, 3/18 studies for study attrition, 10/18 for prognostic factor measurement, 5/18 for outcome measurement, 13/18 for confounders and 13/18 for statistical analyses. Study quality limited the strength of the conclusions drawn from these studies. The most important source of potential bias across the studies was insufficient adjustment for potential confounders; such as existing DU disease in studies evaluating future DU occurrence. Recent work suggests NC evolution is an important predictor of disease progression in SSc. High levels of potential bias relating to study confounding and statistical analysis make it difficult to draw conclusions regarding the prognostic role of NC in SSc. There is strong evidence supporting an association between NC abnormalities (particularly capillary loss) and disease severity (particularly vascular manifestations such as DU, calcinosis and PAH). Evolution of NC appearances may represent a more important predictor of disease progression which could have important implications for the future use of NC in the routine longitudinal assessment and management of SSc. Copyright © 2018 Elsevier Inc. All rights reserved.

Stennis Space Center Verification & Validation Capabilities

NASA Technical Reports Server (NTRS)

Pagnutti, Mary; Ryan, Robert E.; Holekamp, Kara; ONeal, Duane; Knowlton, Kelly; Ross, Kenton; Blonski, Slawomir

2005-01-01

Scientists within NASA s Applied Sciences Directorate have developed a well-characterized remote sensing Verification & Validation (V&V) site at the John C. Stennis Space Center (SSC). This site enables the in-flight characterization of satellite and airborne high spatial and moderate resolution remote sensing systems and their products. The smaller scale of the newer high resolution remote sensing systems allows scientists to characterize geometric, spatial, and radiometric data properties using a single V&V site. The targets and techniques used to characterize data from these newer systems can differ significantly from the techniques used to characterize data from the earlier, coarser spatial resolution systems. Scientists are also using the SSC V&V site to characterize thermal infrared systems and active lidar systems. SSC employs geodetic targets, edge targets, radiometric tarps, atmospheric monitoring equipment, and thermal calibration ponds to characterize remote sensing data products. The SSC Instrument Validation Lab is a key component of the V&V capability and is used to calibrate field instrumentation and to provide National Institute of Standards and Technology traceability. This poster presents a description of the SSC characterization capabilities and examples of calibration data.

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.

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.

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

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

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.

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

Psychological characteristics of systemic sclerosis patients and their correlation with major organ involvement and disease activity.

PubMed

Golemati, Christina V; Moutsopoulos, Haralampos M; Vlachoyiannopoulos, Panayiotis G

2013-01-01

The aim of this paper is to assess the psychological characteristics of personality, depression, anxiety, social support and coping strategies of systemic sclerosis (SSc) patients, their inter-correlations and their association with clinical symptoms. Patients with SSc (n=85) were interviewed and compared to rheumatoid arthritis (RA) patients (n=120) and healthy controls (HCs [n=125]). Psychological characteristics were assessed by the following psychometric scales: centre of epidemiological studies of depression (CES-D), hospital anxiety and depression scale (HAD), Eysenck personality questionnaire (EPQ), short form of social support (SSq), life experiences survey (LES) and ways of coping (WoC). Clinical data were collected at the same time of the interview. Both control groups were matched to SSc patients in terms of gender, age and educational status. Data were analysed with SPSS software. Compared to control groups, SSc patients expressed more symptoms of depression and anxiety, showed less extraversion and reported more negative life events. They coped less often with positive reappraisal, problem solving, seeking of support and assertiveness, while they sought more often divine help, and they expressed wishing and denial. Inactive disease was associated with a lower probability of reporting depressive symptoms and negative life events and with a higher probability of positively reevaluating a problem. Lung dysfunction, skin involvement, esophageal problems and oral aperture correlated with psychological features. Complications in psychological well-being characterise patients with SSc. This finding, as well as that of psychological characteristics correlating with organic factors, is an indication for designing supportive psycho-educational programmes as complementary therapies.

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.

Suspended sediment propagation in a long river reach: spatial and temporal dynamics of the Suspended Sediment Concentration-Water Discharge diagram for several hydrological events in the Northern French Alps.

NASA Astrophysics Data System (ADS)

Antoine, Germain; Jodeau, Magali; Camenen, Benoit; Esteves, Michel

2014-05-01

The relative propagation of water and suspended sediment is a key parameter to understand the suspended sediment transfers at the catchment scale. Several studies have shown the interest of performing detailed investigations of both temporal suspended sediment concentration (SSC) and water discharge signals. Most of them used temporal data from one measurement site, and classified hydrological events by studying the SSC curve as a function of water discharge (SSC-WD diagrams). Theoretical interpretations of these curves have been used to estimate the different sources of suspended sediment supply from sub-catchments, to evaluate the effect of seasons on the dynamics of suspended sediment, or to highlight the effect of a critical change at the catchment scale. However, few studies have focused on the signal propagation along the river channel. In this study, we analyze sampled data from a very well instrumented river reach in the Northern French Alps: the Arc-Isère River system. This gravel-bed river system is characterized by large concentrations of fines sediments, coming from the highly erodible mountains around. To control the hydraulic, sedimentary and chemical parameters from the catchment head, several gauging stations have been established since 2006. The continuous data measured at 4 gauging stations along 120 km of river have been analyzed to estimate the spatial and temporal dynamics of both SSC and water discharge. More precisely, about 40 major hydrological events have been sampled statistically between 2006 and 2012 from the data set and are analyzed in details. The study shows that the mean value of the propagation velocity is equal to 2 m/s and 3 m/s respectively for the SSC signal and the water discharge. These different propagation velocities imply that the suspended sediment mass is not only transported by the advection of the water at the river scale. The dispersion, erosion or deposition processes, and also the suspended sediment and discharge supply from the intermediate sub-catchments must be considered. Moreover, the SSC-WD diagrams are modified from one measurement site to another along the river. The spatial changes of the SSC-WD diagrams highlight different type of events, from local debris flows to generalized natural floods. A conceptual approach is proposed to better take into account the channel erosion or deposition processes in the analysis of these diagrams.

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.

Effectiveness of add-on therapy with domperidone vs alginic acid in proton pump inhibitor partial response gastro-oesophageal reflux disease in systemic sclerosis: randomized placebo-controlled trial.

PubMed

Foocharoen, Chingching; Chunlertrith, Kitti; Mairiang, Pisaln; Mahakkanukrauh, Ajanee; Suwannaroj, Siraphop; Namvijit, Suwassa; Wantha, Orathai; Nanagara, Ratanavadee

2017-02-01

Twice-daily dosing of proton pump inhibitor (PPI), the standard therapy for gastro-oesophageal reflux disease (GERD), is an effective therapy for GERD in SSc. The aim of this study was to compare the efficacy of omeprazole in combination with domperidone vs in combination with algycon in reducing the severity and frequency of reflux symptoms of PPI partial response (PPI-PR) GERD in SSc. Adult SSc patients having PPI-PR GERD were randomly assigned to receive domperidone plus algycon placebo or algycon plus domperidone placebo in a 1:1 ratio plus omeprazole for 4 weeks. The assessment included severity of symptom grading by visual analogue scale, frequency of symptoms by frequency scale for symptoms of GERD and quality of life (QoL) by EuroQol five-dimensions questionnaire scoring. One hundred and forty-eight SSc-GERD patients were enrolled, of whom 88 had PPI-PR. Eighty cases were randomized for either domperidone (n = 38) or algycon (n = 37) therapy. The majority in both groups had the diffuse SSc subset. At the end of the study, no significant difference in symptom grading was found between groups. After treatment and compared with baseline, the severity of symptoms, frequency scale for symptoms of GERD and QoL significantly improved in both groups. Five (13.2%) and 8 (21.6%) respective cases in the domperidone and algycon groups did not respond. The prevalence of PPI-PR GERD is common. Domperidone and algycon are equally effective treatments in combination with omeprazole. However, ∼17% of patients were non-responsive, so the effectiveness of domperidone, algycon and PPI combination therapy should be further investigated. https://clinicaltrials.gov (NCT01878526). © 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.

Evaluation of measurement uncertainty for purity of a monoterpenic acid by small-scale coulometry

NASA Astrophysics Data System (ADS)

Norte, L. C.; de Carvalho, E. M.; Tappin, M. R. R.; Borges, P. P.

2018-03-01

Purity of the perylic acid (HPe) which is a monoterpenic acid from natural product (NP) with anti-inflammatory and anticancer properties was analyzed by small-scale coulometry (SSC), due to the low availability of HPe on the pharmaceutic market and its high cost. This work aims to present the evaluation of the measurements uncertainty from the purity of HPe by using SSC. Coulometric mean of purity obtained from 5 replicates resulted in 94.23% ± 0.88% (k = 2.06, for an approximately 95% confidence level). These studies aim in the future to develop the production of certified reference materials from NPs.

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

[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.

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.

Development and validation of a scale for mouth handicap in systemic sclerosis: the Mouth Handicap in Systemic Sclerosis scale

PubMed Central

Mouthon, L; Rannou, F; Bérezné, A; Pagnoux, C; Arène, J‐P; Foïs, E; Cabane, J; Guillevin, L; Revel, M; Fermanian, J; Poiraudeau, S

2007-01-01

Objective To develop and assess the reliability and construct validity of a scale assessing disability involving the mouth in systemic sclerosis (SSc). Methods We generated a 34‐item provisional scale from mailed responses of patients (n = 74), expert consensus (n = 10) and literature analysis. A total of 71 other SSc patients were recruited. The test–retest reliability was assessed using the intraclass coefficient correlation and divergent validity using the Spearman correlation coefficient. Factor analysis followed by varimax rotation was performed to assess the factorial structure of the scale. Results The item reduction process retained 12 items with 5 levels of answers (total score range 0–48). The mean total score of the scale was 20.3 (SD 9.7). The test–retest reliability was 0.96. Divergent validity was confirmed for global disability (Health Assessment Questionnaire (HAQ), r = 0.33), hand function (Cochin Hand Function Scale, r = 0.37), inter‐incisor distance (r = −0.34), handicap (McMaster‐Toronto Arthritis questionnaire (MACTAR), r = 0.24), depression (Hospital Anxiety and Depression (HAD); HADd, r = 0.26) and anxiety (HADa, r = 0.17). Factor analysis extracted 3 factors with eigenvalues of 4.26, 1.76 and 1.47, explaining 63% of the variance. These 3 factors could be clinically characterised. The first factor (5 items) represents handicap induced by the reduction in mouth opening, the second (5 items) handicap induced by sicca syndrome and the third (2 items) aesthetic concerns. Conclusion We propose a new scale, the Mouth Handicap in Systemic Sclerosis (MHISS) scale, which has excellent reliability and good construct validity, and assesses specifically disability involving the mouth in patients with SSc. PMID:17502364

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.

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.

Increased risk of mortality in systemic sclerosis-associated digital ulcers: a systematic review and meta-analysis.

PubMed

Meunier, Pauline; Dequidt, Laure; Barnetche, Thomas; Lazaro, Estibaliz; Duffau, Pierre; Richez, Christophe; Couzi, Lionel; Truchetet, Marie-Elise; Seneschal, Julien

2018-06-10

Survival can be threatened in certain forms of systemic sclerosis (SSc) so clear prognostic factors are needed. The aim of this meta-analysis was to assess the association between the presence of digital ulcers (DUs) and mortality in SSc. We performed a systematic review and meta-analysis in the Pubmed and Scopus databases from the earliest records to May 2017. Two research strategies were performed: « systemic sclerosis » and « digital ulcers » (strategy A); « systemic sclerosis » and « mortality » (strategy B). The primary outcome was the mortality associated with the presence of DUs in patients with SSc. The literature search identified 1473 citations. Fifty-nine studies were examined for full text. Ten articles were included for the meta-analysis. SSc patients with DUs had an increased pooled mortality risk: RR = 1.53 (IC 95%: [1.23-1.90]). This meta-analysis revealed a higher mortality in SSc patients with associated DUs. Having DUs may be a predictive factor of developing organ involvement such as pulmonary or cardiovascular events that could be associated with poor survival. It suggests that early screening of DUs in SSc patients is important to identify patients most at risk of poor survival. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Comparison of Self-Efficacy for Managing Chronic Disease between patients with systemic sclerosis and other chronic conditions: a systematic review.

PubMed

Thombs, Brett D; Kwakkenbos, Linda; Riehm, Kira E; Saadat, Nazanin; Fedoruk, Claire

2017-02-01

The complexity and burden of systemic sclerosis (SSc) pose challenges to developing and sustaining disease management self-efficacy. The objective of this systematic review was to compare scores on a commonly used self-efficacy measure, the Self-Efficacy for Managing Chronic Disease (SEMCD) Scale, between SSc and other diseases. Data sources included the CINAHL, EMBASE, MEDLINE, and Scopus databases, searched through January 25, 2016, and reference lists of included articles and relevant reviews. Studies in any language that reported total SEMCD scores or individual item scores in adult non-psychiatric medical patients were eligible. We identified one eligible non-intervention study of SSc patients (n = 553), 13 other non-intervention studies, and 21 studies with pre-intervention data for patients enrolled in a self-management program or a trial of a program. Of 13 non-intervention studies with published total score means in cancer, cardiovascular disease, Parkinson's disease, spinal cord injuries, organ transplant candidates and recipients, dialysis, and lupus, SEMCD scores were statistically significantly lower (poorer self-efficacy) in SSc than 6 other disease samples, not significantly different from 6, and significantly higher than lupus patients. Compared to 18 studies of patients in self-management programs or trials with published total score means, SSc patients were similar or lower than 9 samples and significantly higher than 9 samples. Compared to patients with other diseases not enrolled in programs to improve self-efficacy, SSc patients report lower self-efficacy scores than most patient groups. Rigorously tested self-care interventions designed to meet the unique needs of patients with SSc are needed.

Efficacy of early skin-to-skin contact on the rate of exclusive breastfeeding in term neonates: a randomized controlled trial.

PubMed

Sharma, Amit

2016-09-01

Despite multiple benefits of breast milk, the rates of exclusive breastfeeding in developing countries are low. To evaluate the efficacy of early skin -to -skin contact (SSC) on the rate of exclusive breastfeeding (EBF) at 6 weeks of age among term neonates born by vaginal delivery. Term neonates born by vaginal delivery and did not require any resuscitation were randomized at birth to SSC (n=100) and control (n=100) group. Immediately after clamping the umbilical cord, SSC group neonates were placed on the bare bosom of mother and control group neonates were placed under a radiant warmer for a period of 45 minutes each while mothers underwent management of the third stage of labor and episiotomy repair. Pain experienced by mother during episiotomy repair was recorded using a numerical pain scale The primary outcome evaluated was the rate of exclusive breastfeeding at 6 weeks of postnatal age. A significantly higher proportion of neonates were exclusively breastfeed at 6 weeks of age in the SSC group than in the control group (72% vs. 57.6%, p=0.04, relative risk: 1.3, 95% confidence interval: 1.0 -1.6). The pain score during episiotomy repair in mothers of the SSC group was significantly lower than the control group (4.74±0.85 versus 5.34±0.81; P <0.01). Early SSC significantly improved the rate of exclusively breastfeeding at 6 weeks of age among healthy term neonates. An important additional effect was a decrease in the amount of pain that mothers in the SSC group experienced during episiotomy repair.

Cough is less common and less severe in systemic sclerosis-associated interstitial lung disease compared to other fibrotic interstitial lung diseases.

PubMed

Cheng, Jasmine Z; Wilcox, Pearce G; Glaspole, Ian; Corte, Tamera J; Murphy, Darra; Hague, Cameron J; Ryerson, Christopher J

2017-11-01

The objectives of this study were to determine the prevalence and characteristics of cough in idiopathic pulmonary fibrosis (IPF), chronic hypersensitivity pneumonitis (HP) and systemic sclerosis-associated interstitial lung disease (SSc-ILD). Cough severity was measured in consecutive patients with IPF (n = 77), HP (n = 32) and SSc-ILD (n = 67) using a 10-cm visual analogue scale (VAS). Dyspnoea and quality of life were measured using established questionnaires. Cough severity was compared across ILD subtypes and predictors of cough severity were determined using multivariate analysis. Cough was more common in IPF and chronic HP compared to SSc-ILD (87% and 83% vs 68%, P = 0.02). The median (interquartile range) VAS score was 39 (17-65) in the IPF cohort, 29 (11-48) in HP and 18 (0-33) in SSc-ILD (P < 0.0001). Cough was more often productive in chronic HP and IPF (63% and 43% vs 21%, P < 0.001). Cough severity was independently predicted only by ILD diagnosis and higher dyspnoea score. Cough severity was not associated with other common causes of cough. Cough was a significant predictor of quality of life in IPF and SSc-ILD with adjustment for age, sex, dyspnoea and ILD severity; however, cough was not associated with quality of life in chronic HP. Cough is more frequent, more severe and more often productive in IPF and chronic HP compared to SSc-ILD, despite similar ILD severity in these cohorts. Cough severity is strongly and independently associated with dyspnoea and pulmonary function, and is a significant contributor to reduced quality of life in both IPF and SSc-ILD. © 2017 Asian Pacific Society of Respirology.

FAD: A full-acceptance detector for physics at the SSC

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

Bjorken, J.D.

1992-09-01

For high energy pp collisions, the concepts 4{pi}'' and full acceptance'' are distinct. At the SSC, the appropriate variables for describing phase space are the lego variables: pseudorapidity {eta} and azimuthal angle {phi}. While most of 4{pi} is covered by pseudorapidities less than 3 or 4 in magnitude, at the SSC there is very interesting physics out to {eta}'s of 9 to 12. For over a year I have been attempting to encourage an initiative at the SSC to provide a detector which could cover the missing acceptance of the two big detectors, which in particular have no appreciable chargedmore » particle tracking with good momentum resolution beyond rapidities of 2.5 or so. The nonnegotiable criteria for an FAD are for me the following: 1. All charged particles are seen and their momenta measured well, provided pt is not too large. 2. All photons are seen and their momenta are measured well. 3. The physics of rapidity-gaps is not compromised. This means angular coverage from 90{degrees} down to tens of microradians. The above criteria cannot be met on day one of SSC commissioning with the amount of funds available. But I believe a staged approach is feasible, with a lot of interesting physics available along the way. The basic philosophy underlying the FAD idea is that it should first and most be a survey instrument, sensitive to almost everything, but optimized for almost nothing. Its strength is in the perception of complex patterns individual events, used as a signature of new and/or interesting physics. Examples of such patterns will be given later.« less

FAD: A full-acceptance detector for physics at the SSC

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

Bjorken, J.D.

1992-09-01

For high energy pp collisions, the concepts ``4{pi}`` and ``full acceptance`` are distinct. At the SSC, the appropriate variables for describing phase space are the lego variables: pseudorapidity {eta} and azimuthal angle {phi}. While most of 4{pi} is covered by pseudorapidities less than 3 or 4 in magnitude, at the SSC there is very interesting physics out to {eta}`s of 9 to 12. For over a year I have been attempting to encourage an initiative at the SSC to provide a detector which could cover the missing acceptance of the two big detectors, which in particular have no appreciable chargedmore » particle tracking with good momentum resolution beyond rapidities of 2.5 or so. The nonnegotiable criteria for an FAD are for me the following: 1. All charged particles are seen and their momenta measured well, provided pt is not too large. 2. All photons are seen and their momenta are measured well. 3. The physics of rapidity-gaps is not compromised. This means angular coverage from 90{degrees} down to tens of microradians. The above criteria cannot be met on day one of SSC commissioning with the amount of funds available. But I believe a staged approach is feasible, with a lot of interesting physics available along the way. The basic philosophy underlying the FAD idea is that it should first and most be a survey instrument, sensitive to almost everything, but optimized for almost nothing. Its strength is in the perception of complex patterns individual events, used as a signature of new and/or interesting physics. Examples of such patterns will be given later.« less

Effectiveness and meaningful use of paediatric surgical safety checklists and their implementation strategies: a systematic review with narrative synthesis

PubMed Central

Lagoo, Janaka; Lopushinsky, Steven R; Haynes, Alex B; Bain, Paul; Flageole, Helene; Skarsgard, Erik D; Brindle, Mary E

2017-01-01

Objective To examine the effectiveness and meaningful use of paediatric surgical safety checklists (SSCs) and their implementation strategies through a systematic review with narrative synthesis. Summary background data Since the launch of the WHO SSC, checklists have been integrated into surgical systems worldwide. Information is sparse on how SSCs have been integrated into the paediatric surgical environment. Methods A broad search strategy was created using Pubmed, Embase, CINAHL, Cochrane Central, Web of Science, Science Citation Index and Conference Proceedings Citation Index. Abstracts and full texts were screened independently, in duplicate for inclusion. Extracted study characteristic and outcomes generated themes explored through subgroup analyses and idea webbing. Results 1826 of 1921 studies were excluded after title and abstract review (kappa 0.77) and 47 after full-text review (kappa 0.86). 20 studies were of sufficient quality for narrative synthesis. Clinical outcomes were not affected by SSC introduction in studies without implementation strategies. A comprehensive SSC implementation strategy in developing countries demonstrated improved outcomes in high-risk surgeries. Narrative synthesis suggests that meaningful compliance is inconsistently measured and rarely achieved. Strategies involving feedback improved compliance. Stakeholder-developed implementation strategies, including team-based education, achieved greater acceptance. Three studies suggest that parental involvement in the SSC is valued by parents, nurses and physicians and may improve patient safety. Conclusions A SSC implementation strategy focused on paediatric patients and their families can achieve high acceptability and good compliance. SSCs’ role in improving measures of paediatric surgical outcome is not well established, but they may be effective when used within a comprehensive implementation strategy especially for high-risk patients in low-resource settings. PMID:29042377

Stennis Space Center Verification & Validation Capabilities

NASA Technical Reports Server (NTRS)

Pagnutti, Mary; Ryan, Robert E.; Holekamp, Kara; O'Neal, Duane; Knowlton, Kelly; Ross, Kenton; Blonski, Slawomir

2007-01-01

Scientists within NASA#s Applied Research & Technology Project Office (formerly the Applied Sciences Directorate) have developed a well-characterized remote sensing Verification & Validation (V&V) site at the John C. Stennis Space Center (SSC). This site enables the in-flight characterization of satellite and airborne high spatial resolution remote sensing systems and their products. The smaller scale of the newer high resolution remote sensing systems allows scientists to characterize geometric, spatial, and radiometric data properties using a single V&V site. The targets and techniques used to characterize data from these newer systems can differ significantly from the techniques used to characterize data from the earlier, coarser spatial resolution systems. Scientists have used the SSC V&V site to characterize thermal infrared systems. Enhancements are being considered to characterize active lidar systems. SSC employs geodetic targets, edge targets, radiometric tarps, atmospheric monitoring equipment, and thermal calibration ponds to characterize remote sensing data products. Similar techniques are used to characterize moderate spatial resolution sensing systems at selected nearby locations. The SSC Instrument Validation Lab is a key component of the V&V capability and is used to calibrate field instrumentation and to provide National Institute of Standards and Technology traceability. This poster presents a description of the SSC characterization capabilities and examples of calibration data.

Systemic sclerosis and occupational risk factors: role of solvents and cleaning products.

PubMed

Maître, Anne; Hours, Martine; Bonneterre, Vincent; Arnaud, Joëlle; Arslan, Marie Tülin; Carpentier, Patrick; Bergeret, Alain; de Gaudemaris, Régis

2004-12-01

To analyze occupational and non-occupational exposure factors suspected of being associated with scleroderma (SSc), with a view to inculpating or excluding certain potentially toxic substances (e.g., solvents), thereby contributing to the recognition of such toxins in the field of occupational health. The study comprised 10 men and 83 women diagnosed with SSc between 1995 and 1999 (American College of Rheumatology criteria) and early SSc, and 206 age and sex matched controls. The SSc registry is all-inclusive in the French administrative departments of Isere and Savoie so controls were randomly selected from the general population (using telephone directories) in these departments to ensure full representation. Exposure factors were analyzed for each subject by a personal questionnaire, and an individual evaluation was carried out by an industrial expert. Data were analyzed by conditional logistical regression adjusting for educational level. Construction workers were at significantly higher risk of contracting SSc; odds ratio (OR) = 4.01 (95% confidence interval 1.14-14.09). Analysis by industrial experts identified exposure to certain toxic substances regularly used by these same workers as risk factors for SSc: cleaning products: OR = 1.66 (0.90-3.08) (both sexes) and OR = 1.71 (0.92-3.20) (women only); solvents: OR = 3.23 (1.58-6.63) (both sexes) and OR = 2.80 (1.28-6.11) (women only); synthetic adhesives: OR 25.36 (1.36-472.28) (on 3 exposed cases). Exposure to either cleaning products or solvents emerged as a risk factor for SSc. Exposure factors should be characterized and results of all studies compared to implement appropriate preventive measures in relevant workplaces.

Complete super-sample lensing covariance in the response approach

NASA Astrophysics Data System (ADS)

Barreira, Alexandre; Krause, Elisabeth; Schmidt, Fabian

2018-06-01

We derive the complete super-sample covariance (SSC) of the matter and weak lensing convergence power spectra using the power spectrum response formalism to accurately describe the coupling of super- to sub-survey modes. The SSC term is completely characterized by the survey window function, the nonlinear matter power spectrum and the full first-order nonlinear power spectrum response function, which describes the response to super-survey density and tidal field perturbations. Generalized separate universe simulations can efficiently measure these responses in the nonlinear regime of structure formation, which is necessary for lensing applications. We derive the lensing SSC formulae for two cases: one under the Limber and flat-sky approximations, and a more general one that goes beyond the Limber approximation in the super-survey mode and is valid for curved sky applications. Quantitatively, we find that for sky fractions fsky ≈ 0.3 and a single source redshift at zS=1, the use of the flat-sky and Limber approximation underestimates the total SSC contribution by ≈ 10%. The contribution from super-survey tidal fields to the lensing SSC, which has not been included in cosmological analyses so far, is shown to represent about 5% of the total lensing covariance on multipoles l1,l2 gtrsim 300. The SSC is the dominant off-diagonal contribution to the total lensing covariance, making it appropriate to include these tidal terms and beyond flat-sky/Limber corrections in cosmic shear analyses.

Suspended-sediment loads in the lower Stillaguamish River, Snohomish County, Washington, 2014–15

USGS Publications Warehouse

Anderson, Scott A.; Curran, Christopher A.; Grossman, Eric E.

2017-08-03

Continuous records of discharge and turbidity at a U.S. Geological Survey (USGS) streamgage in the lower Stillaguamish River were paired with discrete measurements of suspended-sediment concentration (SSC) in order to estimate suspended-sediment loads over the water years 2014 and 2015. First, relations between turbidity and SSC were developed and used to translate the continuous turbidity record into a continuous estimate of SSC. Those concentrations were then used to predict suspended-sediment loads based on the current discharge record, reported at daily intervals. Alternative methods were used to in-fill a small number of days with either missing periods of turbidity or discharge records. Uncertainties in our predictions at daily and annual time scales were estimated based on the parameter uncertainties in our turbidity-SSC regressions. Daily loads ranged from as high as 121,000 tons during a large autumn storm to as low as –56 tons, when tidal return flow moved more sediment upstream than river discharge did downstream. Annual suspended-sediment loads for both water years were close to 1.4 ± 0.2 million tons.

Contrastive Numerical Investigations on Thermo-Structural Behaviors in Mass Concrete with Various Cements

PubMed Central

Zhou, Wei; Feng, Chuqiao; Liu, Xinghong; Liu, Shuhua; Zhang, Chao; Yuan, Wei

2016-01-01

This work is a contrastive investigation of numerical simulations to improve the comprehension of thermo-structural coupled phenomena of mass concrete structures during construction. The finite element (FE) analysis of thermo-structural behaviors is used to investigate the applicability of supersulfated cement (SSC) in mass concrete structures. A multi-scale framework based on a homogenization scheme is adopted in the parameter studies to describe the nonlinear concrete behaviors. Based on the experimental data of hydration heat evolution rate and quantity of SSC and fly ash Portland cement, the hydration properties of various cements are studied. Simulations are run on a concrete dam section with a conventional method and a chemo-thermo-mechanical coupled method. The results show that SSC is more suitable for mass concrete structures from the standpoint of temperature control and crack prevention. PMID:28773517

Contrastive Numerical Investigations on Thermo-Structural Behaviors in Mass Concrete with Various Cements.

PubMed

Zhou, Wei; Feng, Chuqiao; Liu, Xinghong; Liu, Shuhua; Zhang, Chao; Yuan, Wei

2016-05-20

This work is a contrastive investigation of numerical simulations to improve the comprehension of thermo-structural coupled phenomena of mass concrete structures during construction. The finite element (FE) analysis of thermo-structural behaviors is used to investigate the applicability of supersulfated cement (SSC) in mass concrete structures. A multi-scale framework based on a homogenization scheme is adopted in the parameter studies to describe the nonlinear concrete behaviors. Based on the experimental data of hydration heat evolution rate and quantity of SSC and fly ash Portland cement, the hydration properties of various cements are studied. Simulations are run on a concrete dam section with a conventional method and a chemo-thermo-mechanical coupled method. The results show that SSC is more suitable for mass concrete structures from the standpoint of temperature control and crack prevention.

Symptoms of depression and anxiety in Serbian patients with systemic sclerosis: impact of disease severity and socioeconomic factors.

PubMed

Ostojic, Predrag; Zivojinovic, Sladjana; Reza, Tamara; Damjanov, Nemanja

2010-08-01

This study aimed to assess symptoms of depression and anxiety in Serbian patients with systemic sclerosis (SSc) and to estimate the impact of disease severity and socioeconomic factors on development of depression and anxiety in SSc. Thirty-five patients with SSc and 30 age- and gender-matched healthy individuals participated. Symptoms of depression and anxiety were evaluated using the Beck's depression inventory and Zung's anxiety self-assessment scale. We estimated the impact of gender, age, economic status, marital status, disease duration, disease subset (limited or diffuse), and some clinical features on development of depressive symptoms and anxiety in patients with SSc. Symptoms of depression were found in 68.6% of patients (compared with 23.3% in the control group), were more frequent in patients with longer disease duration and in female and older patients, and were more common in unemployed and retired patients than in employed individuals. No differences in anxiety and depressive symptoms was noticed between patients with limited and diffuse SSc or those with or without restrictive lung disease, pulmonary hypertension, finger-tip ulcers, and heart involvement. Symptoms of depression were associated with severe pain. Symptoms of anxiety were found in 80% of patients compared with 13.3% of healthy individuals and were equally as frequent in patients of different gender, age, socioeconomic status, and disease duration and severity. Symptoms of depression and anxiety are common in Serbian patients with SSc. Depressive symptoms depended mostly on socioeconomic factors, disease duration, and pain intensity, whereas disease severity had no significant impact on development of depressive symptoms and anxiety.

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.

Specific oxidative stress parameters differently correlate with nailfold capillaroscopy changes and organ involvement in systemic sclerosis.

PubMed

Riccieri, Valeria; Spadaro, Antonio; Fuksa, Leos; Firuzi, Omidreza; Saso, Luciano; Valesini, Guido

2008-02-01

Oxidative stress is suggested to be involved in the pathogenesis of systemic sclerosis (SSc). The aim of the present study was to clarify such a hypothesis by determination of four different plasmatic parameters of oxidative stress, and to define its role in the microvascular damage, assessed by nailfold capillaroscopy (NC). Plasma samples of 18 patients with SSc were analyzed. The biomarkers measured were: total antioxidant capacity, hydroperoxides (ROOHs), and sulfhydryl (SH) and carbonyl (CO) groups. Each patient had a detailed clinical assessment and underwent an NC. The results showed significantly increased ROOHs in SSc patients compared to control group (5.02 +/- 0.24 vs 3.28 +/- 0.19 micromol/l; p < 0.05). Plasmatic levels of SH groups were significantly lower in SSc (0.466 +/- 0.08 mmol/l) compared to control group (0.542 +/- 0.04 mmol/l; p < 0.002). Plasma levels of ROOHs correlated with the capillaroscopy semiquantitative rating scale score (p < 0.05) and with the rating system for avascular areas (p < 0.03). The levels of CO groups inversely correlated with modified Rodnan's skin score (p < 0.039) and were lower in patients with pulmonary fibrosis (p < 0.045), while the levels of SH groups were lower in those presenting gastrointestinal involvement (p < 0.029). The obtained data indicate augmented free radical-mediated injury in SSc and also show correlations among oxidative abnormalities, some clinical findings, and signs of a more severe microvascular involvement. These results give more evidence to the connection between oxidative impairment and SSc.

Computational Plume Modeling of COnceptual ARES Vehicle Stage Tests

NASA Technical Reports Server (NTRS)

Allgood, Daniel C.; Ahuja, Vineet

2007-01-01

The plume-induced environment of a conceptual ARES V vehicle stage test at the NASA Stennis Space Center (NASA-SSC) was modeled using computational fluid dynamics (CFD). A full-scale multi-element grid was generated for the NASA-SSC B-2 test stand with the ARES V stage being located in a proposed off-center forward position. The plume produced by the ARES V main power plant (cluster of five RS-68 LOX/LH2 engines) was simulated using a multi-element flow solver - CRUNCH. The primary objective of this work was to obtain a fundamental understanding of the ARES V plume and its impingement characteristics on the B-2 flame-deflector. The location, size and shape of the impingement region were quantified along with the un-cooled deflector wall pressures, temperatures and incident heating rates. Issues with the proposed tests were identified and several of these addressed using the CFD methodology. The final results of this modeling effort will provide useful data and boundary conditions in upcoming engineering studies that are directed towards determining the required facility modifications for ensuring safe and reliable stage testing in support of the Constellation Program.

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.

Temporal dynamics of suspended sediment transport in a glacierized Andean basin

NASA Astrophysics Data System (ADS)

Mao, Luca; Carrillo, Ricardo

2017-06-01

Suspended sediment transport can affect water quality and aquatic ecosystems, and its quantification is of the highest importance for river and watershed management. Suspended sediment concentration (SSC) and discharge were measured at two locations in the Estero Morales, a Chilean Andean stream draining a small basin (27 km2) hosting glacierized areas of about 1.8 km2. Approximately half of the suspended sediment yield (470 t year- 1 km- 2) was transported during the snowmelt period and half during glacier melting. The hysteresis patterns between discharge and SSC were calculated for each daily hydrograph and were analysed to shed light on the location and activity of different sediment sources at the basin scale. During snowmelt, an unlimited supply of fine sediments is provided in the lower and middle part of the basin and hysteresis patterns tend to be clockwise as the peaks in SSC precede the peak of discharge in daily hydrographs. Instead, during glacier melting the source of fine sediments is the proglacial area, producing counterclockwise hysteresis. It is suggested that the analysis of hysteretic patterns over time provides a simple concept for interpreting variability of location and activity of sediment sources at the basin scale.

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.

Use of the nominal group technique to identify stakeholder priorities and inform survey development: an example with informal caregivers of people with scleroderma.

PubMed

Rice, Danielle B; Cañedo-Ayala, Mara; Turner, Kimberly A; Gumuchian, Stephanie T; Malcarne, Vanessa L; Hagedoorn, Mariët; Thombs, Brett D

2018-03-02

The nominal group technique (NGT) allows stakeholders to directly generate items for needs assessment surveys. The objective was to demonstrate the use of NGT discussions to develop survey items on (1) challenges experienced by informal caregivers of people living with systemic sclerosis (SSc) and (2) preferences for support services. Three NGT groups were conducted. In each group, participants generated lists of challenges and preferred formats for support services. Participants shared items, and a master list was compiled, then reviewed by participants to remove or merge overlapping items. Once a final list of items was generated, participants independently rated challenges on a scale from 1 (not at all important) to 10 (extremely important) and support services on a scale from 1 (not at all likely to use) to 10 (very likely to use). Lists generated in the NGT discussions were subsequently reviewed and integrated into a single list by research team members. SSc patient conferences held in the USA and Canada. Informal caregivers who previously or currently were providing care for a family member or friend with SSc. A total of six men and seven women participated in the NGT discussions. Mean age was 59.8 years (SD=12.6). Participants provided care for a partner (n=8), parent (n=1), child (n=2) or friend (n=2). A list of 61 unique challenges was generated with challenges related to gaps in information, resources and support needs identified most frequently. A list of 18 unique support services was generated; most involved online or in-person delivery of emotional support and educational material about SSc. The NGT was an efficient method for obtaining survey items directly from SSc caregivers on important challenges and preferences for support services. © 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.

Replacement of Hydrochlorofluorocarbon (HCFC) -225 Solvent for Cleaning and Verification Sampling of NASA Propulsion Oxygen Systems Hardware, Ground Support Equipment, and Associated Test Systems

NASA Technical Reports Server (NTRS)

Burns, H. D.; Mitchell, M. A.; McMillian, J. H.; Farner, B. R.; Harper, S. A.; Peralta, S. F.; Lowrey, N. M.; Ross, H. R.; Juarez, A.

2015-01-01

Since the 1990's, NASA's rocket propulsion test facilities at Marshall Space Flight Center (MSFC) and Stennis Space Center (SSC) have used hydrochlorofluorocarbon-225 (HCFC-225), a Class II ozone-depleting substance, to safety clean and verify the cleanliness of large scale propulsion oxygen systems and associated test facilities. In 2012 through 2014, test laboratories at MSFC, SSC, and Johnson Space Center-White Sands Test Facility collaborated to seek out, test, and qualify an environmentally preferred replacement for HCFC-225. Candidate solvents were selected, a test plan was developed, and the products were tested for materials compatibility, oxygen compatibility, cleaning effectiveness, and suitability for use in cleanliness verification and field cleaning operations. Honewell Soltice (TradeMark) Performance Fluid (trans-1-chloro-3,3, 3-trifluoropropene) was selected to replace HCFC-225 at NASA's MSFC and SSC rocket propulsion test facilities.

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.

Effects of topical application of silver sulfadiazine cream, triple antimicrobial ointment, or hyperosmolar nanoemulsion on wound healing, bacterial load, and exuberant granulation tissue formation in bandaged full-thickness equine skin wounds.

PubMed

Harmon, Caroline C Gillespie; Hawkins, Jan F; Li, Jianming; Connell, Sean; Miller, Margaret; Saenger, Megan; Freeman, Lynetta J

2017-05-01

OBJECTIVE To determine the effects of 3 topically applied treatments (1% silver sulfadiazine cream [SSC], triple antimicrobial ointment [TAO], and hyperosmolar nanoemulsion [HNE]) on microbial counts, exuberant granulation tissue (EGT) development, and reepithelialization of contaminated wounds at the distal aspect of the limbs of horses. ANIMALS 8 healthy adult horses. PROCEDURES A 2.5 × 2.5-cm, full-thickness, cutaneous wound was created at the dorsal aspect of each metacarpus and metatarsus (1 wound/limb/horse), covered with nonadhesive dressing, and bandaged. Wounds were inoculated with bacteria and fungi the next day. Each wound on a given horse was randomly assigned to 1 of 4 treatment groups (SSC, TAO, HNE, or no topical treatment [control]). Bandage changes, culture of wound samples, treatments, photography for wound measurements, and biopsy were performed at predetermined time points. Time (days) until wound closure, number of EGT excisions, microbial counts, and scores for selected histologic characteristics were compared among groups. RESULTS Median time to wound closure for all groups was 42 days. Time to wound closure and histologic characteristics of wound healing did not differ among groups. Least squares mean microbial counts were significantly higher for HNE-treated wounds on days 9 and 21, compared with SSC-treated and TAO-treated wounds, but not controls. Proportions of SSC-treated (7/8) or HNE-treated (5/8) wounds needing EGT excision were significantly greater than that of TAO-treated (1/8) wounds. The proportion of SSC-treated wounds with EGT excision was greater than that of controls (3/8). CONCLUSIONS AND CLINICAL RELEVANCE None of the treatments resulted in more rapid wound closure, compared with that for untreated control wounds under the study conditions. When treatment is warranted, TAO may help to limit EGT formation.

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.

Clinical significance of fibromyalgia syndrome in different rheumatic diseases: Relation to disease activity and quality of life.

PubMed

El-Rabbat M, Sarah; Mahmoud, Nermeen K; Gheita, Tamer A

2017-04-11

To describe the frequencies of fibromyalgia syndrome (FMS) in various rheumatic diseases; rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Behçets disease (BD) patients and to study the relation to clinical manifestations and quality of life (QoL). 160 patients (50 RA, 50 SLE, 30 SSc and 30 BD) and matched corresponding healthy controls were included. Disease activity was assessed using disease activity score in 28 joints (DAS28) for RA, SLE Disease Activity index (SLEDAI), modified Rodnan skin score for SSc and BD Current Activity Form (BDCAF). The QoL was also recorded. Severity in FMS cases was estimated using the revised Fibromyalgia Impact Questionnaire score. In the RA, SLE, SSc and BD patients, FMS was found in 14%, 18%, 6.67% and 3.33% respectively compared to 2.1%, 3%, 3.3% and 0% in their corresponding controls. In RA patients, DAS28 was significantly higher in those with FMS (p=0.009) and significantly correlated with both Widespread Pain Index (WPI) (p=0.011) and Symptom Severity (SS) scale (p=0.012). The QoL scale in those with FMS was significantly worse (62.3±7.9) compared to those without (71.7±14.4) (p=0.023). In SLE patients, The WPI and SS both significantly correlated with the presence of thrombosis (r=0.28, p=0.049 and r=0.43, p=0.002 respectively). The SS scale tended to correlate with the SLEDAI (r=0.28, p=0.05). In BD patients, BDCAF and WPI significantly correlated (p=0.03). Fibromyalgia syndrome is more frequent in rheumatic diseases, could be related to the disease activity in RA and BD patients and to thrombosis in SLE and affected the QoL in RA. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Subscale Diffuser Testing, E-3 produces first steam

NASA Image and Video Library

2007-10-25

Phase 2 of the A-3 Test Facility Subscale Diffuser Risk Mitigation Project at Stennis Space Center reached a milestone Oct. 25 when the E-3 Test Facility produced superheated (500+ degrees) steam for approximately 3 seconds at more than 400 psi. The test team, led by Barry Robinson of NASA's Test Projects Office, followed that success with further tests to lengthen the duration of steam production. On Nov. 1, they were able to maintain a consistent pressure and temperature of steam for 60 seconds. In December, the team began Phase 3 of the testing, providing data for the design and procurement to build the full-scale version of the steam diffuser for SSC's A-3 Test Stand.

Subscale Diffuser Testing, E-3 produces first steam

NASA Technical Reports Server (NTRS)

2007-01-01

Phase 2 of the A-3 Test Facility Subscale Diffuser Risk Mitigation Project at Stennis Space Center reached a milestone Oct. 25 when the E-3 Test Facility produced superheated (500+ degrees) steam for approximately 3 seconds at more than 400 psi. The test team, led by Barry Robinson of NASA's Test Projects Office, followed that success with further tests to lengthen the duration of steam production. On Nov. 1, they were able to maintain a consistent pressure and temperature of steam for 60 seconds. In December, the team began Phase 3 of the testing, providing data for the design and procurement to build the full-scale version of the steam diffuser for SSC's A-3 Test Stand.

Construction and Utilization of a Beowulf Computing Cluster: A User's Perspective

NASA Technical Reports Server (NTRS)

Woods, Judy L.; West, Jeff S.; Sulyma, Peter R.

2000-01-01

Lockheed Martin Space Operations - Stennis Programs (LMSO) at the John C Stennis Space Center (NASA/SSC) has designed and built a Beowulf computer cluster which is owned by NASA/SSC and operated by LMSO. The design and construction of the cluster are detailed in this paper. The cluster is currently used for Computational Fluid Dynamics (CFD) simulations. The CFD codes in use and their applications are discussed. Examples of some of the work are also presented. Performance benchmark studies have been conducted for the CFD codes being run on the cluster. The results of two of the studies are presented and discussed. The cluster is not currently being utilized to its full potential; therefore, plans are underway to add more capabilities. These include the addition of structural, thermal, fluid, and acoustic Finite Element Analysis codes as well as real-time data acquisition and processing during test operations at NASA/SSC. These plans are discussed as well.

Commentary: The Observed Association between Autistic Severity Measured by the Social Responsiveness Scale (SRS) and General Psychopathology-- A Response to Hus et al.()

ERIC Educational Resources Information Center

Constantino, John N.; Frazier, Thomas W.

2013-01-01

In their analysis of the accumulated data from the clinically ascertained Simons Simplex Collection (SSC), Hus et al. (2013) provide a large-scale clinical replication of previously reported associations (see Constantino, Hudziak & Todd, 2003) between quantitative autistic traits [as measured by the Social Responsiveness Scale (SRS)] and…

[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.

Validation of the Social Appearance Anxiety Scale in Patients with Systemic Sclerosis: A Scleroderma Patient-centered Intervention Network Cohort Study.

PubMed

Mills, Sarah D; Kwakkenbos, Linda; Carrier, Marie-Eve; Gholizadeh, Shadi; Fox, Rina S; Jewett, Lisa R; Gottesman, Karen; Roesch, Scott C; Thombs, Brett D; Malcarne, Vanessa L

2018-01-17

Systemic sclerosis (SSc) is an autoimmune disease that can cause disfiguring changes in appearance. This study examined the structural validity, internal consistency reliability, convergent validity, and measurement equivalence of the Social Appearance Anxiety Scale (SAAS) across SSc disease subtypes. Patients enrolled in the Scleroderma Patient-centered Intervention Network Cohort completed the SAAS and measures of appearance-related concerns and psychological distress. Confirmatory factor analysis (CFA) was used to examine the structural validity of the SAAS. Multiple-group CFA was used to determine if SAAS scores can be compared across patients with limited and diffuse disease subtypes. Cronbach's alpha was used to examine internal consistency reliability. Correlations of SAAS scores with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression were used to examine convergent validity. SAAS scores were hypothesized to be positively associated with all convergent validity measures, with correlations significant and moderate to large in size. A total of 938 patients with SSc were included. CFA supported a one-factor structure (CFI: .92; SRMR: .04; RMSEA: .08), and multiple-group CFA indicated that the scalar invariance model best fit the data. Internal consistency reliability was good in the total sample (α = .96) and in disease subgroups. Overall, evidence of convergent validity was found with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression. The SAAS can be reliably and validly used to assess fear of appearance evaluation in patients with SSc, and SAAS scores can be meaningfully compared across disease subtypes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Controlling the digital ulcerative disease in systemic sclerosis is associated with improved hand function.

PubMed

Mouthon, Luc; Carpentier, Patrick H; Lok, Catherine; Clerson, Pierre; Gressin, Virginie; Hachulla, Eric; Bérezné, Alice; Diot, Elisabeth; Van Kien, Aurélie Khau; Jego, Patrick; Agard, Christian; Duval-Modeste, Anne-Bénédicte; Sparsa, Agnès; Puzenat, Eve; Richard, Marie-Aleth

2017-06-01

Ischemic digital ulcers (DU) represent a major complication of systemic sclerosis (SSc). We investigated the impact of controlling the ulcerative disease on disability, pain, and quality of life in SSc patients receiving bosentan. ECLIPSE (Study AC-052-517) is a 2-year prospective, multicenter, and observational study. Patients with SSc who experienced at least 1 DU in the previous year and received bosentan were included between October 2009 and March 2011. Disability scores [Cochin Hand Function Scale (CHFS) and Health Assessment Questionnaire Disability Index (HAQ-DI)], pain scores (visual analog scale), and quality-of-life scores (SF-36) were collected at inclusion and 1 year later (primary endpoint). A controlled ulcerative disease was defined by the absence of ongoing/new DU episode between inclusion and 1-year follow-up. Data were available at 1 year for 120 patients out of 190 included. During follow-up, 46 (38.3%) patients experienced a new DU episode. The number of DU per patient decreased from 1.4 ± 1.8 at inclusion to 0.6 ± 1.6 (p < 0.0001) at 1 year. Disability scores decreased from 1.0 ± 0.7 to 0.9 ± 0.7 (p = 0.04) for the HAQ-DI and from 29 ± 20 to 25 ± 20 (p = 0.005) for the CHFS; the pain score decreased from 4.3 ± 3.1 to 2.9 ± 2.8 (p < 0.0001). This improvement was attributed to patients with a controlled ulcerative disease (48.3%), who significantly improved HAQ-DI (p = 0.04), CHFS (p = 0.04), and pain score (p = 0.046). In patients with SSc, control of the ulcerative disease for 1 year was associated with significant attenuation of hand disability. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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.

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.

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

Towards environmental management of water turbidity within open coastal waters of the Great Barrier Reef.

PubMed

Macdonald, Rachael K; Ridd, Peter V; Whinney, James C; Larcombe, Piers; Neil, David T

2013-09-15

Water turbidity and suspended sediment concentration (SSC) are commonly used as part of marine monitoring and water quality plans. Current management plans utilise threshold SSC values derived from mean-annual turbidity concentrations. Little published work documents typical ranges of turbidity for reefs within open coastal waters. Here, time-series turbidity measurements from 61 sites in the Great Barrier Reef (GBR) and Moreton Bay, Australia, are presented as turbidity exceedance curves and derivatives. This contributes to the understanding of turbidity and SSC in the context of environmental management in open-coastal reef environments. Exceedance results indicate strong spatial and temporal variability in water turbidity across inter/intraregional scales. The highest turbidity across 61 sites, at 50% exceedance (T50) is 15.3 NTU and at 90% exceedance (T90) 4.1 NTU. Mean/median turbidity comparisons show strong differences between the two, consistent with a strongly skewed turbidity regime. Results may contribute towards promoting refinement of water quality management protocols. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

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

"Named Small but Doing Great": An Investigation of Small-Scale Chemistry Experimentation for Effective Undergraduate Practical Work

ERIC Educational Resources Information Center

Tesfamariam, Gebrekidan Mebrahtu; Lykknes, Annette; Kvittingen, Lise

2017-01-01

In theory, practical work is an established part of university-level chemistry courses. However, mainly due to budget constraints, large class size, time constraints and inadequate teacher preparations, practical activities are frequently left out from chemistry classroom instruction in most developing countries. Small-scale chemistry (SSC)…

Modeling and Control of State-Affine Probabilistic Systems for Atomic-Scale Dynamics

DTIC Science & Technology

2007-06-01

Analysis for Nonlinear Systems. New York: Spring -Verlag, 1987. [5] M. Itoh, "Atomic-scale homoepitaxial growth simulations of reconstructed III-V surfaces...Ridge, NJ; 1995. -- SSC function of the Node 182 [2] M. K. Weldon , K. T. Queeney, J. Eng Jr., K. Raghavachari, and Y. J. Chabal, "The surface science

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.

Arthroscopic Repair of Massive Cuff Tears With Large Subscapularis Tendon Ruptures (Lafosse III/IV): A Prospective Magnetic Resonance Imaging-Controlled Case Series of 26 Cases With a Minimum Follow-up of 1 Year.

PubMed

Grueninger, Patrick; Nikolic, Nikola; Schneider, Joerg; Lattmann, Thomas; Platz, Andreas; Chmiel, Corinne; Meier, Christoph

2015-11-01

To prospectively assess arthroscopic repair of massive cuff tears (MCT) in a highly selective patient group with large subscapularis (SSC) tendon tears by means of clinical results and magnetic resonance imaging (MRI) studies. Between April 2009 and December 2010, 26 patients with MCT were treated with arthroscopic rotator cuff repair. Only lesions involving a large tear of the SSC tendon (Lafosse III or IV) in combination with a complete tear of the supraspinatus (SSP) tendon and a tear of at least the anterior third of the infraspinatus (ISP) tendon were included. Minimum follow-up was 1 year. Pre- and postoperative assessment included a standardized clinical examination, subjective patient outcome, and MRI (structural integrity, fatty muscle infiltration, and muscular mass). Mean follow-up was 17 months (range, 12 to 34 months). MRI was performed in 25 patients. In 21 (84%) the cuff repair was intact. A partial retear of the SSC was found in 2 patients (8%). In 2 patients (8%) a full-thickness retear of the posterosuperior cuff was observed (1 SSP, 1 SSP/ISP). A significant increase of the muscle mass and decrease of fatty infiltration was observed for the SSC and SSP but not for the ISP. The mean Constant-Murley score improved from 36 to 86 points (P < .001) with all its subscores as well (P < .001). Muscular strength improved for the SSC (4.9 v 3.0, P < .001), SSP (4.6 v 2.9, P < .001), and ISP (4.8 v 3.4, P < .001). Overall patient satisfaction was high (3.6 ± 0.8). Arthroscopic repair of MCT involving the ISP, SSP, and large tears of the SSC provides a reliable tendon healing, in particular for the SSC tendon, combined with good functional results. Level IV, therapeutic case series. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

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

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.

[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.

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.

NASA Technology Evaluation for Environmental Risk Mitigation Remediation Technology Collaboration Development

NASA Technical Reports Server (NTRS)

Romeo, James

2013-01-01

NASA is committed to finding solutions to agency cleanup problems that are better, cheaper, and more effective than the status quo. Unfortunately, some potential solutions involve innovative technologies for which NASA remediation managers may not have a high level of understanding or confidence. Since 2004, NASA's Stennis Space Center (SSC) in Mississippi has been pumping groundwater contaminated with trichloroethylene (TCE) and other halogenated volatile organic compounds (HVOC) from their cleanup location designated "Area G" through extraction wells to an aboveground treatment system. Over time, however, the effectiveness of this treatment strategy has diminished and an alternative approach is needed. In 2012, professionals from NASA's Principal Center for Technology Evaluation for Environmental Risk Mitigation (TEERM) introduced SSC managers to an innovative technology for enhancing the performance of SSC's existing pump and treat system. The technology, generally referred to as in situ chemical oxidation (ISCO), involves slowly and continuously injecting a strong but safe chemical oxidant into the groundwater. Treatment is enhanced by a "surfactant-type effect" which causes residual contamination from saturated soil to be released into the dissolved-phase where it can be readily oxidized. Any dissolved-phase contamination that was not oxidized can be collected by the extraction well network and treated aboveground. SSC was not familiar with the technology so to increase their confidence, TEERM identified a contractor who was willing to demonstrate their product and process at a significantly reduced price. An initial, small-scale demonstration of ISCO began at sse in March 2012 and completed in August 2012. This successful demonstration was followed by three larger-scale ISCO demonstrations between August and December 2012. The contractor's innovative Continuous Injection System (CIS) incorporated "green" and sustainable technologies and practices. A slow injection rate was maintained autonomously by the CIS, eliminating the need for multiple mobilizations of personnel and powered equipment. The CIS was calibrated to deliver only as much reagent as the formation would accept without "short circuiting", minimizing material waste. Public utility water pressure was used to mix, dilute, and inject the reagent. NASA personnel were trained to operate and maintain the system and remote monitoring and injection control capabilities were developed, further reducing the need for contractor mobilizations to the site. An integrated solar photovoltaic panel was used to power the control valves and web monitoring telemetry. SSC provided hydrogen peroxide for the process using their existing supplier for the aboveground pump and treat systems. The only consumable required from the contractor was their proprietary activator to catalyze SSC's peroxide.

Early skin-to-skin contact for mothers and their healthy newborn infants.

PubMed

Moore, Elizabeth R; Bergman, Nils; Anderson, Gene C; Medley, Nancy

2016-11-25

Mother-infant separation post birth is common. In standard hospital care, newborn infants are held wrapped or dressed in their mother's arms, placed in open cribs or under radiant warmers. Skin-to-skin contact (SSC) begins ideally at birth and should last continually until the end of the first breastfeeding. SSC involves placing the dried, naked baby prone on the mother's bare chest, often covered with a warm blanket. According to mammalian neuroscience, the intimate contact inherent in this place (habitat) evokes neuro-behaviors ensuring fulfillment of basic biological needs. This time frame immediately post birth may represent a 'sensitive period' for programming future physiology and behavior. To assess the effects of immediate or early SSC for healthy newborn infants compared to standard contact on establishment and maintenance of breastfeeding and infant physiology. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 December 2015), made personal contact with trialists, consulted the bibliography on kangaroo mother care (KMC) maintained by Dr Susan Ludington, and reviewed reference lists of retrieved studies. Randomized controlled trials that compared immediate or early SSC with usual hospital care. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Quality of the evidence was assessed using the GRADE approach. We included 46 trials with 3850 women and their infants; 38 trials with 3472 women and infants contributed data to our analyses. Trials took place in 21 countries, and most recruited small samples (just 12 trials randomized more than 100 women). Eight trials included women who had SSC after cesarean birth. All infants recruited to trials were healthy, and the majority were full term. Six trials studied late preterm infants (greater than 35 weeks' gestation). No included trial met all criteria for good quality with respect to methodology and reporting; no trial was successfully blinded, and all analyses were imprecise due to small sample size. Many analyses had statistical heterogeneity due to considerable differences between SSC and standard care control groups. Results for womenSSC women were more likely than women with standard contact to be breastfeeding at one to four months post birth, though there was some uncertainty in this estimate due to risks of bias in included trials (average risk ratio (RR) 1.24, 95% confidence interval (CI) 1.07 to 1.43; participants = 887; studies = 14; I² = 41%; GRADE: moderate quality). SSC women also breast fed their infants longer, though data were limited (mean difference (MD) 64 days, 95% CI 37.96 to 89.50; participants = 264; studies = six; GRADE:low quality); this result was from a sensitivity analysis excluding one trial contributing all of the heterogeneity in the primary analysis. SSC women were probably more likely to exclusively breast feed from hospital discharge to one month post birth and from six weeks to six months post birth, though both analyses had substantial heterogeneity (from discharge average RR 1.30, 95% CI 1.12 to 1.49; participants = 711; studies = six; I² = 44%; GRADE: moderate quality; from six weeks average RR 1.50, 95% CI 1.18 to 1.90; participants = 640; studies = seven; I² = 62%; GRADE: moderate quality).Women in the SCC group had higher mean scores for breastfeeding effectiveness, with moderate heterogeneity (IBFAT (Infant Breastfeeding Assessment Tool) score MD 2.28, 95% CI 1.41 to 3.15; participants = 384; studies = four; I² = 41%). SSC infants were more likely to breast feed successfully during their first feed, with high heterogeneity (average RR 1.32, 95% CI 1.04 to 1.67; participants = 575; studies = five; I² = 85%). Results for infantsSSC infants had higher SCRIP (stability of the cardio-respiratory system) scores overall, suggesting better stabilization on three physiological parameters. However, there were few infants, and the clinical significance of the test was unclear because trialists reported averages of multiple time points (standardized mean difference (SMD) 1.24, 95% CI 0.76 to 1.72; participants = 81; studies = two; GRADE low quality). SSC infants had higher blood glucose levels (MD 10.49, 95% CI 8.39 to 12.59; participants = 144; studies = three; GRADE: low quality), but similar temperature to infants in standard care (MD 0.30 degree Celcius (°C) 95% CI 0.13 °C to 0.47 °C; participants = 558; studies = six; I² = 88%; GRADE: low quality). Women and infants after cesarean birthWomen practicing SSC after cesarean birth were probably more likely to breast feed one to four months post birth and to breast feed successfully (IBFAT score), but analyses were based on just two trials and few women. Evidence was insufficient to determine whether SSC could improve breastfeeding at other times after cesarean. Single trials contributed to infant respiratory rate, maternal pain and maternal state anxiety with no power to detect group differences. SubgroupsWe found no differences for any outcome when we compared times of initiation (immediate less than 10 minutes post birth versus early 10 minutes or more post birth) or lengths of contact time (60 minutes or less contact versus more than 60 minutes contact). Evidence supports the use of SSC to promote breastfeeding. Studies with larger sample sizes are necessary to confirm physiological benefit for infants during transition to extra-uterine life and to establish possible dose-response effects and optimal initiation time. Methodological quality of trials remains problematic, and small trials reporting different outcomes with different scales and limited data limit our confidence in the benefits of SSC for infants. Our review included only healthy infants, which limits the range of physiological parameters observed and makes their interpretation difficult.

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.

Modifying soil water status and improving stand establishment in a water repellent soil using surfactant coated seed.

NASA Astrophysics Data System (ADS)

Kostka, Stanley; Lampe, Mark; van Mondfrans, Jan; Madsen, Matthew; McMillan, Mica

2015-04-01

Surfactant seed coating (SSC) is a technology being developed cooperatively by scientists at the USDA, Agricultural Research Service and Aquatrols to improve stand establishment in water repellent soils, particularly under arid conditions. Early SSC studies have demonstrated that surfactant coatings can dramatically increase soil water content, turfgrass density, cover, and biomass for Kentucky bluegrass, tall fescue and perennial ryegrass sown in water repellent soils under greenhouse conditions. However, in these studies, surfactant loads were excessive (≥ 40 wt% of seed mass). The objective of the current study was to ascertain if a lower surfactant treatment level (10 wt%) would improve emergence and stand establishment in a severely water repellent sandy soil under field conditions. Research was conducted on a golf course near Utrecht, NL. At the time of planting water drop penetration time (WDPT) of the soil was approximately 300 s, indicating severe water repellency. Chewings fescue (Festuca rubra subsp. commutata) seed was treated with ASET-4001 surfactant at a loading rate of 10 wt% using two different proprietary coating procedures (US Patent Application 20100267554). The two different ASET-4001 coatings were compared against untreated seed in a randomized complete block design with four replicates. In order to maximize abiotic stresses, the only applied water came from rainfall. Assessments of stand establishment were made every 7-14 days for three months using a subjective visual assessment of percent grass cover and sward quality based on a 1-10 scale (where 10 is best). At six months post-sowing, 20 mm x 300 mm soil cores were randomly removed from each plot and soil wetting front depth measured. Improved emergence of the surfactant coated seeds over the untreated seeds began to appear 7 days after sowing. However, there were no differences between the two SSC treatments. Establishment was influenced by weather conditions. From mid-June to early July, ratings were similar between all treatments. However, with the onset of warmer more stressful growing conditions in mid-July, stand establishment ratings for the SSC treatments were higher than for the untreated control. From 16 July to 18 August, stand establishment ratings for the SSC treatments were between 9.1 and 9.8. In the untreated control plots, 16 July ratings were at 7.1 and dropped precipitously to 5.3 by 18 August. The visual differences between treatments suggested that rootzone water may be greater in the SSC treatments. Mean wetting front depths in cores collected from the SSC plots were at minimum 2x greater than untreated controls (200 mm vs 100 mm) confirming that SSC resulted in greater rootzone water distribution. SSC improved emergence and stand establishment of Chewings fescue and modified the soil wetting pattern in severely water repellent sand for at least six months. SSC may provide a sustainable strategy to improve turfgrass establishment under water stress conditions or when irrigation is limited.

Evaluation of Skin Surface as an Alternative Source of Reference DNA Samples: A Pilot Study.

PubMed

Albujja, Mohammed H; Bin Dukhyil, Abdul Aziz; Chaudhary, Abdul Rauf; Kassab, Ahmed Ch; Refaat, Ahmed M; Babu, Saranya Ramesh; Okla, Mohammad K; Kumar, Sachil

2018-01-01

An acceptable area for collecting DNA reference sample is a part of the forensic DNA analysis development. The aim of this study was to evaluate skin surface cells (SSC) as an alternate source of reference DNA sample. From each volunteer (n = 10), six samples from skin surface areas (forearm and fingertips) and two traditional samples (blood and buccal cells) were collected. Genomic DNA was extracted and quantified then genotyped using standard techniques. The highest DNA concentration of SSC samples was collected using the tape/forearm method of collection (2.1 ng/μL). Cotton swabs moistened with ethanol yielded higher quantities of DNA than swabs moistened with salicylic acid, and it gave the highest percentage of full STR profiles (97%). This study supports the use of SSC as a noninvasive sampling technique and as a extremely useful source of DNA reference samples among certain cultures where the use of buccal swabs can be considered socially unacceptable. © 2017 American Academy of Forensic Sciences.

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).

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.

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

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.

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

Social/economic costs and health-related quality of life in patients with scleroderma in Europe.

PubMed

López-Bastida, Julio; Linertová, Renata; Oliva-Moreno, Juan; Serrano-Aguilar, Pedro; Posada-de-la-Paz, Manuel; Kanavos, Panos; Taruscio, Domenica; Schieppati, Arrigo; Iskrov, Georgi; Péntek, Márta; Delgado, Claudia; von der Schulenburg, Johann Mathias; Persson, Ulf; Chevreul, Karine; Fattore, Giovanni

2016-04-01

The aim of this study was to determine the economic burden from a societal perspective and the health-related quality of life (HRQOL) of patients with systemic sclerosis (SSc; scleroderma) in Europe. We conducted a cross-sectional study of patients with SSc (involving both localised and systemic sclerosis) from Germany, Italy, Spain, France, the UK, Hungary and Sweden. Data on demographic characteristics, healthcare resource utilisation, informal care, labour productivity losses and HRQOL were collected from the questionnaires completed by patients or their caregivers. HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. A total of 589 patients completed the questionnaire. The rate of patients with localised scleroderma, limited cutan and diffuse cutan SSc were 28, 68 and 4 %, respectively. Average annual costs varied from country to country and ranged from € 4607 to € 30,797 (reference year: 2012). Estimated direct healthcare costs ranged from € 1413 to € 17,300; direct non-healthcare costs ranged from € 1875 to € 4684 and labour productivity losses ranged from € 1701 to € 14,444. The mean EQ-5D index score for adult SSc patients varied from 0.49 to 0.75 and the mean EQ-5D visual analogue scale score was between 58.72 and 65.86. The main strengths of this study lie in our bottom-up approach to costing and our evaluation of SSs patients from a broad societal perspective. This type of analysis is very unusual in the international literature on rare diseases in comparison with other illnesses. We concluded that SSc patients incur considerable societal costs and experience substantial deterioration in HRQOL.

Nailfold capillaroscopy for prediction of novel future severe organ involvement in systemic sclerosis.

PubMed

Smith, Vanessa; Riccieri, Valeria; Pizzorni, Carmen; Decuman, Saskia; Deschepper, Ellen; Bonroy, Carolien; Sulli, Alberto; Piette, Yves; De Keyser, Filip; Cutolo, Maurizio

2013-12-01

Assessment of associations of nailfold videocapillaroscopy (NVC) scleroderma (systemic sclerosis; SSc) ("early," "active," and "late") with novel future severe clinical involvement in 2 independent cohorts. Sixty-six consecutive Belgian and 82 Italian patients with SSc underwent NVC at baseline. Images were blindly assessed and classified into normal, early, active, or late NVC pattern. Clinical evaluation was performed for 9 organ systems (general, peripheral vascular, skin, joint, muscle, gastrointestinal tract, lung, heart, and kidney) according to the Medsger disease severity scale (DSS) at baseline and in the future (18-24 months of followup). Severe clinical involvement was defined as category 2 to 4 per organ of the DSS. Logistic regression analysis (continuous NVC predictor variable) was performed. The OR to develop novel future severe organ involvement was stronger according to more severe NVC patterns and similar in both cohorts. In simple logistic regression analysis the OR in the Belgian/Italian cohort was 2.16 (95% CI 1.19-4.47, p = 0.010)/2.33 (95% CI 1.36-4.22, p = 0.002) for the early NVC SSc pattern, 4.68/5.42 for the active pattern, and 10.14/12.63 for the late pattern versus the normal pattern. In multiple logistic regression analysis, adjusting for disease duration, subset, and vasoactive medication, the OR was 2.99 (95% CI 1.31-8.82, p = 0.007)/1.88 (95% CI 1.00-3.71, p = 0.050) for the early NVC SSc pattern, 8.93/3.54 for the active pattern, and 26.69/6.66 for the late pattern versus the normal pattern. Capillaroscopy may be predictive of novel future severe organ involvement in SSc, as attested by 2 independent cohorts.

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.

Measurement Sets and Sites Commonly used for Characterizations

NASA Technical Reports Server (NTRS)

Pagnutti, Mary; Holekamp, Kara; Ryan, Robert; Blonski, Slawomir; Sellers, Richard; Davis, Bruce; Zanoni, Vicki

2002-01-01

Scientists with NASA's Earth Science Applications Directorate are creating a well-characterized Verification & Validation (V&V) site at the Stennis Space Center (SSC). This site enables the in-flight characterization of remote sensing systems and the data that they require. The data are predominantly acquired by commercial, high-spatial resolution satellite systems, such as IKONOS and QuickBird 2, and airborne systems. The smaller scale of these newer high-resolution remote sensing systems allows scientists to characterize the geometric, spatial, and radiometric data properties using a single V&V site. The targets and techniques used to characterize data from these newer systems can differ significantly from the earlier, coarser spatial resolution systems. Scientists are also using the SSC V&V site to characterize thermal infrared systems and active Light Detection and Ranging (LIDAR) systems. SSC employs geodetic targets, edge targets, radiometric tarps, and thermal calibration ponds to characterize remote sensing data products. This paper presents a proposed set of required measurements for visible-through-longwave infrared remote sensing systems, and a description of the Stennis characterization. Other topics discussed inslude: 1) use of ancillary atmospheric and solar measurements taken at SSC that support various characterizations, 2) other sites used for radiometric, geometric, and spatial characterization in the continental United States,a nd 3) the need for a standardized technique to be adopted by the Committee on Earth Observation Satellites (CEOS) and other organizations.

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

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.

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.

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.

An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Scleroderma-associated Interstitial Lung Disease: the LOTUSS Trial.

PubMed

Khanna, Dinesh; Albera, Carlo; Fischer, Aryeh; Khalidi, Nader; Raghu, Ganesh; Chung, Lorinda; Chen, Dan; Schiopu, Elena; Tagliaferri, Margit; Seibold, James R; Gorina, Eduard

2016-09-01

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) shares a number of clinical features and pathogenic mechanisms with idiopathic pulmonary fibrosis (IPF). This study was designed to evaluate the tolerability of the IPF treatment pirfenidone in SSc-ILD. The known gastrointestinal, skin, and liver adverse events (AE) of pirfenidone are of importance given the involvement of these organs in SSc. All patients received pirfenidone and were randomized 1:1 to either a 2- or 4-week titration starting at 801 mg/day and finishing at a maintenance dose of 2403 mg/day. Patients received pirfenidone for 16 weeks in total. Assessments included treatment-emergent AE (TEAE) and exploratory disease outcomes. Sixty-three patients were randomized; 96.8% experienced a TEAE and more patients reported TEAE during the titration versus the maintenance period. The most commonly reported TEAE were consistent with those observed for pirfenidone in IPF (nausea, headache, fatigue) and were similar regardless of titration schedule. More patients discontinued treatment because of TEAE in the 2- versus 4-week titration group (5 vs 1, respectively); all discontinuation events occurred > 3 weeks after reaching the full dose of pirfenidone. Mycophenolate mofetil (MMF), taken by 63.5% of patients in addition to pirfenidone, did not appear to affect tolerability. Exploratory disease outcomes remained largely unchanged. Pirfenidone showed an acceptable tolerability profile in SSc-ILD, although a longer titration may be associated with better tolerability. Tolerability was not affected by concomitant MMF. The present findings support further investigation of pirfenidone in future clinical trials in patients with SSc-ILD. ClinicalTrials.gov; www.clinicaltrials.gov NCT01933334.

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.

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

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.

Functional disability and its predictors in systemic sclerosis: a study from the DeSScipher project within the EUSTAR group.

PubMed

Jaeger, Veronika K; Distler, Oliver; Maurer, Britta; Czirják, Laszlo; Lóránd, Veronika; Valentini, Gabriele; Vettori, Serena; Del Galdo, Francesco; Abignano, Giuseppina; Denton, Christopher; Nihtyanova, Svetlana; Allanore, Yannick; Avouac, Jerome; Riemekasten, Gabriele; Siegert, Elise; Huscher, Dörte; Matucci-Cerinic, Marco; Guiducci, Serena; Frerix, Marc; Tarner, Ingo H; Garay Toth, Beata; Fankhauser, Beat; Umbricht, Jörg; Zakharova, Anastasia; Mihai, Carina; Cozzi, Franco; Yavuz, Sule; Hunzelmann, Nicolas; Rednic, Simona; Vacca, Alessandra; Schmeiser, Tim; Riccieri, Valeria; García de la Peña Lefebvre, Paloma; Gabrielli, Armando; Krummel-Lorenz, Brigitte; Martinovic, Duska; Ancuta, Codrina; Smith, Vanessa; Müller-Ladner, Ulf; Walker, Ulrich A

2018-03-01

The multisystem manifestations of SSc can greatly impact patients' quality of life. The aim of this study was to identify factors associated with disability in SSc. SSc patients from the prospective DeSScipher cohort who had completed the scleroderma health assessment questionnaire (SHAQ), a disability score that combines the health assessment questionnaire and five visual analogue scales, were included in this analysis. The effect of factors possibly associated with disability was analysed with multiple linear regressions. The mean SHAQ and HAQ scores of the 944 patients included were 0.87 (s.d. = 0.66) and 0.92 (s.d. = 0.78); 59% of the patients were in the mild to moderate difficulty SHAQ category (0 ⩽ SHAQ < 1), 34% in the moderate to severe disability category (1 ⩽ SHAQ < 2) and 7% in the severe to very severe disability category (2 ⩽ SHAQ ⩽ 3). The means of the visual analogue scales scores were in order of magnitude: overall disease severity (37 mm), RP (31 mm), pulmonary symptoms (24 mm), gastrointestinal symptoms (20 mm) and digital ulcers (19 mm). In multiple regression, the main factors associated with high SHAQ scores were the presence of dyspnoea [modified New York Heart Association (NYHA) class IV (regression coefficient B = 0.62), modified NYHA class III (B = 0.53) and modified NYHA class II (B = 0.21; all vs modified NYHA class I)], FM (B = 0.37), muscle weakness (B = 0.27), digital ulcers (B = 0.20) and gastrointestinal symptoms (oesophageal symptoms, B = 0.16; stomach symptoms, B = 0.15; intestinal symptoms, B = 0.15). SSc patients perceive dyspnoea, pain, digital ulcers, muscle weakness and gastrointestinal symptoms as the main factors driving their level of disability, unlike physicians who emphasize objective measures of disability. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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

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.

Building the Superconducting Super Collider, 1989-1993: The Problem of Project Management

NASA Astrophysics Data System (ADS)

Riordan, Michael

2011-04-01

In attempting to construct the Superconducting Super Collider, US particle physicists faced a challenge unprecedented in the history of science. The SSC was the biggest and costliest pure scientific project ever, comparable in overall scale to the Manhattan Project or the Panama Canal - an order of magnitude larger than any previous particle accelerator or collider project. Managing such an enormous endeavor involved coordinating conventional-construction, magnet-manufacturing, and detector-building efforts costing over a billion dollars apiece. Because project-management experience at this scale did not exist within the physics community, the Universities Research Association and the US Department of Energy turned to companies and individuals from the military-industrial complex, with mixed results. The absence of a strong, qualified individual to serve as Project Manager throughout the duration of the project was a major problem. I contend that these problems in its project management contributed importantly to the SSC's 1993 demise. Research supported by NSF Award No. 823296.

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.

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.

The effect of skin-to-skin contact at birth, early versus immediate, on the duration of exclusive human lactancy in full-term newborns treated at the Clínica Universidad de La Sabana: study protocol for a randomized clinical trial.

PubMed

Agudelo, Sergio; Gamboa, Oscar; Rodríguez, Fabio; Cala, Sandra; Gualdrón, Nathalie; Obando, Evelyn; Padrón, María Lucía

2016-10-26

Human lactancy is a simple and cost-effective strategy that influences infant and maternal mortality rates. Skin-to-skin contact (SSC) is an immediate postpartum period strategy that has proven to benefit the initiation and continuation of human lactation and to decrease hospitalization during the first week of life. This study aims to determine the effect of SSC initiation at birth (immediate versus early) in healthy, full-term newborns treated at the Universidad de La Sabana Clinic on the duration of exclusive human lactation. A randomized, blind clinical trial will be performed with full-term healthy newborns born at the Universidad de La Sabana Clinic. The blind trial participants will be those persons measuring the results and analyzing the data. The sample size will be calculated for a type I error of 5 %, a two-tailed type II error of 20 %, and an estimated percentage loss of 30 %; 150 infants will be included in each group. Randomization will be performed using permuted, size-6 blocks. Descriptive analysis will be conducted using central tendency and dispersion measurements. A bivariate analysis will be performed to determine which variables are associated with exclusive lactancy at 6 months. For continuous variables, Student's t test will be used for independent samples, and the Wilcoxon rank sum test will be used if the assumptions of normality for the t tests are not fulfilled. The assumption of normality will be evaluated using the Shapiro-Wilk and Kolmogorov-Smirnov tests. Categorical variables in contingency tables will be constructed to assess the independence between variables using the chi-square test, or Fisher's exact test when the assumption of the number of cases is not met by the values in the contingency tables multiplied by two. This will be calculated as a measurement of the effect of relative risk (RR) with confidence intervals; the adjusted measurements will be calculated using a multivariate regression Poisson model. Variables with significant results will be used in the bivariate analysis, and those with biological plausibility will be used for the adjustment. The analysis will be carried out for a two-tailed type I error level of 5 %. The Stata 11 program will be used for data analysis. An interim analysis will be performed upon the submission of half the expected events (106), setting limits for the early termination of the trial according to the method proposed by Pampallona and Tsiatis (1994). There will be two SSC randomization groups: early versus immediate. After completing the neonatal adaptation process and based on the group assignment, the mother will be left with her newborn child in hospital accommodation. Prior to discharge, the Infant Breast-Feeding Assessment Tool (IBFAT) will be applied. Monitoring will initially be performed with a face-to-face assessment between 3 and 10 days of life, followed by monthly telephone calls for 6 months to verify lactation status. SSC at birth has shown benefits in the short and long term for both the mother and the full-term newborn. Although the meta-analysis that have been done have shown the benefits of this technique, multiple differences in the SSC interventions have been identified because criteria such as the initiation or duration of SSC (dose) have not been unified. Colombia has a malnutrition risk of 11,4 % in the total population for the period 2012-2014, so it is necessary to promote strategies that generate a positive impact on the duration of human lactation, providing support from the clinical setting of humanized delivery which is included in the IAMI strategy (Instituciones Amigas de la Mujer y la Infancia - Friends of Women and Children Institution). Therefore, we propose that the initiation time of SSC in full-term new-borns is related to the duration of exclusive human lactation. Registered ClinicalTrials.gov Identifier: NCT 02687685 . Registered on 2 February 2016. This study is not yet open for participant recruitment.

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.

Report of the Task Force on SSC Magnet System Test Site

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

NONE

1984-10-01

The Task Force on SSC Magnet Systems test Site was appointed by Maury Tigner, Director of the SSC, Phase 1 in August 1984. In brief, the charge asked the Task Force to make a critical evaluation of potential test sites for a major SSC magnet System Test Facility (STF) with regard to: (1) availability of the needed space, utilities, staff and other requirements on the desired time scale; and (2) the cost of preparing the sites for the tests and for operating the facilities during the test period. The charge further suggests that, by virtue of existing facilities and availabilitymore » of experienced staff, BNL and FNAL are the two best candidate sites and that is therefore appears appropriate to restrict the considerations of the Task Force to these sites. During the subsequent deliberations of the Task Force, no new facts were revealed that altered the assumptions of the charge in this regard. The charge does not ask for a specific site recommendation for the STF. Indeed, an agreement on such a recommendation would be difficult to achieve considering the composition of the Task Force, wherein a large fraction of the membership is drawn from the two contending laboratories. Instead, we have attempted to describe the purpose of the facility, outline a productive test program, list the major facilities required, carefully review the laboratories` responses to the facility requirements, and make objective comparisons of the specific features and capabilities offered.« less

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.

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.

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

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.

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

Planning for Plume Diagnostics for Ground Testing of J-2X Engines at the SSC

NASA Technical Reports Server (NTRS)

SaintCyr, William W.; Tejwani, Gopal D.; McVay, Gregory P.; Langford, Lester A.; SaintCyr, William W.

2010-01-01

John C. Stennis Space Center (SSC) is the premier test facility for liquid rocket engine development and certification for the National Aeronautics and Space Administration (NASA). Therefore, it is no surprise that the SSC will play the most prominent role in the engine development testing and certification for the J-2X engine. The Pratt & Whitney Rocketdyne J-2X engine has been selected by the Constellation Program to power the Ares I Upper Stage Element and the Ares V Earth Departure Stage in NASA s strategy of risk mitigation for hardware development by building on the Apollo program and other lessons learned to deliver a human-rated engine that is on an aggressive development schedule, with first demonstration flight in 2010 and human test flights in 2012. Accordingly, J-2X engine design, development, test, and evaluation is to build upon heritage hardware and apply valuable experience gained from past development and testing efforts. In order to leverage SSC s successful and innovative expertise in the plume diagnostics for the space shuttle main engine (SSME) health monitoring,1-10 this paper will present a blueprint for plume diagnostics for various proposed ground testing activities for J-2X at SSC. Complete description of the SSC s test facilities, supporting infrastructure, and test facilities is available in Ref. 11. The A-1 Test Stand is currently being prepared for testing the J-2X engine at sea level conditions. The A-2 Test Stand is currently being used for testing the SSME and may also be used for testing the J-2X engine at sea level conditions in the future. Very recently, ground-breaking ceremony for the new A-3 rocket engine test stand took place at SSC on August 23, 2007. A-3 is the first large - scale test stand to be built at the SSC since the A and B stands were constructed in the 1960s. The A-3 Test Stand will be used for testing J-2X engines under vacuum conditions simulating high altitude operation at approximately 30,480 m (100,000 ft). To achieve the simulated altitude environment, chemical steam generators using isopropyl alcohol, LOX, and RELEASED - Printed documents may be obsolete; validate prior to use. water would run for the duration of the test and would generate approximately 2096 Kg/s of steam to reduce pressure in the test cell and downstream of the engine. The testing at the A-3 Test Stand is projected to begin in late 2010, meanwhile the J-2X component testing on A-1 is scheduled to begin later this year.

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.

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.

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.

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.

Workplace barriers encountered by employed persons with systemic sclerosis.

PubMed

Poole, Janet L; Anwar, Sahar; Mendelson, Cindy; Allaire, Saralynn

2016-01-01

Systemic sclerosis (SSc) is an auto-immune connective tissue disease characterized by fibrosis of skin, blood vessels, and internal organs that results in significant disability. To identify the work barriers faced by people with systemic sclerosis (SSc) in maintaining employment. Thirty-six people with SSc who were working more than 8 hours per week completed the Work Experience Survey, which contains lists of potential work barriers, including the ability to travel to and from work; get around at work; perform essential job functions, including physical, cognitive, and task-related activities; work with others; and manage work conditions. Thirty-three participants completed and returned the questionnaires, most of whom were female, and working full time and in professional careers. Principal disease symptoms included fatigue, Raynaud's phenomenon, esophageal involvement, and leg or hand/wrist pain. All participants reported some barriers with a mean of 18 barriers per participant. At least three quarters of participants cited outside temperature (82%), cold temperatures inside the workplace (76%), and household work (76%), as barriers. The next most common barriers were using both hands (64%), arranging and taking part in social activities (64%), being able to provide self-care (61%) and working 8 hours (58%). Participants reported a wide range of barriers, from cold temperatures, to physical job, fatigue related, and non-workplace demands, in maintaining the worker role. The barriers reflect the disease symptoms they reported. Identifying workplace barriers facilitates the creation of job accommodations or adaptations that will allow people with SSc to continue working.

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.

Biomechanical podiatric evaluation in an Italian cohort of patients with systemic sclerosis: A pilot study.

PubMed

Bongi, Susanna Maddali; Ravenni, Giovanni; Ciampi, Benedetta; Del Rosso, Angela; El Aoufy, Khadija

2016-12-01

Foot problems are often present in Systemic Sclerosis (SSc) patients, however studies regarding podiatric problems related to SSc are lacking and there are no data evaluating the foot biomechanical changes. The aim of the present pilot study was to evaluate podiatric problems in an Italian cohort of SSc patients by assessing received podiatric services, foot pain and disability and biomechanical foot deformity. 25 consecutive SSc patients were enrolled from the Division of Rheumatology, University of Florence. All SSc patients were assessed by: Standards of Care for People with Foot Musculoskeletal Health problems: Audit Tool, Foot Function Index (FFI), Weight and non-weight bearing foot joint assessment, (Foot Posture Index (FPI) and Gait Cycle), Health Assessment Questionnaire (HAQ) and Medical Outcomes Survey Short Form 36 (SF-36). Audit Tool - Only 7 (28%) out of the 25 patients with SSc had a specific podiatric assessment and treatment: no patient received a foot health assessment within the first 6 months of disease diagnosis and no patient received information about foot involvement. 1 patient (4%) received foot assessment every year; 1 patient (4%) received specific information about the disease and 5 patients (20%) received information about the benefits of using adapted footwear and insoles. FFI - Values of pain, disability and activity limitations, reported in FFI, are 4.7±5.1, 5.1±3.2 and 3.2±3.1 (M±DS), respectively. Non-weight bearing foot joint assessment shows a rearfoot varus deformity in 64% of patients, forefoot varus deformity in 42% and 6% forefoot valgus deformity. Weight bearing foot joint assessment, through FPI shows a pronated foot 20% of patients with and 34% with highly pronated overall foot posture. Gait analysis shows that 64% of patients has a contact of the calcaneus in invertion while 36% in eversion. In the midstance, 78% have the foot in pronation and 22% in supination, while in propulsion 12% presents a takeoff of the foot in supination and 88% in the pronation. HAQ result is 1.13±0.80, SFI and SMI scales of SF-36 have scores of 32.38±10.65 and 38.67±11.40, respectively. Our results shows that podiatric problems in SSc patients are common, serious but foot assessment and health care are inadequate. Thus, foot health information should be improved in order to better empower patients to self-manage low risk problems and help identify high-risk problems, which require specialist care.

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.

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.

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.

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.

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.

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.

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.

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.

75 FR 31424 - New England Fishery Management Council; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

... Fishery Management Council; Public Meeting AGENCY: National Marine Fisheries Service (NMFS), National... economic zone (EEZ). Recommendations from this group will be brought to the full Council for formal.... Tuesday, June 22, 2010 The SSC will review the Ecosystem-Based Fishery Management draft policy paper...

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

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.

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

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

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.

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.

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

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...

Factor structure and convergent validity of the Derriford Appearance Scale-24 using standard scoring versus treating ‘not applicable’ responses as missing data: a Scleroderma Patient-centered Intervention Network (SPIN) cohort study

PubMed Central

Merz, Erin L; Kwakkenbos, Linda; Carrier, Marie-Eve; Gholizadeh, Shadi; Mills, Sarah D; Fox, Rina S; Jewett, Lisa R; Williamson, Heidi; Harcourt, Diana; Assassi, Shervin; Furst, Daniel E; Gottesman, Karen; Mayes, Maureen D; Moss, Tim P; Thombs, Brett D; Malcarne, Vanessa L

2018-01-01

Objective Valid measures of appearance concern are needed in systemic sclerosis (SSc), a rare, disfiguring autoimmune disease. The Derriford Appearance Scale-24 (DAS-24) assesses appearance-related distress related to visible differences. There is uncertainty regarding its factor structure, possibly due to its scoring method. Design Cross-sectional survey. Setting Participants with SSc were recruited from 27 centres in Canada, the USA and the UK. Participants who self-identified as having visible differences were recruited from community and clinical settings in the UK. Participants Two samples were analysed (n=950 participants with SSc; n=1265 participants with visible differences). Primary and secondary outcome measures The DAS-24 factor structure was evaluated using two scoring methods. Convergent validity was evaluated with measures of social interaction anxiety, depression, fear of negative evaluation, social discomfort and dissatisfaction with appearance. Results When items marked by respondents as ‘not applicable’ were scored as 0, per standard DAS-24 scoring, a one-factor model fit poorly; when treated as missing data, the one-factor model fit well. Convergent validity analyses revealed strong correlations that were similar across scoring methods. Conclusions Treating ‘not applicable’ responses as missing improved the measurement model, but did not substantively influence practical inferences that can be drawn from DAS-24 scores. Indications of item redundancy and poorly performing items suggest that the DAS-24 could be improved and potentially shortened. PMID:29511009

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

NASA Astrophysics Data System (ADS)

van Hunen, Jeroen; Phethean, Jordan

2014-05-01

Volcanic passive margins (VPMs) are areas of continental rifting where the amount of newly formed igneous crust is larger than normal, in some areas up to 30 km. In comparison, magma-poor margins have initial oceanic crustal thicknesses of less than 7 km (Simon et al., 2009; Franke, 2012). The mechanism for the formation of these different types of margins is debated, and proposed mechanisms include: 1) variation in rifting speed (van Wijk et al., 2001), variation in rifting history (Armitage et al., 2010), enhanced melting from mantle plumes (e.g. White and McKenzie, 1989), and enhanced movement of mantle material through the melting zone by sublithospheric small-scale convection (SSC) driven by lithospheric detachments (Simon et al., 2009). Understanding the mechanism is important to constrain the petroleum potential of VPM. In this study, we use a numerical modelling approach to further elaborate the effect of SSC on the rate of crust production during continental rifting. Conceptually, SSC results in patterns of upwelling (and downwelling) mantle material with a typical horizontal wavelength of a 100 to a few 100 km (van Hunen et al., 2005). If occurring shallowly enough, such upwellings lead to decompression melting (Raddick et al., 2002). Subsequent mantle depletion has multiple effects on buoyancy (from both latent heat consumption and compositional changes), which, in turn, can affect mantle dynamics under the MOR, and can potentially enhance SSC and melting further. We use two- and three-dimensional Cartesian flow models to examine the mantle dynamics associated with continental rifting, using a linear viscous rheology (in addition to a semi-brittle stress limiter to localize rifting) in which melting (parameterized using (Katz et al., 2003)) leads to mantle depletion and crust accumulation at the surface. The newly formed crust is advected away with the diverging plates. A parameter sensitivity study of the effects of mantle viscosity, spreading rate, mantle temperature, and a range material parameters have indicated the following results. Decompression melting leads to a colder (from consumption of latent heat of melting) and therefore thermally denser, but compositionally more buoyant residue. The competition between thermal and compositional buoyancy determines the mantle dynamics after rifting initiation. For a mantle viscosity > ~ 1022 Pa s, no SSC occurs, and a uniform 7-8 km-thick oceanic crust forms. For mantle viscosity < ~ 1021 Pa s, SSC might be vigorous and can form passive margins with a crustal thickness > 10-20 km. If thermal density effects dominate, a convection inversion may occur for low mantle viscosities, and mantle downwellings underneath the rift/ridge area can result in a significant upwelling return flow that enhances further decompression melting, and can 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.

Efficacy of Autologous Microfat Graft on Facial Handicap in Systemic Sclerosis Patients

PubMed Central

Sautereau, Nolwenn; Daumas, Aurélie; Truillet, Romain; Jouve, Elisabeth; Magalon, Jéremy; Veran, Julie; Casanova, Dominique; Frances, Yves; Magalon, Guy

2016-01-01

Background: Autologous adipose tissue injection is used in plastic surgery for correction of localized tissue atrophy and has also been successfully offered for treatment of localized scleroderma. We aimed to evaluate whether patients with systemic sclerosis (SSc) and facial handicap could also benefit from this therapy. Methods: We included 14 patients (mean age of 53.8 ± 9.6 years) suffering from SSc with facial handicap defined by Mouth Handicap in Systemic Sclerosis Scale (MHISS) score more than or equal to 20, a Rodnan skin score on the face more than or equal to 1, and maximal mouth opening of less than 55 mm. Autologous adipose tissue injection was performed under local anesthesia using the technique of subcutaneous microinjection. The main objective of this study was an improvement of the MHISS score 6 months after the surgical treatment. Results: The procedure was well tolerated. We observed a mean decrease in the MHISS score of 10.7 points (±5.1; P < 0.0001) at 6 months (35% improvement). Secondary efficacy parameters assessing perioral skin sclerosis, maximum mouth opening, sicca syndrome, and facial pain significantly improved at 3 and 6 months postsurgery. At a 6-month follow-up, 75% of patients were satisfied or very satisfied of the adipose tissue microinjection therapy. Conclusions: Our study suggests that subcutaneous perioral microfat injection in patients with SSc is beneficial in the treatment of facial handicap, skin sclerosis, mouth opening limitation, sicca syndrome, and facial pain. Thus, this minimally invasive approach offers a new hope for face therapy for patients with SSc. PMID:27257590

Efficacy of Autologous Microfat Graft on Facial Handicap in Systemic Sclerosis Patients.

PubMed

Sautereau, Nolwenn; Daumas, Aurélie; Truillet, Romain; Jouve, Elisabeth; Magalon, Jéremy; Veran, Julie; Casanova, Dominique; Frances, Yves; Magalon, Guy; Granel, Brigitte

2016-03-01

Autologous adipose tissue injection is used in plastic surgery for correction of localized tissue atrophy and has also been successfully offered for treatment of localized scleroderma. We aimed to evaluate whether patients with systemic sclerosis (SSc) and facial handicap could also benefit from this therapy. We included 14 patients (mean age of 53.8 ± 9.6 years) suffering from SSc with facial handicap defined by Mouth Handicap in Systemic Sclerosis Scale (MHISS) score more than or equal to 20, a Rodnan skin score on the face more than or equal to 1, and maximal mouth opening of less than 55 mm. Autologous adipose tissue injection was performed under local anesthesia using the technique of subcutaneous microinjection. The main objective of this study was an improvement of the MHISS score 6 months after the surgical treatment. The procedure was well tolerated. We observed a mean decrease in the MHISS score of 10.7 points (±5.1; P < 0.0001) at 6 months (35% improvement). Secondary efficacy parameters assessing perioral skin sclerosis, maximum mouth opening, sicca syndrome, and facial pain significantly improved at 3 and 6 months postsurgery. At a 6-month follow-up, 75% of patients were satisfied or very satisfied of the adipose tissue microinjection therapy. Our study suggests that subcutaneous perioral microfat injection in patients with SSc is beneficial in the treatment of facial handicap, skin sclerosis, mouth opening limitation, sicca syndrome, and facial pain. Thus, this minimally invasive approach offers a new hope for face therapy for patients with SSc.

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.

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.

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.

Systemic sclerosis patients with and without pulmonary arterial hypertension: a nailfold capillaroscopy study.

PubMed

Riccieri, Valeria; Vasile, Massimiliano; Iannace, Nicoletta; Stefanantoni, Katia; Sciarra, Iliana; Vizza, Carmine D; Badagliacca, Roberto; Poscia, Roberto; Papa, Silvia; Mezzapesa, Mario; Nocioni, Martina; Valesini, Guido

2013-08-01

Pulmonary arterial hypertension (PAH) is a complication of SSc due to increased vascular resistance, and abnormal vascularity is a well-known feature of the disease as shown by nailfold videocapillaroscopy (NVC). This study investigated for specific NVC changes in SSc patients with and without PAH to assess any useful difference. Twenty-four SSc patients, 12 with PAH and 12 without, entered the study. Evidence of PAH was defined as increased systolic pulmonary artery pressure (PAP) (≥35 mmHg), indirectly assessed by echocardiography and confirmed by right heart catheterization (mPAP > 25 mmHg). NVC was performed, and a semi-quantitative rating scale, a rating system for avascular areas and a specific NVC pattern evaluation, namely early, active and late, were used. An NVC score >1 was more frequently found in patients with PAH than those without, 11 cases (92%) vs 5 cases (42%) (P = 0.03); an avascular areas grade >1 was present in 10 (83%) and 2 (17%) cases, respectively (P = 0.003); and a more severe NC pattern (active/late) was described in 11 (92%) and 5 (42%) patients, respectively (P = 0.03). When we compared the mPAP with NVC parameters, we found significant correlations between mPAP values and the NVC score (P < 0.005) and with the avascular areas score (P < 0.001). Our results underline the relevance of early microvascular assessment in patients at risk of developing a severe complication such as PAH that can amplify the systemic microvascular impairment in SSc. More severe NVC abnormalities should lead to strict cardiopulmonary surveillance and a complete NVC study is indicated.

Proceedings of the workshop on physics at current accelerators and supercolliders

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

Hewett, J L; White, A R; Zeppenfeld, D

1993-06-02

This report contains papers from the workshop on SSC physics. The topics of these papers include: electroweak physics; electroweak symmetry breaking; heavy flavors; searches for new phenomena; strong interactions and full acceptance physics; and event simulation. These paper have been cataloged separately on the data base.

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.

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.

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.

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

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.

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.

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

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.

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.

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

[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.

River discharge controlling a tidal delta: the interplay between monsoon input and tidal reworking in SW Bangladesh

NASA Astrophysics Data System (ADS)

Hale, R. P.; Goodbred, S. L., Jr.; Bain, R. L.; Wilson, C.; Best, J.; Reed, M. J.

2015-12-01

The Ganges-Brahmaputra-Meghna River system (GBM) is among the world's largest in terms of both annual water and sediment discharge. The subaerial delta (110,000 km2) is home to ~160 million people, in addition to the ecologically and economically critical Sundarbans National Forest (SNF). Recent sediment budgets suggest that ~15% of the 1 x 109 t yr-1 sediment load carried by the GBM is subsequently advected along shore and inland via tidal activity, to the otherwise-abandoned SW portion of the delta. A unit-scale estimate based on observed offshore suspended sediment concentrations (SSC) >1.0 g L-1 suggests that sufficient sediment is available in the system to maintain the elevation of the subaerial delta plain, even under current relative sea-level-rise rates. Recent work measuring sedimentation within SNF corroborates this finding, and understanding these sediment delivery dynamics will be critical for protecting the future of nearby regions that are heavily populated, but drastically altered by human activities. Cross-channel hydrodynamic surveys were conducted to estimate what fraction of the water (and sediment) is diverted from the major tidal channels toward the SNF interior. Measurements including profiles of velocity and SSC were collected on spring and neap tides during the dry and monsoon seasons, along transects bracketing major conduit channels into the SNF. During the dry season, we observe water flux at the southern end of the study area to be in approximate equilibrium regardless of tidal range, with SSC <0.3 g L-1 during neap tides, and <1.0 g L-1 during spring tides. North of the SNF conduit channels, we observe equilibrium water discharge and similarly low SSC during neap tides, but a modest ebb dominance and surface SSC >1.0 g L-1 during spring tides. This suggests the possibility of additional inputs of water and sediment from an adjacent tidal channel, as well as a potential source for the deposition observed on the Sundarbans platform during spring-tide flooding. Within channels in SNF, near-bed SSC increase by >5x from neap to spring tides, to a peak of ~1.0 g L-1. Sediment grab samples collected in a distributary channel show a moderate fining trend with distance from the major conduit, which has implications for the sedimentation rates observed on the tidal delta plain.

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...

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...

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...

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...

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

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.

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

Diagnostic performance of indirect MR arthrography for the diagnosis of rotator cuff tears at 3.0 T.

PubMed

Lee, Ji Hyun; Yoon, Young Cheol; Jee, Sukkyung

2015-06-01

Indirect magnetic resonance (MR) arthrography is a non-invasive method for shoulder imaging. However, there are no studies that have examined the diagnostic performance of indirect MR arthrography for the diagnosis of rotator cuff tears in a large patient population. To assess the diagnostic performance of indirect fast spin-echo (FSE) MR arthrography for the diagnosis of rotator cuff tears at 3.0 T. A total of 149 patients who had undergone indirect shoulder MR arthrography followed by arthroscopic surgery were enrolled in this retrospective study. Two musculoskeletal radiologists evaluated images from each patient for the presence of supraspinatus-infraspinatus (SSP-ISP) or subscapularis (SSC) tendon tears. Using the arthroscopic findings as the reference standard, the overall diagnostic performance and detection rates for SSP-ISP and SSC tendon tears were calculated. The sensitivity, specificity, and accuracy of readers I and II for the diagnosis of SSP-ISP tendon tears were 94% and 95%, 89% and 85%, and 93% and 93%, respectively. The sensitivity of imaging for detection of SSP-ISP tendon tears by readers I and II were 100% and 100% for full-thickness tears and 84% and 86% for partial-thickness tears, respectively. The sensitivity, specificity, and accuracy of readers I and II for the diagnosis of SSC tendon tears were 80% and 76%, 89% and 93%, and 85% and 85%, respectively. Indirect MR arthrography is useful for the detection of SSP-ISP and SSC tendon tears. © The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Synchrotron Self-Compton Emission from the Crab and Other Pulsars

NASA Astrophysics Data System (ADS)

Harding, Alice K.; Kalapotharakos, Constantinos

2015-09-01

Results of a simulation of synchrotron self-Compton (SSC) emission from a rotation-powered pulsar are presented. The radiating particles are assumed to be both accelerated primary electrons and a spectrum of electron-positron pairs produced in cascades near the polar cap. They follow trajectories in a slot gap using 3D force-free magnetic field geometry, gaining pitch angles through resonant cyclotron absorption of radio photons, radiating and scattering synchrotron emission at high altitudes out to and beyond the light cylinder. Full angular dependence of the synchrotron photon density is simulated in the scattering and all processes are treated in the inertial observer frame. Spectra for the Crab and Vela pulsars as well as two energetic millisecond pulsars, B1821-24 and B1937+21, are simulated using this model. The simulation of the Crab pulsar radiation can reproduce both the flux level and the shape of the observed optical to hard X-ray emission assuming a pair multiplicity of {M}+=3× {10}5, as well as the very-high-energy emission above 50 GeV detected by MAGIC and VERITAS, with both the synchrotron and SSC components reflecting the shape of the pair spectrum. Simulations of Vela, B1821-24, and B1937+21, for {M}+ up to 105, do not produce pair SSC emission that is detectable by current telescopes, indicating that only Crab-like pulsars produce significant SSC components. The pair synchrotron emission matches the observed X-ray spectrum of the millisecond pulsars, and the predicted peak of this emission at 1-10 MeV would be detectable with planned Compton telescopes.

Adherence to surviving sepsis guidelines among pediatric intensivists

PubMed Central

Thabet, Farah C.; Zahraa, Jihad N.; Chehab, May S.

2017-01-01

Objectives: To assess the compliance with the 2006 American College of Critical Care-Pediatric Advanced Life Support (ACCM-PALS) guidelines for sepsis management, and the 2012 surviving sepsis campaign (SSC), for the management of pediatric patients with sepsis and to identify the main barriers to adherence to these guidelines. Methods: In November 2015, a prospective cohort study in which a web based electronic survey using a case scenario to explore the usual management of a child with severe sepsis was designed and sent to all consultant pediatric intensivists practicing in Kingdom of Saudi Arabia (KSA). Adherences to 2012 SSC guidelines and to 4 algorithmic time-specific goals outlined in the ACCM-PALS guidelines were measured. Results: Sixty-one (76%) of 80 consultant pediatric intensivists working in KSA responded to the survey. Of the 61 respondents, 94% reported administering antibiotics within one hour of the child presentation, 98% reported starting resuscitation by giving fluid boluses, 93% reported starting vasopressor if the patient remained hypotensive despite fluid resuscitation, and 86% reported they would start hydrocortisone in case of catecholamine refractory shock. In total, 80% of the intensivists reported full adherence to all of the 4 components in the ACCM-PALS bundle; 50% reported that the absence of a locally written protocol was the main barrier to adherence to the SSC guidelines. Conclusion: Pediatric intensivists reported good adherence to the 2006 ACCM-PALS guidelines and 2012 SSC guidelines with some variability in interpretation of the recommendations. The absence of a written protocol was the main reported barrier to adherence to these guidelines. PMID:28578440

Adherence to surviving sepsis guidelines among pediatric intensivists. A national survey.

PubMed

Thabet, Farah C; Zahraa, Jihad N; Chehab, May S

2017-06-01

To assess the compliance with the 2006 American College of Critical Care-Pediatric Advanced Life Support (ACCM-PALS) guidelines for sepsis management, and the 2012 surviving sepsis campaign (SSC), for the management of pediatric patients with sepsis and to identify the main barriers to adherence to these guidelines. Methods: In November 2015, a prospective cohort study in which a web based electronic survey using a case scenario to explore the usual management of a child with severe sepsis was designed and sent to all consultant pediatric intensivists practicing in Kingdom of Saudi Arabia (KSA). Adherences to 2012 SSC guidelines and to 4 algorithmic time-specific goals outlined in the ACCM-PALS guidelines were measured. Results: Sixty-one (76%) of 80 consultant pediatric intensivists working in KSA responded to the survey. Of the 61 respondents, 94% reported administering antibiotics within one hour of the child presentation, 98% reported starting resuscitation by giving fluid boluses, 93% reported starting vasopressor if the patient remained hypotensive despite fluid resuscitation, and 86% reported they would start hydrocortisone in case of catecholamine refractory shock. In total, 80% of the intensivists reported full adherence to all of the 4 components in the ACCM-PALS bundle; 50% reported that the absence of a locally written protocol was the main barrier to adherence to the SSC guidelines. Conclusion: Pediatric intensivists reported good adherence to the 2006 ACCM-PALS guidelines and 2012 SSC guidelines with some variability in interpretation of the recommendations. The absence of a written protocol was the main reported barrier to adherence to these guidelines.

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

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

[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.

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.

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.

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.

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).

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

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.

Pertinent spatio-temporal scale of observation to understand suspended sediment yield control factors in the Andean region: the case of the Santa River (Peru)

NASA Astrophysics Data System (ADS)

Morera, S. B.; Condom, T.; Vauchel, P.; Guyot, J.-L.; Galvez, C.; Crave, A.

2013-11-01

Hydro-sedimentology development is a great challenge in Peru due to limited data as well as sparse and confidential information. This study aimed to quantify and to understand the suspended sediment yield from the west-central Andes Mountains and to identify the main erosion-control factors and their relevance. The Tablachaca River (3132 km2) and the Santa River (6815 km2), located in two adjacent Andes catchments, showed similar statistical daily rainfall and discharge variability but large differences in specific suspended-sediment yield (SSY). In order to investigate the main erosion factors, daily water discharge and suspended sediment concentration (SSC) datasets of the Santa and Tablachaca rivers were analysed. Mining activity in specific lithologies was identified as the major factor that controls the high SSY of the Tablachaca (2204 t km2 yr-1), which is four times greater than the Santa's SSY. These results show that the analysis of control factors of regional SSY at the Andes scale should be done carefully. Indeed, spatial data at kilometric scale and also daily water discharge and SSC time series are needed to define the main erosion factors along the entire Andean range.

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.

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

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.

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.

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

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.

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.

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.

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.

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

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.

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

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

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.

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.

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

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.

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

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.

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.

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

[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.

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

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.

An Assessment of the Measurement Equivalence of English and French Versions of the Center for Epidemiologic Studies Depression (CES-D) Scale in Systemic Sclerosis

PubMed Central

Delisle, Vanessa C.; Kwakkenbos, Linda; Hudson, Marie; Baron, Murray; Thombs, Brett D.

2014-01-01

Objectives Center for Epidemiologic Studies Depression (CES-D) Scale scores in English- and French-speaking Canadian systemic sclerosis (SSc) patients are commonly pooled in analyses, but no studies have evaluated the metric equivalence of the English and French CES-D. The study objective was to examine the metric equivalence of the CES-D in English- and French-speaking SSc patients. Methods The CES-D was completed by 1007 English-speaking and 248 French-speaking patients from the Canadian Scleroderma Research Group Registry. 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 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 CES-D items, including items 3 (Blues), 10 (Fearful), and 11 (Sleep). Prior to accounting for DIF, French-speaking patients had 0.08 of a standard deviation (SD) lower latent scores for the Positive factor (95% confidence interval [CI]−0.25 to 0.08) and 0.09 SD higher scores (95% CI−0.07 to 0.24) for the Negative factor than English-speaking patients. After DIF correction, there was no change on the Positive factor and a non-significant increase of 0.04 SD on the Negative factor for French-speaking patients (difference = 0.13 SD, 95% CI−0.03 to 0.28). Conclusions The English and French versions of the CES-D, despite minor DIF on several items, are substantively equivalent and can be used in studies that combine data from English- and French-speaking Canadian SSc patients. PMID:25036894

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.

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...

Randomized, controlled trial of Interpersonal and Social Rhythm Therapy for young people with bipolar disorder.

PubMed

Inder, Maree L; Crowe, Marie T; Luty, Suzanne E; Carter, Janet D; Moor, Stephanie; Frampton, Christopher M; Joyce, Peter R

2015-03-01

This randomized, controlled clinical trial compared the effect of interpersonal and social rhythm therapy (IPSRT) to that of specialist supportive care (SSC) on depressive outcomes (primary), social functioning, and mania outcomes over 26-78 weeks in young people with bipolar disorder receiving psychopharmacological treatment. Subjects were aged 15-36 years, recruited from a range of sources, and the patient groups included bipolar I disorder, bipolar II disorder, and bipolar disorder not otherwise specified. Exclusion criteria were minimal. Outcome measures were the Longitudinal Interval Follow-up Evaluation and the Social Adjustment Scale. Paired-sample t-tests were used to determine the significance of change from baseline to outcome period. Analyses of covariance were used to determine the impact of therapy, impact of lifetime and current comorbidity, interaction between comorbidity and therapy, and impact of age at study entry on depression. A group of 100 participants were randomized to IPSRT (n = 49) or SSC (n = 51). The majority had bipolar I disorder (78%) and were female (76%), with high levels of comorbidity. After treatment, both groups had improved depressive symptoms, social functioning, and manic symptoms. Contrary to our hypothesis, there was no significant difference between therapies. There was no impact of lifetime or current Axis I comorbidity or age at study entry. There was a relative impact of SSC for patients with current substance use disorder. IPSRT and SSC used as an adjunct to pharmacotherapy appear to be effective in reducing depressive and manic symptoms and improving social functioning in adolescents and young adults with bipolar disorder and high rates of comorbidity. Identifying effective treatments that particularly address depressive symptoms is important in reducing the burden of bipolar disorder. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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

[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.

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.

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

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

[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.

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

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.

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.

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

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

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.

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.

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

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.

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.

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.

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

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

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.

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.

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

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

Accelerating proof of concept for small molecule drugs using solid-state chemistry.

PubMed

Byrn, Stephen R; Zografi, George; Chen, Xiaoming Sean

2010-09-01

In this perspective we have shown that the process of "proof of concept" (POC) in the early part of drug development can be greatly accelerated by close attention to the underlying solid-state chemistry (SSC) of a new chemical entity. POC seeks data that provide confidence in the therapeutic activity and safety of a new chemical entity, which can rapidly lead to a key "GO/NO-GO" decision point for further development. Due to the high cost of the development of new chemical entities and the current low overall productivity of obtaining successful candidates, the pharmaceutical industry is being required to develop accelerated POC strategies. The success of accelerated approaches to POC depends on a full understanding of the SSC of drugs in relation to solubility and stability. Dissolution-limited absorption due to poor solubility of drug substances is particularly important because it can lead to low exposure in animals and undesired bioavailability in humans. Choosing a desirable solid form with sufficient solubility and acceptable stability is essential in developing formulations for POC with superior quality. In this perspective we present an approach that utilizes SSC as part of a novel 2-year development strategy for reaching the pivotal clinical trial stage of development.

Velocity and sediment surge: What do we see at times of very shallow water on intertidal mudflats?

NASA Astrophysics Data System (ADS)

Zhang, Qian; Gong, Zheng; Zhang, Changkuan; Townend, Ian; Jin, Chuang; Li, Huan

2016-02-01

A self-designed "bottom boundary layer hydrodynamic and suspended sediment concentration (SSC) measuring system" was built to observe the hydrodynamic and the SSC processes over the intertidal mudflats at the middle part of the Jiangsu coast during August 8-10, 2013. Velocity profiles within 10 cm of the mudflat surface were obtained with a vertical resolution as fine as 1 mm. An ADCP was used to extend the profile over the full water depth with a resolution of 10 cm and the vertical SSC profile was measured at intervals using Optical Backscatter Sensors (OBS). At the same time, water levels and wave conditions were measured with a Tide and Wave Recorder. Measured data suggested that the vertical structure of velocity profiles within 10 cm above the bed maintains a logarithmic distribution during the whole tidal cycle except the slack-water periods. Shallow flows during both the early-flood period and the later-ebb period are characterized by a relatively large vertical velocity gradient and a "surge" feature. We conclude that the very shallow water stages are transient and may not contribute much to the whole water and sediment transport, while they can play a significant role in the formation and evolution of micro-topographies on tidal flats.

Synchrotron Self-Compton Emission from the Crab and Other Pulsars

NASA Technical Reports Server (NTRS)

Harding, Alice K.; Kalapotharakos, Konstantinos

2015-01-01

Results of a simulation of synchrotron-self Compton (SSC) emission from a rotation-powered pulsar are presented. The radiating particles are assumed to be both accelerated primary electrons and a spectrum of electron-positron pairs produced in cascades near the polar cap. They follow trajectories in a slot gap using 3D force-free magnetic field geometry, gaining pitch angles through resonant cyclotron absorption of radio photons, radiating and scattering synchrotron emission at high altitudes out to and beyond the light cylinder. Full angular dependence of the synchrotron photon density is simulated in the scattering and all processes are treated in the inertial observer frame. Spectra for the Crab and Vela pulsars as well as two energetic millisecond pulsars, B1821-24 and B1937+21 are simulated using this model. The simulation of the Crab pulsar radiation can reproduce both the flux level and the shape of the observed optical to hard X-ray emission assuming a pair multiplicity of M+ = 3x10(exp 5), as well as the very-high- energy emission above 50 GeV detected by MAGIC and VERITAS, with both the synchrotron and SSC components reflecting the shape of the pair spectrum. Simulations of Vela, B1821-24 and B1937+21, for M+ up to 10(exp 5), do not produce pair SSC emission that is detectable by current telescopes, indicating that only Crab-like pulsars produce significant SSC components. The pair synchrotron emission matches the observed X-ray spectrum of the millisecond pulsars and the predicted peak of this emission at 1-10 MeV would be detectable with planned Compton telescopes.

Facility Activation and Characterization for IPD Turbopump Testing at NASA Stennis Space Center

NASA Technical Reports Server (NTRS)

Sass, J. P.; Pace, J. S.; Raines, N. G.; Meredith, T. O.; Taylor, S. A.; Ryan, H. M.

2005-01-01

The Integrated Powerhead Demonstrator (IPD) is a 250K lbf (1.1 MN) thrust cryogenic hydrogen/oxygen engine technology demonstrator that utilizes a full flow staged combustion engine cycle. The Integrated Powerhead Demonstrator (IPD) is, in part, supported by NASA. IPD is also supported through the Department of Defense's Integrated High Payoff Rocket Propulsion Technology (IHPRPT) program, which seeks to increase the performance and capability of today's state-of-the-art rocket propulsion systems while decreasing costs associated with military and commercial access to space. The primary industry participants include Boeing-Rocketdyne and GenCorp Aerojet. The IPD Program recently achieved two major milestones. The first was the successful completion of the IPD Oxidizer Turbopump (OTP) hot-fire test project at the NASA John C. Stennis Space Center (SSC) E-1 test facility in June 2003. A total of nine IPD Workhorse Preburner tests were completed, and subsequently 12 IPD OTP hot-fire tests were completed. The second major milestone was the successful completion of the IPD Fuel Turbopump (FTP) cold-flow test project at the NASA SSC E-1 test facility in November 2003. A total of six IPD FTP cold-flow tests were completed. The next phase of development involves IPD integrated engine system testing also at the NASA SSC E-1 test facility scheduled to begin in early 2005. Following and overview of the NASA SSC E-1 test facility, this paper addresses the facility aspects pertaining to the activation and testing of the IPD oxidizer and fuel turbopumps. In addition, some of the facility challenges encountered and the lessons learned during the test projects shall be detailed.

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.

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.

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.

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.

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

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

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

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.

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.

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.

Facility Activation and Characterization for IPD Workhorse Preburner and Oxidizer Turbopump Hot-Fire Testing at NASA Stennis Space Center

NASA Technical Reports Server (NTRS)

Sass, J. P.; Raines, N. G.; Ryan, H. M.

2004-01-01

The Integrated Powerhead Demonstrator (IPD) is a 250K lbf (1.1 MN) thrust cryogenic hydrogen/oxygen engine technology demonstrator that utilizes a full flow staged combustion engine cycle. The Integrated Powerhead Demonstrator (IPD) is part of NASA's Next Generation Launch Technology (NGLT) program, which seeks to provide safe, dependable, cost-cutting technologies for future space launch systems. The project also is part of the Department of Defense's Integrated High Payoff Rocket Propulsion Technology (IHPRPT) program, which seeks to increase the performance and capability of today s state-of-the-art rocket propulsion systems while decreasing costs associated with military and commercial access to space. The primary industry participants include Boeing-Rocketdyne and GenCorp Aerojet. The intended full flow engine cycle is a key component in achieving all of the aforementioned goals. The IPD Program recently achieved a major milestone with the successful completion of the IPD Oxidizer Turbopump (OTP) hot-fire test project at the NASA John C. Stennis Space Center (SSC) E-1 test facility in June 2003. A total of nine IPD Workhorse Preburner tests were completed, and subsequently 12 IPD OTP hot-fire tests were completed. The next phase of development involves IPD integrated engine system testing also at the NASA SSC E-1 test facility scheduled to begin in late 2004. Following an overview of the NASA SSC E-1 test facility, this paper addresses the facility aspects pertaining to the activation and testing of the IPD Workhorse Preburner and the IPD Oxidizer Turbopump. In addition, some of the facility challenges encountered during the test project shall be addressed.

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.

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.

Geodynamic Modeling of the Subduction Zone around the Japanese Islands

NASA Astrophysics Data System (ADS)

Honda, S.

2017-06-01

In this review, which focuses on our research, we describe the development of the thermomechanical modeling of subduction zones, paying special attention to those around the Japanese Islands. Without a sufficient amount of data and observations, models tended to be conceptual and general. However, the increasing power of computational tools has resulted in simple analytical and numerical models becoming more realistic, by incorporating the mantle flow around the subducting slab. The accumulation of observations and data has made it possible to construct regional models to understand the detail of the subduction processes. Recent advancements in the study of the seismic tomography and geology around the Japanese Islands has enabled new aspects of modeling the mantle processes. A good correlation between the seismic velocity anomalies and the finger-like distribution of volcanoes in northeast Japan has been recognized and small-scale convection (SSC) in the mantle wedge has been proposed to explain such a feature. The spatial and temporal evolution of the distribution of past volcanoes may reflect the characteristics of the flow in the mantle wedge, and points to the possibility of the flip-flopping of the finger-like pattern of the volcano distribution and the migration of volcanic activity from the back-arc side to the trench side. These observations are found to be qualitatively consistent with the results of the SSC model. We have also investigated the expected seismic anisotropy in the presence of SSC. The fast direction of the P-wave anisotropy generally shows the trench-normal direction with a reduced magnitude compared to the case without SSC. An analysis of full 3D seismic anisotropy is necessary to confirm the existence and nature of SSC. The 3D mantle flow around the subduction zone of plate-size scale has been modeled. It was found that the trench-parallel flow in the sub-slab mantle around the northern edge of the Pacific plate at the junction between the Aleutian arc and the Kurile arc is generally weak and we have suggested the possible contribution of a hot anomaly in the sub-slab mantle as the origin of possible trench-parallel flow there. A 3D mantle flow model of the back-arc around the junction between the northeast Japan arc and the Kurile arc shows a trench-normal flow at a shallow depth. As a result, the expected seismic anisotropy shows the fast direction normal to the arc, even in the region of oblique subduction. This result is generally consistent with observations there. The existence of a hot anomaly in the sub-slab mantle under the Pacific plate was proposed from an analysis of the seismic tomography, and we have studied its possible origins. The origin of a hot anomaly adjacent to the cold downgoing flow, typically observed in internally heated convection, is preferable to that of a hot anomaly, such as a plume head, carried far from the subduction zone. The nature of the western edge of the stagnant slab under northeast China has been investigated with modeling studies, which take into account the subduction history and the phase changes in the mantle. It is likely to be a ridge-type plate boundary between the extinct Izanagi plate and the Pacific plate. Thus, we have concluded that the slab gap under northeast China is not a breakage of the stagnant slab. Further studies have suggested that the existence of the rheological weakening of the slab in the transition zone, and the additional effects of a hot anomaly in the sub-slab mantle under the Pacific plate, may explain the differences in slab morphology under the northern Okhotsk arc and the northeast Japan arc.

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.

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.

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.

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.

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...

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...

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...

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...

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...

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...

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...

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...

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

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

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...

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.

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.

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

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.

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.

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.

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.

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.

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

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.

A multi-approach and multi-scale study on water quantity and quality changes in the Tapajós River basin, Amazon

NASA Astrophysics Data System (ADS)

Bezerra Nóbrega, Rodolfo Luiz; Lamparter, Gabriele; Hughes, Harold; Chenjerayi Guzha, Alphonce; Santos Silva Amorim, Ricardo; Gerold, Gerhard

2018-04-01

We analyzed changes in water quantity and quality at different spatial scales within the Tapajós River basin (Amazon) based on experimental fieldwork, hydrological modelling, and statistical time-trend analysis. At a small scale, we compared the river discharge (Q) and suspended-sediment concentrations (SSC) of two adjacent micro-catchments ( < 1 km2) with similar characteristics but contrasting land uses (forest vs. pasture) using empirical data from field measurements. At an intermediary scale, we simulated the hydrological responses of a sub-basin of the Tapajós (Jamanxim River basin, 37 400 km2), using a hydrological model (SWAT) and land-use change scenario in order to quantify the changes in the water balance components due to deforestation. At the Tapajós' River basin scale, we investigated trends in Q, sediments, hydrochemistry, and geochemistry in the river using available data from the HYBAM Observation Service. The results in the micro-catchments showed a higher runoff coefficient in the pasture (0.67) than in the forest catchment (0.28). At this scale, the SSC were also significantly greater during stormflows in the pasture than in the forest catchment. At the Jamanxim watershed scale, the hydrological modelling results showed a 2 % increase in Q and a 5 % reduction of baseflow contribution to total Q after a conversion of 22 % of forest to pasture. In the Tapajós River, however, trend analysis did not show any significant trend in discharge and sediment concentration. However, we found upward trends in dissolved organic carbon and NO3- over the last 20 years. Although the magnitude of anthropogenic impact has shown be scale-dependent, we were able to find changes in the Tapajós River basin in streamflow, sediment concentration, and water quality across all studied scales.

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.

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

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

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.

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.

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.

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...

Measurement Sets and Sites Commonly Used for Characterization

NASA Technical Reports Server (NTRS)

Pagnutti, Mary; Holekamp, Kara; Ryan, Robert; Sellers, Richard; Davis, Bruce; Zanoni, Vicki

2002-01-01

Scientists at NASA's Earth Science Applications Directorate are creating a well-characterized Verification & Validation (V&V) site at the Stennis Space Center. This site enables the in-flight characterization of remote sensing systems and the data they acquire. The data are predominantly acquired by commercial, high spatial resolution satellite systems, such as IKONOS and QuickBird 2, and airborne systems. The smaller scale of these newer high resolution remote sensing systems allows scientists to characterize the geometric, spatial, and radiometric data properties using a single V&V site. The targets and techniques used to characterize data from these newer systems can differ significantly from the techniques used to characterize data from the earlier, coarser spatial resolution systems. Scientists are also using the SSC V&V site to characterize thermal infrared systems and active LIDAR systems. SSC employs geodetic targets, edge targets, radiometric tarps, and thermal calibration ponds to characterize remote sensing data products. This paper presents a proposed set of required measurements for visible through long-wave infrared remote sensing systems and a description of the Stennis characterization. Other topics discussed include: 1) The use of ancillary atmospheric and solar measurements taken at SSC that support various characterizations; 2) Additional sites used for radiometric, geometric, and spatial characterization in the continental United States; 3) The need for a standardized technique to be adopted by CEOS and other organizations.

Application of ultrasound and air stripping for the removal of aromatic hydrocarbons from spent sulfidic caustic for use in autotrophic denitrification as an electron donor.

PubMed

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

2013-01-01

Spent sulfidic caustic (SSC) produced from petroleum industry can be reused to denitrify nitrate-nitrogen via a biological nitrogen removal process as an electron donor for sulfur-based autotrophic denitrification, because it has a large amount of dissolved sulfur. However, SSC has to be refined because it also contains some aromatic hydrocarbons, typically benzene, toluene, ethylbenzene, xylene (BTEX) and phenol that are recalcitrant organic compounds. In this study, laboratory-scale ultrasound irradiation and air stripping treatment were applied in order to remove these aromatic hydrocarbons. In the ultrasound system, both BTEX and phenol were exponentially removed by ultrasound irradiation during 60 min of reaction time to give the greatest removal efficiency of about 80%. Whereas, about 95% removal efficiency of BTEX was achieved, but not any significant phenol removal, within 30 min in the air stripping system, indicating that air stripping was a more efficient method than ultrasound irradiation. However, since air stripping did not remove any significant phenol, an additional process for degrading phenol was required. Accordingly, we applied a combined ultrasound and air stripping process. In these experiments, the removal efficiencies of BTEX and phenol were improved compared to the application of ultrasound and air stripping alone. Thus, the combined ultrasound and air stripping treatment is appropriate for refining SSC.

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.

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.

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.

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.

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.

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.

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.

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

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

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

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.

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.

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

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

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.

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.

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.

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.

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

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…

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

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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

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

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.

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.

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.

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...

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.

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

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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

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.

Sediment Concentration and Its Relation to Catchment Characteristics in Forested Headwater Streams of the Sierra Nevada, California

NASA Astrophysics Data System (ADS)

Wagenbrenner, J.; Safeeq, M.; Hunsaker, C. T.

2017-12-01

Sediment yields are highly variable and controlled by multiple topographic, geomorphic, and hydrologic factors that make its generalization or prediction challenging. We examined the characteristics of sediment concentration across ten headwater catchments located in the Kings River Experimental Watersheds, Sierra Nevada, California. Study catchments ranged from 50 to 475 ha and spanned from 1,782 to 2,373 m in elevation in the rain-snow transition zone. Mean annual streamflow ranged from 281 to 408 mm in the low elevation Providence and 436 to 656 mm in the high elevation Bull catchments. We measured suspended sediment concentration (SSC) and bedload sediment yield from 2004-2016. We related these outputs to catchment mean elevation, relief, slope, and drainage density as natural controls and runoff ratio, baseflow index, recession constant, and slope of the flow duration curve as hydrologic controls. The SSC were higher in the high elevation Bull catchments (64 ± 34 mg L-1) as compared to low elevation Providence catchments (30 ± 17 mg L-1). Measured SSC in both Bull and Providence declined with increasing catchment mean elevation (R > - 0.5). We found slope of the flow duration curve (R = 0.85) and recession constant (R = -0.91) as the two of best predictors of SSC in Providence. In Bull, drainage area (R = 0.87) and baseflow index (R = -0.78) were the two best predictors of SSC. The intercept and slope of the suspended sediment yield - discharge rating curve (SSY-Q) in Providence was positively related to catchment relief. In contrast, the SSY-Q intercept increased and SSY-Q slope declined with increasing relief in Bull. The mean annual bedload sediment yield varied between 0.4 Mg km-2 and 4.2 Mg km-2 across the ten watersheds, and bedload contributed a relatively small fraction to the total sediment load. Mean bedload sediment yields across the catchments were most associated with catchment slope and relief. These preliminary results provide insight on the dynamics of sediment yield and the natural range of variability in small headwater Sierra Nevada streams. These results can guide selection of appropriate predictor variables for catchment-scale sediment yield models that inform forest management.

Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial.

PubMed

Granel, Brigitte; Daumas, Aurélie; Jouve, Elisabeth; Harlé, Jean-Robert; Nguyen, Pierre-Sébastien; Chabannon, Christian; Colavolpe, Nathalie; Reynier, Jean-Charles; Truillet, Romain; Mallet, Stéphanie; Baiada, Antoine; Casanova, Dominique; Giraudo, Laurent; Arnaud, Laurent; Veran, Julie; Sabatier, Florence; Magalon, Guy

2015-12-01

In patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune diseases. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability. We did an open-label, single arm, at one study site with 6-month follow-up among 12 female SSc patients with Cochin Hand Function Scale score >20/90. Autologous SVF was obtained from lipoaspirates, using an automated processing system, and subsequently injected into the subcutaneous tissue of each finger in contact with neurovascular pedicles. Primary outcome was the number and the severity of adverse events related to SVF-based therapy. Secondary endpoints were changes in hand disability and fibrosis, vascular manifestations, pain and quality of life from baseline to 2 and 6 months after cell therapy. All enrolled patients had surgery, and there were no dropouts or patients lost to follow-up. No severe adverse events occurred during the procedure and follow-up. Four minor adverse events were reported and resolved spontaneously. A significant improvement in hand disability and pain, Raynaud's phenomenon, finger oedema and quality of life was observed. This study outlines the safety of the autologous SVF cells injection in the hands of patients with SSc. Preliminary assessments at 6 months suggest potential efficacy needing confirmation in a randomised placebo-controlled trial on a larger population. GFRS (Groupe Francophone de Recherche sur la Sclérodermie). NCT01813279. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

[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.

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.

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.

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.

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.

Hydrogen peroxide propulsion for smaller satellites (SSC98-VIII-1)

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

Whitehead, J C

1998-07-13

As satellite designs shrink, providing maneuvering and control capability falls outside the realm of available propulsion technology. While cold gas has been used on the smallest satellites, hydrogen peroxide propellant is suggested as the next step in performance and cost before hydrazine. Minimal toxicity and a small scale enable benchtop propellant preparation and development testing. Progress toward low-cost thrusters and self-pressurizing tank systems is described.

NASA's Space Launch System Takes Shape

NASA Technical Reports Server (NTRS)

Askins, Bruce R.; Robinson, Kimberly F.

2017-01-01

Significant hardware and software for NASA's Space Launch System (SLS) began rolling off assembly lines in 2016, setting the stage for critical testing in 2017 and the launch of new capability for deep-space human exploration. (Figure 1) At NASA's Michoud Assembly Facility (MAF) near New Orleans, LA, full-scale test articles are being joined by flight hardware. Structural test stands are nearing completion at NASA's Marshall Space Flight Center (MSFC), Huntsville, AL. An SLS booster solid rocket motor underwent test firing, while flight motor segments were cast. An RS-25 and Engine Control Unit (ECU) for early SLS flights were tested at NASA's Stennis Space Center (SSC). The upper stage for the first flight was completed, and NASA completed Preliminary Design Review (PDR) for a new, powerful upper stage. The pace of production and testing is expected to increase in 2017. This paper will discuss the technical and programmatic highlights and challenges of 2016 and look ahead to plans for 2017.

Multi-band implications of external-IC flares

NASA Astrophysics Data System (ADS)

Richter, Stephan; Spanier, Felix

2015-02-01

Very fast variability on scales of minutes is regularly observed in Blazars. The assumption that these flares are emerging from the dominant emission zone of the very high energy (VHE) radiation within the jet challenges current acceleration and radiation models. In this work we use a spatially resolved and time dependent synchrotron-self-Compton (SSC) model that includes the full time dependence of Fermi-I acceleration. We use the (apparent) orphan γ -ray flare of Mrk501 during MJD 54952 and test various flare scenarios against the observed data. We find that a rapidly variable external radiation field can reproduce the high energy lightcurve best. However, the effect of the strong inverse Compton (IC) cooling on other bands and the X-ray observations are constraining the parameters to rather extreme ranges. Then again other scenarios would require parameters even more extreme or stronger physical constraints on the rise and decay of the source of the variability which might be in contradiction with constraints derived from the size of the black hole's ergosphere.

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.

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.

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

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.

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.

Replacement of HCFC-225 Solvent for Cleaning NASA Propulsion Oxygen Systems

NASA Technical Reports Server (NTRS)

Lowrey, Nikki M.; Mitchell, Mark A.

2015-01-01

Since the 1990's, when the Class I Ozone Depleting Substance (ODS) chlorofluorocarbon-113 (CFC-113) was banned, NASA's propulsion test facilities at Marshall Space Flight Center (MSFC) and Stennis Space Center (SSC) have relied upon hydrochlorofluorocarbon-225 (HCFC-225) to safely clean and verify the cleanliness of large scale propulsion oxygen systems. Effective January 1, 2015, the production, import, export, and new use of HCFC-225, a Class II ODS, was prohibited by the Clean Air Act. In 2012 through 2014, leveraging resources from both NASA and the Defense Logistics Agency - Aviation Hazardous Minimization and Green Products Branch, test labs at MSFC, SSC, and Johnson Space Center's White Sands Test Facility (WSTF) collaborated to seek out, test, and qualify a replacement for HCFC-225 that is both an effective cleaner and safe for use with oxygen systems. This presentation summarizes the tests performed, results, and lessons learned. It also demonstrates the benefits of cross-agency collaboration in a time of limited resources.

Results of the Test Program for Replacement of AK-225G Solvent for Cleaning NASA Propulsion Oxygen Systems

NASA Technical Reports Server (NTRS)

Lowrey, Nikki M.; Mitchell, Mark A.

2016-01-01

Since the 1990's, when the Class I Ozone Depleting Substance (ODS) chlorofluorocarbon-113 (CFC-113) was banned, NASA's propulsion test facilities at Marshall Space Flight Center (MSFC) and Stennis Space Center (SSC) have relied upon the solvent AsahiKlin AK-225 (hydrochlorofluorocarbon-225ca/cb or HCFC-225ca/cb) and, more recently AK-225G (the single isomer form, HCFC-225cb) to safely clean and verify the cleanliness of large scale propulsion oxygen systems. Effective January 1, 2015, the production, import, export, and new use of Class II Ozone Depleting Substances, including AK-225G, was prohibited in the United States by the Clean Air Act. In 2012 through 2014, NASA test labs at MSFC, SSC, and Johnson Space Center's White Sands Test Facility (WSTF) collaborated to seek out, test, and qualify a solvent replacement for AK-225G that is both an effective cleaner and safe for use with oxygen systems. This paper summarizes the tests performed, results, and lessons learned.

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

Differential regulation of cell functions by CSD peptide subdomains

PubMed Central

2013-01-01

Background In fibrotic lung diseases, expression of caveolin-1 is decreased in fibroblasts and monocytes. The effects of this deficiency are reversed by treating cells or animals with the caveolin-1 scaffolding domain peptide (CSD, amino acids 82–101 of caveolin-1) which compensates for the lack of caveolin-1. Here we compare the function of CSD subdomains (Cav-A, Cav-B, Cav-C, Cav-AB, and Cav-BC) and mutated versions of CSD (F92A and T90A/T91A/F92A). Methods Migration toward the chemokine CXCL12 and the associated expression of F-actin, CXCR4, and pSmad 2/3 were studied in monocytes from healthy donors and SSc patients. Fibrocyte differentiation was studied using PBMC from healthy donors and SSc patients. Collagen I secretion and signaling were studied in fibroblasts derived from the lung tissue of healthy subjects and SSc patients. Results Cav-BC and CSD at concentrations as low as 0.01 μM inhibited the hypermigration of SSc monocytes and TGFβ-activated Normal monocytes and the differentiation into fibrocytes of SSc and Normal monocytes. While CSD also inhibited the migration of poorly migrating Normal monocytes, Cav-A (and other subdomains to a lesser extent) promoted the migration of Normal monocytes while inhibiting the hypermigration of TGFβ-activated Normal monocytes. The effects of versions of CSD on migration may be mediated in part via their effects on CXCR4, F-actin, and pSmad 2/3 expression. Cav-BC was as effective as CSD in inhibiting fibroblast collagen I and ASMA expression and MEK/ERK signaling. Cav-C and Cav-AB also inhibited collagen I expression, but in many cases did not affect ASMA or MEK/ERK. Cav-A increased collagen I expression in scleroderma lung fibroblasts. Full effects on fibroblasts of versions of CSD required 5 μM peptide. Conclusions Cav-BC retains most of the anti-fibrotic functions of CSD; Cav-A exhibits certain pro-fibrotic functions. Results obtained with subdomains and mutated versions of CSD further suggest that the critical functional residues in CSD depend on the cell type and readout being studied. Monocytes may be more sensitive to versions of CSD than fibroblasts and endothelial cells because the baseline level of caveolin-1 in monocytes is much lower than in these other cell types. PMID:24011378

Differential regulation of cell functions by CSD peptide subdomains.

PubMed

Reese, Charles; Dyer, Shanice; Perry, Beth; Bonner, Michael; Oates, James; Hofbauer, Ann; Sessa, William; Bernatchez, Pascal; Visconti, Richard P; Zhang, Jing; Hatfield, Corey M; Silver, Richard M; Hoffman, Stanley; Tourkina, Elena

2013-09-08

In fibrotic lung diseases, expression of caveolin-1 is decreased in fibroblasts and monocytes. The effects of this deficiency are reversed by treating cells or animals with the caveolin-1 scaffolding domain peptide (CSD, amino acids 82-101 of caveolin-1) which compensates for the lack of caveolin-1. Here we compare the function of CSD subdomains (Cav-A, Cav-B, Cav-C, Cav-AB, and Cav-BC) and mutated versions of CSD (F92A and T90A/T91A/F92A). Migration toward the chemokine CXCL12 and the associated expression of F-actin, CXCR4, and pSmad 2/3 were studied in monocytes from healthy donors and SSc patients. Fibrocyte differentiation was studied using PBMC from healthy donors and SSc patients. Collagen I secretion and signaling were studied in fibroblasts derived from the lung tissue of healthy subjects and SSc patients. Cav-BC and CSD at concentrations as low as 0.01 μM inhibited the hypermigration of SSc monocytes and TGFβ-activated Normal monocytes and the differentiation into fibrocytes of SSc and Normal monocytes. While CSD also inhibited the migration of poorly migrating Normal monocytes, Cav-A (and other subdomains to a lesser extent) promoted the migration of Normal monocytes while inhibiting the hypermigration of TGFβ-activated Normal monocytes. The effects of versions of CSD on migration may be mediated in part via their effects on CXCR4, F-actin, and pSmad 2/3 expression. Cav-BC was as effective as CSD in inhibiting fibroblast collagen I and ASMA expression and MEK/ERK signaling. Cav-C and Cav-AB also inhibited collagen I expression, but in many cases did not affect ASMA or MEK/ERK. Cav-A increased collagen I expression in scleroderma lung fibroblasts. Full effects on fibroblasts of versions of CSD required 5 μM peptide. Cav-BC retains most of the anti-fibrotic functions of CSD; Cav-A exhibits certain pro-fibrotic functions. Results obtained with subdomains and mutated versions of CSD further suggest that the critical functional residues in CSD depend on the cell type and readout being studied. Monocytes may be more sensitive to versions of CSD than fibroblasts and endothelial cells because the baseline level of caveolin-1 in monocytes is much lower than in these other cell types.

An experimental study of perovskite-structured mixed ionic- electronic conducting oxides and membranes

NASA Astrophysics Data System (ADS)

Zeng, Pingying

In recent decades, ceramic membranes based on mixed ionic and electronic conducting (MIEC) perovskite-structured oxides have received many attentions for their applications for air separation, or as a membrane reactor for methane oxidation. While numerous perovskite oxide materials have been explored over the past two decades; there are hardly any materials with sufficient practical economic value and performance for large scale applications, which justifies continuing the search for new materials. The main purposes of this thesis study are: (1) develop several novel SrCoO3-delta based MIEC oxides, SrCoCo1-xMxO3-delta, based on which membranes exhibit excellent oxygen permeability; (2) investigate the significant effects of the species and concentration of the dopants M (metal ions with fixed valences) on the various properties of these membranes; (3) investigate the significant effects of sintering temperature on the microstructures and performance of oxygen permeation membranes; and (4) study the performance of oxygen permeation membranes as a membrane reactor for methane combustion. To stabilize the cubic phase structure of the SrCoO3-delta oxide, various amounts of scandium was doped into the B-site of SrCoO 3-delta to form a series of new perovskite oxides, SrScxCoCo 1-xO3-delta (SSCx, x = 0-0.7). The significant effects of scandium-doping concentration on the phase structure, electrical conductivity, sintering performance, thermal and structural stability, cathode performance, and oxygen permeation performance of the SSCx membranes, were systematically studied. Also for a more in-depth understanding, the rate determination steps for the oxygen transport process through the membranes were clarified by theoretical and experimental investigation. It was found that only a minor amount of scandium (5 mol%) doping into the B-site of SrCoO3-delta can effectively stabilize the cubic phase structure, and thus significantly improve the electrical conductivity and oxygen permeability of the SrCoO3-delta membrane. Among all the disk-shaped SSCx (x = 0-0.7) membranes with a thickness of 0.91 mm, both SSC0.05 and SSC0.1 exhibit the highest oxygen permeation rate of about 3.2 mL.cm-2.min-1 (STP) at 900 °C, SSC0.1 also shows excellent cathode performance for a solid oxide fuel cell. Therefore SSC0.1 is of special interest, and thus investigated regarding the performance as a membrane reactor for methane combustion. The performance was evaluated based on the results of methane conversion rates and CO 2 selectivity. Inspired by the above findings, a series of mixed-conducting perovskite oxides SrCo0.95M0.05O3-delta (SCM, M = Bi5+, Zr4+, Ce4+, Sc3+ , La3+, Y3+, Al3+, Zn 2+) were prepared to study the effects of different dopants M on the performance of SrCo0.95M0.05O3-delta. It was found that the M cations significantly affect the crystal phase structure, grain growth, membrane porosity, electrical conductivity, and the oxygen permeability of the SCM membranes. Specifically, it is postulated in this study that the formation of the cubic perovskite structure is dependent on the electron configuration in the outer orbits of M cations, which may provide theoretical guidance for future development of high oxygen permeation ceramic membranes based on the perovskite materials. To study the significant effects of grain sizes on the oxygen permeation behaviors of La0.6Sr0.4Co0.2Fe0.8O3-delta (LSCF) and SrSc0.1Co0.9O 3-delta (SSC0.1) membranes, the LSCF and SSC0.1 membranes were sintered at various temperatures to form different microstructures. Properties of these membranes with varied grain sizes were compared. Results showed that the oxygen permeation rate of the LSCF membrane increases with increasing the grain size, however, it is interesting that the oxygen permeation rate of the SSC0.1 membrane decreases with increasing the grain size. This implies that oxygen transport occurs more, however, less rapidly along grain boundaries than through the bulks in the LSCF and SSC0.1 membranes, respectively. A LSCF hollow fiber membrane and a SSC0.1 planar membrane were applied as membrane reactors for methane combustion. To improve their performances, LSCF powder and SSC0.1 powder were dip-coated and spray-coated on the permeation sides of LSCF hollow fiber membranes and SSC0.1 planar membranes, respectively. The exhaust gas components were analyzed by Gas Chromatography (GC). The performance was evaluated based on the results of methane conversion rates and CO 2 selectivity. The highest CO2 selectivity of the LSCF hollow fiber membrane and the SSC0.1 planar membrane is about 88 and 85 %, respectively. This indicates that the application of an oxygen permeation membrane as methane combustion reactor is feasible.

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.

Evaluation of the Subscapularis Tendon Tears on 3T Magnetic Resonance Arthrography: Comparison of Diagnostic Performance of T1-Weighted Spectral Presaturation with Inversion-Recovery and T2-Weighted Turbo Spin-Echo Sequences.

PubMed

Lee, Hoseok; Ahn, Joong Mo; Kang, Yusuhn; Oh, Joo Han; Lee, Eugene; Lee, Joon Woo; Kang, Heung Sik

2018-01-01

To compare the T1-weighted spectral presaturation with inversion-recovery sequences (T1 SPIR) with T2-weighted turbo spin-echo sequences (T2 TSE) on 3T magnetic resonance arthrography (MRA) in the evaluation of the subscapularis (SSC) tendon tear with arthroscopic findings as the reference standard. This retrospective study included 120 consecutive patients who had undergone MRA within 3 months between April and December 2015. Two musculoskeletal radiologists blinded to the arthroscopic results evaluated T1 SPIR and T2 TSE images in separate sessions for the integrity of the SSC tendon, examining normal/articular-surface partial-thickness tear (PTTa)/full-thickness tear (FTT). Diagnostic performance of T1 SPIR and T2 TSE was calculated with arthroscopic results as the reference standard, and sensitivity, specificity, and accuracy were compared using the McNemar test. Interobserver agreement was measured with kappa (κ) statistics. There were 74 SSC tendon tears (36 PTTa and 38 FTT) confirmed by arthroscopy. Significant differences were found in the sensitivity and accuracy between T1 SPIR and T2 TSE using the McNemar test, with respective rates of 95.9-94.6% vs. 71.6-75.7% and 90.8-91.7% vs. 79.2-83.3% for detecting tear; 55.3% vs. 31.6-34.2% and 85.8% vs. 78.3-79.2%, respectively, for FTT; and 91.7-97.2% vs. 58.3-61.1% and 89% vs. 78-79.3%, respectively, for PTTa. Interobserver agreement for T1 SPIR was almost perfect for T1 SPIR (κ = 0.839) and substantial for T2 TSE (κ = 0.769). T1-weighted spectral presaturation with inversion-recovery sequences is more sensitive and accurate compared to T2 TSE in detecting SSC tendon tear on 3T MRA.

Tributaries affect the thermal response of lakes to climate change

NASA Astrophysics Data System (ADS)

Råman Vinnå, Love; Wüest, Alfred; Zappa, Massimiliano; Fink, Gabriel; Bouffard, Damien

2018-01-01

Thermal responses of inland waters to climate change varies on global and regional scales. The extent of warming is determined by system-specific characteristics such as fluvial input. Here we examine the impact of ongoing climate change on two alpine tributaries, the Aare River and the Rhône River, and their respective downstream peri-alpine lakes: Lake Biel and Lake Geneva. We propagate regional atmospheric temperature effects into river discharge projections. These, together with anthropogenic heat sources, are in turn incorporated into simple and efficient deterministic models that predict future water temperatures, river-borne suspended sediment concentration (SSC), lake stratification and river intrusion depth/volume in the lakes. Climate-induced shifts in river discharge regimes, including seasonal flow variations, act as positive and negative feedbacks in influencing river water temperature and SSC. Differences in temperature and heating regimes between rivers and lakes in turn result in large seasonal shifts in warming of downstream lakes. The extent of this repressive effect on warming is controlled by the lakes hydraulic residence time. Previous studies suggest that climate change will diminish deep-water oxygen renewal in lakes. We find that climate-related seasonal variations in river temperatures and SSC shift deep penetrating river intrusions from summer towards winter. Thus potentially counteracting the otherwise negative effects associated with climate change on deep-water oxygen content. Our findings provide a template for evaluating the response of similar hydrologic systems to on-going climate change.

[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.

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

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

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

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.

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.

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.

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.

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

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

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

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

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.

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.

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.

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.

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

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).

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.

Estimation of suspended sediment concentration from turbidity measurements using artificial neural networks.

PubMed

Bayram, Adem; Kankal, Murat; Onsoy, Hizir

2012-07-01

Suspended sediment concentration (SSC) is generally determined from the direct measurement of sediment concentration of river or from sediment transport equations. Direct measurement is very costly and cannot be conducted for all river gauge stations. Therefore, correct estimation of suspended sediment amount carried by a river is very important in terms of water pollution, channel navigability, reservoir filling, fish habitat, river aesthetics and scientific interests. This study investigates the feasibility of using turbidity as a surrogate for SSC as in situ turbidity meters are being increasingly used to generate continuous records of SSC in rivers. For this reason, regression analysis (RA) and artificial neural networks (ANNs) were employed to estimate SSC based on in situ turbidity measurements. The SSC was firstly experimentally determined for the surface water samples collected from the six monitoring stations along the main branch of the stream Harsit, Eastern Black Sea Basin, Turkey. There were 144 data for each variable obtained on a fortnightly basis during March 2009 and February 2010. In the ANN method, the used data for training, testing and validation sets are 108, 24 and 12 of total 144 data, respectively. As the results of analyses, the smallest mean absolute error (MAE) and root mean square error (RMSE) values for validation set were obtained from the ANN method with 11.40 and 17.87, respectively. However these were 19.12 and 25.09 for RA. It was concluded that turbidity could be a surrogate for SSC in the streams, and the ANNs method used for the estimation of SSC provided acceptable results.

Computerized nailfold video capillaroscopy--a new tool for assessment of Raynaud's phenomenon.

PubMed

Anderson, Marina E; Allen, P Danny; Moore, Tonia; Hillier, Val; Taylor, Christopher J; Herrick, Ariane L

2005-05-01

To develop a computer based nailfold video capillaroscopy system with enhanced image quality and to assess its disease-subgroup resolving power in patients with primary and secondary Raynaud's phenomenon (RP). Using frame registration software, digitized video images from the microscope were combined to form a panoramic mosaic of the nailfold. Capillary dimensions (apex, arterial, venous, and total width) and density were measured onscreen. Significantly, the new system could guarantee analysis of the same set of capillaries by 2 observers. Forty-eight healthy control subjects, 21 patients with primary RP, 40 patients with limited cutaneous systemic sclerosis (lcSSc), and 11 patients with diffuse cutaneous SSc (dcSSc) were studied. Intra- and interobserver variability were calculated in a subset of 30 subjects. The number of loops/mm was significantly lower, and all 4 capillary dimensions significantly greater, in SSc patients versus controls plus primary RP patients (p < 0.001 for all measures). When comparing control (+ primary RP) patients with SSc patients (lcSSc + dcSSc) the most powerful discriminator was found to be the number of loops/mm. Results for intra- and interobserver reproducibility showed that the limits of agreement were closer when both observers measured the same capillaries. The key feature of the newly developed system is that it improves reproducibility of nailfold capillary measurements by allowing reidentification of the same capillaries by different observers. By allowing access to previous measurements, the new system should improve reliability in longitudinal studies, and therefore has the potential of being a valuable outcome measure of microvessel disease/involvement in clinical trials of scleroderma spectrum disorders.

Characterization of the HLA-DRβ1 third hypervariable region amino acid sequence according to charge and parental inheritance in systemic sclerosis.

PubMed

Gentil, Coline A; Gammill, Hilary S; Luu, Christine T; Mayes, Maureen D; Furst, Dan E; Nelson, J Lee

2017-03-07

Specific HLA class II alleles are associated with systemic sclerosis (SSc) risk, clinical characteristics, and autoantibodies. HLA nomenclature initially developed with antibodies as typing reagents defining DRB1 allele groups. However, alleles from different DRB1 allele groups encode the same third hypervariable region (3rd HVR) sequence, the primary T-cell recognition site, and 3rd HVR charge differences can affect interactions with T cells. We considered 3rd HVR sequences (amino acids 67-74) irrespective of the allele group and analyzed parental inheritance considered according to the 3rd HVR charge, comparing SSc patients with controls. In total, 306 families (121 SSc and 185 controls) were HLA genotyped and parental HLA-haplotype origin was determined. Analysis was conducted according to DRβ1 3rd HVR sequence, charge, and parental inheritance. The distribution of 3rd HVR sequences differed in SSc patients versus controls (p = 0.007), primarily due to an increase of specific DRB1*11 alleles, in accord with previous observations. The 3rd HVR sequences were next analyzed according to charge and parental inheritance. Paternal transmission of DRB1 alleles encoding a +2 charge 3rd HVR was significantly reduced in SSc patients compared with maternal transmission (p = 0.0003, corrected for analysis of four charge categories p = 0.001). To a lesser extent, paternal transmission was increased when charge was 0 (p = 0.021, corrected for multiple comparisons p = 0.084). In contrast, paternal versus maternal inheritance was similar in controls. SSc patients differed from controls when DRB1 alleles were categorized according to 3rd HVR sequences. Skewed parental inheritance was observed in SSc patients but not in controls when the DRβ1 3rd HVR was considered according to charge. These observations suggest that epigenetic modulation of HLA merits investigation in SSc.

Decreased Interleukin-20 Expression in Scleroderma Skin Contributes to Cutaneous Fibrosis

PubMed Central

Kudo, Hideo; Jinnin, Masatoshi; Asano, Yoshihide; Trojanowska, Maria; Nakayama, Wakana; Inoue, Kuniko; Honda, Noritoshi; Kajihara, Ikko; Makino, Katsunari; Fukushima, Satoshi; Ihn, Hironobu

2014-01-01

Objective To clarify the role of interleukin-20 (IL-20) in the regulatory mechanism of extracellular matrix expression and to determine the contribution of IL-20 to the phenotype of systemic sclerosis (SSc). Methods Protein and messenger RNA (mRNA) levels of collagen, Fli-1, IL-20, and IL-20 receptor (IL-20R) were analyzed using polymerase chain reaction (PCR) array, immunoblotting, immunohistochemical staining, enzyme-linked immunosorbent assay, and real-time PCR. Results PCR array revealed that IL-20 decreased gene expression of α2(I) collagen (0.03-fold), Smad3 (0.02-fold), and endoglin (0.05-fold) in cultured normal dermal fibroblasts. Fli-1 protein expression was induced by IL-20 (~2-fold). The inhibition of collagen by IL-20, the induction of Fli-1 by IL-20, and the reduction of Smad3 and endoglin by IL-20 were also observed in SSc fibroblasts. Serum IL-20 levels were reduced only slightly in SSc patients but were significantly decreased in patients with scleroderma spectrum disorders (the prodromal stage of SSc) compared with those in normal subjects (111.3 pg/ml versus 180.4 pg/ml; P < 0.05). On the other hand, IL-20 mRNA expression in SSc skin was decreased compared with that in normal skin (P < 0.05), which may result in the induction of collagen synthesis in SSc dermal fibroblasts. IL-20R was expressed in normal and SSc fibroblasts. Moreover, IL-20 supplementation by injection into the skin reversed skin fibrosis induced by bleomycin in mice (~0.5-fold). Conclusion IL-20 reduces basal collagen transcription via Fli-1 induction, while down-regulation of Smad3 and endoglin may cancel the effect of transforming growth factor β in SSc fibroblasts. To confirm the therapeutic value of IL-20 and IL-20R, their function and expression in vivo should be further studied. PMID:24470401

Decreased interleukin-20 expression in scleroderma skin contributes to cutaneous fibrosis.

PubMed

Kudo, Hideo; Jinnin, Masatoshi; Asano, Yoshihide; Trojanowska, Maria; Nakayama, Wakana; Inoue, Kuniko; Honda, Noritoshi; Kajihara, Ikko; Makino, Katsunari; Fukushima, Satoshi; Ihn, Hironobu

2014-06-01

To clarify the role of interleukin-20 (IL-20) in the regulatory mechanism of extracellular matrix expression and to determine the contribution of IL-20 to the phenotype of systemic sclerosis (SSc). Protein and messenger RNA (mRNA) levels of collagen, Fli-1, IL-20, and IL-20 receptor (IL-20R) were analyzed using polymerase chain reaction (PCR) array, immunoblotting, immunohistochemical staining, enzyme-linked immunosorbent assay, and real-time PCR. PCR array revealed that IL-20 decreased gene expression of α2(I) collagen (0.03-fold), Smad3 (0.02-fold), and endoglin (0.05-fold) in cultured normal dermal fibroblasts. Fli-1 protein expression was induced by IL-20 (~2-fold). The inhibition of collagen by IL-20, the induction of Fli-1 by IL-20, and the reduction of Smad3 and endoglin by IL-20 were also observed in SSc fibroblasts. Serum IL-20 levels were reduced only slightly in SSc patients but were significantly decreased in patients with scleroderma spectrum disorders (the prodromal stage of SSc) compared with those in normal subjects (111.3 pg/ml versus 180.4 pg/ml; P < 0.05). On the other hand, IL-20 mRNA expression in SSc skin was decreased compared with that in normal skin (P < 0.05), which may result in the induction of collagen synthesis in SSc dermal fibroblasts. IL-20R was expressed in normal and SSc fibroblasts. Moreover, IL-20 supplementation by injection into the skin reversed skin fibrosis induced by bleomycin in mice (~0.5-fold). IL-20 reduces basal collagen transcription via Fli-1 induction, while down-regulation of Smad3 and endoglin may cancel the effect of transforming growth factor β in SSc fibroblasts. To confirm the therapeutic value of IL-20 and IL-20R, their function and expression in vivo should be further studied. Copyright © 2014 by the American College of Rheumatology.

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.

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

PubMed Central

2014-01-01

Introduction A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy. Methods Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis. Conclusion Our results suggest a role of PPARG gene in the development of SSc. PMID:24401602

Anti-Ephrin Type-B Receptor 2 (EphB2) and Anti-Three Prime Histone mRNA EXonuclease 1 (THEX1) Autoantibodies in Scleroderma and Lupus

PubMed Central

Azzouz, Doua F.; Martin, Gabriel V.; Arnoux, Fanny; Balandraud, Nathalie; Martin, Thierry; Dubucquoi, Sylvain; Hachulla, Eric; Farge-Bancel, Dominique; Tiev, Kiet; Cabane, Jean; Bardin, Nathalie; Chiche, Laurent; Martin, Marielle; Caillet, Eléonore C.; Kanaan, Sami B.; Harlé, Jean Robert; Granel, Brigitte; Diot, Elisabeth; Roudier, Jean; Auger, Isabelle; Lambert, Nathalie C.

2016-01-01

In a pilot ProtoArray analysis, we identified 6 proteins out of 9483 recognized by autoantibodies (AAb) from patients with systemic sclerosis (SSc). We further investigated the 6 candidates by ELISA on hundreds of controls and patients, including patients with Systemic Lupus Erythematosus (SLE), known for high sera reactivity and overlapping AAb with SSc. Only 2 of the 6 candidates, Ephrin type-B receptor 2 (EphB2) and Three prime Histone mRNA EXonuclease 1 (THEX1), remained significantly recognized by sera samples from SSc compared to controls (healthy or with rheumatic diseases) with, respectively, 34% versus 14% (P = 2.10−4) and 60% versus 28% (P = 3.10−8). Above all, EphB2 and THEX1 revealed to be mainly recognized by SLE sera samples with respectively 56%, (P = 2.10−10) and 82% (P = 5.10−13). As anti-EphB2 and anti-THEX1 AAb were found in both diseases, an epitope mapping was realized on each protein to refine SSc and SLE diagnosis. A 15-mer peptide from EphB2 allowed to identify 35% of SLE sera samples (N = 48) versus only 5% of any other sera samples (N = 157), including SSc sera samples. AAb titers were significantly higher in SLE sera (P<0.0001) and correlated with disease activity (p<0.02). We could not find an epitope on EphB2 protein for SSc neither on THEX1 for SSc or SLE. We showed that patients with SSc or SLE have AAb against EphB2, a protein involved in angiogenesis, and THEX1, a 3’-5’ exoribonuclease involved in histone mRNA degradation. We have further identified a peptide from EphB2 as a specific and sensitive tool for SLE diagnosis. PMID:27617966

Prevalence of subclinical atherosclerosis is increased in systemic sclerosis and is associated with serum proteins: a cross-sectional, controlled study of carotid ultrasound.

PubMed

Schiopu, Elena; Au, Karen M; McMahon, Maureen A; Kaplan, Mariana J; Divekar, Anagha; Singh, Ram R; Furst, Daniel E; Clements, Philip J; Ragvendra, Nagesh; Zhao, Wenpu; Maranian, Paul; Khanna, Dinesh

2014-04-01

SSc is associated with an increased prevalence of atherosclerosis (ATS). This study assessed the prevalence of subclinical ATS as measured by carotid US and explored serum proteins to identify potential biomarkers of SSc-ATS. Forty-six SSc female patients and 46 age- and ethnicity-matched controls underwent carotid US to assess the presence of plaque and carotid intima media thickness (CIMT). Abstracted data included demographics, ATS risk factors and serum measurements [cholesterol, proinflammatory high-density lipoprotein (piHDL), CRP, lipoproteins]. Serum cytokines/proteins analyses included circulating type I IFN activity by quantifying IFN-inducible genes, soluble junctional adhesion molecule A (sJAM-A) and 100 serum proteins by using a microplate-based multiplex platform. Proteins significant at P < 0.05 on bivariate analyses for the presence of plaque were used to develop a composite measure. Patients with SSc had more plaque (45.6% vs 19.5%, P = 0.01) but similar CIMT compared with controls. Multiplex analysis detected significant associations between serum proteins of inflammation, vasculopathy and fibrosis with ATS in SSc, including IL-2, IL-6, CRP, keratinocyte growth factor, intercellular adhesion molecule 1, endoglin, plasminogen activator inhibitor 1 and insulin-like growth factor binding protein 3 associated with carotid plaque. Myeloid progenitor inhibitory factor 1, serum amyloid A, thrombomodulin, N-terminal pro-brain natriuretic peptide (BNP), and Clara cell secretory protein 16 kD correlated with CIMT. The median composite score for the plaque group was 6 and for the no plaque group it was 2 (P < 0.0001). Patients with SSc have a higher prevalence of carotid plaque than matched controls, and patients with SSc-plaque vs patients without plaque have elevated serum proteins implicated in both vasculopathy and fibrosis. Further studies are needed to evaluate the role of these proteins in SSc compared with healthy controls.

Nailfold Capillaroscopy - Its Role in Diagnosis and Differential Diagnosis of Microvascular Damage in Systemic Sclerosis.

PubMed

Lambova, Sevdalina; Hermann, W; Muller-Ladner, Ulf

2013-01-01

In the nailfold area, specific diagnostic microvascular abnormalities are easily recognized via capillaroscopic examination in systemic sclerosis (SSc). They are termed "scleroderma" type capillaroscopic pattern, which includes presence of dilated, giant capillaries, haemorrhages, avascular areas, and neoangiogenic capillaries and are observed in the majority of SSc patients (in more than 90%). LeRoy and Medsger (2001) proposed criteria for early diagnosis of SSc with inclusion of the abnormal capillaroscopic changes and suggested to prediagnose SSc prior to the development of other manifestations of the disease. It is a new era in the diagnosis of SSc. At present, an international multicenter project is performed. It aims validation of criteria for very early diagnosis of SSc (project VEDOSS (Very Early Diagnosis of Systemic Sclerosis) and is organized by European League Against Rheumatism (EULAR) Scleroderma Trials and Reasearch. Very recently the first results of the VEDOSS project were processed and new EULAR/ACR (American College of Rheumatology) classification criteria have been validated and published (2013), in which the characteristic capillaroscopic changes have been included. Our observations confirm the high frequency of the specific capillaroscopic changes of the fingers in SSc, which have been found in 97.2% of the cases from the studied patient population. We have performed for the first time capillaroscopic examinations of the toes in SSc. Interestingly,"scleroderma type" capillaroscopic pattern was also found at the toes in a high proportion of patients - 66.7%, but it is significantly less frequent as compared with fingers (97.2%, p<0.05). In our opinion, the examination of the toes of SSc patients should be considered as it suggests an additional opportunity for evaluation of the microvascular changes in these patients although the observed changes are in a lower proportion of cases. Thus, capillaroscopic examination is a cornerstone for the very early diagnosis of SSc. Patients with clinical symptoms of peripheral vasospasm (Raynaud's phenomenon (RP)) in association with puffy fingers and/or sclerodactyly should be carefully examined. Hence, appearance of "scleroderma" type capillaroscopic changes in RP patients should be interpreted in the clinical context, because some of the components of this pattern may be observed in several other connective tissue diseases such as mixed connective tissue disease, undifferentiated connective tissue disease that are termed "scleroderma-like" capillaroscopic changes. Capillaroscopic examination is an obligatory screening method in these cases, but the pathologic capillaroscopic changes are not specific and their interpretation is in clinical context.

Investigating the Effects of Variable Water Type for VIIRS Calibration

NASA Astrophysics Data System (ADS)

Bowers, J.; Ladner, S.; Martinolich, P.; Arnone, R.; Lawson, A.; Crout, R. L.; Vandermeulen, R. A.

2016-02-01

The Naval Research Laboratory - Stennis Space Center (NRL-SSC) currently provides calibration and validation support for the Visible Infrared Imaging Radiometer Suite (VIIRS) satellite ocean color products. NRL-SSC utilizes the NASA Ocean Biology Processing Group (OBPG) methodology for on-orbit vicarious calibration with in situ data collected in blue ocean water by the Marine Optical Buoy (MOBY). An acceptable calibration consists of 20-40 satellite to in situ matchups that establish the radiance correlation at specific points within the operating range of the VIIRS instrument. While the current method improves the VIIRS performance, the MOBY data alone does not represent the full range of radiance values seen in the coastal oceans. However, by utilizing data from the AERONET-OC coastal sites we expand our calibration matchups to cover a more realistic range of continuous values particularly in the green and red spectral regions of the sensor. Improved calibration will provide more accurate data to support daily operations and enable construction of valid climatology for future reference.

Practical barriers to the implementation of early goal directed therapy in the UK: trainee skills and awareness.

PubMed

McNally, S J; MacKinnon, M; Hawkins, M

2009-08-01

The Surviving Sepsis Campaign (SSC) recommends Early Goal Directed Therapy (EGDT) in the treatment of septic shock, which requires key critical care skills and knowledge. This study evaluates the availability of these skills in Specialist Registrars in acute hospital specialities in the UK. A questionnaire was sent to Specialist Registrars in Anaesthetics, General Surgery and General Medicine throughout Scotland. One hundred and eighty five responses were obtained. One hundred percent of anaesthetists, 70% of surgeons and 51% of physicians were aware of EGDT Only 62 trainees (6% of surgeons, 79% of anaesthetists, 19% of physicians) had the full complement of skills and knowledge to implement EGDT. This study demonstrates that non-anaesthetic registrars in the UK lack both knowledge and skills required to provide EGDT. The main deficit was in awareness, demonstrating that knowledge of EGDT is not penetrating into specialities beyond anaesthesia. It is now time for the SSC to specifically target non-anaesthetic specialities.

Comparative Analyses of the Teaching Methods and Evaluation Practices in English Subject at Secondary School Certificate (SSC) and General Certificate of Education (GCE O-Level) in Pakistan

ERIC Educational Resources Information Center

Behlol, Malik Ghulam; Anwar, Mohammad

2011-01-01

The study was conducted to compare the teaching methods and evaluation practices in English subject at secondary school certificate (SSC) and general certificate of education GCE-O-level in Pakistan. The population of the study was students, teachers and experts at SSC and 0-level in the Punjab province. Purposive and random sampling techniques…

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

Compton scattering of self-absorbed synchrotron emission

NASA Astrophysics Data System (ADS)

Gao, He; Lei, Wei-Hua; Wu, Xue-Feng; Zhang, Bing

2013-11-01

Synchrotron self-Compton (SSC) scattering is an important emission mechanism in many astronomical sources, such as gamma-ray bursts (GRBs) and active galactic nuclei. We give a complete presentation of the analytical approximations for the Compton scattering of synchrotron emission with both weak and strong synchrotron self-absorption. All possible orders of the characteristic synchrotron spectral breaks (νa, νm and νc) are studied. In the weak self-absorption regime, i.e. νa < νc, the electron energy distribution is not modified by the self-absorption process. The shape of the SSC component broadly resembles that of synchrotron, but with the following features: The SSC flux increases linearly with frequency up to the SSC break frequency corresponding to the self-absorption frequency νa; and the presence of a logarithmic term in the high-frequency range of the SSC spectra makes it harder than the power-law approximation. In the strong absorption regime, i.e. νa > νc, heating of low-energy electrons due to synchrotron absorption leads to pile-up of electrons, and form a thermal component besides the broken power-law component. This leads to two-component (thermal + non-thermal) spectra for both the synchrotron and SSC spectral components. For νc < νa < νm, the spectrum is thermal (non-thermal) dominated if ν _a > √{ν _m ν _c} (ν _a < √{ν _m ν _c}). Similar to the weak-absorption regime, the SSC spectral component is broader than the simple broken power-law approximation. We derive the critical condition for strong absorption (electron pile-up), and discuss a case of GRB reverse shock emission in a wind medium, which invokes νa > max(νm, νc).

Language, learning, and memory in children with and without single-suture craniosynostosis.

PubMed

Kapp-Simon, Kathleen A; Wallace, Erin; Collett, Brent R; Cradock, Mary Michaeleen; Crerand, Canice E; Speltz, Matthew L

2016-05-01

OBJECTIVE The language and memory functions of children with and without single-suture craniosynostosis (SSC) were compared at school age (mean 7.45 years, standard deviation [SD] 0.54 years). The children in this cohort were originally recruited in infancy and prior to cranial surgery for those with SSC. METHODS Individual evaluations of 179 school-aged children with SSC and 183 controls were conducted (70% of the original cohort) using standardized measures of language, learning, and memory. Parents participated in an interview about specialized education interventions and school progress. Parents and teachers completed questionnaires about language development. RESULTS Children with SSC (cases) obtained lower scores than controls on all measures. The adjusted differences in language, learning, and memory scores were modest, with SD ranging from 0.0 to -0.4 (p values ranged from 0.001 to 0.99). Censored normal regression was used to account for intervention services received prior to the school-age evaluation; this increased case-control differences (SD range 0.1 to -0.5, p value range 0.001 to 0.50). Mean scores for cases in each SSC diagnostic group were lower than those for controls, with the greatest differences observed among children with unilateral coronal craniosynostosis. CONCLUSIONS Children with SSC continue to show poorer performance than controls on language, learning, and memory tasks at early elementary school age, even when controlling for known confounders, although mean differences are small. Multidisciplinary care, including direct psychological assessment, for children with SSC should extend through school age with a specific focus on language and conceptual learning, as these are areas of potential risk. Future research is needed to investigate language, memory, and learning for this population during the middle to high school years.

Comparison of fluvial suspended-sediment concentrations and particle-size distributions measured with in-stream laser diffraction and in physical samples

USGS Publications Warehouse

Czuba, Jonathan A.; Straub, Timothy D.; Curran, Christopher A.; Landers, Mark N.; Domanski, Marian M.

2015-01-01

Laser-diffraction technology, recently adapted for in-stream measurement of fluvial suspended-sediment concentrations (SSCs) and particle-size distributions (PSDs), was tested with a streamlined (SL), isokinetic version of the Laser In-Situ Scattering and Transmissometry (LISST) for measuring volumetric SSCs and PSDs ranging from 1.8-415 µm in 32 log-spaced size classes. Measured SSCs and PSDs from the LISST-SL were compared to a suite of 22 datasets (262 samples in all) of concurrent suspended-sediment and streamflow measurements using a physical sampler and acoustic Doppler current profiler collected during 2010-12 at 16 U.S. Geological Survey streamflow-gaging stations in Illinois and Washington (basin areas: 38 – 69,264 km2). An unrealistically low computed effective density (mass SSC / volumetric SSC) of 1.24 g/ml (95% confidence interval: 1.05-1.45 g/ml) provided the best-fit value (R2 = 0.95; RMSE = 143 mg/L) for converting volumetric SSC to mass SSC for over 2 orders of magnitude of SSC (12-2,170 mg/L; covering a substantial range of SSC that can be measured by the LISST-SL) despite being substantially lower than the sediment particle density of 2.67 g/ml (range: 2.56-2.87 g/ml, 23 samples). The PSDs measured by the LISST-SL were in good agreement with those derived from physical samples over the LISST-SL's measureable size range. Technical and operational limitations of the LISST-SL are provided to facilitate the collection of more accurate data in the future. Additionally, the spatial and temporal variability of SSC and PSD measured by the LISST-SL is briefly described to motivate its potential for advancing our understanding of suspended-sediment transport by rivers.

Quantifying the direct public health care cost of systemic sclerosis

PubMed Central

Morrisroe, Kathleen; Stevens, Wendy; Sahhar, Joanne; Ngian, Gene-Siew; Rabusa, Candice; Ferdowsi, Nava; Hill, Catherine; Proudman, Susanna; Nikpour, Mandana

2017-01-01

Abstract To quantify the direct healthcare cost of systemic sclerosis (SSc) and identify its determinants. Healthcare use was captured through data linkage, wherein clinical and medication data for SSc patients from the state of Victoria enrolled in the Australian Scleroderma Cohort Study were linked with the Victorian hospital admissions and emergency presentations data sets, and the Medicare Benefits Schedule which contains all government subsidized ambulatory care services, for the period 2011-2015. Medication cost was determined from the Pharmaceutical Benefits Scheme. Costs were extrapolated to all Australian SSc patients based on SSc prevalence of 21.1 per 100,000 and an Australian population of 24,304,682 in 2015. Determinants of healthcare cost were estimated using logistic regression. Total healthcare utilization cost to the Australian government extrapolated to all Australian SSc patients from 2011 to 2015 was Australian Dollar (AUD)$297,663,404.77, which is an average annual cost of AUD$59,532,680.95 (US Dollar [USD]$43,816,040.08) and annual cost per patient of AUD$11,607.07 (USD$8,542.80). Hospital costs, including inpatient hospitalization and emergency department presentations, accounted for the majority of these costs (44.4% of total), followed by medication cost (31.2%) and ambulatory care cost (24.4%). Pulmonary arterial hypertension (PAH) and gastrointestinal (GIT) involvement were the major determinants of healthcare cost (OR 2.3 and 1.8, P = .01 for hospitalizations; OR 2.8 and 2.0, P = .01 for ambulatory care; OR 7.8 and 1.6, P < .001 and P = .03 for medication cost, respectively). SSc is associated with substantial healthcare utilization and direct economic burden. The most costly aspects of SSc are PAH and GIT involvement. PMID:29310332

Quantifying the direct public health care cost of systemic sclerosis: A comprehensive data linkage study.

PubMed

Morrisroe, Kathleen; Stevens, Wendy; Sahhar, Joanne; Ngian, Gene-Siew; Rabusa, Candice; Ferdowsi, Nava; Hill, Catherine; Proudman, Susanna; Nikpour, Mandana

2017-12-01

To quantify the direct healthcare cost of systemic sclerosis (SSc) and identify its determinants. Healthcare use was captured through data linkage, wherein clinical and medication data for SSc patients from the state of Victoria enrolled in the Australian Scleroderma Cohort Study were linked with the Victorian hospital admissions and emergency presentations data sets, and the Medicare Benefits Schedule which contains all government subsidized ambulatory care services, for the period 2011-2015. Medication cost was determined from the Pharmaceutical Benefits Scheme. Costs were extrapolated to all Australian SSc patients based on SSc prevalence of 21.1 per 100,000 and an Australian population of 24,304,682 in 2015. Determinants of healthcare cost were estimated using logistic regression. Total healthcare utilization cost to the Australian government extrapolated to all Australian SSc patients from 2011 to 2015 was Australian Dollar (AUD)$297,663,404.77, which is an average annual cost of AUD$59,532,680.95 (US Dollar [USD]$43,816,040.08) and annual cost per patient of AUD$11,607.07 (USD$8,542.80). Hospital costs, including inpatient hospitalization and emergency department presentations, accounted for the majority of these costs (44.4% of total), followed by medication cost (31.2%) and ambulatory care cost (24.4%). Pulmonary arterial hypertension (PAH) and gastrointestinal (GIT) involvement were the major determinants of healthcare cost (OR 2.3 and 1.8, P = .01 for hospitalizations; OR 2.8 and 2.0, P = .01 for ambulatory care; OR 7.8 and 1.6, P < .001 and P = .03 for medication cost, respectively). SSc is associated with substantial healthcare utilization and direct economic burden. The most costly aspects of SSc are PAH and GIT involvement.

Anti-fibrotic characteristics of Vγ9+ γδ T cells in systemic sclerosis.

PubMed

Markovits, Noa; Bendersky, Anna; Loebstein, Ronen; Brusel, Marina; Kessler, Efrat; Bank, Ilan

2016-01-01

γδ T cells of the Vγ9Vδ2 subtype secrete anti-fibrotic cytokines upon isopentenyl pyrophosphate (IPP) stimulation. In this study, we sought to compare IPP and Zoledronate, an up-regulator of IPP, effects on proliferation and cytokine secretion of Vγ9+ T cells from systemic sclerosis (SSc) patients and healthy controls (HCs). We also examined the effect of IPP-triggered peripheral blood mononuclear cells (PBMC) on fibroblast procolla- gen secretion. PBMC from SSc patients and HCs were stimulated by increasing concentrations of Zoledronate, with or without IPP, and Vγ9+ T cell percentages were calculated using FACScan analysis. Subsequently, PBMC were cultured with IPP or toxic shock syndrome toxin-1 (TSST-1), and contents of the anti-fibrotic cytokines tumour necrosis factor (TNF)-α and interferon (IFN)-γ were measured by ELISA kits. Finally, supernatants of IPP-triggered Vγ9+ T cells from SSc patients were added to fibroblast cultures, and relative intensities of procollagen α1 chains were determined by densinometry. Higher concentrations of Zoledronate were required for maximal proliferation of Vγ9+ T cells in 9 SSc patients compared to 9 HCs, irrespective of exogenous IPP. When compared to stimulation by TSST-1, a non-Vγ9+ selective reagent, secretion of the anti-fibrotic cytokines TNF-α and IFN-γ in response to IPP was relatively diminished in SSc but not in HCs. Reduction of procollagen secretion by fibroblasts cultured with supernatants of IPP-stimulated PBMC was observed only in some SSc patients. Activated Vγ9+ T cells could act as anti-fibrotic mediators in SSc, although decreased responsiveness to IPP may play a role in the pathological fibrosis of this disease.

Influence of joint angular velocity on electrically evoked concentric force potentiation induced by stretch-shortening cycle in young adults.

PubMed

Fukutani, Atsuki; Kurihara, Toshiyuki; Isaka, Tadao

2015-01-01

During a stretch- shortening cycle (SSC), muscle force attained during concentric contractions (shortening phase) is potentiated by the preceding eccentric contractions (lengthening phase). The purpose of this study was to examine the influence of joint angular velocity on force potentiation induced by SSC (SSC effect). Twelve healthy men (age, 24.2 ± 3.2 years; height, 1.73 ± 0.05 m; body mass, 68.1 ± 11.0 kg) participated in this study. Ankle joint angle was passively moved by a dynamometer, with range of motion from dorsiflexion (DF) 15° to plantarflexion (PF) 15°. Muscle contractions were evoked by tetanic electrical stimulation. Joint angular velocity of concentric contraction was set at 30°/s and 150°/s. Magnitude of SSC effect was calculated as the ratio of joint torque obtained by concentric contraction with preliminary eccentric contraction trial relative to that obtained by concentric contraction without preliminary eccentric contraction trial. As a result, magnitude of SSC effect calculated at three joint angles was significantly larger in the 150°/s condition than in the 30°/s condition (p < 0.05). These results indicate that the magnitude of SSC effect is affected by joint angular velocity, which is larger when joint angular velocity is larger. This phenomenon would be caused by insufficient duration to increase activation level in the large joint angular velocity condition. When the duration to increase activation level is insufficient due to short contraction duration, preactivation (one of the factors of SSC effect) leads to a significant increase in joint torque.

Whole-lung volume and density in spirometrically-gated inspiratory and expiratory CT in systemic sclerosis: correlation with static volumes at pulmonary function tests.

PubMed

Camiciottoli, G; Diciotti, S; Bartolucci, M; Orlandi, I; Bigazzi, F; Matucci-Cerinic, M; Pistolesi, M; Mascalchi, M

2013-03-01

Spiral low-dose computed tomography (LDCT) permits to measure whole-lung volume and density in a single breath-hold. To evaluate the agreement between static lung volumes measured with LDCT and pulmonary function test (PFT) and the correlation between the LDCT volumes and lung density in restrictive lung disease. Patients with Systemic Sclerosis (SSc) with (n = 24) and without (n = 16) pulmonary involvement on sequential thin-section CT and patients with chronic obstructive pulmonary disease (COPD)(n = 29) underwent spirometrically-gated LDCT at 90% and 10% of vital capacity to measure inspiratory and expiratory lung volumes and mean lung attenuation (MLA). Total lung capacity and residual volume were measured the same day of CT. Inspiratory [95% limits of agreement (95% LoA)--43.8% and 39.2%] and expiratory (95% LoA -45.8% and 37.1%) lung volumes measured on LDCT and PFT showed poor agreement in SSc patients with pulmonary involvement, whereas they were in substantial agreement (inspiratory 95% LoA -14.1% and 16.1%; expiratory 95% LoA -13.5% and 23%) in SSc patients without pulmonary involvement and in inspiratory scans only (95% LoA -23.1% and 20.9%) of COPD patients. Inspiratory and expiratory LDCT volumes, MLA and their deltas differentiated both SSc patients with or without pulmonary involvement from COPD patients. LDCT lung volumes and density were not correlated in SSc patients with pulmonary involvement, whereas they did correlate in SSc without pulmonary involvement and in COPD patients. In restrictive lung disease due to SSc there is poor agreement between static lung volumes measured using LDCT and PFT and the relationship between volume and density values on CT is altered.

[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.

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.

Potential immunologic targets for treating fibrosis in systemic sclerosis: a review focused on leukocytes and cytokines.

PubMed

Hasegawa, Minoru; Takehara, Kazuhiko

2012-12-01

Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis. Although the pathogenesis remains unclear, a variety of cells contribute to the fibrotic process via interactions with each other and production of various cytokines. Recent literature related to the immunologic pathogenesis and future strategies for treating the fibrosis of SSc are discussed and, especially, this literature-based review that includes the authors' perspective, focused on leukocytes and cytokines. A PubMed search for articles published between January 2005 and January 2012 was conducted using the following keywords: systemic sclerosis, leukocyte, cytokine, growth factor, and chemokine. The reference lists of identified articles were searched for further articles. Targeting profibrogenic cytokines, including transforming growth factor-β, is still a very active area of research in SSc and most cellular studies have focused on the roles of fibroblasts in SSc. However, a growing number of recent studies indicate a role for B cells in the development of SSc and other autoimmune diseases such as systemic lupus erythematosus. Therefore, B-cell-targeted therapies, including currently available monoclonal antibodies against CD19, CD20, CD22, and B-cell-activating factor, belonging to the tumor necrosis factor family represent possible treatment options. Furthermore, the modulation of T-cell costimulatory molecules such as a recombinant fusion protein of cytotoxic T-lymphocyte antigen-4 may be as effective in SSc as it is in treating other autoimmune diseases. Approaches to antagonize interleukin (IL)-1, IL-6, or IL-17A signaling may also be attractive. This review describes recent advances in the treatment of fibrosis in SSc patients focused on immunologic strategies, such as leukocyte- or cytokine-targeted therapies. Copyright © 2012 Elsevier Inc. All rights reserved.

Pulmonary function tests as outcomes for systemic sclerosis interstitial lung disease.

PubMed

Caron, Melissa; Hoa, Sabrina; Hudson, Marie; Schwartzman, Kevin; Steele, Russell

2018-06-30

Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc). We performed a systematic review to characterise the use and validation of pulmonary function tests (PFTs) as surrogate markers for systemic sclerosis-associated interstitial lung disease (SSc-ILD) progression.Five electronic databases were searched to identify all relevant studies. Included studies either used at least one PFT measure as a longitudinal outcome for SSc-ILD progression ( i.e. outcome studies) and/or reported at least one classical measure of validity for the PFTs in SSc-ILD ( i.e. validation studies).This systematic review included 169 outcome studies and 50 validation studies. Diffusing capacity of the lung for carbon monoxide ( D LCO ) was cumulatively the most commonly used outcome until 2010 when it was surpassed by forced vital capacity (FVC). FVC (% predicted) was the primary endpoint in 70.4% of studies, compared to 11.3% for % predicted D LCO Only five studies specifically aimed to validate the PFTs: two concluded that D LCO was the best measure of SSc-ILD extent, while the others did not favour any PFT. These studies also showed respectable validity measures for total lung capacity (TLC).Despite the current preference for FVC, available evidence suggests that D LCO and TLC should not yet be discounted as potential surrogate markers for SSc-ILD progression. Copyright ©ERS 2018.

Test Facilities Capability Handbook: Volume 1 - Stennis Space Center (SSC); Volume 2 - Marshall Space Flight Center (MSFC)

NASA Technical Reports Server (NTRS)

Hensarling, Paula L.

2007-01-01

The John C. Stennis Space Center (SSC) is located in Southern Mississippi near the Mississippi-Louisiana state line. SSC is chartered as the National Aeronautics and Space Administration (NASA) Center of Excellence for large space transportation propulsion system testing. This charter has led to many unique test facilities, capabilities and advanced technologies provided through the supporting infrastructure. SSC has conducted projects in support of such diverse activities as liquid, and hybrid rocket testing and development; material development; non-intrusive plume diagnostics; plume tracking; commercial remote sensing; test technology and more. On May 30, 1996 NASA designated SSC the lead center for rocket propulsion testing, giving the center total responsibility for conducting and/or managing all NASA rocket engine testing. Test services are now available not only for NASA but also for the Department of Defense, other government agencies, academia, and industry. This handbook was developed to provide a summary of the capabilities that exist within SSC. It is intended as a primary resource document, which will provide the reader with the top-level capabilities and characteristics of the numerous test facilities, test support facilities, laboratories, and services. Due to the nature of continually evolving programs and test technologies, descriptions of the Center's current capabilities are provided. Periodic updates and revisions of this document will be made to maintain its completeness and accuracy.

Differential diagnosis of critical digital ischemia in systemic sclerosis: Report of five cases and review of the literature.

PubMed

Sharp, Charlotte A; Akram, Qasim; Hughes, Michael; Muir, Lindsay; Herrick, Ariane L

2016-10-01

Critical digital ischemia is a rare, but serious complication of systemic sclerosis (SSc) and is not always due solely to the non-inflammatory angiopathy that characterizes the SSc disease process. Our objective was to illustrate the range of presentations and causes of critical digital ischemia in patients with SSc in order to highlight how optimal management is dependent upon establishing the correct diagnosis. Five cases exemplifying differential diagnoses were identified and their case notes reviewed in order to extract clinically relevant data and images. A review of the literature was performed in PubMed in English. Causes of critical digital ischemia included typical micro-angiopathic changes and proximal (large vessel) disease. One case highlighted the difficulty of ascertaining whether an inflammatory cause is also present in SSc/SLE overlap syndrome. Two cases demonstrated embolic causes (thromboembolism due to atrial fibrillation and septic emboli). Critical digital ischemia in patients with SSc requires thorough investigation in order to avoid missing additional potentially modifiable causes including large vessel disease, inflammation, embolism, infection, and paraneoplastic syndromes. A firm evidence base for current medical and surgical interventions is lacking, highlighting the need for further research into the optimum management of this rare, but painful, debilitating, and limb-threatening complication of SSc. Copyright © 2016 Elsevier Inc. All rights reserved.

Digital ulcers in systemic sclerosis.

PubMed

Hughes, Michael; Herrick, Ariane L

2017-01-01

Digital ulcers (DUs) are a common visible manifestation of the progressive vascular disease that characterizes the SSc disease process. DUs not only impact significantly on patients' quality of life and hand function, but are also a biomarker of internal organ involvement and of disease severity. The aetiology of (digital) vascular disease in SSc is multifactorial, and many of these factors are potentially amenable to therapeutic intervention. The management of DU disease in SSc is multifaceted. Patient education and non-pharmacological interventions (e.g. smoking cessation) should not be neglected. There are a number of drug therapies available to prevent (e.g. phosphodiesterase type-5 inhibitors and ET receptor-1 antagonists) and treat (e.g. i.v. iloprost) DUs. DUs are also important for two other reasons: firstly, as a primary end point in SSc-related clinical trials; and secondly, DUs are included in the ACR/EULAR SSc classification criteria. However, the reliability of rheumatologists to grade DUs is poor to moderate at best, and this poses challenges in both clinical practice and research. The purpose of this review is to provide the reader with a description of the spectrum of DU disease in SSc including pathophysiology, epidemiology and clinical burden, all of which inform the multifaceted approach to management. © 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.

Epstein-Barr virus infection induces aberrant TLR activation pathway and fibroblast-myofibroblast conversion in scleroderma.

PubMed

Farina, Antonella; Cirone, Mara; York, Michael; Lenna, Stefania; Padilla, Cristina; Mclaughlin, Sarah; Faggioni, Alberto; Lafyatis, Robert; Trojanowska, Maria; Farina, Giuseppina A

2014-04-01

Scleroderma (SSc) is a complex and heterogeneous connective tissue disease mainly characterized by autoimmunity, vascular damage, and fibrosis that mostly involve the skin and lungs. Epstein-Barr virus (EBV) is a lymphotropic γ-herpesvirus that has co-evolved with human species, infecting >95% of the adult population worldwide, and has been a leading candidate in triggering several autoimmune diseases. Here we show that EBV establishes infection in the majority of fibroblasts and endothelial cells in the skin of SSc patients, characterized by the expression of the EBV noncoding small RNAs (EBERs) and the increased expression of immediate-early lytic and latency mRNAs and proteins. We report that EBV is able to persistently infect human SSc fibroblasts in vitro, inducing an aberrant innate immune response in infected cells. EBV-Toll-like receptor (TLR) aberrant activation induces the expression of selected IFN-regulatory factors (IRFs), IFN-stimulated genes (ISGs), transforming growth factor-β1 (TGFβ1), and several markers of fibroblast activation, such as smooth muscle actin and Endothelin-1, and all of these genes play a key role in determining the profibrotic phenotype in SSc fibroblasts. These findings imply that EBV infection occurring in mesenchymal, endothelial, and immune cells of SSc patients may underlie the main pathological features of SSc including autoimmunity, vasculopathy, and fibrosis, and provide a unified disease mechanism represented by EBV reactivation.

Quantitative nailfold capillaroscopy findings in a population with connective tissue disease and in normal healthy controls.

PubMed Central

Kabasakal, Y; Elvins, D M; Ring, E F; McHugh, N J

1996-01-01

OBJECTIVE: To describe and quantify the morphological characteristics of nailfold capillaries that distinguish different forms of connective tissue disease from healthy controls. METHODS: A CCD video microscope with fibreoptic illumination and PC based image processing was used to visualise nailfold capillaries and to quantify findings in 23 patients with systemic sclerosis (SSc), 22 patients with systemic lupus erythematosus (SLE), 21 patients with undifferentiated connective tissue disease (UCTD), and 38 healthy controls. RESULTS: Capillary density was reduced in SSc (5.2 (SD 1.3) capillaries/mm) compared with other patient groups and controls. The average number of enlarged capillaries/finger was high in all disease groups (5.5-6.6) compared with controls (2). However, giant capillaries were most frequent in SSc (43%) and were not present in controls. Mild and moderate avascular areas were present in all groups (35%-68%), but severe avascularity was most frequent in SSc (44%) compared with other patients (18%-19%) and controls (0%). The greatest frequency of extensive haemorrhage was in SSc (35%). CONCLUSIONS: There is a range of abnormal capillary findings in patients with connective tissue disease and healthy controls. However, certain abnormalities such as a reduced number of capillaries, severe avascularity, giant capillaries, and haemorrhage are most commonly associated with SSc. Videomicroscopy with image processing offers many technical advantages that can be exploited in further studies of nailfold capillaries. Images PMID:8774177

A Data Mining Approach to Determine Sepsis Guideline Impact on Inpatient Mortality and Complications.

PubMed

Pruinelli, Lisiane; Yadav, Pranjul; Hangsleben, Andrew; Johnson, Jakob; Dey, Sanjoy; McCarty, Maribet; Kumar, Vipin; Delaney, Connie W; Steinbach, Michael; Westra, Bonnie L; Simon, György J

2016-01-01

Sepsis incidents have doubled from 2000 through 2008, and hospitalizations for these diagnoses have increased by 70%. The use of the Surviving Sepsis Campaign (SSC) guidelines can lead to earlier diagnosis and treatment; however, the effectiveness of the SSC guidelines in preventing complications for this population is unclear. The overall purpose of this study was to apply SSC guideline recommendations to EHR data for patients with severe sepsis or septic shock and determine guideline compliance as well as its impact on inpatient mortality and sepsis complications. Propensity Score Matching in conjuction with Bootstrap Simulation were used to match patients with and without exposure to the SSC recommendations. Findings showed that EHR data could be used to estimate compliance with SSC recommendations as well as the effect of compliance on outcomes. Compliance with guideline recommendations ranged from 9% to 100%. For individual recommendations with sufficient data, association with outcomes varied. Checking lactate influenced four outcomes; however, two were negative and two positive. Use of a ventilator for patients with respiratory distress had a positive association with three outcomes.

Development of Flat Roof Construction with Waterproofing from Modified Self-Compacting Concrete

NASA Astrophysics Data System (ADS)

Bogdanov, R. R.; Ibragimov, R. A.

2017-11-01

The given article considers the issues of increase of building flat roof durability by application of the modified self-compacting concrete (SSC). When SSC was modified, a complex modifier was developed and the optimization of the complex modifier composition was carried out using a three-factor experiment. The physico-mechanical properties of the obtained SSC are determined. The microstructure and phase composition of the modified cement stone were studied. On the basis of the studies carried out, namely, X-ray phase analysis and electron microscopy, it was concluded that the reduced content of calcium hydroxide in the samples with a complex modifier is due to the adsorption of calcium hydroxide on highly dispersed particles and the reaction of interaction with metakaolin also contributing to reduction in the content of calcium hydroxide in cement stone. The received data allow one to speak about SSC high operational characteristics. With the mark for the spreading of cone P5, the modified SSC has a class of compressive strength B50, high frost resistance (F600) and water resistance (W16).

Beam dynamics simulation of HEBT for the SSC-linac injector

NASA Astrophysics Data System (ADS)

Li, Xiao-Ni; Yuan, You-Jin; Xiao, Chen; He, Yuan; Wang, Zhi-Jun; Sheng, Li-Na

2012-11-01

The SSC-linac (a new injector for the Separated Sector Cyclotron) is being designed in the HIRFL (Heavy Ion Research Facility in Lanzhou) system to accelerate 238U34+ from 3.72 keV/u to 1.008 MeV/u. As a part of the SSC-linac injector, the HEBT (high energy beam transport) has been designed by using the TRACE-3D code and simulated by the 3D PIC (particle-in-cell) Track code. The total length of the HEBT is about 12 meters and a beam line of about 6 meters are shared with the exiting beam line of the HIRFL system. The simulation results show that the particles can be delivered efficiently in the HEBT and the particles at the exit of the HEBT well match the acceptance of the SSC for further acceleration. The dispersion is eliminated absolutely in the HEBT. The space-charge effect calculated by the Track code is inconspicuous. According to the simulation, more than 60 percent of the particles from the ion source can be transported into the acceptance of the SSC.

An immunogenetic study of familial scleroderma.

PubMed Central

de Juan, M D; Belzunegui, J; Belmonte, I; Barado, J; Figueroa, M; Cancio, J; Vidal, S; Cuadrado, E

1994-01-01

OBJECTIVE--To study the role of the HLA system in the genetic susceptibility to familial systemic sclerosis (SSc). METHODS--HLA class I antigens were determined by classic serological methods and HLA-DRB, -DQA and -DQB genes were analysed by genetic typing in 36 individuals belonging to two families with several individuals affected by SSc. RESULTS--The results did not show any association of the inheritance to SSc with any particular HLA allele in these families but revealed a striking frequency of ANA autoantibodies in healthy spouses of the members of these families. CONCLUSION--The otherwise infrequent familial incidence of SSc does not appear to be primarily linked to the HLA system in this study but it is suggested that other unknown exogenous environmental factors could be implicated in the development of the disease in families. PMID:7979601

Lightweight, fire-retardant, crashworthy aircraft seat cushioning

NASA Technical Reports Server (NTRS)

Haslim, Leonard A.; Mcdonough, Paul T.

1991-01-01

A two page discussion of non-aerospace seating applications and the design of NASA's safety seat cushioning (SSC) is presented. The SSC was designed for both safety and comfort in order to replace polyurethane cushioning which is flammable and produces lethal fumes upon combustion. The SSC is composed of advanced fabric reinforced composites and is lightweight, fire-retardent, and crashworthy. The seat design consists of central elliptical tubular spring supports made of fire-resistant and fatigue-durable composites surrounded by a fire-blocking sheath. The cushioning is made crashworthy by incorporating energy-absorbing, viscoelastic layers between the nested, elliptical-hoop springs. The design is intended to provide comfortable seating that meets aircraft-loading requirements without using the conventional polyurethane materials. The designs of an aircraft seat and structural components of the SSC are also presented.

Efficient spot size converter for higher-order mode fiber-chip coupling.

PubMed

Lai, Yaxiao; Yu, Yu; Fu, Songnian; Xu, Jing; Shum, Perry Ping; Zhang, Xinliang

2017-09-15

We propose and demonstrate a silicon-based spot size converter (SSC), composed of two identical tapered channel waveguides and a Y-junction. The SSC is designed for first-order mode fiber-to-chip coupling on the basis of mode petal separation and the recombination method. Compared with a traditional on-chip SSC, this method is superior with reduced coupling loss when dealing with a higher-order mode. To the best of our knowledge, we present the first experimental observations of a higher-order SSC which is fully compatible with a standard fabrication process. Average coupling losses of 3 and 5.5 dB are predicted by simulation and demonstrated experimentally. A fully covered 3 dB bandwidth over a 1515-1585 nm wavelength range is experimentally observed.

SPRITE: the Spitzer proposal review website

NASA Astrophysics Data System (ADS)

Crane, Megan K.; Storrie-Lombardi, Lisa J.; Silbermann, Nancy A.; Rebull, Luisa M.

2008-07-01

The Spitzer Science Center (SSC), located on the campus of the California Institute of Technology, supports the science operations of NASA's infrared Spitzer Space Telescope. The SSC issues an annual Call for Proposals inviting investigators worldwide to submit Spitzer Space Telescope proposals. The Spitzer Proposal Review Website (SPRITE) is a MySQL/PHP web database application designed to support the SSC proposal review process. Review panel members use the software to view, grade, and write comments about the proposals, and SSC support team members monitor the grading and ranking process and ultimately generate a ranked list of all the proposals. The software is also used to generate, edit, and email award letters to the proposers. This work was performed at the California Institute of Technology under contract to the National Aeronautics and Space Administration.

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.

Composite cathode materials development for intermediate temperature solid oxide fuel cell systems

NASA Astrophysics Data System (ADS)

Qin, Ya

Solid oxide fuel cell (SOFC) systems are of particular interest as electrochemical power systems that can operate on various hydrocarbon fuels with high fuel-to-electrical energy conversion efficiency. Within the SOFC stack, La0.8Sr 0.2Ga0.8Mg0.115Co0.085O3-delta (LSGMC) has been reported as an optimized composition of lanthanum gallate based electrolytes to achieve higher oxygen ionic conductivity at intermediate temperatures, i.e., 500-700°C. The electrocatalytic properties of interfaces between LSGMC electrolytes and various candidate intermediate-temperature SOFC cathodes have been investigated. Sm0.5Sr0.5CoO 3-delta (SSC), and La0.6Sr0.4Co0.2Fe 0.8O3-delta (LSCF), in both pure and composite forms with LSGMC, were investigated with regards to both oxygen reduction and evolution, A range of composite cathode compositions, having ratios of SSC (in wt.%) with LSGMC (wt.%) spanning the compositions 9:1, 8:2, 7:3, 6:4 and 5:5, were investigated to determine the optimal cathode-electrolyte interface performance at intermediate temperatures. All LSGMC electrolyte and cathode powders were synthesized using the glycine-nitrate process (GNP). Symmetrical electrochemical cells were investigated with three-electrode linear dc polarization and ac impedance spectroscopy to characterize the kinetics of the interfacial reactions in detail. Composite cathodes were found to perform better than the single phase cathodes due to significantly reduced polarization resistances. Among those composite SSC-LSGMC cathodes, the 7:3 composition has demonstrated the highest current density at the equivalent overpotential values, indicating that 7:3 is an optimal mixing ratio of the composite cathode materials to achieve the best performance. For the composite SC-LSGMC cathode/LSGMC interface, the cathodic overpotential under 1 A/cm2 current density was as low as 0.085 V at 700°C, 0.062V at 750°C and 0.051V at 800°C in air. Composite LSCF-LSGMC cathode/LSGMC interfaces were found to have about twice the exchange current density of composite SSC-LSGMC/LSGMC interfaces at 700°C. In this research effort, it has been found that: (1) the glycine-nitrate combustion process is favorable to produce perovskite-type oxide powders with good phase purity and negligible intermediate or contaminant phases; (2) The electrochemical performance for both the SSC-LSGMC and LSCF-LSGMC composite electrode materials on LSGMC confirm their potential for use in intermediate temperature SOFC applications; (3) The composite LSCF-LSGMC electrode exhibited much higher current density than the composite SSC-LSGMC electrode in the current dc polarization measurements; and (4) Primary market study results showed promising commercialization feasibility of these new materials sets, provided production is scaled up (with dramatic cost reductions).

Enhancement of thioredoxin/glutaredoxin-mediated L-cysteine synthesis from S-sulfocysteine increases L-cysteine production in Escherichia coli

PubMed Central

2012-01-01

Background Escherichia coli has two L-cysteine biosynthetic pathways; one is synthesized from O-acetyl L-serine (OAS) and sulfate by L-cysteine synthase (CysK), and another is produced via S-sulfocysteine (SSC) from OAS and thiosulfate by SSC synthase (CysM). SSC is converted into L-cysteine and sulfite by an uncharacterized reaction. As thioredoxins (Trx1 and Trx2) and glutaredoxins (Grx1, Grx2, Grx3, Grx4, and NrdH) are known as reductases of peptidyl disulfides, overexpression of such reductases might be a good way for improving L-cysteine production to accelerate the reduction of SSC in E. coli. Results Because the redox enzymes can reduce the disulfide that forms on proteins, we first tested whether these enzymes catalyze the reduction of SSC to L-cysteine. All His-tagged recombinant enzymes, except for Grx4, efficiently convert SSC into L-cysteine in vitro. Overexpression of Grx1 and NrdH enhanced a 15-40% increase in the E. coliL-cysteine production. On the other hand, disruption of the cysM gene cancelled the effect caused by the overexpression of Grx1 and NrdH, suggesting that its improvement was due to the efficient reduction of SSC under the fermentative conditions. Moreover, L-cysteine production in knockout mutants of the sulfite reductase genes (ΔcysI and ΔcysJ) and the L-cysteine synthase gene (ΔcysK) each decreased to about 50% of that in the wild-type strain. Interestingly, there was no significant difference in L-cysteine production between wild-type strain and gene deletion mutant of the upstream pathway of sulfite (ΔcysC or ΔcysH). These results indicate that sulfite generated from the SSC reduction is available as the sulfur source to produce additional L-cysteine molecule. It was finally found that in the E. coliL-cysteine producer that co-overexpress glutaredoxin (NrdH), sulfite reductase (CysI), and L-cysteine synthase (CysK), there was the highest amount of L-cysteine produced per cell. Conclusions In this work, we showed that Grx1 and NrdH reduce SSC to L-cysteine, and the generated sulfite is then utilized as the sulfur source to produce additional L-cysteine molecule through the sulfate pathway in E. coli. We also found that co-overexpression of NrdH, CysI, and CysK increases L-cysteine production. Our results propose that the enhancement of thioredoxin/glutaredoxin-mediated L-cysteine synthesis from SSC is a novel method for improvement of L-cysteine production. PMID:22607201

Reflectance spectroscopy for the assessment of soil salt content in soils of the yellow river delta of China

USGS Publications Warehouse

Weng, Yongling; Gong, P.; Zhu, Z.

2008-01-01

There has been growing interest in the use of reflectance spectroscopy as a rapid and inexpensive tool for soil characterization. In this study, we collected 95 soil samples from the Yellow River Delta of China to investigate the level of soil salinity in relation to soil spectra. Sample plots were selected based on a field investigation and the corresponding soil salinity classification map to maximize variations of saline characteristics in the soil. Spectral reflectances of air-dried soil samples were measured using an Analytical Spectral Device (ASD) spectrometer (350-2500 nm) with an artificial light source. In the Yellow River Delta, the dominant chemical in the saline soil was NaCl and MgCl2. Soil spectra were analysed using two-thirds of the available samples, with the remaining one-third withheld for validation purposes. The analysis indicated that with some preprocessing, the reflectance at 1931-2123 nm and 2153-2254 nm was highly correlated with soil salt content (SSC). In the spectral region of 1931-2123 nm, the correlation R ranged from -0.80 to -0.87. In the region of 2153-2254 nm, the SSC was positively correlated with preprocessed reflectance (0.79-0.88). The preprocessing was done by fitting a convex hull to the reflectance curve and dividing the spectral reflectance by the value of the corresponding convex hull band by band. This process is called continuum removal, and the resulting ratio is called continuum removed reflectance (CR reflectance). However, the SSC did not have a high correlation with the unprocessed reflectance, and the correlation was always negative in the entire spectrum (350-2500 nm) with the strongest negative correlation at 1981 nm (R = -0.63). Moreover, we found a strong correlation (R=0.91) between a soil salinity index (SSI: Constructed using CR reflectance at 2052 nm and 2203 nm) and SSC. We estimated SSC as a function of SSI and SSI' (SSI': Constructed using unprocessed reflectance at 2052 nm and 2203 nm) using univariate regression. Validation of the estimation of SSC was conducted by comparing the estimated SSC with the holdout sample points. The comparison produced an estimated root mean squared error (RMSE) of 0.986 (SSC ranging from 0.06 to 12.30 g kg-1) and R2 of 0.873 for SSC with SSI as independent variable and RMSE of 1.248 and R2 of 0.8 for SSC with SSI' as independent variable. This study showed that a soil salinity index developed for CR reflectance at 2052 nm and 2203 nm on the basis of spectral absorption features of saline soil can be used as a quick and inexpensive method for soil salt-content estimation.

Astro Camp Goes to Florida

NASA Image and Video Library

2007-08-08

Katie Craig, daughter of former Stennis Space Center Deputy Director Mark Craig, launches a 'balloon rocket' with the help of Rebecca Compretta, Astro Camp coordinator at SSC. SSC took Astro Camp on the road to Florida this week to engage children and their parents during activities surrounding the Aug. 8 launch of Space Shuttle Endeavour on NASA's STS-118 mission to the International Space Station. Astro Camp is SSC's popular space camp program designed to inspire and educate students using science and math principles.

Astro Camp Goes to Florida

NASA Technical Reports Server (NTRS)

2007-01-01

Katie Craig, daughter of former Stennis Space Center Deputy Director Mark Craig, launches a 'balloon rocket' with the help of Rebecca Compretta, Astro Camp coordinator at SSC. SSC took Astro Camp on the road to Florida this week to engage children and their parents during activities surrounding the Aug. 8 launch of Space Shuttle Endeavour on NASA's STS-118 mission to the International Space Station. Astro Camp is SSC's popular space camp program designed to inspire and educate students using science and math principles.

Species composition and assemblages of ichthyoplankton during summer in the East China Sea

NASA Astrophysics Data System (ADS)

Lin, Han-Yang; Chiu, Mei-Yun; Shih, Yu-Ming; Chen, I.-Shiung; Lee, Ming-An; Shao, Kwang-Tsao

2016-09-01

The East China Sea (ECS) is one of the most important fish spawning and nursery grounds in the north Pacific. Even though summer is an important spawning season for many fishes in the region, large-scale molecular identification studies on ichthyoplankton during this season are few. In this study, we sampled 8,933 fish eggs and 12,161 fish larvae from 25 stations during the summer of 2009. Using DNA barcoding, a number of the fish eggs and larvae were identified and classified into 45 and 124 taxa, respectively. Principal component analysis (PCA) categorized the inshore stations of the Changjiang Diluted Water area as having the hydrographic features of low sea surface temperature (SST), salinity (SSS) and high chlorophyll a (SSC) contents, whereas the continental shelf and offshore stations under the influence of the Kuroshio Current displayed the opposite results. Ichthyoplankton was more abundant at the inshore stations than the offshore stations, but species diversity was lower at the former locations. Species compositions of both fish eggs and fish larvae at the 25 stations were categorized into three different assemblages based on a non-metric multidimensional scaling analysis. Combining the assemblage patterns of ichthyoplankton with the results of the PCA and satellite images of SST and SSC showed that the assemblage patterns of fish eggs were correlated with water mass, while those of the fish larvae were not.

75 FR 32375 - New England Fishery Management Council; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-08

...: (978) 465-0492. SUPPLEMENTARY INFORMATION: Tuesday, June 22, 2010 Following introductions and any... the Scientific and Statistical Committee's (SSC) report on its most recent meeting. The SSC's topics...

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.

Safety and effectiveness of skin-to-skin contact in the NICU to support neurodevelopment in vulnerable preterm infants.

PubMed

Carbasse, Aurélia; Kracher, Sylvie; Hausser, Martine; Langlet, Claire; Escande, Benoît; Donato, Lionel; Astruc, Dominique; Kuhn, Pierre

2013-01-01

Skin-to-skin contact (SSC) is a cornerstone of neurodevelopmentally supportive and family-oriented care for very low-birth-weight preterm infants (VPIs). However, performing SSC with unstable and/or ventilated VPIs remains challenging for caregiving teams and/or controversial in the literature. We first aimed to assess the safety and effectiveness of SSC with vulnerable VPIs in a neonatal intensive care unit over 12 months. Our second aim was to evaluate the impact of the respiratory support (intubation or not) and of the infant's weight (above or below 1000 g) on the effects of SSC. Vital signs, body temperature, and oxygen requirement data were prospectively recorded by each infant's nurse before (baseline), during (3 time points), and after their first or first 2 SSC episodes. We compared the variations of each parameter from baseline (analysis of variance for repeated measures with post hoc analysis when appropriate). We studied 141 SSCs in 96 VPIs of 28 (24-33) weeks' gestational age, at 12 (0-55) days of postnatal age, and at a postmenstrual age of 30.5 (±1.5) weeks. During SSC, there were statistically significant increases in oxygen saturation (Sao2) (P < .001) with decreases in oxygen requirement (P = .043), a decrease in heart rate toward stability (P < .01) but a transient and moderate decrease in mean axillary temperature following the transfer from bed to mother (P < .05). Apneas/bradycardias requiring minor intervention occurred in 19 (13%) SSCs, without need for SSC termination. These variations were similar for intubated newborns (18%) as compared with newborns on nasal continuous positive airway pressure (52%) or breathing room air (30%). However, ventilated infants exhibited a significant increase in transcutaneous partial pressure of carbon dioxide (TcPco2) (P = .01), although remaining in a clinically acceptable range, and a greater decrease in oxygen requirements during SSC (P < .001) than nonventilated infants. Skin-to-skin contact in the neonatal intensive care unit seems safe and effective even in ventilated VPIs. Recording physiologic data of infants before, during, and after SCC provides data needed to secure changes of practice in SCC.

A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis.

PubMed

Taroni, Jaclyn N; Greene, Casey S; Martyanov, Viktor; Wood, Tammara A; Christmann, Romy B; Farber, Harrison W; Lafyatis, Robert A; Denton, Christopher P; Hinchcliff, Monique E; Pioli, Patricia A; Mahoney, J Matthew; Whitfield, Michael L

2017-03-23

Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. We identified a common pathogenic gene expression signature-an immune-fibrotic axis-indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. Our results suggest that the innate immune system is central to SSc disease processes but that subtle distinctions exist between tissues. Our approach provides a framework for examining molecular signatures of disease in fibrosis and autoimmune diseases and for leveraging publicly available data to understand common and tissue-specific disease processes in complex human diseases.

Biomarkers to identify ILD and predict lung function decline in scleroderma lung disease or idiopathic pulmonary fibrosis.

PubMed

Kennedy, Barry; Branagan, Peter; Moloney, Fiachra; Haroon, Muhammad; O'Connell, Oisin J; O'Connor, Terence M; O'Regan, Kevin; Harney, Sinead; Henry, Michael T

2015-09-14

SSc-ILD and IPF demonstrate significant morbidity and mortality. Predicting disease progression is challenging in both diseases. We sought a serum biomarker that could identify patients with SSc-ILD or IPF and prospectively predict short-term decline in lung function in these patients. 10 healthy controls, 5 SSc w/o ILD, 6 SSc-ILD and 13 IPF patients underwent venesection. An array of cytokines including KL-6, SP-D and MMP7 were measured. PFTs were obtained at baseline and six months. Cytokine measurements were correlated with PFTs. KL-6 in IPF patients (633 ng/ml, IQR 492-1675) was significantly elevated compared to controls (198 ng/ml, IQR 52-360, p<0.01) and SSc w/o ILD patients (192 ng/ml, IQR 0-524, p<0.05); KL-6 in SSc-ILD patients (836 ng/ml, IQR 431-1303) was significantly higher than in controls (p<0.05). SP-D was significantly higher in IPF patients (542 ng/ml, IQR 305-577) compared to controls (137 ng/ml, IQR 97-284, p<0.01) or to SSc w/o ILD patients (169 ng/ml, IQR 137-219, p<0.05). In comparison with controls (0.0 ng/ml, IQR 0.0-0.6), MMP7 was significantly higher in both IPF patients (2.85 ng/ml, IQR 1.5-3.6, p<0.05) and SSc-ILD patients (5.41 ng/ml, IQR 2.6-7.2, p<0.001). Using a cut-off level of 459ng/ml for KL-6 and of 1.28 ng/ml for MMP7, 18 out of 19 patients with ILD had a serum value of either KL-6 or MMP7 above these thresholds. For all ILD patients, baseline serum SP-D correlated with ΔFVC %pred over six months (r=-0.63, p=0.005, 95% CI -0.85 to -0.24). Combining KL-6 with MMP7 may be a useful screening tool for patients at risk of ILD. SP-D may predict short-term decline in lung function.

Searching Novel Therapeutic Targets for Scleroderma: P2X7-Receptor Is Up-regulated and Promotes a Fibrogenic Phenotype in Systemic Sclerosis Fibroblasts

PubMed Central

Gentile, Daniela; Lazzerini, Pietro E.; Gamberucci, Alessandra; Natale, Mariarita; Selvi, Enrico; Vanni, Francesca; Alì, Alessandra; Taddeucci, Paolo; Del-Ry, Silvia; Cabiati, Manuela; Della-Latta, Veronica; Abraham, David J.; Morales, Maria A.; Fulceri, Rosella; Laghi-Pasini, Franco; Capecchi, Pier L.

2017-01-01

Objectives: Systemic sclerosis (SSc) is a connective tissue disorder presenting fibrosis of the skin and internal organs, for which no effective treatments are currently available. Increasing evidence indicates that the P2X7 receptor (P2X7R), a nucleotide-gated ionotropic channel primarily involved in the inflammatory response, may also have a key role in the development of tissue fibrosis in different body districts. This study was aimed at investigating P2X7R expression and function in promoting a fibrogenic phenotype in dermal fibroblasts from SSc patients, also analyzing putative underlying mechanistic pathways. Methods: Fibroblasts were isolated by skin biopsy from 9 SSc patients and 8 healthy controls. P2X7R expression, and function (cytosolic free Ca2+ fluxes, α-smooth muscle actin [α-SMA] expression, cell migration, and collagen release) were studied. Moreover, the role of cytokine (interleukin-1β, interleukin-6) and connective tissue growth factor (CTGF) production, and extracellular signal-regulated kinases (ERK) activation in mediating P2X7R-dependent pro-fibrotic effects in SSc fibroblasts was evaluated. Results: P2X7R expression and Ca2+ permeability induced by the selective P2X7R agonist 2′-3′-O-(4-benzoylbenzoyl)ATP (BzATP) were markedly higher in SSc than control fibroblasts. Moreover, increased αSMA expression, cell migration, CTGF, and collagen release were observed in lipopolysaccharides-primed SSc fibroblasts after BzATP stimulation. While P2X7-induced cytokine changes did not affect collagen production, it was completely abrogated by inhibition of the ERK pathway. Conclusion: In SSc fibroblasts, P2X7R is overexpressed and its stimulation induces Ca2+-signaling activation and a fibrogenic phenotype characterized by increased migration and collagen production. These data point to the P2X7R as a potential, novel therapeutic target for controlling exaggerated collagen deposition and tissue fibrosis in patients with SSc. PMID:28955239

Netrin-1 Regulates Fibrocyte Accumulation in the Decellularized Fibrotic Sclerodermatous Lung Microenvironment and in Bleomycin-Induced Pulmonary Fibrosis.

PubMed

Sun, Huanxing; Zhu, Yangyang; Pan, Hongyi; Chen, Xiaosong; Balestrini, Jenna L; Lam, TuKiet T; Kanyo, Jean E; Eichmann, Anne; Gulati, Mridu; Fares, Wassim H; Bai, Hanwen; Feghali-Bostwick, Carol A; Gan, Ye; Peng, Xueyan; Moore, Meagan W; White, Eric S; Sava, Parid; Gonzalez, Anjelica L; Cheng, Yuwei; Niklason, Laura E; Herzog, Erica L

2016-05-01

Fibrocytes are collagen-producing leukocytes that accumulate in patients with systemic sclerosis (SSc; scleroderma)-related interstitial lung disease (ILD) via unknown mechanisms that have been associated with altered expression of neuroimmune proteins. The extracellular matrix (ECM) influences cellular phenotypes. However, a relationship between the lung ECM and fibrocytes in SSc has not been explored. The aim of this study was to use a novel translational platform based on decellularized human lungs to determine whether the lung ECM of patients with scleroderma controls the development of fibrocytes from peripheral blood mononuclear cells. We performed biomechanical evaluation of decellularized scaffolds prepared from lung explants from healthy control subjects and patients with scleroderma, using tensile testing and biochemical and proteomic analysis. Cells obtained from healthy controls and patients with SSc-related ILD were cultured on these scaffolds, and CD45+pro-ColIα1+ cells meeting the criteria for fibrocytes were quantified. The contribution of the neuromolecule netrin-1 to fibrosis was assessed using neutralizing antibodies in this system and by administering bleomycin via inhalation to netrin-1(+/-) mice. Compared with control lung scaffolds, lung scaffolds from patients with SSc-related ILD showed aberrant anatomy, enhanced stiffness, and abnormal ECM composition. Culture of control cells in lung scaffolds from patients with SSc-related ILD increased production of pro-ColIα1+ cells, which was stimulated by enhanced stiffness and abnormal ECM composition. Cells from patients with SSc-related ILD demonstrated increased pro-ColIα1 responsiveness to lung scaffolds from scleroderma patients but not enhanced stiffness. Enhanced detection of netrin-1-expressing CD14(low) cells in patients with SSc-related ILD was observed, and antibody-mediated netrin-1 neutralization attenuated detection of CD45+pro-ColIα1+ cells in all settings. Netrin-1(+/-) mice were protected against bleomycin-induced lung fibrosis and fibrocyte accumulation. Factors present in the lung matrices of patients with scleroderma regulate fibrocyte accumulation via a netrin-1-dependent pathway. Netrin-1 regulates bleomycin-induced pulmonary fibrosis in mice. Netrin-1 might be a novel therapeutic target in SSc-related ILD. © 2016, American College of Rheumatology.

Spatial variability of sediment transport processes over intra‐ and subtidal timescales within a fringing coral reef system

USGS Publications Warehouse

Pomeroy, Andrew; Lowe, Ryan J.; Ghisalberti, Marco; Winter, Gundula; Storlazzi, Curt D.; Cuttler, Michael V. W.

2018-01-01

Sediment produced on fringing coral reefs that is transported along the bed or in suspension affects ecological reef communities as well as the morphological development of the reef, lagoon, and adjacent shoreline. This study quantified the physical process contribution and relative importance of incident waves, infragravity waves, and mean currents to the spatial and temporal variability of sediment in suspension. Estimates of bed shear stresses demonstrate that incident waves are the key driver of the SSC variability spatially (reef flat, lagoon, and channels) but cannot not fully describe the SSC variability alone. The comparatively small but statistically significant contribution to the bed shear stress by infragravity waves and currents, along with the spatial availability of sediment of a suitable size and volume, is also important. Although intra‐tidal variability in SSC occurs in the different reef zones, the majority of the variability occurs over longer slowly varying (subtidal) time scales, which is related to the arrival of large incident waves at a reef location. The predominant flow pathway, which can transport suspended sediment, consists of cross‐reef flow across the reef flat that diverges in the lagoon and returns offshore through channels. This pathway is primarily due to subtidal variations in wave‐driven flows, but can also be driven alongshore by wind stresses when the incident waves are small. Higher frequency (intra‐tidal) current variability also occur due to both tidal flows, as well as variations in the water depth that influence wave transmission across the reef and wave‐driven currents.

Feasibility of modified surviving sepsis campaign guidelines in a resource-restricted setting based on a cohort study of severe S. aureus sepsis [corrected].

PubMed

Mahavanakul, Weera; Nickerson, Emma K; Srisomang, Pramot; Teparrukkul, Prapit; Lorvinitnun, Pichet; Wongyingsinn, Mingkwan; Chierakul, Wirongrong; Hongsuwan, Maliwan; West, T Eoin; Day, Nicholas P; Limmathurotsakul, Direk; Peacock, Sharon J

2012-01-01

The Surviving Sepsis Campaign (SSC) guidelines describe best practice for the management of severe sepsis and septic shock in developed countries, but most deaths from sepsis occur where healthcare is not sufficiently resourced to implement them. Our objective was to define the feasibility and basis for modified guidelines in a resource-restricted setting. We undertook a detailed assessment of sepsis management in a prospective cohort of patients with severe sepsis caused by a single pathogen in a 1,100-bed hospital in lower-middle income Thailand. We compared their management with the SSC guidelines to identify care bundles based on existing capabilities or additional activities that could be undertaken at zero or low cost. We identified 72 patients with severe sepsis or septic shock associated with S. aureus bacteraemia, 38 (53%) of who died within 28 days. One third of patients were treated in intensive care units (ICUs). Numerous interventions described by the SSC guidelines fell within existing capabilities, but their implementation was highly variable. Care available to patients on general wards covered the fundamental principles of sepsis management, including non-invasive patient monitoring, antimicrobial administration and intravenous fluid resuscitation. We described two additive care bundles, one for general wards and the second for ICUs, that if consistently performed would be predicted to improve outcome from severe sepsis. It is feasible to implement modified sepsis guidelines that are scaled to resource availability, and that could save lives prior to the publication of international guidelines for developing countries.

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.

Sternal Skin Conductance: A reasonable surrogate for Hot Flash Measurement?

PubMed Central

Pachman, Deirdre R.; Loprinzi, Charles L.; Novotny, Paul J; Satele, Daniel V; Linquist, Breanna M.; Wolf, Sherry; Barton, Debra L.

2013-01-01

Objective The aim of this study was to examine the accuracy of a new sternal skin conductance (SSC) device for the measurement of hot flashes, and secondly, to assess the acceptability of the device by women. Methods Three small descriptive pilot studies were performed utilizing two sequential prototypes of the SSC device developed by an engineering device company in the Midwest. The devices were worn either in a monitored setting for 24 hours or in an ambulatory setting for 5 weeks. During the study period, women recorded hot flashes in a prospective hot flash diary and also answered questions about the acceptability of wearing the SSC device. Results The first prototype was not able to collect any analyzable skin conductance data due to various malfunction issues; including poor conductance and battery failure. However, 16 patients did wear the device for 5 weeks and reported that wearing the device was acceptable, although 31% stated that it did interfere with daily activities. Hot flash data from the second prototype revealed a concordance rate between patient reported and device recorded hot flashes of 24%. Conclusions Findings from these studies support the discordance between SSC recorded and patient reported hot flashes. In addition, the studies reveal further limitations of SSC monitoring, including difficulties with data collection and lack of consistency in interpretation. Based on these results and other recent trials identifying issues with SSC methodology, it is time to find a better physiologic surrogate measure for hot flashes. PMID:23571528

Implication of IL-2/IL-21 region in systemic sclerosis genetic susceptibility

PubMed Central

Diaz-Gallo, Lina-Marcela; Simeon, Carmen P; Broen, Jasper C; Ortego-Centeno, Norberto; Beretta, Lorenzo; Vonk, Madelon C; Carreira, Patricia E; Vargas, Sofia; Román-Ivorra, José Andrés; González-Gay, Miguel A; Tolosa, Carlos; López-Longo, Francisco Javier; Espinosa, Gerard; Vicente, Esther F; Hesselstrand, Roger; Riemekasten, Gabriela; Witte, Torsten; Distler, Jörg H W; Voskuyl, Alexandre E; Schuerwegh, Annemie J; Shiels, Paul G; Nordin, Annika; Padyukov, Leonid; Hoffmann-Vold, Anna-Maria; Scorza, Raffaella; Lunardi, Claudio; Airo, Paolo; van Laar, Jacob M; Hunzelmann, Nicolas; Gathof, Birgit S; Kreuter, Alexander; Herrick, Ariane; Worthington, Jane; Denton, Christopher P; Zhou, Xiaodong; Arnett, Frank C; Fonseca, Carmen; Koeleman, Bobby PC; Assasi, Shervin; Radstake, Timothy R D J; Mayes, Maureen D; Martín, Javier

2013-01-01

Objective The interleukin 2 (IL-2) and interleukin 21 (IL-21) locus at chromosome 4q27 has been associated with several autoimmune diseases, and both genes are related to immune system functions. The aim of this study was to evaluate the role of the IL-2/IL-21 locus in systemic sclerosis (SSc). Patients and methods The case control study included 4493 SSc Caucasian patients and 5856 healthy controls from eight Caucasian populations (Spain, Germany, The Netherlands, USA, Italy, Sweden, UK and Norway). Four single nucleotide polymorphisms (rs2069762, rs6822844, rs6835457 and rs907715) were genotyped using TaqMan allelic discrimination assays. Results We observed evidence of association of the rs6822844 and rs907715 variants with global SSc (pc=6.6E-4 and pc=7.2E-3, respectively). Similar statistically significant associations were observed for the limited cutaneous form of the disease. The conditional regression analysis suggested that the most likely genetic variation responsible for the association was the rs6822844 polymorphism. Consistently, the rs2069762A-rs6822844T-rs6835457G-rs907715T allelic combination showed evidence of association with SSc and limited cutaneous SSc subtype (pc=1.7E-03 and pc=8E-4, respectively). Conclusions These results suggested that the IL-2/IL-21 locus influences the genetic susceptibility to SSc. Moreover, this study provided further support for the IL-2/IL-21 locus as a common genetic factor in autoimmune diseases. PMID:23172754

Sawtooth-wave prebuncher with dual-gaps in Linac injector for HIRFL-SSC

NASA Astrophysics Data System (ADS)

Zhang, Xiaohu; Yuan, Youjin; Xia, Jiawen; Yin, Xuejun; Jin, Peng; Xu, Zhe; Du, Heng; Li, Zhongshan; Qiao, Jian; Wang, Kedong

2018-01-01

An RFQ structure is normally composed of radial matcher, shaper, gentle buncher and accelerator section with changing cell geometry. Bunching is started in the shaper, and adiabatic bunching is done in gentle buncher section. The beam preforms from DC beam to bunch beam through the RFQ and the longitudinal emittance for the ions linacs is defined initially in the RFQ, in which the beam bunch has been shaped. In the present SSC-Linac injector, an RFQ has been designed to accelerate the continuous beam from 3.728 keV/u to 143 keV/u. The heavy ions beam is injected into the SSC (Separated Sector Cyclotron) with the kinetic energy of 1.025 MeV/u after four IH DTLs. The rf frequency of the SSC is 13.417 MHz, and the frequency of the heavy ions RFQ is set to four times of the rf frequency of the SSC. In order to increase the longitudinal capture efficiency of the SSC and suppress the longitudinal emittance at the exit of RFQ, an external MHB (Multi-Harmonics Buncher) is proposed in front of the RFQ. The fundamental frequency of the MHB is the same as the rf frequency of the cyclotron. The scheme of dual-gaps prebuncher with the sawtooth waveform is firstly carried out through multi-harmonics synthetic technology. The multi-particle beam dynamic simulations of the MHB have been done by the BEAMPATH code.

The strength and hemispheric asymmetry of Equatorial Ionization Anomaly during two geomagnetic storms in 2013 from Global Ionosphere Map and SAMI2

NASA Astrophysics Data System (ADS)

Luo, Weihua; Zhu, Zhengping; Lan, Jiaping

2016-08-01

The variations of the strength and the hemispheric asymmetry of EIA were studied by Global Ionosphere Map (GIM) and SAMI2 during two geomagnetic storm periods in March and June 2013. Compared with the 30-days median TEC, the TEC at the two crests of EIA had small variations while the TEC at the trough had a more remarkable variation for the two storms after the SSC. The TEC difference between the two EIA peaks had an increase or decrease several hours after the SSC, the asymmetry between the two crests of EIA represented by the defined asymmetry index has no obvious variations except several hours after the SSC, and EIA strength represented by the Crest-to-Trough Ratio (CTR) had a remarkable increase one day after the SSC day for March storm and decrease several hours after the SSC for June storm. The variations last several hours, with more than 40% variations compared with the value during the quiet period. The EIA peaks were also found to move toward the equator after the SSC during the two storms. The simulation from SAMI2 and HWM07 also shows that EIA crests would move toward the equator during storm time and EIA strength would decrease, which suggests that the disturbed neutral wind and disturbed electric field may be important factors affecting the EIA during the storm periods.

Noncanonical transforming growth factor β signaling in scleroderma fibrosis

PubMed Central

Trojanowska, Maria

2014-01-01

Purpose of review Persistent transforming growth factor β (TGF-β) signaling is the major factor contributing to scleroderma (SSc) fibrosis. This review will summarize recent progress on the noncanonical TGF-β signaling pathways and their role in SSc fibrosis. Recent findings Canonical TGF-β signaling involves activation of the TGF-β receptors and downstream signal transducers Smad2/3. The term noncanonical TGF-β signaling includes a variety of intracellular signaling pathways activated by TGF-β independently of Smad2/3 activation. There is evidence that these pathways play important role in SSc fibrosis. In a subset of SSc fibroblasts, a multiligand receptor complex consisting of TGF-β and CCN2 receptors drives constitutive activation of the Smad1 pathway. CCN2 is also a primary effector of this pathway, thus establishing an autocrine loop that amplifies TGF-β signaling. SSc fibroblasts also demonstrate reduced expression of endogenous antagonists of TGF-β signaling including transcriptional repressors, Friend leukemia integration-1 and perixosome proliferator-activated receptor-γ, as well as inhibitor of Smad3 phosphorylation, PTEN. PTEN is a key mediator of the cross-talk between the sphingosine kinase and the TGF-β pathways. Summary Discovery of the role of noncanonical TGF-β signaling in fibrosis offers new molecular targets for the antifibrotic therapies. Due to the heterogeneous nature of SSc, knowledge of these pathways could help to tailor the therapy to the individual patient depending on the activation status of a specific profibrotic pathway. PMID:19713852

Disturbed angiogenesis in systemic sclerosis: high levels of soluble endoglin.

PubMed

Wipff, J; Avouac, J; Borderie, D; Zerkak, D; Lemarechal, H; Kahan, A; Boileau, C; Allanore, Y

2008-07-01

SSc is a CTD characterized by early generalized microangiopathy with disturbed angiogenesis. Soluble endoglin (sENG), a serum anti-angiogenic protein, has recently been described as a major actor in pre-eclampsia, another severe vascular disease with abnormal angiogenesis. The aim of this study was to investigate, in a cross-sectional study, sENG levels together with other serum vascular markers. Serum levels of sENG were assessed by ELISA in consecutive SSc patients and controls matched for age and sex. We also measured by ELISA serum levels of VEGF and asymmetric dimethylarginine (ADMA), as respective markers of angiogenesis and endothelial dysfunction. We included 235 unrelated subjects: 187 SSc patients and 48 controls. Higher concentrations of sENG (P = 0.002) and sVEGF (P < 0.0001) were found in SSc patients compared with controls whereas there was no difference for ADMA. In multivariate analysis, sENG levels were significantly increased in SSc patients with cutaneous ulcerations (P = 0.0003), positive for ACAs (P = 0.009) and with abnormal diffusing capacity for carbon monoxide divided by alveolar volume (P = 0.03). Soluble ENG levels negatively correlated with ADMA, but no relationship was found between sENG and sVEGF. This study shows increased values of sENG in a large SSc cohort and a relevant association with a vascular phenotype. The predictive value of the biomarker sENG and its potential role on cellular endothelial disturbances remain to be determined.

Predictive value of European Scleroderma Group Activity Index in an early scleroderma cohort.

PubMed

Nevskaya, Tatiana; Baron, Murray; Pope, Janet E

2017-07-01

To estimate the effect of disease activity, as measured by the European Scleroderma Research Group Activity Index (EScSG-AI), on the risk of subsequent organ damage in a large systemic sclerosis (SSc) cohort. Of 421 SSc patients from the Canadian Scleroderma Research Group database with disease duration of ⩽ 3 years, 197 who had no evidence of end-stage organ damage initially and available 3 year follow-up were included. Disease activity was assessed by the EScSG-AI with two variability measures: the adjusted mean EScSG-AI (the area under the curve of the EScSG-AI over the observation period) and persistently active disease/flare. Outcomes were based on the Medsger severity scale and included accrual of a new severity score (Δ ⩾ 1) overall and within organ systems or reaching a significant level of deterioration in health status. After adjustment for covariates, the adjusted mean EScSG-AI was the most consistent predictor of risk across the study outcomes over 3 years in dcSSc: disease progression defined as Δ ⩾ 1 in any major internal organ, significant decline in forced vital capacity and diffusing capacity of carbon monoxide, severity of visceral disease and HAQ Disability Index worsening. In multivariate analysis, progression of lung disease was predicted solely by adjusted mean EScSG-AI, while the severity of lung disease was predicted the adjusted mean EScSG-AI, older age, modified Rodnan skin score (mRSS) and initial severity. The EScSG-AI was associated with patient- and physician-assessed measures of health status and overpowered the mRSS in predicting disease outcomes. Disease activity burden quantified with the adjusted mean EScSG-AI predicted the risk of deterioration in health status and severe organ involvement in dcSSc. The EScSG-AI is more responsive when done repeatedly and averaged. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Pulsed versus continuous wave low-level light therapy on osteoarticular signs and symptoms in limited scleroderma (CREST syndrome): a case report

NASA Astrophysics Data System (ADS)

Barolet, Daniel

2014-11-01

Limited cutaneous systemic sclerosis (lcSSc) was formerly known as CREST syndrome in reference to the associated clinical features: calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasias. The transforming growth factor beta has been identified as a major player in the pathogenic process, where low-level light therapy (LLLT) has been shown to modulate this cytokine superfamily. This case study was conducted to assess the efficacy of 940 nm using millisecond pulsing and continuous wave (CW) modes on osteoarticular signs and symptoms associated with lcSSc. The patient was treated two to three times a week for 13 weeks using a sequential pulsing mode on one elbow and a CW mode on the other. Efficacy assessments included inflammation, symptoms, pain, health scales, patient satisfaction, clinical global impression, and adverse effects monitoring. Considerable functional and morphologic improvements were observed after LLLT, with the best results seen with the pulsing mode. No adverse effects were noted. Pulsed LLLT represents a treatment alternative for osteoarticular signs and symptoms in limited scleroderma (CREST syndrome).

Design, Activation, and Operation of the J2-X Subscale Simulator (JSS)

NASA Technical Reports Server (NTRS)

Saunders, Grady P.; Raines, Nickey G.; Varner, Darrel G.

2009-01-01

The purpose of this paper is to give a detailed description of the design, activation, and operation of the J2-X Subscale Simulator (JSS) installed in Cell 1 of the E3 test facility at Stennis Space Center, MS (SSC). The primary purpose of the JSS is to simulate the installation of the J2-X engine in the A3 Subscale Rocket Altitude Test Facility at SSC. The JSS is designed to give aerodynamically and thermodynamically similar plume properties as the J2-X engine currently under development for use as the upper stage engine on the ARES I and ARES V spacecraft. The JSS is a scale pressure fed, LOX/GH fueled rocket that is geometrically similar to the J2-X from the throat to the nozzle exit plane (NEP) and is operated at the same oxidizer to fuel ratios and chamber pressures. This paper describes the heritage hardware used as the basis of the JSS design, the newly designed rocket hardware, igniter systems used, and the activation and operation of the JSS.

The challenge of establishing treatment efficacy for cutaneous vascular manifestations of systemic sclerosis.

PubMed

Pauling, John D

2018-05-01

The cutaneous vascular manifestations of systemic sclerosis (SSc) comprise Raynaud's phenomenon, cutaneous ulceration, telangiectasia formation and critical digital ischaemia; each of which are associated with significant disease-related morbidity. Despite the availability of multiple classes of vasodilator therapy, many of which have been the subject of RCTs, a limited number of pharmacological interventions are currently approved for the management of cutaneous vascular manifestations of SSc. Areas covered: A major challenge has been demonstrating treatment efficacy with examples of promising therapies yielding contrasting results in controlled trial settings. Differences between consensus best-practice guidelines, evidence-based recommendations and marketing approvals in different jurisdictions has resulted in geographic variation in clinical practice concerning the management of cutaneous vascular manifestations of SSc. Difficulty demonstrating treatment efficacy risks waning industry engagement for drug development programmes in this field. This article highlights the key challenges in establishing treatment efficacy and barriers that must be overcome to support successful clinical trial programmes across the spectrum of cutaneous vascular manifestations of SSc. Expert commentary: The paucity of approved treatments for cutaneous vascular manifestations of SSc relates as much to challenges in clinical trial design and the need for reliable clinical trial endpoints, as to lack of therapeutic options.

Disturbed balance between serum levels of receptor tyrosine kinases Tie-1, Tie-2 and angiopoietins in systemic sclerosis.

PubMed

Gerlicz, Zofia; Dziankowska-Bartkowiak, Bozena; Dziankowska-Zaborszczyk, Elzbieta; Sysa-Jedrzejowska, Anna

2014-01-01

The aim of this study was to determine the characteristic factors for vascular development and maintenance levels as well as correlation between Tie-1 receptors, Tie-2 receptors and the corresponding ligands--angiopoietins--in systemic sclerosis (SSc) patients. Serum levels of Tie-1, Tie-2, Ang-1 and Ang-2 were measured in 25 SSc patients and healthy controls. There was a statistically significant difference in serum Tie-1 (p = 0.009) and Ang-2 (p = 0.001) levels in SSc patients compared with healthy controls. Significant correlations between Tie-1 and Tie-2 (ρ = 0.70, p = 0.0001) and between Tie-1 and Ang-2 (ρ = -0.92, p = 0.002) were found in the SSc group. Serum levels of Tie-2 were positively associated with esophagus changes (U = 2.03, p = 0.041) and Ang-1 was negatively correlated with duration of Raynaud's phenomenon (ρ = -0.75, p = 0.00008). The increase in serum concentration of Tie-1 and Ang-2 in patients with SSc may confirm a molecular imbalance between receptor tyrosine kinases Tie and their ligands. © 2014 S. Karger AG, Basel.

Become your own advocate: Advice from women living with scleroderma

PubMed Central

MENDELSON, CINDY; POOLE, JANET L.

2008-01-01

Purpose Systemic sclerosis (SSC) affects 300,000 people in the USA and has a significant effect on an individual’s functional ability. The purpose of this study was to outline the key components of living with the illness and to identify the information that those who are newly diagnosed would need to initiate a successful course of disease self-management. The results will provide the groundwork for development and testing of a self-paced education program for patients with SSC. Method Focus groups were conducted with 11 women diagnosed with SSC. Results Analysis of the transcripts yielded three themes, Secure Effective Medical Management, Live Your Life, and Learn Everything You Can. The thread Become Your Own Advocate wove these three themes together and illustrated that taking control of SSC is ultimately a function of self-advocacy. Conclusion For patients with SSC, taking control of their illness was a necessary component of maintaining the highest quality of life possible. A positive attitude, a strong support system, a commitment to moving forward with life, and access to high-quality, timely information all provided the participants with the tools to develop and implement a strategy of self-advocacy in disease management. PMID:17852224

Experiencing work as a daily challenge: the case of scleroderma.

PubMed

Mendelson, Cindy; Poole, Janet L; Allaire, Saralynn

2013-01-01

Little is known about the physical and discretionary aspects of work that people with scleroderma (SSc) find difficult. This article describes the findings from a study that explored the challenges and adaptations made by individuals with SSc to continue to work. Thirty-two employed individuals with SSc participated. Participants were predominantly women (82%), white (79%), and well educated (M = 16.9 years). The average age was 47.3 years, and 60.6% were married. Mean disease duration was 9.7 years, and 56.2% had diffuse SSc. Mean years on the job was 10.2 (SD ± 8.8), and 71.9% worked at least 35 hours per week. Participants engaged in a single structured interview about work-related challenges and adaptations. Content and thematic analysis was used to identify key themes across the interviews. Employees with SSc experienced Work as a daily challenge. This central theme described the general work experience for most participants. Three subthemes described their specific experiences: The work environment: Opportunities, challenges, and accommodations; Career planning; and Supportive others. The participants were anxious to find scenarios that allowed them to continue to work. Worksite accommodations and flexibility in scheduling can make the difference between working and disability.

Neuropathic pain in Systemic Sclerosis patients: A cross-sectional study.

PubMed

Sousa-Neves, Joana; Cerqueira, Marcos; Santos-Faria, Daniela; Afonso, Carmo; Teixeira, Filipa

2018-01-31

To investigate if patients with Systemic Sclerosis (SSc) show a higher prevalence of neuropathic pain (NP) in comparison with controls. To study the relationship between clinical variables of the disease and NP among SSc patients. 48 patients and 45 controls were included. Presence of NP was assessed applying the DN4 "Douleur Neuropathique en 4 Questions" questionnaire. Different clinical variables were also assessed in patients. Statistical analysis included parametric, nonparametric tests and multivariate logistic regression. NP was significantly higher in SSc patients (56.2% vs 13.3%, p<0.001). Mean Modified Rodnan Skin Score was independently associated with the presence of NP (p<0.05, OR 1.90). Peripheral nervous system involvement in SSc is not well studied and, as far as the authors are aware, this is the first study published evaluating NP in SSc patients and controls. These findings should raise the awareness of the clinician to recognize and address the presence of NP in these patients, especially in those with severe skin involvement. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Ratios of total suspended solids to suspended sediment concentrations by particle size

USGS Publications Warehouse

Selbig, W.R.; Bannerman, R.T.

2011-01-01

Wet-sieving sand-sized particles from a whole storm-water sample before splitting the sample into laboratory-prepared containers can reduce bias and improve the precision of suspended-sediment concentrations (SSC). Wet-sieving, however, may alter concentrations of total suspended solids (TSS) because the analytical method used to determine TSS may not have included the sediment retained on the sieves. Measuring TSS is still commonly used by environmental managers as a regulatory metric for solids in storm water. For this reason, a new method of correlating concentrations of TSS and SSC by particle size was used to develop a series of correction factors for SSC as a means to estimate TSS. In general, differences between TSS and SSC increased with greater particle size and higher sand content. Median correction factors to SSC ranged from 0.29 for particles larger than 500m to 0.85 for particles measuring from 32 to 63m. Great variability was observed in each fraction-a result of varying amounts of organic matter in the samples. Wide variability in organic content could reduce the transferability of the correction factors. ?? 2011 American Society of Civil Engineers.

A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis

PubMed Central

2012-01-01

Introduction CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population. Methods A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls. Three CD226 single nucleotide polymorphisms (SNPs), rs763361, rs3479968 and rs727088, were genotyped using Taqman 5'allelic discrimination assays. Results Pooled analyses showed no evidence of association of the three SNPs, neither with the global disease nor with the analyzed subphenotypes. However, haplotype block analysis revealed a significant association for the TCG haplotype (SNP order: rs763361, rs34794968, rs727088) with lung fibrosis positive patients (PBonf = 3.18E-02 OR 1.27 (1.05 to 1.54)). Conclusion Our data suggest that the tested genetic variants do not individually influence SSc susceptibility but a CD226 three-variant haplotype is related with genetic predisposition to SSc-related pulmonary fibrosis. PMID:22531499

Balancing preterm infants' developmental needs with parents' readiness for skin-to-skin care: a phenomenological study.

PubMed

Kymre, Ingjerd Gåre; Bondas, Terese

2013-07-11

The aim of this article is to articulate the essence and constituents of neonatal intensive care unit (NICU) nurses' experiences in enacting skin-to-skin care (SSC) for preterm newborns and their parents. SSC is commonly employed in high-tech NICUs, which entails a movement from maternal-infant separation. Parents' opportunities for performing the practice have been addressed to NICU staff, with attitude and environment having crucial influence. The study was carried out with a reflective lifeworld research approach. Data were collected in Denmark, Sweden, and Norway by open-dialogue interviews with a purposive sample of 18 NICU nurses to achieve the essence of and variation within the phenomenon. NICU nurses experience balancing what they consider preterm newborns' current and developmental needs, with readiness in both parents for SSC. They share an experience of a change in the history of NICU care to increased focus on the meaning of proximity and touch for the infants' development. The phenomenon of enacting SSC is characterized by a double focus with steady attention to signals from both parents and newborns. Thereby, a challenge emerges from the threshold of getting started as the catalyst to SSC.

The prevalence of infectious agents in patients with systemic sclerosis.

PubMed

Bilgin, Hüseyin; Kocabaş, Hilal; Keşli, Recep

2015-01-01

Systemic sclerosis (SSc) is an autoimmune disease characterized by microvascular injury, excessive extracellular matrix deposition, and fibrosis in the skin and internal organs. Bacterial and viral infectious agents have been suspected to be contributing factors in the development and progression of the pathologic features of SSc. In this study, 30 SSc patients who were admitted to the rheumatology unit of the Konya Training and Research Hospital and 30 healthy controls were included. The presence of 9 different antibodies (IgM and IgG) against Helicobacter pylori, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and parvovirus B19 were investigated in sera samples obtained from the 60 participants using an enzyme-linked immunosorbent assay method. The characteristics of current and past infections with H. pylori, CMV, EBV, and parvovirus B19 were evaluated by determining the seropositivity of the tested bacterial and viral agents. The prevalences of H. pylori, CMV, EBV, and parvovirus B19 were determined to be higher in patients with SSc than in the control group. SSc is associated with a higher rate of certain infections, which deserves further investigation in order to assess the role of infections in disease etiology/pathogenesis.

Parental experiences of providing skin-to-skin care to their newborn infant—Part 1: A qualitative systematic review

PubMed Central

Anderzén-Carlsson, Agneta; Lamy, Zeni Carvalho; Eriksson, Mats

2014-01-01

Aim To describe parental experiences of providing skin-to-skin care (SSC) to their newborn infants. Background SSC care for newborn infants has been reported to have positive physiological and psychological benefits to the infants and their parents. No systematic review regarding parental experiences has been identified. Design In this first part of a meta-study, the findings of a systematic literature review on parental experience of SSC care are presented. Data sources Four databases were searched, without year or language limitations, up until December 2013. Manual searches were performed in reference lists and in a bibliography of the topic. Review methods After a quality-appraisal process, data from the original articles were extracted and analysed using qualitative content analysis. Results The systematic and manual searches led to the inclusion of 29 original qualitative papers from nine countries, reporting experiences from 401 mothers and 94 fathers. Two themes that characterized the provision of SSC emerged: a restoring experience and an energy-draining experience. Conclusion This review has added scientific and systematic knowledge about parental experiences of providing SSC. Further research about fathers’ experiences is recommended. PMID:25319746

Systemic Sclerosis Disease Modification Clinical Trials Design: Quo Vadis?

PubMed Central

Mendoza, Fabian A.; Keyes-Elstein, Lynette L.; Jimenez, Sergio A.

2012-01-01

The purpose of this manuscript is to discuss relevant aspects of clinical trials for Systemic Sclerosis (SSc) and to identify important considerations for the design of SSc disease modification clinical trials. Placebo randomized controlled trials with appropriate identification of SSc patients with diffuse progressive SSc skin involvement of recent onset, along with a rescue strategy for patients with worsening lung and skin involvement are suggested. If change in skin thickening is a major outcome of the study, the selection of patients with recent onset of disease and a predetermined degree of skin involvement are crucial requirements. The trial duration should be of at least 12 months. Sample size calculations should consider differences that exceed the Minimal Important Difference. Other relevant trial designs and potential threats to study validity are also discussed. Previous SSc-disease modifying trials have been beset by high dropout rates. Analyses on the subset of subjects completing the trial or applying the last-observation-carried-forward approach can potentially lead to biased estimates and false conclusions. Strategies for retention of subjects should be included at the design stage and analyses to account for missing data should be performed. PMID:22422541

Sperm-storage defects and live birth in Drosophila females lacking spermathecal secretory cells.

PubMed

Schnakenberg, Sandra L; Matias, Wilfredo R; Siegal, Mark L

2011-11-01

Male Drosophila flies secrete seminal-fluid proteins that mediate proper sperm storage and fertilization, and that induce changes in female behavior. Females also produce reproductive-tract secretions, yet their contributions to postmating physiology are poorly understood. Large secretory cells line the female's spermathecae, a pair of sperm-storage organs. We identified the regulatory regions controlling transcription of two genes exclusively expressed in these spermathecal secretory cells (SSC): Spermathecal endopeptidase 1 (Send1), which is expressed in both unmated and mated females, and Spermathecal endopeptidase 2 (Send2), which is induced by mating. We used these regulatory sequences to perform precise genetic ablations of the SSC at distinct time points relative to mating. We show that the SSC are required for recruiting sperm to the spermathecae, but not for retaining sperm there. The SSC also act at a distance in the reproductive tract, in that their ablation: (1) reduces sperm motility in the female's other sperm-storage organ, the seminal receptacle; and (2) causes ovoviviparity--the retention and internal development of fertilized eggs. These results establish the reproductive functions of the SSC, shed light on the evolution of live birth, and open new avenues for studying and manipulating female fertility in insects.

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.

Experimentally-Derived Fibroblast Gene Signatures Identify Molecular Pathways Associated with Distinct Subsets of Systemic Sclerosis Patients in Three Independent Cohorts

PubMed Central

Johnson, Michael E.; Mahoney, J. Matthew; Taroni, Jaclyn; Sargent, Jennifer L.; Marmarelis, Eleni; Wu, Ming-Ru; Varga, John; Hinchcliff, Monique E.; Whitfield, Michael L.

2015-01-01

Genome-wide expression profiling in systemic sclerosis (SSc) has identified four ‘intrinsic’ subsets of disease (fibroproliferative, inflammatory, limited, and normal-like), each of which shows deregulation of distinct signaling pathways; however, the full set of pathways contributing to this differential gene expression has not been fully elucidated. Here we examine experimentally derived gene expression signatures in dermal fibroblasts for thirteen different signaling pathways implicated in SSc pathogenesis. These data show distinct and overlapping sets of genes induced by each pathway, allowing for a better understanding of the molecular relationship between profibrotic and immune signaling networks. Pathway-specific gene signatures were analyzed across a compendium of microarray datasets consisting of skin biopsies from three independent cohorts representing 80 SSc patients, 4 morphea, and 26 controls. IFNα signaling showed a strong association with early disease, while TGFβ signaling spanned the fibroproliferative and inflammatory subsets, was associated with worse MRSS, and was higher in lesional than non-lesional skin. The fibroproliferative subset was most strongly associated with PDGF signaling, while the inflammatory subset demonstrated strong activation of innate immune pathways including TLR signaling upstream of NF-κB. The limited and normal-like subsets did not show associations with fibrotic and inflammatory mediators such as TGFβ and TNFα. The normal-like subset showed high expression of genes associated with lipid signaling, which was absent in the inflammatory and limited subsets. Together, these data suggest a model by which IFNα is involved in early disease pathology, and disease severity is associated with active TGFβ signaling. PMID:25607805

Summary of dipole field angle measurements on 50mm-aperture SSC Collider Dipole Magnet Protoypes

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

Marks, J.; DiMarco, J.; Kuzminski, J.

At several stages in the production of the SSC collider dipole magnets and their final installation the magnetic field angle needs to be known. A simple device using a permanent magnet which aligns itself with the magnetic field had been developed at FNAL to survey the direction of the magnetic dipole field with respect to the vertical (as determined by gravity) along the magnet axis. The determination of the dipole field angle was part of the field quality characterization of a series of thirteen full-length 50mm-aperture SSC Collider Dipole Magnet Prototypes which were built for R&D purposes at FNAL. Measurementsmore » with the first developed FAP system were performed on a regular basis through several stages of the magnet production process with the intention of fabrication quality control. Part of these included measurements performed before and after cryogenic testing: these data are summarized here. The performance of a second system with an improved probe and data acquisition system was tested on part of the DCA series as well. This paper includes a presentation of time stability, noise and angular resolution data of this second probe. Another alternative instrument to determine the dipole field angle is the ``mole`` rotating coil system developed at BNL used mainly to measure the multipole components of the magnetic field. In the case of magnet DCA320, a comparison is made between the field angle as determined by the mole and those determined by both of the FAPS.« less