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Sample records for identify early events

  1. Clustering of transcriptional profiles identifies changes to insulin signaling as an early event in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Jackson, Harriet M; Soto, Ileana; Graham, Leah C; Carter, Gregory W; Howell, Gareth R

    2013-11-25

    Alzheimer's disease affects more than 35 million people worldwide but there is no known cure. Age is the strongest risk factor for Alzheimer's disease but it is not clear how age-related changes impact the disease. Here, we used a mouse model of Alzheimer's disease to identify age-specific changes that occur prior to and at the onset of traditional Alzheimer-related phenotypes including amyloid plaque formation. To identify these early events we used transcriptional profiling of mouse brains combined with computational approaches including singular value decomposition and hierarchical clustering. Our study identifies three key events in early stages of Alzheimer's disease. First, the most important drivers of Alzheimer's disease onset in these mice are age-specific changes. These include perturbations of the ribosome and oxidative phosphorylation pathways. Second, the earliest detectable disease-specific changes occur to genes commonly associated with the hypothalamic-adrenal-pituitary (HPA) axis. These include the down-regulation of genes relating to metabolism, depression and appetite. Finally, insulin signaling, in particular the down-regulation of the insulin receptor substrate 4 (Irs4) gene, may be an important event in the transition from age-related changes to Alzheimer's disease specific-changes. A combination of transcriptional profiling combined with computational analyses has uncovered novel features relevant to Alzheimer's disease in a widely used mouse model and offers avenues for further exploration into early stages of AD.

  2. Identifying jet quantum numbers event by event

    International Nuclear Information System (INIS)

    Teper, M.J.

    1979-12-01

    A method is proposed to identify the parton that gives rise to any particular jet. The method improves with the number of particles in the jet, and should indicate which of the jets in a three jet event at PETRA is the gluon jet. (author)

  3. Identifying Adverse Drug Events by Relational Learning.

    Science.gov (United States)

    Page, David; Costa, Vítor Santos; Natarajan, Sriraam; Barnard, Aubrey; Peissig, Peggy; Caldwell, Michael

    2012-07-01

    The pharmaceutical industry, consumer protection groups, users of medications and government oversight agencies are all strongly interested in identifying adverse reactions to drugs. While a clinical trial of a drug may use only a thousand patients, once a drug is released on the market it may be taken by millions of patients. As a result, in many cases adverse drug events (ADEs) are observed in the broader population that were not identified during clinical trials. Therefore, there is a need for continued, post-marketing surveillance of drugs to identify previously-unanticipated ADEs. This paper casts this problem as a reverse machine learning task , related to relational subgroup discovery and provides an initial evaluation of this approach based on experiments with an actual EMR/EHR and known adverse drug events.

  4. Assessing quantitative EEG spectrograms to identify non-epileptic events.

    Science.gov (United States)

    Goenka, Ajay; Boro, Alexis; Yozawitz, Elissa

    2017-09-01

    To evaluate the sensitivity and specificity of quantitative EEG (QEEG) spectrograms in order to distinguish epileptic from non-epileptic events. Seventeen patients with paroxysmal non-epileptic events, captured during EEG monitoring, were retrospectively assessed using QEEG spectrograms. These patients were compared to a control group of 13 consecutive patients (ages 25-60 years) with epileptic seizures of similar semiology. Assessment of raw EEG was employed as the gold standard against which epileptic and non-epileptic events were validated. QEEG spectrograms, available using Persyst 12 EEG system integration software, were each assessed with respect to their usefulness to distinguish epileptic from non-epileptic seizures. The given spectrogram was interpreted as indicating a seizure if, at the time of the clinically identified event, it showed a visually significant change from baseline. Eighty-two clinically identified paroxysmal events were analysed (46 non-epileptic and 36 epileptic). The "seizure detector trend analysis" spectrogram correctly classified 33/46 (71%) non-epileptic events (no seizure indicated during a clinically identified event) vs. 29/36 (81%) epileptic seizures (seizure indicated during a clinically identified event) (p=0.013). Similarly, "rhythmicity spectrogram", FFT spectrogram, "asymmetry relative spectrogram", and integrated-amplitude EEG spectrogram detected 28/46 (61%), 30/46 (65%), 22/46 (48%) and 27/46 (59%) non-epileptic events vs. 27/36 (75%), 25/36 (69%), 25/36 (69%) and 27/36 (75%) epileptic events, respectively. High sensitivities and specificities for QEEG seizure detection analyses suggest that QEEG may have a role at the bedside to facilitate early differentiation between epileptic seizures and non-epileptic events in order to avoid unnecessary administration of antiepileptic drugs and possible iatrogenic consequences.

  5. Identifying Wind and Solar Ramping Events: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Florita, A.; Hodge, B. M.; Orwig, K.

    2013-01-01

    Wind and solar power are playing an increasing role in the electrical grid, but their inherent power variability can augment uncertainties in power system operations. One solution to help mitigate the impacts and provide more flexibility is enhanced wind and solar power forecasting; however, its relative utility is also uncertain. Within the variability of solar and wind power, repercussions from large ramping events are of primary concern. At the same time, there is no clear definition of what constitutes a ramping event, with various criteria used in different operational areas. Here the Swinging Door Algorithm, originally used for data compression in trend logging, is applied to identify variable generation ramping events from historic operational data. The identification of ramps in a simple and automated fashion is a critical task that feeds into a larger work of 1) defining novel metrics for wind and solar power forecasting that attempt to capture the true impact of forecast errors on system operations and economics, and 2) informing various power system models in a data-driven manner for superior exploratory simulation research. Both allow inference on sensitivities and meaningful correlations, as well as the ability to quantify the value of probabilistic approaches for future use in practice.

  6. Identifying Prominent Life Events on Twitter

    OpenAIRE

    Dickinson, Thomas; Fernández, Miriam; Thomas, Lisa A.; Mulholland, Paul; Briggs, Pam; Alani, Harith

    2015-01-01

    Social media is a common place for people to post and share digital reflections of their life events, including major events such as getting married, having children, graduating, etc. Although the creation of such posts is straightforward, the identification of events on online media remains a challenge. Much research in recent years focused on extracting major events from Twitter, such as earthquakes, storms, and floods. This paper however, targets the automatic detection of personal life ev...

  7. Text mining electronic health records to identify hospital adverse events

    DEFF Research Database (Denmark)

    Gerdes, Lars Ulrik; Hardahl, Christian

    2013-01-01

    Manual reviews of health records to identify possible adverse events are time consuming. We are developing a method based on natural language processing to quickly search electronic health records for common triggers and adverse events. Our results agree fairly well with those obtained using manu...

  8. Identifying risk event in Indonesian fresh meat supply chain

    Science.gov (United States)

    Wahyuni, H. C.; Vanany, I.; Ciptomulyono, U.

    2018-04-01

    The aim of this paper is to identify risk issues in Indonesian fresh meat supply chain from the farm until to the “plate”. The critical points for food safety in physical fresh meat product flow are also identified. The paper employed one case study in the Indonesian fresh meat company by conducting observations and in-depth three stages of interviews. At the first interview, the players, process, and activities in the fresh meat industry were identified. In the second interview, critical points for food safety were recognized. The risk events in each player and process were identified in the last interview. The research will be conducted in three stages, but this article focuses on risk identification process (first stage) only. The second stage is measuring risk and the third stage focuses on determining the value of risk priority. The results showed that there were four players in the fresh meat supply chain: livestock (source), slaughter (make), distributor and retail (deliver). Each player has different activities and identified 16 risk events in the fresh meat supply chain. Some of the strategies that can be used to reduce the occurrence of such risks include improving the ability of laborers on food safety systems, improving cutting equipment and distribution processes

  9. Performance Analysis: Work Control Events Identified January - August 2010

    Energy Technology Data Exchange (ETDEWEB)

    De Grange, C E; Freeman, J W; Kerr, C E; Holman, G; Marsh, K; Beach, R

    2011-01-14

    This performance analysis evaluated 24 events that occurred at LLNL from January through August 2010. The analysis identified areas of potential work control process and/or implementation weaknesses and several common underlying causes. Human performance improvement and safety culture factors were part of the causal analysis of each event and were analyzed. The collective significance of all events in 2010, as measured by the occurrence reporting significance category and by the proportion of events that have been reported to the DOE ORPS under the ''management concerns'' reporting criteria, does not appear to have increased in 2010. The frequency of reporting in each of the significance categories has not changed in 2010 compared to the previous four years. There is no change indicating a trend in the significance category and there has been no increase in the proportion of occurrences reported in the higher significance category. Also, the frequency of events, 42 events reported through August 2010, is not greater than in previous years and is below the average of 63 occurrences per year at LLNL since 2006. Over the previous four years, an average of 43% of the LLNL's reported occurrences have been reported as either ''management concerns'' or ''near misses.'' In 2010, 29% of the occurrences have been reported as ''management concerns'' or ''near misses.'' This rate indicates that LLNL is now reporting fewer ''management concern'' and ''near miss'' occurrences compared to the previous four years. From 2008 to the present, LLNL senior management has undertaken a series of initiatives to strengthen the work planning and control system with the primary objective to improve worker safety. In 2008, the LLNL Deputy Director established the Work Control Integrated Project Team to develop the core requirements and graded

  10. Identifying early Earth microfossils in unsilicified sediments

    Science.gov (United States)

    Javaux, Emmanuelle J.; Asael, Dan; Bekker, Andrey; Debaille, Vinciane; Derenne, Sylvie; Hofmann, Axel; Mattielli, Nadine; Poulton, Simon

    2013-04-01

    The search for life on the early Earth or beyond Earth requires the definition of biosignatures, or "indices of life". These traditionally include fossil molecules, isotopic fractionations, biosedimentary structures and morphological fossils interpreted as remnants of life preserved in rocks. This research focuses on traces of life preserved in unsilicified siliciclastic sediments. Indeed, these deposits preserve well sedimentary structures indicative of past aqueous environments and organic matter, including the original organic walls of microscopic organisms. They also do not form in hydrothermal conditions which may be source of abiotic organics. At our knowledge, the only reported occurrence of microfossils preserved in unsilicified Archean sediments is a population of large organic-walled vesicles discovered in shales and siltstones of the 3.2 Ga Moodies Group, South Africa. (Javaux et al, Nature 2010). These have been interpreted as microfossils based on petrographic and geochemical evidence for their endogenicity and syngeneity, their carbonaceous composition, cellular morphology and ultrastructure, occurrence in populations, taphonomic features of soft wall deformation, and the geological context plausible for life, as well as lack of abiotic explanation falsifying a biological origin. Demonstrating that carbonaceous objects from Archaean rocks are truly old and truly biological is the subject of considerable debate. Abiotic processes are known to produce organics and isotopic signatures similar to life. Spheroidal pseudofossils may form as self-assembling vesicles from abiotic CM, e.g. in prebiotic chemistry experiments (Shoztak et al, 2001), from meteoritic lipids (Deamer et al, 2006), or hydrothermal fluids (Akashi et al, 1996); by artifact of maceration; by migration of abiotic or biotic CM along microfractures (VanZuilen et al, 2007) or along mineral casts (Brasier et al, 2005), or around silica spheres formed in silica-saturated water (Jones and

  11. Identifying events that impact self-efficacy in physics learning

    Directory of Open Access Journals (Sweden)

    Vashti Sawtelle

    2012-09-01

    Full Text Available We present a method of analyzing the development of self-efficacy in real time using a framework of self-efficacy opportunities (SEOs. Considerable research has shown a connection between self-efficacy, or the confidence in one’s own ability to perform a task, and success in science fields. Traditional methods of investigating the development of self-efficacy have required participants to recollect past events. This reliance on participant memory makes it difficult to understand what impact particular events may have on developing self-efficacy in the moment. We use video recordings of three undergraduate Modeling Instruction students solving a physics problem to characterize SEOs in a moment-by-moment analysis. We then validate these characterizations of the development of self-efficacy by reviewing the problem-solving session with the participants and find evidence that the SEOs identified are taken up and impact self-efficacy. This characterization and validation of SEOs in the moment represents a first step towards establishing a methodology for analyzing the development of self-efficacy in real time.

  12. Scaled biotic disruption during early Eocene global warming events

    NARCIS (Netherlands)

    Gibbs, S.J.; Bown, P.R.; Murphy, B.H.; Sluijs, A.; Edgar, K.M.; Pälike, H.; Bolton, C.T.; Zachos, J.C.

    2012-01-01

    Late Paleocene and early Eocene hyperthermals are transient warming events associated with massive perturbations of the global carbon cycle, and are considered partial analogues for current anthropogenic climate change. Because the magnitude of carbon release varied between the events, they are

  13. Quantitative proteomic assessment of very early cellular signaling events

    DEFF Research Database (Denmark)

    Dengjel, Joern; Akimov, Vyacheslav; Olsen, Jesper V

    2007-01-01

    Technical limitations have prevented proteomic analyses of events occurring less than 30 s after signal initiation. We developed an automated, continuous quench-flow system allowing quantitative proteomic assessment of very early cellular signaling events (qPACE) with a time resolution of 1 s...

  14. Abnormal early cleavage events predict early embryo demise: sperm oxidative stress and early abnormal cleavage.

    Science.gov (United States)

    Burruel, Victoria; Klooster, Katie; Barker, Christopher M; Pera, Renee Reijo; Meyers, Stuart

    2014-10-13

    Human embryos resulting from abnormal early cleavage can result in aneuploidy and failure to develop normally to the blastocyst stage. The nature of paternal influence on early embryo development has not been directly demonstrated although many studies have suggested effects from spermatozoal chromatin packaging, DNA damage, centriolar and mitotic spindle integrity, and plasma membrane integrity. The goal of this study was to determine whether early developmental events were affected by oxidative damage to the fertilizing sperm. Survival analysis was used to compare patterns of blastocyst formation based on P2 duration. Kaplan-Meier survival curves demonstrate that relatively few embryos with short (P2 times reached blastocysts, and the two curves diverged beginning on day 4, with nearly all of the embryos with longer P2 times reaching blastocysts by day 6 (p < .01). We determined that duration of the 2nd to 3rd mitoses were sensitive periods in the presence of spermatozoal oxidative stress. Embryos that displayed either too long or too short cytokineses demonstrated an increased failure to reach blastocyst stage and therefore survive for further development. Although paternal-derived gene expression occurs later in development, this study suggests a specific role in early mitosis that is highly influenced by paternal factors.

  15. Why conventional detection methods fail in identifying the existence of contamination events.

    Science.gov (United States)

    Liu, Shuming; Li, Ruonan; Smith, Kate; Che, Han

    2016-04-15

    Early warning systems are widely used to safeguard water security, but their effectiveness has raised many questions. To understand why conventional detection methods fail to identify contamination events, this study evaluates the performance of three contamination detection methods using data from a real contamination accident and two artificial datasets constructed using a widely applied contamination data construction approach. Results show that the Pearson correlation Euclidean distance (PE) based detection method performs better for real contamination incidents, while the Euclidean distance method (MED) and linear prediction filter (LPF) method are more suitable for detecting sudden spike-like variation. This analysis revealed why the conventional MED and LPF methods failed to identify existence of contamination events. The analysis also revealed that the widely used contamination data construction approach is misleading. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Operational early warning platform for extreme meteorological events

    Science.gov (United States)

    Mühr, Bernhard; Kunz, Michael

    2015-04-01

    Operational early warning platform for extreme meteorological events Most natural disasters are related to extreme weather events (e.g. typhoons); weather conditions, however, are also highly relevant for humanitarian and disaster relief operations during and after other natural disaster like earthquakes. The internet service "Wettergefahren-Frühwarnung" (WF) provides various information on extreme weather events, especially when these events are associated with a high potential for large damage. The main focus of the platform is on Central Europe, but major events are also monitored worldwide on a daily routine. WF provides high-resolution forecast maps for many weather parameters which allow detailed and reliable predictions about weather conditions during the next days in the affected areas. The WF service became operational in February 2004 and is part of the Center for Disaster Management and Risk Reduction Technology (CEDIM) since 2007. At the end of 2011, CEDIM embarked a new type of interdisciplinary disaster research termed as forensic disaster analysis (FDA) in near real time. In case of an imminent extreme weather event WF plays an important role in CEDIM's FDA group. It provides early and precise information which are always available and updated several times during a day and gives advice and assists with articles and reports on extreme events.

  17. Early molecular events in the development of the diabetic cardiomyopathy.

    NARCIS (Netherlands)

    Monkemann, H.; Vriese, A.S. de; Blom, H.J.; Kluijtmans, L.A.J.; Heil, S.G.; Schild, H.H.; Golubnitschaja, O.

    2002-01-01

    Oxidative damage to DNA has been well documented in cardiac cells isolated from diabetic patients and rats with streptozotocin-induced diabetes mellitus (DM). This study evaluates possible molecular mechanisms for early events in the development of DM-induced cardiomyopathy. Methods: To analyze the

  18. Social anxiety and negative early life events in university students.

    Science.gov (United States)

    Binelli, Cynthia; Ortiz, Ana; Muñiz, Armando; Gelabert, Estel; Ferraz, Liliana; S Filho, Alaor; Crippa, José Alexandre S; Nardi, Antonio E; Subirà, Susana; Martín-Santos, Rocío

    2012-06-01

    There is substantial evidence regarding the impact of negative life events during childhood on the aetiology of psychiatric disorders. We examined the association between negative early life events and social anxiety in a sample of 571 Spanish University students. In a cross-sectional survey conducted in 2007, we collected data through a semistructured questionnaire of sociodemographic variables, personal and family psychiatric history, and substance abuse. We assessed the five early negative life events: (i) the loss of someone close, (ii) emotional abuse, (iii) physical abuse, (iv) family violence, and (v) sexual abuse. All participants completed the Liebowitz Social Anxiety Scale. Mean (SD) age was 21 (4.5), 75% female, LSAS score was 40 (DP = 22), 14.2% had a psychiatric family history and 50.6% had negative life events during childhood. Linear regression analyses, after controlling for age, gender, and family psychiatric history, showed a positive association between family violence and social score (p = 0.03). None of the remaining stressors produced a significant increase in LSAS score (p > 0.05). University students with high levels of social anxiety presented higher prevalence of negative early life events. Thus, childhood family violence could be a risk factor for social anxiety in such a population.

  19. Identifying Preserved Storm Events on Beaches from Trenches and Cores

    Science.gov (United States)

    Wadman, H. M.; Gallagher, E. L.; McNinch, J.; Reniers, A.; Koktas, M.

    2014-12-01

    Recent research suggests that even small scale variations in grain size in the shallow stratigraphy of sandy beaches can significantly influence large-scale morphology change. However, few quantitative studies of variations in shallow stratigraphic layers, as differentiated by variations in mean grain size, have been conducted, in no small part due to the difficulty of collecting undisturbed sediment cores in the energetic lower beach and swash zone. Due to this lack of quantitative stratigraphic grain size data, most coastal morphology models assume that uniform grain sizes dominate sandy beaches, allowing for little to no temporal or spatial variations in grain size heterogeneity. In a first-order attempt to quantify small-scale, temporal and spatial variations in beach stratigraphy, thirty-five vibracores were collected at the USACE Field Research Facility (FRF), Duck, NC, in March-April of 2014 using the FRF's Coastal Research and Amphibious Buggy (CRAB). Vibracores were collected at set locations along a cross-shore profile from the toe of the dune to a water depth of ~1m in the surf zone. Vibracores were repeatedly collected from the same locations throughout a tidal cycle, as well as pre- and post a nor'easter event. In addition, two ~1.5m deep trenches were dug in the cross-shore and along-shore directions (each ~14m in length) after coring was completed to allow better interpretation of the stratigraphic sequences observed in the vibracores. The elevations of coherent stratigraphic layers, as revealed in vibracore-based fence diagrams and trench data, are used to relate specific observed stratigraphic sequences to individual storm events observed at the FRF. These data provide a first-order, quantitative examination of the small-scale temporal and spatial variability of shallow grain size along an open, sandy coastline. The data will be used to refine morphological model predictions to include variations in grain size and associated shallow stratigraphy.

  20. Scaled biotic disruption during early Eocene global warming events

    Directory of Open Access Journals (Sweden)

    S. J. Gibbs

    2012-11-01

    Full Text Available Late Paleocene and early Eocene hyperthermals are transient warming events associated with massive perturbations of the global carbon cycle, and are considered partial analogues for current anthropogenic climate change. Because the magnitude of carbon release varied between the events, they are natural experiments ideal for exploring the relationship between carbon cycle perturbations, climate change and biotic response. Here we quantify marine biotic variability through three million years of the early Eocene that include five hyperthermals, utilizing a method that allows us to integrate the records of different plankton groups through scenarios ranging from background to major extinction events. Our long time-series calcareous nannoplankton record indicates a scaling of biotic disruption to climate change associated with the amount of carbon released during the various hyperthermals. Critically, only the three largest hyperthermals, the Paleocene–Eocene Thermal Maximum (PETM, Eocene Thermal Maximum 2 (ETM2 and the I1 event, show above-background variance, suggesting that the magnitude of carbon input and associated climate change needs to surpass a threshold value to cause significant biotic disruption.

  1. Identifying and Synchronizing Health Information Technology (HIT) Events from FDA Medical Device Reports.

    Science.gov (United States)

    Kang, Hong; Wang, Frank; Zhou, Sicheng; Miao, Qi; Gong, Yang

    2017-01-01

    Health information technology (HIT) events, a subtype of patient safety events, pose a major threat and barrier toward a safer healthcare system. It is crucial to gain a better understanding of the nature of the errors and adverse events caused by current HIT systems. The scarcity of HIT event-exclusive databases and event reporting systems indicates the challenge of identifying the HIT events from existing resources. FDA Manufacturer and User Facility Device Experience (MAUDE) database is a potential resource for HIT events. However, the low proportion and the rapid evolvement of HIT-related events present challenges for distinguishing them from other equipment failures and hazards. We proposed a strategy to identify and synchronize HIT events from MAUDE by using a filter based on structured features and classifiers based on unstructured features. The strategy will help us develop and grow an HIT event-exclusive database, keeping pace with updates to MAUDE toward shared learning.

  2. Timing of Childhood Events and Early-Adult Household Formation.

    Science.gov (United States)

    Hill, Martha S.; And Others

    1996-01-01

    Identified a number of risk factors contributing to early household formation. Found that for girls, factors included mother's educational level and birth order; for boys, parental divorce at any stage of childhood. Risk factors common to boys and girls were age of mother at time of child's birth and race. (HTH)

  3. Identifying early indicators in bipolar disorder: a qualitative study.

    Science.gov (United States)

    Benti, Liliane; Manicavasagar, Vijaya; Proudfoot, Judy; Parker, Gordon

    2014-06-01

    The identification of early markers has become a focus for early intervention in bipolar disorder. Using a retrospective, qualitative methodology, the present study compares the early experiences of participants with bipolar disorder to those with unipolar depression up until their first diagnosed episode. The study focuses on differences in early home and school environments as well as putative differences in personality characteristics between the two groups. Finally we a compare and contrast prodromal symptoms in these two populations. Thirty-nine participants, 20 diagnosed with unipolar depression and 19 diagnosed with bipolar disorder, took part in the study. A semi-structured interview was developed to elicit information about participants' experiences prior to their first episode. Participants with bipolar disorder reported disruptive home environments, driven personality features, greater emotion dysregulation and adverse experiences during the school years, whereas participants with depression tended to describe more supportive home environments, and more compliant and introvert personality traits. Retrospective data collection and no corroborative evidence from other family members. No distinction was made between bipolar I and bipolar II disorder nor between melancholic and non-melancholic depression in the sample. Finally the study spanned over a 12-month period which does not allow for the possibility of diagnostic reassignment of some of the bipolar participants to the unipolar condition. These findings indicate that there may be benefits in combining both proximal and distal indicators in identifying a bipolar disorder phenotype which, in turn, may be relevant to the development of early intervention programs for young people with bipolar disorder.

  4. Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

    Science.gov (United States)

    Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

    2015-01-01

    We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury.

  5. Early events governing memory CD8+ T-cell differentiation.

    Science.gov (United States)

    Obar, Joshua J; Lefrançois, Leo

    2010-08-01

    Understanding the regulation of the CD8(+) T-cell response and how protective memory cells are generated has been intensely studied. It is now appreciated that a naive CD8(+) T cell requires at least three signals to mount an effective immune response: (i) TCR triggering, (ii) co-stimulation and (iii) inflammatory cytokines. Only recently have we begun to understand the molecular integration of those signals and how early events regulate the fate decisions of the responding CD8(+) T cells. This review will discuss the recent findings about both the extracellular and intracellular factors that regulate the destiny of responding CD8(+) T cells.

  6. Early event related fields during visually evoked pain anticipation.

    Science.gov (United States)

    Gopalakrishnan, Raghavan; Burgess, Richard C; Plow, Ela B; Floden, Darlene P; Machado, Andre G

    2016-03-01

    Pain experience is not only a function of somatosensory inputs. Rather, it is strongly influenced by cognitive and affective pathways. Pain anticipatory phenomena, an important limitation to rehabilitative efforts in the chronic state, are processed by associative and limbic networks, along with primary sensory cortices. Characterization of neurophysiological correlates of pain anticipation, particularly during very early stages of neural processing is critical for development of therapeutic interventions. Here, we utilized magnetoencephalography to study early event-related fields (ERFs) in healthy subjects exposed to a 3 s visual countdown task that preceded a painful stimulus, a non-painful stimulus or no stimulus. We found that the first countdown cue, but not the last cue, evoked critical ERFs signaling anticipation, attention and alertness to the noxious stimuli. Further, we found that P2 and N2 components were significantly different in response to first-cues that signaled incoming painful stimuli when compared to non-painful or no stimuli. The findings indicate that early ERFs are relevant neural substrates of pain anticipatory phenomena and could be potentially serve as biomarkers. These measures could assist in the development of neurostimulation approaches aimed at curbing the negative effects of pain anticipation during rehabilitation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Analysis of early initiating event(s) in radiation-induced thymic lymphomagenesis

    International Nuclear Information System (INIS)

    Muto, Masahiro; Ying Chen; Kubo, Eiko; Mita, Kazuei

    1996-01-01

    Since the T cell receptor rearrangement is a sequential process and unique to the progeny of each clone, we investigated the early initiating events in radiation-induced thymic lymphomagenesis by comparing the oncogenic alterations with the pattern of γ T cell receptor (TCR) rearrangements. We reported previously that after leukemogenic irradiation, preneoplastic cells developed, albeit infrequently, from thymic leukemia antigen-2 + (TL-2 + ) thymocytes. Limited numbers of TL-2 + cells from individual irradiated B10.Thy-1.1 mice were injected into B10.Thy-1.2 mice intrathymically, and the common genetic changes among the donor-type T cell lymphomas were investigated with regard to p53 gene and chromosome aberrations. The results indicated that some mutations in the p53 gene had taken place in these lymphomas, but there was no common mutation among the donor-type lymphomas from individual irradiated mice, suggesting that these mutations were late-occurring events in the process of oncogenesis. On the other hand, there were common chromosome aberrations or translocations such as trisomy 15, t(7F; 10C), t(1A; 13D) or t(6A; XB) among the donor-type lymphomas derived from half of the individual irradiated mice. This indicated that the aberrations/translocations, which occurred in single progenitor cells at the early T cell differentiation either just before or after γ T cell receptor rearrangements, might be important candidates for initiating events. In the donor-type lymphomas from the other half of the individual irradiated mice, microgenetic changes were suggested to be initial events and also might take place in single progenitor cells just before or right after γ TCR rearrangements. (author)

  8. A Novel Approach For Event-By-Event Early Gluon Fields

    Science.gov (United States)

    Fries, Rainer J.; Rose, Steven

    2017-08-01

    We report on efforts to construct an event generator that calculates the classical gluon field generated at early times in high energy nuclear collisions. Existing approaches utilize numerical solutions of the Yang-Mills equations after the collision. In contrast we employ the analytically known recursion relation in the forward light cone. The few lowest orders are expected to lead to reliable results for times of up to the inverse saturation scale, τ0 ∼ 1 /Qs. In these proceedings we sketch some calculational details, and show some preliminary results.

  9. Detection of rain events in radiological early warning networks with spectro-dosimetric systems

    Science.gov (United States)

    Dąbrowski, R.; Dombrowski, H.; Kessler, P.; Röttger, A.; Neumaier, S.

    2017-10-01

    Short-term pronounced increases of the ambient dose equivalent rate, due to rainfall are a well-known phenomenon. Increases in the same order of magnitude or even below may also be caused by a nuclear or radiological event, i.e. by artificial radiation. Hence, it is important to be able to identify natural rain events in dosimetric early warning networks and to distinguish them from radiological events. Novel spectrometric systems based on scintillators may be used to differentiate between the two scenarios, because the measured gamma spectra provide significant nuclide-specific information. This paper describes three simple, automatic methods to check whether an dot H*(10) increase is caused by a rain event or by artificial radiation. These methods were applied to measurements of three spectrometric systems based on CeBr3, LaBr3 and SrI2 scintillation crystals, investigated and tested for their practicability at a free-field reference site of PTB.

  10. Master Logic Diagram: An Approach to Identify Initiating Events of HTGRs

    Science.gov (United States)

    Purba, J. H.

    2018-02-01

    Initiating events of a nuclear power plant being evaluated need to be firstly identified prior to applying probabilistic safety assessment on that plant. Various types of master logic diagrams (MLDs) have been proposedforsearching initiating events of the next generation of nuclear power plants, which have limited data and operating experiences. Those MLDs are different in the number of steps or levels and different in the basis for developing them. This study proposed another type of MLD approach to find high temperature gas cooled reactor (HTGR) initiating events. It consists of five functional steps starting from the top event representing the final objective of the safety functions to the basic event representing the goal of the MLD development, which is an initiating event. The application of the proposed approach to search for two HTGR initiating events, i.e. power turbine generator trip and loss of offsite power, is provided. The results confirmed that the proposed MLD is feasiblefor finding HTGR initiating events.

  11. WANO Activities Related to Identifying and Reducing the Likelihood for Recurring Events

    International Nuclear Information System (INIS)

    Llewellyn, Michael

    2003-01-01

    Since its inception, WANO has encouraged members to share operating experience and events information through the WANO Operating Experience Programme. Preventing recurring events is a prime reason for sharing events information. Over 2500 events have been shared through WANO since 1989. However, a review of WANO activities in 1997 identified that this information was not being used very well by WANO members, and that WANO was not adding much 'value' to the events sharing process. At the time, WANO only provided the 'postal exchange' function for events sharing, and was not reviewing events across WANO to help members focus on the really important issues. Often, these very important issues involve recurring events. As a result of the 1997 review of the WANO operating experience process, WANO re-sourced and developed new analysis capabilities and began producing new types of reports for its members. The resource commitment includes four seconded engineers (one from each WANO Regional Centre) brought to Paris to staff a WANO Operating Experience Central Team. This team analyses events across WANO, writes WANO event reports, provides operating experience-related training, and provides technical support to members to improve their use of operating experience information. One focus area for events analysis by WANO is the identification and subsequent industry notification of recurring events. As a result of the 1997 review of WANO activities, in 1998 WANO began production of several new types of event-based reports to communicate significant industry events to our members. A key focus of analysis of these significant events is whether they are recurring events (that is, very similar to previous events either at that NPP or another NPP in the industry). The reports are called Significant Operating Experience Reports (SOERs) and Significant Event Reports (SERs). Significant Operating Experience Reports (SOERs) are written by WANO when several event reports indicate that

  12. Alternative splicing events identified in human embryonic stem cells and neural progenitors.

    Directory of Open Access Journals (Sweden)

    Gene W Yeo

    2007-10-01

    Full Text Available Human embryonic stem cells (hESCs and neural progenitor (NP cells are excellent models for recapitulating early neuronal development in vitro, and are key to establishing strategies for the treatment of degenerative disorders. While much effort had been undertaken to analyze transcriptional and epigenetic differences during the transition of hESC to NP, very little work has been performed to understand post-transcriptional changes during neuronal differentiation. Alternative RNA splicing (AS, a major form of post-transcriptional gene regulation, is important in mammalian development and neuronal function. Human ESC, hESC-derived NP, and human central nervous system stem cells were compared using Affymetrix exon arrays. We introduced an outlier detection approach, REAP (Regression-based Exon Array Protocol, to identify 1,737 internal exons that are predicted to undergo AS in NP compared to hESC. Experimental validation of REAP-predicted AS events indicated a threshold-dependent sensitivity ranging from 56% to 69%, at a specificity of 77% to 96%. REAP predictions significantly overlapped sets of alternative events identified using expressed sequence tags and evolutionarily conserved AS events. Our results also reveal that focusing on differentially expressed genes between hESC and NP will overlook 14% of potential AS genes. In addition, we found that REAP predictions are enriched in genes encoding serine/threonine kinase and helicase activities. An example is a REAP-predicted alternative exon in the SLK (serine/threonine kinase 2 gene that is differentially included in hESC, but skipped in NP as well as in other differentiated tissues. Lastly, comparative sequence analysis revealed conserved intronic cis-regulatory elements such as the FOX1/2 binding site GCAUG as being proximal to candidate AS exons, suggesting that FOX1/2 may participate in the regulation of AS in NP and hESC. In summary, a new methodology for exon array analysis was introduced

  13. Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

    Science.gov (United States)

    Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

    2015-01-01

    PURPOSE We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. METHODS Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. RESULTS The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. CONCLUSION Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury. PMID:26081719

  14. Nurses' knowledge to identify early acute kidney injury.

    Science.gov (United States)

    Nascimento, Roseli Aparecida Matheus do; Assunção, Murillo Santucci Cesar; Silva, João Manoel; Amendola, Cristina Prata; Carvalho, Taysa Martindo de; Lima, Emerson Quintino; Lobo, Suzana Margareth Ajeje

    2016-01-01

    To evaluate the knowledgeof nurses on early identification of acute kidney injury (AKI) in intensive care, emergency and hospitalization units. A prospective multi-center study was conducted with 216 nurses, using a questionnaire with 10 questions related to AKI prevention, diagnosis, and treatment. 57.2% of nurses were unable to identify AKI clinical manifestations, 54.6% did not have knowledge of AKI incidence in patients admitted to the ICU, 87.0% of the nurses did not know how to answer as regards the AKI mortality rate in patients admitted to the ICU, 67.1% answered incorrectly that slight increases in serum creatinine do not have an impact on mortality, 66.8% answered incorrectly to the question on AKI prevention measures, 60.4% answered correctly that loop diuretics for preventing AKI is not recommended, 77.6% answered correctly that AKI does not characterize the need for hemodialysis, and 92.5% said they had no knowledge of the Acute Kidney Injury Networkclassification. Nurses do not have enough knowledge to identify early AKI, demonstrating the importance of qualification programs in this field of knowledge. Avaliar o conhecimento do enfermeiro na identificação precoce da Injúria Renal Aguda (IRA) em Unidade de Terapia Intensiva, Unidade de Internação e Emergência. Estudo multicêntrico, prospectivo.Participaram do estudo 216 enfermeiros,por meio de questionário com 10 questões relacionadas à prevenção, ao diagnóstico e ao tratamento da IRA. 57,2% não souberam identificar as manifestações clínicas da IRA, 54,6% não têm conhecimento da incidência de IRA em pacientes internados na UTI, 87,0% dos enfermeiros não souberam responder ao índice de mortalidade de IRA em pacientes internados na UTI, 67,1% responderam incorretamente que aumentos discretos da creatinina sérica não têm impacto na mortalidade, 66,8% responderam incorretamente à questão sobre as medidas de prevenção da IRA, 60,4% acertaram quando responderam que não

  15. Visual Indicators on Vaccine Boxes as Early Warning Tools to Identify Potential Freeze Damage.

    Science.gov (United States)

    Angoff, Ronald; Wood, Jillian; Chernock, Maria C; Tipping, Diane

    2015-07-01

    The aim of this study was to determine whether the use of visual freeze indicators on vaccines would assist health care providers in identifying vaccines that may have been exposed to potentially damaging temperatures. Twenty-seven sites in Connecticut involved in the Vaccine for Children Program participated. In addition to standard procedures, visual freeze indicators (FREEZEmarker ® L; Temptime Corporation, Morris Plains, NJ) were affixed to each box of vaccine that required refrigeration but must not be frozen. Temperatures were monitored twice daily. During the 24 weeks, all 27 sites experienced triggered visual freeze indicator events in 40 of the 45 refrigerators. A total of 66 triggered freeze indicator events occurred in all 4 types of refrigerators used. Only 1 of the freeze events was identified by a temperature-monitoring device. Temperatures recorded on vaccine data logs before freeze indicator events were within the 35°F to 46°F (2°C to 8°C) range in all but 1 instance. A total of 46,954 doses of freeze-sensitive vaccine were stored at the time of a visual freeze indicator event. Triggered visual freeze indicators were found on boxes containing 6566 doses (14.0% of total doses). Of all doses stored, 14,323 doses (30.5%) were of highly freeze-sensitive vaccine; 1789 of these doses (12.5%) had triggered indicators on the boxes. Visual freeze indicators are useful in the early identification of freeze events involving vaccines. Consideration should be given to including these devices as a component of the temperature-monitoring system for vaccines.

  16. Using Active Learning to Identify Health Information Technology Related Patient Safety Events.

    Science.gov (United States)

    Fong, Allan; Howe, Jessica L; Adams, Katharine T; Ratwani, Raj M

    2017-01-18

    The widespread adoption of health information technology (HIT) has led to new patient safety hazards that are often difficult to identify. Patient safety event reports, which are self-reported descriptions of safety hazards, provide one view of potential HIT-related safety events. However, identifying HIT-related reports can be challenging as they are often categorized under other more predominate clinical categories. This challenge of identifying HIT-related reports is exacerbated by the increasing number and complexity of reports which pose challenges to human annotators that must manually review reports. In this paper, we apply active learning techniques to support classification of patient safety event reports as HIT-related. We evaluated different strategies and demonstrated a 30% increase in average precision of a confirmatory sampling strategy over a baseline no active learning approach after 10 learning iterations.

  17. Early prediction of adverse events in enhanced recovery based upon the host systemic inflammatory response.

    Science.gov (United States)

    Lane, J C; Wright, S; Burch, J; Kennedy, R H; Jenkins, J T

    2013-02-01

    Early identification of patients experiencing postoperative complications is imperative for successful management. C-reactive protein (CRP) is a nonspecific marker of inflammation used in many specialties to monitor patient condition. The role of CRP measurement early in the elective postoperative colorectal patient is unclear, particularly in the context of enhanced recovery (ERAS). Five hundred and thirty-three consecutive patients who underwent elective colorectal surgery between October 2008 and October 2010 within an established ERAS programme were studied. Patients were separated into a development group of 265 patients and a validation group of 268 patients by chronological order. CRP and white cell count were added to a prospectively maintained ERAS database. The primary outcome of the study was all adverse events (including infective complications, postoperative organ dysfunction and prolonged length of stay) during the initial hospital admission. Significant predictors for adverse events on univariate analysis were submitted to multivariate regression analysis and the resulting model applied to the validation group. The validity and predictive accuracy of the regression model was assessed using receiver operating characteristic curve/area under the curve (AUC) analysis. CRP levels >150 mg/l on postoperative day 2 and a rising CRP on day 3 were independently associated with all adverse events during the hospital admission. A weighted model was applied to the validation group yielding an AUC of 0.65 (95% CI 0.58-0.73) indicating, at best, modest discrimination and predictive accuracy for adverse events. Measurement of CRP in patients after elective colorectal surgery in the first few days after surgery within ERAS can assist in identifying those at risk of adverse events and a prolonged hospital stay. A CRP value of >150 mg/l on day 2 and a rising CRP on day 3 should alert the surgeon to an increased likelihood of such events. © 2012 The Authors

  18. A new index for identifying different types of El Niño Modoki events

    Science.gov (United States)

    Wang, Xin; Tan, Wei; Wang, Chunzai

    2018-04-01

    El Niño Modoki events can be further classified into El Niño Modoki I and II in terms of their opposite impacts on southern China rainfall (Wang and Wang, J Clim 26:1322-1338, 2013) and the Indian Ocean dipole mode (Wang and Wang, Clim Dyn 42:991-1005, 2014). The present paper develops an index to identify the types of El Niño events. The El Niño Modoki II (MII) index is defined as the leading principle component of multivariate empirical orthogonal function analysis of the normalized El Niño Modoki index, Niño4 index and 850 hPa relative vorticity anomalies averaged near the Philippine Sea during autumn. The MII index exhibits dominant variations on interannual (2-3 and 4-5 years) and decadal (10-20 years) timescales. El Niño Modoki II events can be well identified by using the MII index value being larger than 1 standard deviation. Further analyses and numerical model experiments confirm that the MII index can portray the major oceanic and atmospheric features of El Niño Modoki II events. The constructed MII index along with previous ENSO indices can be used for classifying and identifying all types of El Niño events. Because of distinct impacts induced by different types of El Niño events, the implication of the present study is that climate prediction and future climate projection under global warming can be improved by using the MII index and other indices to identify the types of El Niño events.

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

    Science.gov (United States)

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

    2017-09-01

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

  20. Environmental change during the Late Berriasian - Early Valanginian: a prelude to the late Early Valanginian carbon-isotope event?

    Science.gov (United States)

    Morales, Chloé; Schnyder, Johann; Spangenberg, Jorge; Adatte, Thierry; Westermann, Stephane; Föllmi, Karl

    2010-05-01

    The Valanginian period is well known for a positive excursion in marine and terrestrial δ13C records, which has been interpreted as the consequence of a major perturbation in the global carbon cycle (Lini et al., 1992; Erba et al., 2004). In contrast to the positive δ13C excursions of the Early Aptian and latest Cenomanian, marine organic-rich sediments have only been recognized from a few localities (van de Schootbrugge et al., 2003; Reboulet et al., 2003; Gröcke et al., 2005; Westermann et al., in press). The δ13C excursion began in the late Early Valanginian (campylotoxus ammonite zone) and gradually ended during the Late Valanginian. It is associated with a phase of widespread carbonate-platform drowning on the shelf (Föllmi et al., 1994) and a decline in calcareous nannofossils in the pelagic realm (Erba et al., 2004). As a triggering mechanism, numerous authors invoke the formation of the Parañà-Etendeka flood basalt. The correlation of this episode with the Valanginian δ13C event depends, however, on the absolute ages attributed to the Valanginian stage. The recent geological timescale by Ogg et al. (2008) shows that the major eruptional phase occurred during the Late Valanginian. This may imply that the late Early Valanginian δ13C event resulted from a combination of different factors. Important paleoenvironmental change occurred already in the latest Berriasian and earliest Valanginian, prior to the positive δ13C excursion. An increase in nutrient input near the onset of the δ13C excursion (campylotoxus ammonite zone), which may be considered as a trigger of the carbon cycle perturbation, has been identified in different studies, (Hennig, 2003; Duchamp-Alphonse et al., 2007; Bornemann & Mutterlose, 2008). Heterozoan faunal associations became dominant since the Early Valanginian on the northern Tethyan Helvetic platform and may indicate the beginning of sea-water eutrophication (Föllmi et al., 2007). Clay assemblages in the Tethys and Western

  1. An EAS event observed in the early stage of development

    Science.gov (United States)

    Barroso, S. L. C.; Beggio, P. C.; de Carvalho, A. O.; Chinellato, J. A.; Mariano, A.; de Oliveira, R.; Shibuya, E. H.; Brazil-Japan Collaboration of Chacaltaya Emulsion Chamber Experiment

    2008-01-01

    Since 1969 the experiments of Brazil-Japan Collaboration showed the occurrence of a series of events, showing a region with a high concentration of electromagnetic particles, surrounded by isolated and/or groups of showers. These events were named "halo events" or "super-families". Currently, we have more than a dozen of such events. The first of them, due to its aspect, was named "Andromeda". We present here the main characteristics of a similar halo event, named C21S087I075. It has a halo region with many high energy showers in its border. Other small energy showers spread over the central and surrounding blocks (S088, S100, S101, I074). These isolated showers, classified as of hadronic or electromagnetic origin, present a fractional energy distribution compatible with that of a Centauro candidate event (C16S087I037), reported at this symposium [S.L.C. Barroso, P.C. Beggio, J.A. Chinellato, A.O. Carvalho, A. Mariano, R. Oliveira, E.H. Shibuya, in this issue of XIV ISVHECRI]. Moreover, the lateral distribution in the halo region is similar to that observed in other 3 halo events.

  2. Heterologous microarray experiments allow the identification of the early events associated with potato tuber cold sweetening

    Directory of Open Access Journals (Sweden)

    Vitulli Federico

    2008-04-01

    Full Text Available Abstract Background Since its discovery more than 100 years ago, potato (Solanum tuberosum tuber cold-induced sweetening (CIS has been extensively investigated. Several carbohydrate-associated genes would seem to be involved in the process. However, many uncertainties still exist, as the relative contribution of each gene to the process is often unclear, possibly as the consequence of the heterogeneity of experimental systems. Some enzymes associated with CIS, such as β-amylases and invertases, have still to be identified at a sequence level. In addition, little is known about the early events that trigger CIS and on the involvement/association with CIS of genes different from carbohydrate-associated genes. Many of these uncertainties could be resolved by profiling experiments, but no GeneChip is available for the potato, and the production of the potato cDNA spotted array (TIGR has recently been discontinued. In order to obtain an overall picture of early transcriptional events associated with CIS, we investigated whether the commercially-available tomato Affymetrix GeneChip could be used to identify which potato cold-responsive gene family members should be further studied in detail by Real-Time (RT-PCR (qPCR. Results A tomato-potato Global Match File was generated for the interpretation of various aspects of the heterologous dataset, including the retrieval of best matching potato counterparts and annotation, and the establishment of a core set of highly homologous genes. Several cold-responsive genes were identified, and their expression pattern was studied in detail by qPCR over 26 days. We detected biphasic behaviour of mRNA accumulation for carbohydrate-associated genes and our combined GeneChip-qPCR data identified, at a sequence level, enzymatic activities such as β-amylases and invertases previously reported as being involved in CIS. The GeneChip data also unveiled important processes accompanying CIS, such as the induction of redox

  3. Utilization of Satellite Data to Identify and Monitor Changes in Frequency of Meteorological Events

    Science.gov (United States)

    Mast, J. C.; Dessler, A. E.

    2017-12-01

    Increases in temperature and climate variability due to human-induced climate change is increasing the frequency and magnitude of extreme heat events (i.e., heatwaves). This will have a detrimental impact on the health of human populations and habitability of certain land locations. Here we seek to utilize satellite data records to identify and monitor extreme heat events. We analyze satellite data sets (MODIS and AIRS land surface temperatures (LST) and water vapor profiles (WV)) due to their global coverage and stable calibration. Heat waves are identified based on the frequency of maximum daily temperatures above a threshold, determined as follows. Land surface temperatures are gridded into uniform latitude/longitude bins. Maximum daily temperatures per bin are determined and probability density functions (PDF) of these maxima are constructed monthly and seasonally. For each bin, a threshold is calculated at the 95th percentile of the PDF of maximum temperatures. Per each bin, an extreme heat event is defined based on the frequency of monthly and seasonal days exceeding the threshold. To account for the decreased ability of the human body to thermoregulate with increasing moisture, and to assess lethality of the heat events, we determine the wet-bulb temperature at the locations of extreme heat events. Preliminary results will be presented.

  4. Early Vocabulary Development of Australian Indigenous Children: Identifying Strengths

    Directory of Open Access Journals (Sweden)

    Brad M. Farrant

    2014-01-01

    Full Text Available The current study sought to increase our understanding of the factors involved in the early vocabulary development of Australian Indigenous children. Data from the Longitudinal Study of Indigenous Children were available for 573 Indigenous children (291 boys who spoke English (M=37.0 months, SD=5.4 months, at wave 3. Data were also available for 86 children (51 boys who spoke an Indigenous language (M=37.1 months, SD=6.0 months, at wave 3. As hypothesised, higher levels of parent-child book reading and having more children’s books in the home were associated with better English vocabulary development. Oral storytelling in Indigenous language was a significant predictor of the size of children’s Indigenous vocabulary.

  5. Patient-identified events implicated in the development of body dysmorphic disorder.

    Science.gov (United States)

    Weingarden, Hilary; Curley, Erin E; Renshaw, Keith D; Wilhelm, Sabine

    2017-06-01

    Little is known about the causes of body dysmorphic disorder (BDD), but researchers have proposed a diathesis-stress model. This study uses a patient-centered approach to identify stressful events to which patients attribute the development of their BDD symptoms. An Internet-recruited sample of 165 adults with BDD participated. A large minority of participants attributed the development of their BDD to a triggering event. Bullying experiences were the most commonly described type of event. Additionally, most events were interpersonal and occurred during grade school or middle school. There were no differences in severity of psychosocial outcomes between participants who did or did not attribute their BDD to a specific triggering event. However, participants who specifically attributed their BDD development to a bullying experience had poorer psychosocial outcomes (i.e., perceived social support, depression severity, functional impairment, quality of life) compared to those who attributed their BDD development to another type of triggering event. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Life Event Stress and Binge Eating Among Adolescents: The Roles of Early Maladaptive Schemas and Impulsivity.

    Science.gov (United States)

    Zhu, Hong; Luo, Xingwei; Cai, Taisheng; He, Jinbo; Lu, Yao; Wu, Siyao

    2016-10-01

    This study examined the relationships between life event stress, early maladaptive schemas, impulsivity and binge eating among adolescents and investigated the effects of early maladaptive schemas and impulsivity on the relationship between life event stress and binge eating. Specifically, we examined a moderated mediation model in which early maladaptive schemas mediated this relationship and impulsivity moderated the mediation effect. Life event stress, early maladaptive schemas, impulsivity and binge eating were investigated in a sample of 2172 seventh-, eighth- and tenth-grade middle and high school students (mean age = 14.55 years, standard deviation = 1.29). The results indicated that adolescents with greater life event stress, more early maladaptive schemas and higher levels of impulsivity displayed more severe binge eating. In addition, early maladaptive schemas mediated the relationship between life event stress and binge eating, while impulsivity moderated this relationship. Furthermore, impulsivity also moderated the mediation effect of early maladaptive schemas; as impulsivity levels increased, the strength of the association between life event stress and early maladaptive schemas increased. This study illustrates the importance of understanding individual differences and their effects on the relationship between life event stress and binge eating. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Multiple Polyploidization Events across Asteraceae with Two Nested Events in the Early History Revealed by Nuclear Phylogenomics.

    Science.gov (United States)

    Huang, Chien-Hsun; Zhang, Caifei; Liu, Mian; Hu, Yi; Gao, Tiangang; Qi, Ji; Ma, Hong

    2016-11-01

    Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae-Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  8. Tuning and Test of Fragmentation Models Based on Identified Particles and Precision Event Shape Data

    CERN Document Server

    Abreu, P; Adye, T; Ajinenko, I; Alekseev, G D; Alemany, R; Allport, P P; Almehed, S; Amaldi, Ugo; Amato, S; Andreazza, A; Andrieux, M L; Antilogus, P; Apel, W D; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Bambade, P; Barão, F; Barate, R; Barbi, M S; Bardin, Dimitri Yuri; Baroncelli, A; Bärring, O; Barrio, J A; Bartl, Walter; Bates, M J; Battaglia, Marco; Baubillier, M; Baudot, J; Becks, K H; Begalli, M; Beillière, P; Belokopytov, Yu A; Belous, K S; Benvenuti, Alberto C; Berggren, M; Bertini, D; Bertrand, D; Besançon, M; Bianchi, F; Bigi, M; Bilenky, S M; Billoir, P; Bloch, D; Blume, M; Bolognese, T; Bonesini, M; Bonivento, W; Booth, P S L; Bosio, C; Botner, O; Boudinov, E; Bouquet, B; Bourdarios, C; Bowcock, T J V; Bozzo, M; Branchini, P; Brand, K D; Brenke, T; Brenner, R A; Bricman, C; Brown, R C A; Brückman, P; Brunet, J M; Bugge, L; Buran, T; Burgsmüller, T; Buschmann, P; Buys, A; Cabrera, S; Caccia, M; Calvi, M; Camacho-Rozas, A J; Camporesi, T; Canale, V; Canepa, M; Cankocak, K; Cao, F; Carena, F; Carroll, L; Caso, Carlo; Castillo-Gimenez, M V; Cattai, A; Cavallo, F R; Chabaud, V; Charpentier, P; Chaussard, L; Checchia, P; Chelkov, G A; Chen, M; Chierici, R; Chliapnikov, P V; Chochula, P; Chorowicz, V; Chudoba, J; Cindro, V; Collins, P; Contreras, J L; Contri, R; Cortina, E; Cosme, G; Cossutti, F; Cowell, J H; Crawley, H B; Crennell, D J; Crosetti, G; Cuevas-Maestro, J; Czellar, S; Dahl-Jensen, Erik; Dahm, J; D'Almagne, B; Dam, M; Damgaard, G; Dauncey, P D; Davenport, Martyn; Da Silva, W; Defoix, C; Deghorain, A; Della Ricca, G; Delpierre, P A; Demaria, N; De Angelis, A; de Boer, Wim; De Brabandere, S; De Clercq, C; La Vaissière, C de; De Lotto, B; De Min, A; De Paula, L S; De Saint-Jean, C; Dijkstra, H; Di Ciaccio, Lucia; Di Diodato, A; Djama, F; Dolbeau, J; Dönszelmann, M; Doroba, K; Dracos, M; Drees, J; Drees, K A; Dris, M; Durand, J D; Edsall, D M; Ehret, R; Eigen, G; Ekelöf, T J C; Ekspong, Gösta; Elsing, M; Engel, J P; Erzen, B; Espirito-Santo, M C; Falk, E; Fassouliotis, D; Feindt, Michael; Ferrer, A; Fichet, S; Filippas-Tassos, A; Firestone, A; Fischer, P A; Föth, H; Fokitis, E; Fontanelli, F; Formenti, F; Franek, B J; Frenkiel, P; Fries, D E C; Frodesen, A G; Frühwirth, R; Fulda-Quenzer, F; Fuster, J A; Galloni, A; Gamba, D; Gandelman, M; García, C; García, J; Gaspar, C; Gasparini, U; Gavillet, P; Gazis, E N; Gelé, D; Gerber, J P; Gokieli, R; Golob, B; Gopal, Gian P; Gorn, L; Górski, M; Guz, Yu; Gracco, Valerio; Graziani, E; Green, C; Grefrath, A; Gris, P; Grosdidier, G; Grzelak, K; Gumenyuk, S A; Gunnarsson, P; Günther, M; Guy, J; Hahn, F; Hahn, S; Hajduk, Z; Hallgren, A; Hamacher, K; Harris, F J; Hedberg, V; Henriques, R P; Hernández, J J; Herquet, P; Herr, H; Hessing, T L; Higón, E; Hilke, Hans Jürgen; Hill, T S; Holmgren, S O; Holt, P J; Holthuizen, D J; Hoorelbeke, S; Houlden, M A; Hrubec, Josef; Huet, K; Hultqvist, K; Jackson, J N; Jacobsson, R; Jalocha, P; Janik, R; Jarlskog, C; Jarlskog, G; Jarry, P; Jean-Marie, B; Johansson, E K; Jönsson, L B; Jönsson, P E; Joram, Christian; Juillot, P; Kaiser, M; Kapusta, F; Karafasoulis, K; Karlsson, M; Karvelas, E; Katsanevas, S; Katsoufis, E C; Keränen, R; Khokhlov, Yu A; Khomenko, B A; Khovanskii, N N; King, B J; Kjaer, N J; Klapp, O; Klein, H; Klovning, A; Kluit, P M; Köne, B; Kokkinias, P; Koratzinos, M; Korcyl, K; Kostyukhin, V; Kourkoumelis, C; Kuznetsov, O; Kreuter, C; Kronkvist, I J; Krumshtein, Z; Krupinski, W; Kubinec, P; Kucewicz, W; Kurvinen, K L; Lacasta, C; Laktineh, I; Lamsa, J; Lanceri, L; Lane, D W; Langefeld, P; Lapin, V; Laugier, J P; Lauhakangas, R; Leder, Gerhard; Ledroit, F; Lefébure, V; Legan, C K; Leitner, R; Lemonne, J; Lenzen, Georg; Lepeltier, V; Lesiak, T; Libby, J; Liko, D; Lindner, R; Lipniacka, A; Lippi, I; Lörstad, B; Loken, J G; López, J M; Loukas, D; Lutz, P; Lyons, L; Naughton, J M; Maehlum, G; Mahon, J R; Maio, A; Malmgren, T G M; Malychev, V; Mandl, F; Marco, J; Marco, R P; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Martínez-Rivero, C; Martínez-Vidal, F; Martí i García, S; Masik, J; Matorras, F; Matteuzzi, C; Matthiae, Giorgio; Mazzucato, M; McCubbin, M L; McKay, R; McNulty, R; Medbo, J; Merk, M; Meroni, C; Meyer, S; Meyer, W T; Myagkov, A; Michelotto, M; Migliore, E; Mirabito, L; Mitaroff, Winfried A; Mjörnmark, U; Moa, T; Møller, R; Mönig, K; Monge, M R; Morettini, P; Müller, H; Mulders, M; Mundim, L M; Murray, W J; Muryn, B; Myatt, Gerald; Naraghi, F; Navarria, Francesco Luigi; Navas, S; Nawrocki, K; Negri, P; Neumann, W; Neumeister, N; Nicolaidou, R; Nielsen, B S; Nieuwenhuizen, M; Nikolaenko, V; Niss, P; Nomerotski, A; Normand, Ainsley; Oberschulte-Beckmann, W; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Österberg, K; Ouraou, A; Paganini, P; Paganoni, M; Pagès, P; Pain, R; Palka, H; Papadopoulou, T D; Papageorgiou, K; Pape, L; Parkes, C; Parodi, F; Passeri, A; Pegoraro, M; Peralta, L; Pernegger, H; Pernicka, Manfred; Perrotta, A; Petridou, C; Petrolini, A; Petrovykh, M; Phillips, H T; Piana, G; Pierre, F; Plaszczynski, S; Podobrin, O; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Privitera, P; Pukhaeva, N; Pullia, Antonio; Radojicic, D; Ragazzi, S; Rahmani, H; Rames, J; Ratoff, P N; Read, A L; Reale, M; Rebecchi, P; Redaelli, N G; Regler, Meinhard; Reid, D; Renton, P B; Resvanis, L K; Richard, F; Richardson, J; Rídky, J; Rinaudo, G; Ripp, I; Romero, A; Roncagliolo, I; Ronchese, P; Roos, L; Rosenberg, E I; Rosso, E; Roudeau, Patrick; Rovelli, T; Rückstuhl, W; Ruhlmann-Kleider, V; Ruiz, A; Rybicki, K; Saarikko, H; Sacquin, Yu; Sadovskii, A; Sahr, O; Sajot, G; Salt, J; Sánchez, J; Sannino, M; Schimmelpfennig, M; Schneider, H; Schwickerath, U; Schyns, M A E; Sciolla, G; Scuri, F; Seager, P; Sedykh, Yu; Segar, A M; Seitz, A; Sekulin, R L; Serbelloni, L; Shellard, R C; Siegrist, P; Silvestre, R; Simonetti, S; Simonetto, F; Sissakian, A N; Sitár, B; Skaali, T B; Smadja, G; Smirnov, N; Smirnova, O G; Smith, G R; Sokolov, A; Sosnowski, R; Souza-Santos, D; Spassoff, Tz; Spiriti, E; Sponholz, P; Squarcia, S; Stanescu, C; Stapnes, Steinar; Stavitski, I; Stevenson, K; Stichelbaut, F; Stocchi, A; Strauss, J; Strub, R; Stugu, B; Szczekowski, M; Szeptycka, M; Tabarelli de Fatis, T; Tavernet, J P; Chikilev, O G; Thomas, J; Tilquin, A; Timmermans, J; Tkatchev, L G; Todorov, T; Todorova, S; Toet, D Z; Tomaradze, A G; Tomé, B; Tonazzo, A; Tortora, L; Tranströmer, G; Treille, D; Trischuk, W; Tristram, G; Trombini, A; Troncon, C; Tsirou, A L; Turluer, M L; Tyapkin, I A; Tyndel, M; Tzamarias, S; Überschär, B; Ullaland, O; Uvarov, V; Valenti, G; Vallazza, E; van Apeldoorn, G W; van Dam, P; Van Eldik, J; Vassilopoulos, N; Vegni, G; Ventura, L; Venus, W A; Verbeure, F; Verlato, M; Vertogradov, L S; Vilanova, D; Vincent, P; Vitale, L; Vlasov, E; Vodopyanov, A S; Vrba, V; Wahlen, H; Walck, C; Waldner, F; Weierstall, M; Weilhammer, Peter; Weiser, C; Wetherell, Alan M; Wicke, D; Wickens, J H; Wielers, M; Wilkinson, G R; Williams, W S C; Winter, M; Witek, M; Woschnagg, K; Yip, K; Yushchenko, O P; Zach, F; Zaitsev, A; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zevgolatakos, E; Zimin, N I; Zito, M; Zontar, D; Zucchelli, G C; Zumerle, G

    1996-01-01

    Event shape and charged particle inclusive distributions are measured using 750000 decays of the $Z$ to hadrons from the DELPHI detector at LEP. These precise data allow a decisive confrontation with models of the hadronization process. Improved tunings of the JETSET ARIADNE and HERWIG parton shower models and the JETSET matrix element model are obtained by fitting the models to these DELPHI data as well as to identified particle distributions from all LEP experiments. The description of the data distributions by the models is critically reviewed with special importance attributed to identified particles.

  9. Event-by-Event Simulations of Early Gluon Fields in High Energy Nuclear Collisions

    Science.gov (United States)

    Nickel, Matthew; Rose, Steven; Fries, Rainer

    2017-09-01

    Collisions of heavy ions are carried out at ultra relativistic speeds at the Relativistic Heavy Ion Collider and the Large Hadron Collider to create Quark Gluon Plasma. The earliest stages of such collisions are dominated by the dynamics of classical gluon fields. The McLerran-Venugopalan (MV) model of color glass condensate provides a model for this process. Previous research has provided an analytic solution for event averaged observables in the MV model. Using the High Performance Research Computing Center (HPRC) at Texas A&M, we have developed a C++ code to explicitly calculate the initial gluon fields and energy momentum tensor event by event using the analytic recursive solution. The code has been tested against previously known analytic results up to fourth order. We have also have been able to test the convergence of the recursive solution at high orders in time and studied the time evolution of color glass condensate.

  10. Identifying Typhoon Tracks based on Event Synchronization derived Spatially Embedded Climate Networks

    Science.gov (United States)

    Ozturk, Ugur; Marwan, Norbert; Kurths, Jürgen

    2017-04-01

    Complex networks are commonly used for investigating spatiotemporal dynamics of complex systems, e.g. extreme rainfall. Especially directed networks are very effective tools in identifying climatic patterns on spatially embedded networks. They can capture the network flux, so as the principal dynamics of spreading significant phenomena. Network measures, such as network divergence, bare the source-receptor relation of the directed networks. However, it is still a challenge how to catch fast evolving atmospheric events, i.e. typhoons. In this study, we propose a new technique, namely Radial Ranks, to detect the general pattern of typhoons forward direction based on the strength parameter of the event synchronization over Japan. We suggest to subset a circular zone of high correlation around the selected grid based on the strength parameter. Radial sums of the strength parameter along vectors within this zone, radial ranks are measured for potential directions, which allows us to trace the network flux over long distances. We employed also the delay parameter of event synchronization to identify and separate the frontal storms' and typhoons' individual behaviors.

  11. Pluripotent cell models of fanconi anemia identify the early pathological defect in human hemoangiogenic progenitors.

    Science.gov (United States)

    Suzuki, Naoya M; Niwa, Akira; Yabe, Miharu; Hira, Asuka; Okada, Chihiro; Amano, Naoki; Watanabe, Akira; Watanabe, Ken-Ichiro; Heike, Toshio; Takata, Minoru; Nakahata, Tatsutoshi; Saito, Megumu K

    2015-04-01

    Fanconi anemia (FA) is a disorder of genomic instability characterized by progressive bone marrow failure (BMF), developmental abnormalities, and an increased susceptibility to cancer. Although various consequences in hematopoietic stem/progenitor cells have been attributed to FA-BMF, the quest to identify the initial pathological event is still ongoing. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts of six patients with FA and FANCA mutations. An improved reprogramming method yielded iPSC-like colonies from all patients, and iPSC clones were propagated from two patients. Quantitative evaluation of the differentiation ability demonstrated that the differentiation propensity toward the hematopoietic and endothelial lineages is already defective in early hemoangiogenic progenitors. The expression levels of critical transcription factors were significantly downregulated in these progenitors. These data indicate that the hematopoietic consequences in FA patients originate from the early hematopoietic stage and highlight the potential usefulness of iPSC technology for elucidating the pathogenesis of FA-BMF. ©AlphaMed Press.

  12. Age-related differences in event-related potentials for early visual processing of emotional faces.

    Science.gov (United States)

    Hilimire, Matthew R; Mienaltowski, Andrew; Blanchard-Fields, Fredda; Corballis, Paul M

    2014-07-01

    With advancing age, processing resources are shifted away from negative emotional stimuli and toward positive ones. Here, we explored this 'positivity effect' using event-related potentials (ERPs). Participants identified the presence or absence of a visual probe that appeared over photographs of emotional faces. The ERPs elicited by the onsets of angry, sad, happy and neutral faces were recorded. We examined the frontocentral emotional positivity (FcEP), which is defined as a positive deflection in the waveforms elicited by emotional expressions relative to neutral faces early on in the time course of the ERP. The FcEP is thought to reflect enhanced early processing of emotional expressions. The results show that within the first 130 ms young adults show an FcEP to negative emotional expressions, whereas older adults show an FcEP to positive emotional expressions. These findings provide additional evidence that the age-related positivity effect in emotion processing can be traced to automatic processes that are evident very early in the processing of emotional facial expressions. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. Performing drought indices to identify the relationship between agricultural losses and drought events in Spain.

    Science.gov (United States)

    Peña Gallardo, Marina; Serrano, Sergio Martín Vicente; Portugués Santiago, Beguería; Burguera Miquel, Tomás

    2017-04-01

    Drought leads to crop failures reducing the productivity. For this reason, the need of appropriate tool for recognize dry periods and evaluate the impact of drought on crop production is important. In this study, we provide an assessment of the relationship between drought episodes and crop failures in Spain as one of the direct consequences of drought is the diminishing of crop yields. First, different drought indices [the Standardized Precipitation and Evapotranspiration Index (SPEI); the Standardized Precipitation Index (SPI); the self-calibrated Palmer Moisture Anomaly Index (Z-Index), the self-calibrated Crop Moisture Index (CMI) and the Standardized Palmer Drought Index (SPDI)] have been calculated at different time scales in order to identify the dry events occurred in Spain and determine the duration and intensity of each event. Second, the drought episodes have been correlated with crop production estimated and final crop production data provided by the Spanish Crop Insurance System for the available period from 1995 to 2014 at the municipal spatial scale, with the purpose of knowing if the characteristics of the drought episodes are reflected on the agricultural losses. The analysis has been carried out in particular for two types of crop, wheat and barley. The results indicate the existence of an agreement between the most important drought events in Spain and the response of the crop productions and the proportion of hectare insurance. Nevertheless, this agreement vary depending on the drought index applied. Authors found a higher competence of the drought indices calculated at different time scales (SPEI, SPI and SPDI) identifying the begging and end of the drought events and the correspondence with the crop failures.

  14. Physiologically-based toxicokinetic models help identifying the key factors affecting contaminant uptake during flood events

    Energy Technology Data Exchange (ETDEWEB)

    Brinkmann, Markus; Eichbaum, Kathrin [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Kammann, Ulrike [Thünen-Institute of Fisheries Ecology, Palmaille 9, 22767 Hamburg (Germany); Hudjetz, Sebastian [Department of Ecosystem Analysis, Institute for Environmental Research,ABBt – Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Cofalla, Catrina [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Buchinger, Sebastian; Reifferscheid, Georg [Federal Institute of Hydrology (BFG), Department G3: Biochemistry, Ecotoxicology, Am Mainzer Tor 1, 56068 Koblenz (Germany); Schüttrumpf, Holger [Institute of Hydraulic Engineering and Water Resources Management, RWTH Aachen University, Mies-van-der-Rohe-Straße 1, 52056 Aachen (Germany); Preuss, Thomas [Department of Environmental Biology and Chemodynamics, Institute for Environmental Research,ABBt- Aachen Biology and Biotechnology, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany); and others

    2014-07-01

    Highlights: • A PBTK model for trout was coupled with a sediment equilibrium partitioning model. • The influence of physical exercise on pollutant uptake was studies using the model. • Physical exercise during flood events can increase the level of biliary metabolites. • Cardiac output and effective respiratory volume were identified as relevant factors. • These confounding factors need to be considered also for bioconcentration studies. - Abstract: As a consequence of global climate change, we will be likely facing an increasing frequency and intensity of flood events. Thus, the ecotoxicological relevance of sediment re-suspension is of growing concern. It is vital to understand contaminant uptake from suspended sediments and relate it to effects in aquatic biota. Here we report on a computational study that utilizes a physiologically based toxicokinetic model to predict uptake, metabolism and excretion of sediment-borne pyrene in rainbow trout (Oncorhynchus mykiss). To this end, data from two experimental studies were compared with the model predictions: (a) batch re-suspension experiments with constant concentration of suspended particulate matter at two different temperatures (12 and 24 °C), and (b) simulated flood events in an annular flume. The model predicted both the final concentrations and the kinetics of 1-hydroxypyrene secretion into the gall bladder of exposed rainbow trout well. We were able to show that exhaustive exercise during exposure in simulated flood events can lead to increased levels of biliary metabolites and identified cardiac output and effective respiratory volume as the two most important factors for contaminant uptake. The results of our study clearly demonstrate the relevance and the necessity to investigate uptake of contaminants from suspended sediments under realistic exposure scenarios.

  15. Physiologically-based toxicokinetic models help identifying the key factors affecting contaminant uptake during flood events

    International Nuclear Information System (INIS)

    Brinkmann, Markus; Eichbaum, Kathrin; Kammann, Ulrike; Hudjetz, Sebastian; Cofalla, Catrina; Buchinger, Sebastian; Reifferscheid, Georg; Schüttrumpf, Holger; Preuss, Thomas

    2014-01-01

    Highlights: • A PBTK model for trout was coupled with a sediment equilibrium partitioning model. • The influence of physical exercise on pollutant uptake was studies using the model. • Physical exercise during flood events can increase the level of biliary metabolites. • Cardiac output and effective respiratory volume were identified as relevant factors. • These confounding factors need to be considered also for bioconcentration studies. - Abstract: As a consequence of global climate change, we will be likely facing an increasing frequency and intensity of flood events. Thus, the ecotoxicological relevance of sediment re-suspension is of growing concern. It is vital to understand contaminant uptake from suspended sediments and relate it to effects in aquatic biota. Here we report on a computational study that utilizes a physiologically based toxicokinetic model to predict uptake, metabolism and excretion of sediment-borne pyrene in rainbow trout (Oncorhynchus mykiss). To this end, data from two experimental studies were compared with the model predictions: (a) batch re-suspension experiments with constant concentration of suspended particulate matter at two different temperatures (12 and 24 °C), and (b) simulated flood events in an annular flume. The model predicted both the final concentrations and the kinetics of 1-hydroxypyrene secretion into the gall bladder of exposed rainbow trout well. We were able to show that exhaustive exercise during exposure in simulated flood events can lead to increased levels of biliary metabolites and identified cardiac output and effective respiratory volume as the two most important factors for contaminant uptake. The results of our study clearly demonstrate the relevance and the necessity to investigate uptake of contaminants from suspended sediments under realistic exposure scenarios

  16. Translational errors as an early event in prion conversion.

    Science.gov (United States)

    Hatin, I; Bidou, L; Cullin, C; Rousset, J P

    2001-01-01

    A prion is an infectious, altered form of a cellular protein which can self-propagate and affect normal phenotype. Prion conversion has been observed for mammalian and yeast proteins but molecular mechanisms that trigger this process remain unclear. Up to now, only post-translational models have been explored. In this work, we tested the hypothesis that co-translational events may be implicated in the conformation changes of the Ure2p protein of Saccharomyces cerevisiae. This protein can adopt a prion conformation leading to an [URE3] phenotype which can be easily assessed and quantified. We analyzed the effect of two antibiotics, known to affect translation, on [URE3] conversion frequency. For cells treated with G418 we observed a parallel increase of translational errors rate and frequency of [URE3] conversion. By contrast, cycloheximide which was not found to affect translational fidelity, has no influence on the induction of [URE3] phenotype. These results raise the possibility that the mechanism of prion conversion might not only involve alternative structures of strictly identical molecules but also aberrant proteins resulting from translational errors.

  17. Can surveillance systems identify and avert adverse drug events? A prospective evaluation of a commercial application.

    Science.gov (United States)

    Jha, Ashish K; Laguette, Julia; Seger, Andrew; Bates, David W

    2008-01-01

    Computerized monitors can effectively detect and potentially prevent adverse drug events (ADEs). Most monitors have been developed in large academic hospitals and are not readily usable in other settings. We assessed the ability of a commercial program to identify and prevent ADEs in a community hospital. and Measurement We prospectively evaluated the commercial application in a community-based hospital. We examined the frequency and types of alerts produced, how often they were associated with ADEs and potential ADEs, and the potential financial impact of monitoring for ADEs. Among 2,407 patients screened, the application generated 516 high priority alerts. We were able to review 266 alerts at the time they were generated and among these, 30 (11.3%) were considered substantially important to warrant contacting the physician caring for the patient. These 30 alerts were associated with 4 ADEs and 11 potential ADEs. In all 15 cases, the responsible physician was unaware of the event, leading to a change in clinical care in 14 cases. Overall, 23% of high priority alerts were associated with an ADE (95% confidence interval [CI] 12% to 34%) and another 15% were associated with a potential ADE (95% CI 6% to 24%). Active surveillance used approximately 1.5 hours of pharmacist time daily. A commercially available, computer-based ADE detection tool was effective at identifying ADEs. When used as part of an active surveillance program, it can have an impact on preventing or ameliorating ADEs.

  18. Identifying Changes in the Probability of High Temperature, High Humidity Heat Wave Events

    Science.gov (United States)

    Ballard, T.; Diffenbaugh, N. S.

    2016-12-01

    Understanding how heat waves will respond to climate change is critical for adequate planning and adaptation. While temperature is the primary determinant of heat wave severity, humidity has been shown to play a key role in heat wave intensity with direct links to human health and safety. Here we investigate the individual contributions of temperature and specific humidity to extreme heat wave conditions in recent decades. Using global NCEP-DOE Reanalysis II daily data, we identify regional variability in the joint probability distribution of humidity and temperature. We also identify a statistically significant positive trend in humidity over the eastern U.S. during heat wave events, leading to an increased probability of high humidity, high temperature events. The extent to which we can expect this trend to continue under climate change is complicated due to variability between CMIP5 models, in particular among projections of humidity. However, our results support the notion that heat wave dynamics are characterized by more than high temperatures alone, and understanding and quantifying the various components of the heat wave system is crucial for forecasting future impacts.

  19. Signal detection to identify serious adverse events (neuropsychiatric events in travelers taking mefloquine for chemoprophylaxis of malaria

    Directory of Open Access Journals (Sweden)

    Naing C

    2012-08-01

    Full Text Available Cho Naing,1,3 Kyan Aung,1 Syed Imran Ahmed,2 Joon Wah Mak31School of Medical Sciences, 2School of Pharmacy and Health Sciences, 3School of Postgraduate Studies and Research, International Medical University, Kuala Lumpur, MalaysiaBackground: For all medications, there is a trade-off between benefits and potential for harm. It is important for patient safety to detect drug-event combinations and analyze by appropriate statistical methods. Mefloquine is used as chemoprophylaxis for travelers going to regions with known chloroquine-resistant Plasmodium falciparum malaria. As such, there is a concern about serious adverse events associated with mefloquine chemoprophylaxis. The objective of the present study was to assess whether any signal would be detected for the serious adverse events of mefloquine, based on data in clinicoepidemiological studies.Materials and methods: We extracted data on adverse events related to mefloquine chemoprophylaxis from the two published datasets. Disproportionality reporting of adverse events such as neuropsychiatric events and other adverse events was presented in the 2 × 2 contingency table. Reporting odds ratio and corresponding 95% confidence interval [CI] data-mining algorithm was applied for the signal detection. The safety signals are considered significant when the ROR estimates and the lower limits of the corresponding 95% CI are ≥2.Results: Two datasets addressing adverse events of mefloquine chemoprophylaxis (one from a published article and one from a Cochrane systematic review were included for analyses. Reporting odds ratio 1.58, 95% CI: 1.49–1.68 based on published data in the selected article, and 1.195, 95% CI: 0.94–1.44 based on data in the selected Cochrane review. Overall, in both datasets, the reporting odds ratio values of lower 95% CI were less than 2.Conclusion: Based on available data, findings suggested that signals for serious adverse events pertinent to neuropsychiatric event were

  20. Early events of lethal action by tobramycin in Pseudomonas aeruginosa

    International Nuclear Information System (INIS)

    Raulston, J.E.

    1988-01-01

    The immediate activities of the aminoglycoside antibiotic, tobramycin, were investigated in Pseudomonas aeruginosa PAO1. The influence of carbon growth substate and the antibiotic exposure environment in the magnitude of activity were examined. Lethality by 8 μg/ml tobramycin occurred rapidly (1 to 3 minutes). The release of specific cellular components into the supernatant was associated with lethality. This material was initially detected as an increase in UV-absorbance. Magnesium in the reaction mixture provided protection against lethality and leakage, but did not reverse lethal damage after a 3 minute tobramycin treatment. Also, uptake of 3 H-tobramycin was reduced in the presence of magnesium. Cells grown with glucose as a carbon source were more susceptible than organic acid grown cells as was the rapidity and amount of cell damage. Analyses of the leakage material revealed a 2-fold increase of protein in the supernatant after a 1-3 minute treatment which paralleled lethality. A prominent 29 kDa protein was observed by SDS-PAGE in the released material, which has been identified as the periplasmic enzyme, β-lactamase. The immediate activities of tobramycin did not involve (i) release of overall cell protein, (ii) massive loss of total pool amino acids, (iii) cell lysis, (iv) inhibition of proline uptake, (v) release of lipopolysaccharide, or (vi) leakage of ATP. Electron microscopy showed no apparent damage after a 3 minute exposure. 40% inhibition of protein synthesis had occurred by 3 minutes of exposure, while release of UV-absorbing material and lethality were detectable after only 1 minute. Resistant cystic fibrosis isolates of P. aeruginosa did not leak under the same experimental conditions, but one of two susceptible strains examined did show increased UV-absorbance following treatment

  1. Identifying evidence of climate change impact on extreme events in permeable chalk catchments

    Science.gov (United States)

    Butler, A. P.; Nubert, S.

    2009-12-01

    The permeable chalk catchments of southern England are vital for the economy and well being of the UK. Not only important as a water resource, their freely draining soils support intensive agricultural production, and the rolling downs and chalk streams provide important habitants for many protected plant and animal species. Consequently, there are concerns about the potential impact of climate change on such catchments, particularly in relation to groundwater recharge. Of major concern are possible changes in extreme events, such as groundwater floods and droughts, as any increase in the frequency and/or severity of these has important consequences for water resources, ecological systems and local infrastructure. Studies of climate change impact on extreme events for such catchments have indicated that, under medium and high emissions scenarios, droughts are likely to become more severe whilst floods less so. However, given the uncertainties in such predictions and the inherent variability in historic data, producing definitive evidence of changes in flood/drought frequency/severity poses a significant challenge. Thus, there is a need for specific extreme event statistics that can be used as indicators of actual climate change in streamflow and groundwater level observations. Identifying such indicators that are sufficiently robust requires catchments with long historic time series data. One such catchment is the River Lavant, an intermittent chalk stream in West Sussex, UK. Located within this catchment is Chilgrove House, the site of the UK’s longest groundwater monitoring well (with a continuous record of water level observations of varying frequency dating back to 1836). Using a variety of meteorological datasets, the behaviour of the catchment has been modelled, from 1855 to present, using a 'leaky aquifer' conceptual model. Model calibration was based on observed daily streamflow, at a gauging station just outside the town of Chichester, from 1970. Long

  2. Membrane remodeling, an early event in benzo[α]pyrene-induced apoptosis

    International Nuclear Information System (INIS)

    Tekpli, Xavier; Rissel, Mary; Huc, Laurence; Catheline, Daniel; Sergent, Odile; Rioux, Vincent; Legrand, Philippe; Holme, Jorn A.; Dimanche-Boitrel, Marie-Therese; Lagadic-Gossmann, Dominique

    2010-01-01

    Benzo[α]pyrene (B[α]P) often serves as a model for mutagenic and carcinogenic polycyclic aromatic hydrocarbons (PAHs). Our previous work suggested a role of membrane fluidity in B[α]P-induced apoptotic process. In this study, we report that B[α]P modifies the composition of cholesterol-rich microdomains (lipid rafts) in rat liver F258 epithelial cells. The cellular distribution of the ganglioside-GM1 was markedly changed following B[α]P exposure. B[α]P also modified fatty acid composition and decreased the cholesterol content of cholesterol-rich microdomains. B[α]P-induced depletion of cholesterol in lipid rafts was linked to a reduced expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). Aryl hydrocarbon receptor (AhR) and B[α]P-related H 2 O 2 formation were involved in the reduced expression of HMG-CoA reductase and in the remodeling of membrane microdomains. The B[α]P-induced membrane remodeling resulted in an intracellular alkalinization observed during the early phase of apoptosis. In conclusion, B[α]P altered the composition of plasma membrane microstructures through AhR and H 2 O 2 dependent-regulation of lipid biosynthesis. In F258 cells, the B[α]P-induced membrane remodeling was identified as an early apoptotic event leading to an intracellular alkalinization.

  3. Early cell adhesion events differ between osteoporotic and non-osteoporotic osteoblasts.

    Science.gov (United States)

    Perinpanayagam, H; Zaharias, R; Stanford, C; Brand, R; Keller, J; Schneider, G

    2001-11-01

    In osteoporosis, the regenerative capacity of bone is compromised, which may involve altered osteoblast (OB) activity. This could be attributed to an inappropriate synthesis and assembly of an extracellular matrix (ECM), altered cell adhesion to the ECM, or be due to inappropriate downstream activation of adhesion-mediated signaling cascades through proteins such as focal adhesion kinase (FAK). The purpose of our study was to compare early adhesion-mediated events using previously described and characterized clinically derived OBs obtained from human patients undergoing major joint arthroplasty for osteoporosis or osteoarthritis. The presence or absence of osteoporosis was established with a radiographic index. Using light microscopy and crystal violet staining, we show that OB cells derived from sites of osteoporosis do not attach and spread as well as non-osteoporotic (OP) OB cells. OP cells initially have a more rounded morphology, and show significantly less (P attachment to serum-coated tissue culture plastic over a 24 h time period. Immunofluorescent labeling after 24 h of attachment showed that OP OB focal adhesions (FAs) and stress fibers were less defined, and that the OP cells were smaller and had a more motile phenotype. When normalized protein lysates were Western blotted for phosphotyrosine (PY) a band corresponding to pp125FAK was identified. FAK tyrosine phosphorylation was evident at 6 h in both the OP and non-OP OBs, but decreased or was absent through 24 h in OP OBs. These results suggest early adhesion-mediated events, such as cell adhesion, attachment, and FAK signaling via PY may be altered in OP OBs.

  4. Exome sequencing identifies early gastric carcinoma as an early stage of advanced gastric cancer.

    Directory of Open Access Journals (Sweden)

    Guhyun Kang

    Full Text Available Gastric carcinoma is one of the major causes of cancer-related mortality worldwide. Early detection and treatment leads to an excellent prognosis in patients with early gastric cancer (EGC, whereas the prognosis of patients with advanced gastric cancer (AGC remains poor. It is unclear whether EGCs and AGCs are distinct entities or whether EGCs are the beginning stages of AGCs. We performed whole exome sequencing of four samples from patients with EGC and compared the results with those from AGCs. In both EGCs and AGCs, a total of 268 genes were commonly mutated and independent mutations were additionally found in EGCs (516 genes and AGCs (3104 genes. A higher frequency of C>G transitions was observed in intestinal-type compared to diffuse-type carcinomas (P = 0.010. The DYRK3, GPR116, MCM10, PCDH17, PCDHB1, RDH5 and UNC5C genes are recurrently mutated in EGCs and may be involved in early carcinogenesis.

  5. Identifying the null subject: evidence from event-related brain potentials.

    Science.gov (United States)

    Demestre, J; Meltzer, S; García-Albea, J E; Vigil, A

    1999-05-01

    Event-related brain potentials (ERPs) were recorded during spoken language comprehension to study the on-line effects of gender agreement violations in controlled infinitival complements. Spanish sentences were constructed in which the complement clause contained a predicate adjective marked for syntactic gender. By manipulating the gender of the antecedent (i.e., the controller) of the implicit subject while holding constant the gender of the adjective, pairs of grammatical and ungrammatical sentences were created. The detection of such a gender agreement violation would indicate that the parser had established the coreference relation between the null subject and its antecedent. The results showed a complex biphasic ERP (i.e., an early negativity with prominence at anterior and central sites, followed by a centroparietal positivity) in the violating condition as compared to the non-violating conditions. The brain reacts to NP-adjective gender agreement violations within a few hundred milliseconds of their occurrence. The data imply that the parser has properly coindexed the null subject of an infinitive clause with its antecedent.

  6. Extracellular matrix disruption is an early event in the pathogenesis of skeletal disease in mucopolysaccharidosis I.

    Science.gov (United States)

    Heppner, Jonathan M; Zaucke, Frank; Clarke, Lorne A

    2015-02-01

    Progressive skeletal and connective tissue disease represents a significant clinical burden in all of the mucopolysaccharidoses. Despite the introduction of enzyme replacement strategies for many of the mucopolysaccharidoses, symptomatology related to bone and joint disease appears to be recalcitrant to current therapies. In order to address these unmet medical needs a clearer understanding of skeletal and connective tissue disease pathogenesis is required. Historically the pathogenesis of the mucopolysaccharidoses has been assumed to directly relate to progressive storage of glycosaminoglycans. It is now apparent for many lysosomal storage disorders that more complex pathogenic mechanisms underlie patients' clinical symptoms. We have used proteomic and genome wide expression studies in the murine mucopolysaccharidosis I model to identify early pathogenic events occurring in micro-dissected growth plate tissue. Studies were conducted using 3 and 5-week-old mice thus representing a time at which no obvious morphological changes of bone or joints have taken place. An unbiased iTRAQ differential proteomic approach was used to identify candidates followed by validation with multiple reaction monitoring mass spectrometry and immunohistochemistry. These studies reveal significant decreases in six key structural and signaling extracellular matrix proteins; biglycan, fibromodulin, PRELP, type I collagen, lactotransferrin, and SERPINF1. Genome-wide expression studies in embryonic day 13.5 limb cartilage and 5 week growth plate cartilage followed by specific gene candidate qPCR studies in the 5week growth plate identified fourteen significantly deregulated mRNAs (Adamts12, Aspn, Chad, Col2a1, Col9a1, Hapln4, Lum, Matn1, Mmp3, Ogn, Omd, P4ha2, Prelp, and Rab32). The involvement of biglycan, PRELP and fibromodulin; all members of the small leucine repeat proteoglycan family is intriguing, as this protein family is implicated in the pathogenesis of late onset osteoarthritis

  7. A Systematic Review of Early Warning Systems' Effects on Nurses' Clinical Performance and Adverse Events Among Deteriorating Ward Patients.

    Science.gov (United States)

    Lee, Ju-Ry; Kim, Eun-Mi; Kim, Sun-Aee; Oh, Eui Geum

    2018-04-25

    Early warning systems (EWSs) are an integral part of processes that aim to improve the early identification and management of deteriorating patients in general wards. However, the widespread implementation of these systems has not generated robust data regarding nurses' clinical performance and patients' adverse events. This review aimed to determine the ability of EWSs to improve nurses' clinical performance and prevent adverse events among deteriorating ward patients. The PubMed, CINAHL, EMBASE, and Cochrane Library databases were searched for relevant publications (January 1, 1997, to April 12, 2017). In addition, a grey literature search evaluated several guideline Web sites. The main outcome measures were nurses' clinical performance (vital sign monitoring and rapid response team notification) and patients' adverse events (in-hospital mortality, cardiac arrest, and unplanned intensive care unit [ICU] admission). The search identified 888 reports, although only five studies fulfilled the inclusion criteria. The findings of these studies revealed that EWSs implementation had a positive effect on nurses' clinical performance, based on their frequency of documenting vital signs that were related to the patient's clinical deterioration. In addition, postimplementation reductions were identified for cardiac arrest, unplanned ICU admission, and unexpected death. It seems that EWSs can improve nurses' clinical performance and prevent adverse events (e.g., in-hospital mortality, unplanned ICU admission, and cardiac arrest) among deteriorating ward patients. However, additional high-quality evidence is needed to more comprehensively evaluate the effects of EWSs on these outcomes.

  8. Swarm-Aurora: A web-based tool for quickly identifying multi-instrument auroral events

    Science.gov (United States)

    Chaddock, D.; Donovan, E.; Spanswick, E.; Knudsen, D. J.; Frey, H. U.; Kauristie, K.; Partamies, N.; Jackel, B. J.; Gillies, M.; Holmdahl Olsen, P. E.

    2016-12-01

    In recent years there has been a dramatic increase in ground-based auroral imaging systems. These include the continent-wide THEMIS-ASI network, and imagers operated by other programs including GO-Canada, MIRACLE, AGO, OMTI, and more. In the near future, a new Canadian program called TREx will see the deployment of new narrow-band ASIs that will provide multi-wavelength imaging across Western Canada. At the same time, there is an unprecedented fleet of international spacecraft probing geospace at low and high altitudes. We are now in the position to simultaneously observe the magnetospheric drivers of aurora, observe in situ the waves, currents, and particles associated with MI coupling, and the conjugate aurora. Whereas a decade ago, a single magnetic conjunction between one ASI and a low altitude satellite was a relatively rare event, we now have a plethora of triple conjunctions between imagers, low-altitude spacecraft, and near-equatorial magnetospheric probes. But with these riches comes a new level of complexity. It is often difficult to identify the many useful conjunctions for a specific line of inquiry from the multitude of conjunctions where the geospace conditions are often not relevant and/or the imaging is compromised by clouds, moon, or other factors. Swarm-Aurora was designed to facilitate and drive the use of Swarm in situ measurements in auroral science. The project seeks to build a bridge between the Swarm science community, Swarm data, and the complimentary auroral data and community. Swarm-Aurora (http://swarm-aurora.phys.ucalgary.ca) incorporates a web-based tool which provides access to quick-look summary data for a large array of instruments, with Swarm in situ and ground-based ASI data as the primary focus. This web interface allows researchers to quickly and efficiently browse Swarm and ASI data to identify auroral events of interest to them. This allows researchers to be able to easily and quickly identify Swarm overflights of ASIs that

  9. Identifying biologically meaningful hot-weather events using threshold temperatures that affect life-history.

    Directory of Open Access Journals (Sweden)

    Susan J Cunningham

    Full Text Available Increases in the frequency, duration and intensity of heat waves are frequently evoked in climate change predictions. However, there is no universal definition of a heat wave. Recent, intense hot weather events have caused mass mortalities of birds, bats and even humans, making the definition and prediction of heat wave events that have the potential to impact populations of different species an urgent priority. One possible technique for defining biologically meaningful heat waves is to use threshold temperatures (T(thresh above which known fitness costs are incurred by species of interest. We set out to test the utility of this technique using T(thresh values that, when exceeded, affect aspects of the fitness of two focal southern African bird species: the southern pied babbler Turdiodes bicolor (T(thresh = 35.5 °C and the common fiscal Lanius collaris (T(thresh = 33 °C. We used these T(thresh values to analyse trends in the frequency, duration and intensity of heat waves of magnitude relevant to the focal species, as well as the annual number of hot days (maximum air temperature > T(thresh, in north-western South Africa between 1961 and 2010. Using this technique, we were able to show that, while all heat wave indices increased during the study period, most rapid increases for both species were in the annual number of hot days and in the maximum intensity (and therefore intensity variance of biologically meaningful heat waves. Importantly, we also showed that warming trends were not uniform across the study area and that geographical patterns in warming allowed both areas of high risk and potential climate refugia to be identified. We discuss the implications of the trends we found for our focal species, and the utility of the T(thresh technique as a conservation tool.

  10. Early snowmelt events: detection, distribution, and significance in a major sub-arctic watershed

    International Nuclear Information System (INIS)

    Semmens, Kathryn Alese; Ramage, Joan; Bartsch, Annett; Liston, Glen E

    2013-01-01

    High latitude drainage basins are experiencing higher average temperatures, earlier snowmelt onset in spring, and an increase in rain on snow (ROS) events in winter, trends that climate models project into the future. Snowmelt-dominated basins are most sensitive to winter temperature increases that influence the frequency of ROS events and the timing and duration of snowmelt, resulting in changes to spring runoff. Of specific interest in this study are early melt events that occur in late winter preceding melt onset in the spring. The study focuses on satellite determination and characterization of these early melt events using the Yukon River Basin (Canada/USA) as a test domain. The timing of these events was estimated using data from passive (Advanced Microwave Scanning Radiometer—EOS (AMSR-E)) and active (SeaWinds on Quick Scatterometer (QuikSCAT)) microwave remote sensors, employing detection algorithms for brightness temperature (AMSR-E) and radar backscatter (QuikSCAT). The satellite detected events were validated with ground station meteorological and hydrological data, and the spatial and temporal variability of the events across the entire river basin was characterized. Possible causative factors for the detected events, including ROS, fog, and positive air temperatures, were determined by comparing the timing of the events to parameters from SnowModel and National Centers for Environmental Prediction North American Regional Reanalysis (NARR) outputs, and weather station data. All melt events coincided with above freezing temperatures, while a limited number corresponded to ROS (determined from SnowModel and ground data) and a majority to fog occurrence (determined from NARR). The results underscore the significant influence that warm air intrusions have on melt in some areas and demonstrate the large temporal and spatial variability over years and regions. The study provides a method for melt detection and a baseline from which to assess future change

  11. Identify alternative splicing events based on position-specific evolutionary conservation.

    Directory of Open Access Journals (Sweden)

    Liang Chen

    Full Text Available The evolution of eukaryotes is accompanied by the increased complexity of alternative splicing which greatly expands genome information. One of the greatest challenges in the post-genome era is a complete revelation of human transcriptome with consideration of alternative splicing. Here, we introduce a comparative genomics approach to systemically identify alternative splicing events based on the differential evolutionary conservation between exons and introns and the high-quality annotation of the ENCODE regions. Specifically, we focus on exons that are included in some transcripts but are completely spliced out for others and we call them conditional exons. First, we characterize distinguishing features among conditional exons, constitutive exons and introns. One of the most important features is the position-specific conservation score. There are dramatic differences in conservation scores between conditional exons and constitutive exons. More importantly, the differences are position-specific. For flanking intronic regions, the differences between conditional exons and constitutive exons are also position-specific. Using the Random Forests algorithm, we can classify conditional exons with high specificities (97% for the identification of conditional exons from intron regions and 95% for the classification of known exons and fair sensitivities (64% and 32% respectively. We applied the method to the human genome and identified 39,640 introns that actually contain conditional exons and classified 8,813 conditional exons from the current RefSeq exon list. Among those, 31,673 introns containing conditional exons and 5,294 conditional exons classified from known exons cannot be inferred from RefSeq, UCSC or Ensembl annotations. Some of these de novo predictions were experimentally verified.

  12. Palaeoceanographic and biotic response during early Eocene extreme global warming events. Geologica Ultraiectina (328)

    NARCIS (Netherlands)

    Stap, H.L.

    2010-01-01

    Studying past intervals of abrupt global warming and massive carbon release can improve our knowledge in ways relevant to understanding future climate change. Possible paleo-analogues for future climate change are the early Paleogene hyperthermal events, such as the Paleocene-Eocene Thermal Maximum

  13. Neighborhood Disadvantage, Stressful Life Events, and Adjustment among Mexican American Early Adolescents

    Science.gov (United States)

    Roosa, Mark W.; Burrell, Ginger L.; Nair, Rajni L.; Coxe, Stefany; Tein, Jenn-Yun; Knight, George P.

    2010-01-01

    This study examined a stress process model in which stressful life events and association with delinquent peers mediated the relationship of neighborhood disadvantage to Mexican American early adolescents' mental health. The authors also proposed that child gender, child generation, and neighborhood informal social control would moderate the…

  14. Anti-radical power gives insight into early lipid oxidation events during frying

    NARCIS (Netherlands)

    Loon, W.A.M.; Linssen, J.P.H.; Legger, A.; Voragen, A.G.J.

    2006-01-01

    The aim of this research was to use anti-radical power (ARP) to study early lipid oxidation events during frying. The 2,2-diphenyl-1-picrylhydrazyl radical (DPPH¿) test was used to determine the ARP. As oil does not dissolve completely in methanol, which is generally used for the DPPH¿ test, butanol

  15. Reduced Clostridium difficile Tests and Laboratory-Identified Events With a Computerized Clinical Decision Support Tool and Financial Incentive.

    Science.gov (United States)

    Madden, Gregory R; German Mesner, Ian; Cox, Heather L; Mathers, Amy J; Lyman, Jason A; Sifri, Costi D; Enfield, Kyle B

    2018-06-01

    We hypothesized that a computerized clinical decision support tool for Clostridium difficile testing would reduce unnecessary inpatient tests, resulting in fewer laboratory-identified events. Census-adjusted interrupted time-series analyses demonstrated significant reductions of 41% fewer tests and 31% fewer hospital-onset C. difficile infection laboratory-identified events following this intervention.Infect Control Hosp Epidemiol 2018;39:737-740.

  16. Identifying treatment effect heterogeneity in clinical trials using subpopulations of events: STEPP.

    Science.gov (United States)

    Lazar, Ann A; Bonetti, Marco; Cole, Bernard F; Yip, Wai-Ki; Gelber, Richard D

    2016-04-01

    Investigators conducting randomized clinical trials often explore treatment effect heterogeneity to assess whether treatment efficacy varies according to patient characteristics. Identifying heterogeneity is central to making informed personalized healthcare decisions. Treatment effect heterogeneity can be investigated using subpopulation treatment effect pattern plot (STEPP), a non-parametric graphical approach that constructs overlapping patient subpopulations with varying values of a characteristic. Procedures for statistical testing using subpopulation treatment effect pattern plot when the endpoint of interest is survival remain an area of active investigation. A STEPP analysis was used to explore patterns of absolute and relative treatment effects for varying levels of a breast cancer biomarker, Ki-67, in the phase III Breast International Group 1-98 randomized clinical trial, comparing letrozole to tamoxifen as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer. Absolute treatment effects were measured by differences in 4-year cumulative incidence of breast cancer recurrence, while relative effects were measured by the subdistribution hazard ratio in the presence of competing risks using O-E (observed-minus-expected) methodology, an intuitive non-parametric method. While estimation of hazard ratio values based on O-E methodology has been shown, a similar development for the subdistribution hazard ratio has not. Furthermore, we observed that the subpopulation treatment effect pattern plot analysis may not produce results, even with 100 patients within each subpopulation. After further investigation through simulation studies, we observed inflation of the type I error rate of the traditional test statistic and sometimes singular variance-covariance matrix estimates that may lead to results not being produced. This is due to the lack of sufficient number of events within the subpopulations, which we refer to as instability of

  17. Using Lead Concentrations and Stable Lead Isotope Ratios to Identify Contamination Events in Alluvial Soils

    Directory of Open Access Journals (Sweden)

    Diane Saint-Laurent

    2010-01-01

    Full Text Available Soils contaminated with hydrocarbons (C10–C50, polycyclic aromatic hydrocarbons (PAHs, and other contaminants (e.g., As, Cd, Cu, Pb were recently discovered on the banks of the Saint-François and Massawippi rivers. Alluvial soils are contaminated over a distance of 100 kilometers, and the level of the contaminated-hydrocarbon layer in the soil profiles is among the highest at the Windsor and Richmond sites. Concentrations of lead and stable lead isotope ratios (204Pb/206Pb, 207Pb/206Pb, 208Pb/206Pb are also used to identify contamination events. The maximum and minimum values detected in soil profiles for arsenic, cadmium, and lead vary from 3.01 to 37.88 mg kg-1 (As, 0.11 to 0.81 mg kg-1 (Cd 12.32 to 149.13 mg kg-1 (Pb, respectively, while the 207Pb/206Pb isotopic ratio values are between 0.8545 and 0.8724 for all the profiles. The highest values of trace elements (As, Pb and Zn were detected in the hydrocarbon layer (C10–C50, most often located at the bottom of the profiles (160, 200, and 220 cm in depth. The various peaks recorded in the soils and the position of the profiles suggest that various contaminants were transported by the river on several occasions and infiltrated the soil matrix or deposited on floodplains during successive floods. Atmospheric particles which entered the river or deposited on riverbanks must also be considered as another source of pollution recorded in soils.

  18. Using Lead Concentrations and Stable Lead Isotope Ratios to Identify Contamination Events in Alluvial Soils

    International Nuclear Information System (INIS)

    Saint-Laurent, D.; St-Laurent, J.; Hahni, M.; Chapados, C.; Ghaleb, B.

    2010-01-01

    Soils contaminated with hydrocarbons (C10,C50), polycyclic aromatic hydrocarbons (PAHs), and other contaminants (e.g., As, Cd, Cu, Pb) were recently discovered on the banks of the Saint-Francois and Massawippi rivers. Alluvial soils are contaminated over a distance of 100 kilometers, and the level of the contaminated-hydrocarbon layer in the soil profiles is among the highest at the Windsor and Richmond sites. Concentrations of lead and stable lead isotope ratios ( 204 Pb/ 206 Pb, 206 Pb/ 207 Pb, 208 Pb/ 20 '6Pb) are also used to identify contamination events. The maximum and minimum values detected in soil profiles for arsenic, cadmium, and lead vary from 3.01 to 37.88?mg kg -1 (As), 0.11 to 0.81?mg kg-1 (Cd) 12.32 to 149.13?mg kg -1 (Pb), respectively, while the 207 Pb/ 206 Pb isotopic ratio values are between 0.8545 and 0.8724 for all the profiles. The highest values of trace elements (As, Pb and Zn) were detected in the hydrocarbon layer (C10,C50), most often located at the bottom of the profiles (160, 200, and 220 cm in depth). The various peaks recorded in the soils and the position of the profiles suggest that various contaminants were transported by the river on several occasions and infiltrated the soil matrix or deposited on flood plains during successive floods. Atmospheric particles which entered the river or deposited on riverbanks must also be considered as another source of pollution recorded in soils

  19. Positive predictive value of a register-based algorithm using the Danish National Registries to identify suicidal events.

    Science.gov (United States)

    Gasse, Christiane; Danielsen, Andreas Aalkjaer; Pedersen, Marianne Giørtz; Pedersen, Carsten Bøcker; Mors, Ole; Christensen, Jakob

    2018-04-17

    It is not possible to fully assess intention of self-harm and suicidal events using information from administrative databases. We conducted a validation study of intention of suicide attempts/self-harm contacts identified by a commonly applied Danish register-based algorithm (DK-algorithm) based on hospital discharge diagnosis and emergency room contacts. Of all 101 530 people identified with an incident suicide attempt/self-harm contact at Danish hospitals between 1995 and 2012 using the DK-algorithm, we selected a random sample of 475 people. We validated the DK-algorithm against medical records applying the definitions and terminology of the Columbia Classification Algorithm of Suicide Assessment of suicidal events, nonsuicidal events, and indeterminate or potentially suicidal events. We calculated positive predictive values (PPVs) of the DK-algorithm to identify suicidal events overall, by gender, age groups, and calendar time. We retrieved medical records for 357 (75%) people. The PPV of the DK-algorithm to identify suicidal events was 51.5% (95% CI: 46.4-56.7) overall, 42.7% (95% CI: 35.2-50.5) in males, and 58.5% (95% CI: 51.6-65.1) in females. The PPV varied further across age groups and calendar time. After excluding cases identified via the DK-algorithm by unspecific codes of intoxications and injury, the PPV improved slightly (56.8% [95% CI: 50.0-63.4]). The DK-algorithm can reliably identify self-harm with suicidal intention in 52% of the identified cases of suicide attempts/self-harm. The PPVs could be used for quantitative bias analysis and implemented as weights in future studies to estimate the proportion of suicidal events among cases identified via the DK-algorithm. Copyright © 2018 John Wiley & Sons, Ltd.

  20. Spider Transcriptomes Identify Ancient Large-Scale Gene Duplication Event Potentially Important in Silk Gland Evolution.

    Science.gov (United States)

    Clarke, Thomas H; Garb, Jessica E; Hayashi, Cheryl Y; Arensburger, Peter; Ayoub, Nadia A

    2015-06-08

    The evolution of specialized tissues with novel functions, such as the silk synthesizing glands in spiders, is likely an influential driver of adaptive success. Large-scale gene duplication events and subsequent paralog divergence are thought to be required for generating evolutionary novelty. Such an event has been proposed for spiders, but not tested. We de novo assembled transcriptomes from three cobweb weaving spider species. Based on phylogenetic analyses of gene families with representatives from each of the three species, we found numerous duplication events indicative of a whole genome or segmental duplication. We estimated the age of the gene duplications relative to several speciation events within spiders and arachnids and found that the duplications likely occurred after the divergence of scorpions (order Scorpionida) and spiders (order Araneae), but before the divergence of the spider suborders Mygalomorphae and Araneomorphae, near the evolutionary origin of spider silk glands. Transcripts that are expressed exclusively or primarily within black widow silk glands are more likely to have a paralog descended from the ancient duplication event and have elevated amino acid replacement rates compared with other transcripts. Thus, an ancient large-scale gene duplication event within the spider lineage was likely an important source of molecular novelty during the evolution of silk gland-specific expression. This duplication event may have provided genetic material for subsequent silk gland diversification in the true spiders (Araneomorphae). © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. ENERGETIC PARTICLE CROSS-FIELD PROPAGATION EARLY IN A SOLAR EVENT

    Energy Technology Data Exchange (ETDEWEB)

    Laitinen, T.; Dalla, S.; Marsh, M. S. [Jeremiah Horrocks Institute, University of Central Lancashire, PR1 2HE Preston (United Kingdom)

    2013-08-20

    Solar energetic particles (SEPs) have been observed to easily spread across heliographic longitudes, and the mechanisms responsible for this behavior remain unclear. We use full-orbit simulations of a 10 MeV proton beam in a turbulent magnetic field to study to what extent the spread across the mean field can be described as diffusion early in a particle event. We compare the full-orbit code results to solutions of a Fokker-Planck equation including spatial and pitch angle diffusion, and of one including also propagation of the particles along random-walking magnetic field lines. We find that propagation of the particles along meandering field lines is the key process determining their cross-field spread at 1 AU at the beginning of the simulated event. The mean square displacement of the particles an hour after injection is an order of magnitude larger than that given by the diffusion model, indicating that models employing spatial cross-field diffusion cannot be used to describe early evolution of an SEP event. On the other hand, the diffusion of the particles from their initial field lines is negligible during the first 5 hr, which is consistent with the observations of SEP intensity dropouts. We conclude that modeling SEP events must take into account the particle propagation along meandering field lines for the first 20 hr of the event.

  2. ENERGETIC PARTICLE CROSS-FIELD PROPAGATION EARLY IN A SOLAR EVENT

    International Nuclear Information System (INIS)

    Laitinen, T.; Dalla, S.; Marsh, M. S.

    2013-01-01

    Solar energetic particles (SEPs) have been observed to easily spread across heliographic longitudes, and the mechanisms responsible for this behavior remain unclear. We use full-orbit simulations of a 10 MeV proton beam in a turbulent magnetic field to study to what extent the spread across the mean field can be described as diffusion early in a particle event. We compare the full-orbit code results to solutions of a Fokker-Planck equation including spatial and pitch angle diffusion, and of one including also propagation of the particles along random-walking magnetic field lines. We find that propagation of the particles along meandering field lines is the key process determining their cross-field spread at 1 AU at the beginning of the simulated event. The mean square displacement of the particles an hour after injection is an order of magnitude larger than that given by the diffusion model, indicating that models employing spatial cross-field diffusion cannot be used to describe early evolution of an SEP event. On the other hand, the diffusion of the particles from their initial field lines is negligible during the first 5 hr, which is consistent with the observations of SEP intensity dropouts. We conclude that modeling SEP events must take into account the particle propagation along meandering field lines for the first 20 hr of the event

  3. Serious adverse events in a hospital using early warning score - what went wrong?

    DEFF Research Database (Denmark)

    Petersen, John Asger; Mackel, Rebecca; Antonsen, Kristian

    2014-01-01

    AIM: To evaluate the performance of a new early warning score (EWS) system by reviewing all serious adverse events in our hospital over a 6-month time period. METHOD: All incidents of unexpected death (UD), cardiac arrest (CA) and unanticipated intensive care unit admission(UICU) of adult patients...... of EWS were recorded in 87, 94 and 75% of UICU, CA and UD. Patients were monitored according to the escalation protocol in 13, 31 and 13% of UICU, CA and UD. Nurses escalated care and contacted physicians in 64% and 60% of events of UICU and the corresponding proportions for CO were 58% and 55%. On call...

  4. Identifying future research directions for biodiversity, ecosystem services and sustainability : perspectives from early-career researchers

    NARCIS (Netherlands)

    Hossain, S.; Pogue, S.J.; Trenchard, L.; Oudenhoven, van A.P.E.; Washbourne, C-L.; Muiruri, E.W.; Tomczyk, A.M.; García-Llorente, M.; Hale, R.; Hevia, V.; Adams, T.; Tavallali, L.; De, Bell S.; Pye, M.; Resende, F.

    2017-01-01

    We aimed to identify priority research questions in the field of biodiversity, ecosystem services and sustainability (BESS), based on a workshop held during the NRG BESS Conference for Early Career Researchers on BESS, and to compare these to existing horizon scanning exercises. This work highlights

  5. Dissemination of a highly virulent pathogen: tracking the early events that define infection.

    Directory of Open Access Journals (Sweden)

    Rodrigo J Gonzalez

    2015-01-01

    Full Text Available The series of events that occurs immediately after pathogen entrance into the body is largely speculative. Key aspects of these events are pathogen dissemination and pathogen interactions with the immune response as the invader moves into deeper tissues. We sought to define major events that occur early during infection of a highly virulent pathogen. To this end, we tracked early dissemination of Yersinia pestis, a highly pathogenic bacterium that causes bubonic plague in mammals. Specifically, we addressed two fundamental questions: (1 do the bacteria encounter barriers in disseminating to draining lymph nodes (LN, and (2 what mechanism does this nonmotile bacterium use to reach the LN compartment, as the prevailing model predicts trafficking in association with host cells. Infection was followed through microscopy imaging in addition to assessing bacterial population dynamics during dissemination from the skin. We found and characterized an unexpected bottleneck that severely restricts bacterial dissemination to LNs. The bacteria that do not pass through this bottleneck are confined to the skin, where large numbers of neutrophils arrive and efficiently control bacterial proliferation. Notably, bottleneck formation is route dependent, as it is abrogated after subcutaneous inoculation. Using a combination of approaches, including microscopy imaging, we tested the prevailing model of bacterial dissemination from the skin into LNs and found no evidence of involvement of migrating phagocytes in dissemination. Thus, early stages of infection are defined by a bottleneck that restricts bacterial dissemination and by neutrophil-dependent control of bacterial proliferation in the skin. Furthermore, and as opposed to current models, our data indicate an intracellular stage is not required by Y. pestis to disseminate from the skin to draining LNs. Because our findings address events that occur during early encounters of pathogen with the immune response

  6. Sexual Abuse Exposure Alters Early Processing of Emotional Words: Evidence from Event-Related Potentials

    Science.gov (United States)

    Grégoire, Laurent; Caparos, Serge; Leblanc, Carole-Anne; Brisson, Benoit; Blanchette, Isabelle

    2018-01-01

    This study aimed to compare the time course of emotional information processing between trauma-exposed and control participants, using electrophysiological measures. We conceived an emotional Stroop task with two types of words: trauma-related emotional words and neutral words. We assessed the evoked cerebral responses of sexual abuse victims without post-traumatic stress disorder (PTSD) and no abuse participants. We focused particularly on an early wave (C1/P1), the N2pc, and the P3b. Our main result indicated an early effect (55–165 ms) of emotionality, which varied between non-exposed participants and sexual abuse victims. This suggests that potentially traumatic experiences modulate early processing of emotional information. Our findings showing neurobiological alterations in sexual abuse victims (without PTSD) suggest that exposure to highly emotional events has an important impact on neurocognitive function even in the absence of psychopathology. PMID:29379428

  7. Sexual Abuse Exposure Alters Early Processing of Emotional Words: Evidence from Event-Related Potentials

    Directory of Open Access Journals (Sweden)

    Laurent Grégoire

    2018-01-01

    Full Text Available This study aimed to compare the time course of emotional information processing between trauma-exposed and control participants, using electrophysiological measures. We conceived an emotional Stroop task with two types of words: trauma-related emotional words and neutral words. We assessed the evoked cerebral responses of sexual abuse victims without post-traumatic stress disorder (PTSD and no abuse participants. We focused particularly on an early wave (C1/P1, the N2pc, and the P3b. Our main result indicated an early effect (55–165 ms of emotionality, which varied between non-exposed participants and sexual abuse victims. This suggests that potentially traumatic experiences modulate early processing of emotional information. Our findings showing neurobiological alterations in sexual abuse victims (without PTSD suggest that exposure to highly emotional events has an important impact on neurocognitive function even in the absence of psychopathology.

  8. Identifying Adverse Events Using International Classification of Diseases, Tenth Revision Y Codes in Korea: A Cross-sectional Study

    Directory of Open Access Journals (Sweden)

    Minsu Ock

    2018-01-01

    Full Text Available Objectives The use of administrative data is an affordable alternative to conducting a difficult large-scale medical-record review to estimate the scale of adverse events. We identified adverse events from 2002 to 2013 on the national level in Korea, using International Classification of Diseases, tenth revision (ICD-10 Y codes. Methods We used data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC. We relied on medical treatment databases to extract information on ICD-10 Y codes from each participant in the NHIS-NSC. We classified adverse events in the ICD-10 Y codes into 6 types: those related to drugs, transfusions, and fluids; those related to vaccines and immunoglobulin; those related to surgery and procedures; those related to infections; those related to devices; and others. Results Over 12 years, a total of 20 817 adverse events were identified using ICD-10 Y codes, and the estimated total adverse event rate was 0.20%. Between 2002 and 2013, the total number of such events increased by 131.3%, from 1366 in 2002 to 3159 in 2013. The total rate increased by 103.9%, from 0.17% in 2002 to 0.35% in 2013. Events related to drugs, transfusions, and fluids were the most common (19 446, 93.4%, followed by those related to surgery and procedures (1209, 5.8% and those related to vaccines and immunoglobulin (72, 0.3%. Conclusions Based on a comparison with the results of other studies, the total adverse event rate in this study was significantly underestimated. Improving coding practices for ICD-10 Y codes is necessary to precisely monitor the scale of adverse events in Korea.

  9. Origins of Early Adolescents' Hope: Personality, Parental Attachment, and Stressful Life Events

    Science.gov (United States)

    Otis, Kristin L.; Huebner, E. Scott; Hills, Kimberly J.

    2016-01-01

    Psychology has recently increased attention to identifying psychological qualities in individuals that indicate positive mental health, such as hope. In an effort to understand further the origins of hope, we examined the relations among parental attachment, stressful life events, personality variables, and hope in a sample of 647 middle school…

  10. An Early Mathematical Patterning Assessment: identifying young Australian Indigenous children's patterning skills

    Science.gov (United States)

    Papic, Marina

    2015-12-01

    This paper presents an Early Mathematical Patterning Assessment (EMPA) tool that provides early childhood educators with a valuable opportunity to identify young children's mathematical thinking and patterning skills through a series of hands-on and drawing tasks. EMPA was administered through one-to-one assessment interviews to children aged 4 to 5 years in the year prior to formal school. Two hundred and seventeen assessments indicated that the young low socioeconomic and predominantly Australian Indigenous children in the study group had varied patterning and counting skills. Three percent of the study group was able to consistently copy and draw an ABABAB pattern made with coloured blocks. Fifty percent could count to six by ones and count out six items with 4 % of the total group able to identify six items presented in regular formations without counting. The integration of patterning into early mathematics learning is critical to the abstraction of mathematical ideas and relationships and to the development of mathematical reasoning in young children. By using the insights into the children's thinking that the EMPA tool provides, early childhood educators can better inform mathematics teaching and learning and so help close the persistent gap in numeracy between Indigenous and non-Indigenous children.

  11. Systematic procedures for identifying t quarks in p-barp collider events with a muon and jets

    International Nuclear Information System (INIS)

    Barger, V.; Baer, H.; Martin, A.D.; Phillips, R.J.N.

    1984-01-01

    Substantial rates are predicted for events containing a muon and jets resulting from W→tb-bar, Z→tt-bar, and tt-bar hadroproduction, with t→μνb decay. We investigate selective cuts to reject backgrounds from bb-bar, cc-bar, and cs-bar production and to identify the t-quark events. For example, from a data sample containing 50 W +- →e +- ν events, we expect that clean samples of approximately 4 tb-bar-(or t-barb-) and conservatively 4 tt-bar-initiated μ +- +jets events can be selected for a t-quark mass below 45 GeV. We suggest methods for distinguishing the contributions and for determining m/sub t/

  12. Identifying future research directions for biodiversity, ecosystem services and sustainability: perspectives from early-career researchers

    OpenAIRE

    Hossain, S.; Pogue, S.J.; Trenchard, L.; Oudenhoven, van, A.P.E.; Washbourne, C-L.; Muiruri, E.W.; Tomczyk, A.M.; García-Llorente, M.; Hale, R.; Hevia, V.; Adams, T.; Tavallali, L.; De, Bell S.; Pye, M.; Resende, F.

    2017-01-01

    We aimed to identify priority research questions in the field of biodiversity, ecosystem services and sustainability (BESS), based on a workshop held during the NRG BESS Conference for Early Career Researchers on BESS, and to compare these to existing horizon scanning exercises. This work highlights the need for improved data availability through collaboration and knowledge exchange, which, in turn, can support the integrated valuation and sustainable management of ecosystems in response to g...

  13. Using a personality inventory to identify risk of distress and burnout among early stage medical students.

    Science.gov (United States)

    Bughi, Stephanie A; Lie, Desiree A; Zia, Stephanie K; Rosenthal, Jane

    2017-01-01

    Distress and burnout are common among medical students and negatively impact students' physical, mental, and emotional health. Personality inventories such as the Myers-Briggs Type Indicator (MBTI), used in medical education, may have a role in identifying burnout risk early. The authors conducted a cross-sectional survey study among 185 1st year medical students with the MBTI, the general well-being schedule (GWB), and Maslach Burnout Inventory-Student Survey (MBI-SS). Descriptive statistics and one-way MANOVAs were used to identify the prevalence and differences in MBTI preferences and distress/burnout risk. Response rate was 185/185 (100%). Distress (GWB) was reported by 84/185 (45.4%). High scores on exhaustion were reported by 118/182 (64.8%), cynicism by 76/182 (41.8%), and decreased professional efficacy by 38/182 (20.9%) for the three dimensions of the MBI-SS. Only 21/182 (11.5%) of respondents had high scores on all three dimensions of burnout. Students with MBTI preferences for extraversion reported greater positive well-being (P burnout are prevalent early in medical training. The significant difference between extraversion and introversion in relation to distress and burnout deserves further study. Use of a personality inventory may help identify students at risk of burnout and allow appropriate early stress management.

  14. Marine ecosystem resilience during extreme deoxygenation: the Early Jurassic oceanic anoxic event.

    Science.gov (United States)

    Caswell, Bryony A; Frid, Christopher L J

    2017-01-01

    Global warming during the Early Jurassic, and associated widespread ocean deoxygenation, was comparable in scale with the changes projected for the next century. This study quantifies the impact of severe global environmental change on the biological traits of marine communities that define the ecological roles and functions they deliver. We document centennial-millennial variability in the biological trait composition of Early Jurassic (Toarcian) seafloor communities and examine how this changed during the event using biological traits analysis. Environmental changes preceding the global oceanic anoxic event (OAE) produced an ecological shift leading to stressed benthic palaeocommunities with reduced resilience to the subsequent OAE. Changes in traits and ecological succession coincided with major environmental changes; and were of similar nature and magnitude to those in severely deoxygenated benthic communities today despite the very different timescales. Changes in community composition were linked to local redox conditions whereas changes in populations of opportunists were driven by primary productivity. Throughout most of the OAE substitutions by tolerant taxa conserved the trait composition and hence functioning, but periods of severe deoxygenation caused benthic defaunation that would have resulted in functional collapse. Following the OAE recovery was slow probably because the global nature of the event restricted opportunities for recruitment from outside the basin. Our findings suggest that future systems undergoing deoxygenation may initially show functional resilience, but severe global deoxygenation will impact traits and ecosystem functioning and, by limiting the species pool, will slow recovery rates.

  15. Identifying Population Vulnerable to Extreme Heat Events in San Jose, California.

    Science.gov (United States)

    Rivera, A. L.

    2016-12-01

    The extreme heat days not only make cities less comfortable for living but also they are associated with increased morbidity and mortality. Mapping studies have demonstrated spatial variability in heat vulnerability. A study conducted between 2000 and 2011 in New York City shows that deaths during heat waves was more likely to occur in black individuals, at home in census tracts which received greater public assistance. This map project intends to portray areas in San Jose California that are vulnerable to extreme heat events. The variables considered to build a vulnerability index are: land surface temperature, vegetated areas (NDVI), and people exposed to these area (population density).

  16. Early Top-Down Influences on Bistable Perception Revealed by Event-Related Potentials

    Science.gov (United States)

    Pitts, Michael A.; Gavin, William J.; Nerger, Janice L.

    2008-01-01

    A longstanding debate exists in the literature concerning bottom-up vs. top-down influences on bistable perception. Recently, a technique has been developed to measure early changes in brain activity (via ERPs) related to perceptual reversals (Kornmeier & Bach, 2004). An ERP component, the reversal negativity (RN) has been identified, and is…

  17. Atmospheric pCO2 reconstructed across five early Eocene global warming events

    Science.gov (United States)

    Cui, Ying; Schubert, Brian A.

    2017-11-01

    Multiple short-lived global warming events, known as hyperthermals, occurred during the early Eocene (56-52 Ma). Five of these events - the Paleocene-Eocene Thermal Maximum (PETM or ETM1), H1 (or ETM2), H2, I1, and I2 - are marked by a carbon isotope excursion (CIE) within both marine and terrestrial sediments. The magnitude of CIE, which is a function of the amount and isotopic composition of carbon added to the ocean-atmosphere system, varies significantly between marine versus terrestrial substrates. Here we use the increase in carbon isotope fractionation by C3 land plants in response to increased pCO2 to reconcile this difference and reconstruct a range of background pCO2 and peak pCO2 for each CIE, provided two potential carbon sources: methane hydrate destabilization and permafrost-thawing/organic matter oxidation. Although the uncertainty on each pCO2 estimate using this approach is low (e.g., median uncertainty = + 23% / - 18%), this work highlights the potential for significant systematic bias in the pCO2 estimate resulting from sampling resolution, substrate type, diagenesis, and environmental change. Careful consideration of each of these factors is required especially when applying this approach to a single marine-terrestrial CIE pair. Given these limitations, we provide an upper estimate for background early Eocene pCO2 of 463 +248/-131 ppmv (methane hydrate scenario) to 806 +127/-104 ppmv (permafrost-thawing/organic matter oxidation scenario). These results, which represent the first pCO2 proxy estimates directly tied to the Eocene hyperthermals, demonstrate that early Eocene warmth was supported by background pCO2 less than ∼3.5× preindustrial levels and that pCO2 > 1000 ppmv may have occurred only briefly, during hyperthermal events.

  18. Developing a methodology for identifying correlations between LERF and early fatality

    International Nuclear Information System (INIS)

    Kang, Kyung Min; Jae, Moo Sung; Ahn, Kwang Il

    2009-01-01

    The correlations between Large Early Release Frequency (LERF) and Early Fatality need to be investigated for risk-informed application and regulation. In RG-1.174, there are decision-making criteria using the measures of CDF and LERF, while there are no specific criteria on LERF. Since there are both huge uncertainty and large cost need in off-site consequence calculation, a LERF assessment methodology need to be developed and its correlation factor needs to be identified for risk-informed decision-making. This regards, the robust method for estimating off-site consequence has been performed for assessing health effects caused by radioisotopes released from severe accidents of nuclear power plants. And also, MACCS2 code are used for validating source term quantitatively regarding health effects depending on release characteristics of radioisotopes during severe accidents has been performed. This study developed a method for identifying correlations between LERF and Early Fatality and validates the results of the model using MACCS2 code. The results of this study may contribute to defining LERF and finding a measure for risk-informed regulations and risk-informed decision making

  19. BAGE Hypomethylation Is an Early Event in Colon Transformation and Is Frequent in Histologically Advanced Adenomas

    Energy Technology Data Exchange (ETDEWEB)

    Lana, Erica [INSERM U827, Montpellier (France); Brun, Marie-Elisabeth [Institut de Génétique Humaine, CNRS UPR 1142, Montpellier (France); Rivals, Isabelle [Equipe de Statistique Appliquée, ESPCI ParisTech, Paris (France); Selves, Janick; Kirzin, Sylvain [CHU Purpan and INSERM U563, Toulouse (France); Lutsyk, Andriy P. [O.O. Bogomoletz National Medical University, Kyiv (Ukraine); Gordiyuk, Vasily V. [Department of Functional Genomics, Institute of Molecular Biology and Genetics NASU, Kyiv (Ukraine); Bibeau, Frédéric [CRLC, Montpellier (France); Rynditch, Alla [Department of Functional Genomics, Institute of Molecular Biology and Genetics NASU, Kyiv (Ukraine); De Sario, Albertina, E-mail: albertina.de-sario@inserm.fr [INSERM U827, Montpellier (France)

    2009-11-18

    We showed earlier that BAGE (B melanoma antigen) loci are hypermethylated in normal tissues and hypomethylated in 98% of human cancers. More recently, we provided evidence that hypomethylation of BAGE loci represents an informative marker for colon cancer detection. In this study, we show that hypomethylation of BAGE loci was an early event that occurred in 43% of colorectal adenomas. Interestingly, hypomethylation of BAGE loci was frequent (50%) in tubulo-villous and villous adenomas, these adenomas having a high probability of being transformed into colorectal cancers.

  20. BAGE Hypomethylation Is an Early Event in Colon Transformation and Is Frequent in Histologically Advanced Adenomas

    Directory of Open Access Journals (Sweden)

    Alla Rynditch

    2009-11-01

    Full Text Available We showed earlier that BAGE (B melanoma antigen loci are hypermethylated in normal tissues and hypomethylated in 98% of human cancers. More recently, we provided evidence that hypomethylation of BAGE loci represents an informative marker for colon cancer detection. In this study, we show that hypomethylation of BAGE loci was an early event that occurred in 43% of colorectal adenomas. Interestingly, hypomethylation of BAGE loci was frequent (50% in tubulo-villous and villous adenomas, these adenomas having a high probability of being transformed into colorectal cancers.

  1. Identifying Weak Ties from Publicly Available Social Media Data in an Event

    DEFF Research Database (Denmark)

    Prakash Gupta, Jayesh; Menon, Karan; Kärkkäinen, Hannu

    2016-01-01

    The concept of weak ties was introduced by Granovetter through the seminal paper titled "Strength of weak ties". Since then the role of weak ties in general and their specific role as occupying the structural hole has been explored in many different fields. In this study, we identify actual or po...

  2. Positive predictive value of a register-based algorithm using the Danish National Registries to identify suicidal events

    DEFF Research Database (Denmark)

    Gasse, Christiane; Danielsen, Andreas Aalkjaer; Pedersen, Marianne Giørtz

    2018-01-01

    events overall, by gender, age groups, and calendar time. RESULTS: We retrieved medical records for 357 (75%) people. The PPV of the DK-algorithm to identify suicidal events was 51.5% (95% CI: 46.4-56.7) overall, 42.7% (95% CI: 35.2-50.5) in males, and 58.5% (95% CI: 51.6-65.1) in females. The PPV varied...... further across age groups and calendar time. After excluding cases identified via the DK-algorithm by unspecific codes of intoxications and injury, the PPV improved slightly (56.8% [95% CI: 50.0-63.4]). CONCLUSIONS: The DK-algorithm can reliably identify self-harm with suicidal intention in 52......PURPOSE: It is not possible to fully assess intention of self-harm and suicidal events using information from administrative databases. We conducted a validation study of intention of suicide attempts/self-harm contacts identified by a commonly applied Danish register-based algorithm (DK...

  3. Domain-restricted mutation analysis to identify novel driver events in human cancer

    Directory of Open Access Journals (Sweden)

    Sanket Desai

    2017-10-01

    Full Text Available Analysis of mutational spectra across various cancer types has given valuable insights into tumorigenesis. Different approaches have been used to identify novel drivers from the set of somatic mutations, including the methods which use sequence conservation, geometric localization and pathway information. Recent computational methods suggest use of protein domain information for analysis and understanding of the functional consequence of non-synonymous mutations. Similarly, evidence suggests recurrence at specific position in proteins is robust indicators of its functional impact. Building on this, we performed a systematic analysis of TCGA exome derived somatic mutations across 6089 PFAM domains and significantly mutated domains were identified using randomization approach. Multiple alignment of individual domain allowed us to prioritize for conserved residues mutated at analogous positions across different proteins in a statistically disciplined manner. In addition to the known frequently mutated genes, this analysis independently identifies low frequency Meprin and TRAF-Homology (MATH domain in Speckle Type BTB/POZ (SPOP protein, in prostate adenocarcinoma. Results from this analysis will help generate hypotheses about the downstream molecular mechanism resulting in cancer phenotypes.

  4. The Early Eocene equable climate problem: can perturbations of climate model parameters identify possible solutions?

    Science.gov (United States)

    Sagoo, Navjit; Valdes, Paul; Flecker, Rachel; Gregoire, Lauren J

    2013-10-28

    Geological data for the Early Eocene (56-47.8 Ma) indicate extensive global warming, with very warm temperatures at both poles. However, despite numerous attempts to simulate this warmth, there are remarkable data-model differences in the prediction of these polar surface temperatures, resulting in the so-called 'equable climate problem'. In this paper, for the first time an ensemble with a perturbed climate-sensitive model parameters approach has been applied to modelling the Early Eocene climate. We performed more than 100 simulations with perturbed physics parameters, and identified two simulations that have an optimal fit with the proxy data. We have simulated the warmth of the Early Eocene at 560 ppmv CO2, which is a much lower CO2 level than many other models. We investigate the changes in atmospheric circulation, cloud properties and ocean circulation that are common to these simulations and how they differ from the remaining simulations in order to understand what mechanisms contribute to the polar warming. The parameter set from one of the optimal Early Eocene simulations also produces a favourable fit for the last glacial maximum boundary climate and outperforms the control parameter set for the present day. Although this does not 'prove' that this model is correct, it is very encouraging that there is a parameter set that creates a climate model able to simulate well very different palaeoclimates and the present-day climate. Interestingly, to achieve the great warmth of the Early Eocene this version of the model does not have a strong future climate change Charney climate sensitivity. It produces a Charney climate sensitivity of 2.7(°)C, whereas the mean value of the 18 models in the IPCC Fourth Assessment Report (AR4) is 3.26(°)C±0.69(°)C. Thus, this value is within the range and below the mean of the models included in the AR4.

  5. Isolated lung events following radiation for early stage breast cancer: incidence and predictors for primary lung vs metastatic breast cancer

    International Nuclear Information System (INIS)

    Van Buren, Teresa A; Harris, Jay R; Sugarbaker, David J; Schneider, Lindsey; Healey, Elizabeth A

    1995-01-01

    Purpose: 1) To define the incidence of isolated lung events in a cohort of women treated with conservative surgery (CS) and radiation therapy (RT) for early stage breast cancer. 2) Among such patients, to define the relative distribution of primary lung cancer, metastatic breast cancer, and indeterminate lesions; and to identify any predictors for a diagnosis of lung vs metastatic breast cancer. 3) To examine the cohort with respect to whether a higher than expected incidence of lung cancer is seen following breast irradiation. Materials and Methods: Between 1968 and 1986, 1865 patients with clinical stage I-II breast cancer were treated with CS and RT; the median follow-up for surviving patients is 129 months. The study population was limited to patients who developed a subsequent isolated lung event as the first site of distant disease. Isolated lung event was defined as disease limited to the thoracic cavity, without evidence of either uncontrolled local breast disease or metastatic disease elsewhere. Diagnosis of the lung event as a primary lung cancer, a metastatic breast lesion, or an indeterminate lesion was documented from the viewpoint of 1) the pathologic analysis and 2) the clinical impression at the time of the lung event. Results: Sixty six of the 1865 patients (3.5%) developed an isolated lung event. The relative distribution of the pathologic and clinical diagnoses is shown below: The 66 lung events were characterized either as a solitary pulmonary nodule (27), multiple nodules (23), pleural effusion alone (10), unknown (2), or miscellaneous other findings (4). Among the 47 patients for whom pathology was available, the diagnosis remained indeterminate for 24 (51%). For patients with a definitive pathologic diagnosis, 69% ((9(13))) of smokers had a new lung cancer compared to 20% ((2(10))) of non-smokers (p=0.036), and 67% ((10(15))) of patients with a solitary pulmonary nodule had lung cancer compared to 14% ((1(7))) for other lung presentations (p

  6. Identifying anomalously early spring onsets in the CESM large ensemble project

    Science.gov (United States)

    Labe, Zachary; Ault, Toby; Zurita-Milla, Raul

    2017-06-01

    Seasonal transitions from winter to spring impact a wide variety of ecological and physical systems. While the effects of early springs across North America are widely documented, changes in their frequency and likelihood under the combined influences of climate change and natural variability are poorly understood. Extremely early springs, such as March 2012, can lead to severe economical losses and agricultural damage when these are followed by hard freeze events. Here we use the new Community Earth System Model Large Ensemble project and Extended Spring Indices to simulate historical and future spring onsets across the United States and in the particular the Great Lakes region. We found a marked increase in the frequency of March 2012-like springs by midcentury in addition to an overall trend towards earlier spring onsets, which nearly doubles that of observational records. However, changes in the date of last freeze do not occur at the same rate, therefore, causing a potential increase in the threat of plant tissue damage. Although large-scale climate modes, such as the Pacific Decadal Oscillation, have previously dominated decadal to multidecadal spring onset trends, our results indicate a decreased role in natural climate variability and hence a greater forced response by the end of the century for modulating trends. Without a major reduction in greenhouse gas emissions, our study suggests that years like 2012 in the US could become normal by mid-century.

  7. Method for early detection of infectious mononucleosis by identifying Inmono proteins

    Science.gov (United States)

    Willard, Karen E.

    1984-01-01

    Early detection of infectious mononucleosis is carried out using a sample of human blood by isolating and identifying the presence of Inmono proteins in the sample from a two-dimensional protein map with the proteins being characterized by having isoelectric banding as measured in urea of about -16 to -17 with respect to certain isoelectric point standards and molecular mass of about 70 to 75 K daltons as measured in the presence of sodium dodecylsulfate containing polyacrylamide gels, the presence of the Inmono proteins being correlated with the existence of infectious mononucleosis.

  8. Using event related potentials to identify a user's behavioural intention aroused by product form design.

    Science.gov (United States)

    Ding, Yi; Guo, Fu; Zhang, Xuefeng; Qu, Qingxing; Liu, Weilin

    2016-07-01

    The capacity of product form to arouse user's behavioural intention plays a decisive role in further user experience, even in purchase decision, while traditional methods rarely give a fully understanding of user experience evoked by product form, especially the feeling of anticipated use of product. Behavioural intention aroused by product form designs has not yet been investigated electrophysiologically. Hence event related potentials (ERPs) were applied to explore the process of behavioural intention when users browsed different smart phone form designs with brand and price not taken into account for mainly studying the brain activity evoked by variety of product forms. Smart phone pictures with different anticipated user experience were displayed with equiprobability randomly. Participants were asked to click the left mouse button when certain picture gave them a feeling of behavioural intention to interact with. The brain signal of each participant was recorded by Curry 7.0. The results show that pictures with an ability to arouse participants' behavioural intention for further experience can evoke enhanced N300 and LPPs (late positive potentials) in central-parietal, parietal and occipital regions. The scalp topography shows that central-parietal, parietal and occipital regions are more activated. The results indicate that the discrepancy of ERPs can reflect the neural activities of behavioural intention formed or not. Moreover, amplitude of ERPs occurred in corresponding brain areas can be used to measure user experience. The exploring of neural correlated with behavioural intention provide an accurate measurement method of user's perception and help marketers to know which product can arouse users' behavioural intention, maybe taken as an evaluating indicator of product design. Copyright © 2016 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  9. Subclinical alexithymia modulates early audio-visual perceptive and attentional event-related potentials

    Directory of Open Access Journals (Sweden)

    Dyna eDelle-Vigne

    2014-03-01

    Full Text Available Introduction:Previous studies have highlighted the advantage of audio–visual oddball tasks (instead of unimodal ones in order to electrophysiologically index subclinical behavioral differences. Since alexithymia is highly prevalent in the general population, we investigated whether the use of various bimodal tasks could elicit emotional effects in low- versus high-alexithymic scorers. Methods:Fifty students (33 females were split into groups based on low and high scores on the Toronto Alexithymia Scale. During event-related potential recordings, they were exposed to three kinds of audio–visual oddball tasks: neutral (geometrical forms and bips, animal (dog and cock with their respective shouts, or emotional (faces and voices stimuli. In each condition, participants were asked to quickly detect deviant events occurring amongst a train of frequent matching stimuli (e.g., push a button when a sad face–voice pair appeared amongst a train of neutral face–voice pairs. P100, N100, and P300 components were analyzed: P100 refers to visual perceptive processing, N100 to auditory ones, and the P300 relates to response-related stages. Results:High-alexithymic scorers presented a particular pattern of results when processing the emotional stimulations, reflected in early ERP components by increased P100 and N100 amplitudes in the emotional oddball tasks (P100: pConclusions:Our findings suggest that high-alexithymic scorers require heightened early attentional resources when confronted with emotional stimuli.

  10. Lithium-isotope evidence for enhanced silicate weathering during OAE 1a (Early Aptian Selli event)

    Science.gov (United States)

    Lechler, Maria; Pogge von Strandmann, Philip A. E.; Jenkyns, Hugh C.; Prosser, Giacomo; Parente, Mariano

    2015-12-01

    An abrupt rise in temperature, forced by a massive input of CO2 into the atmosphere, is commonly invoked as the main trigger for Oceanic Anoxic Events (OAEs). Global warming initiated a cascade of palaeoenvironmental perturbations starting with increased continental weathering and an accelerated hydrological cycle that delivered higher loads of nutrients to coastal areas, stimulating biological productivity. The end-result was widespread anoxia and deposition of black shales: the hallmarks of OAEs. In order to assess the role of weathering as both an OAE initiator and terminator (via CO2 sequestration) during the Early Aptian OAE 1a (Selli Event, ∼120 Ma) the isotopic ratio of lithium isotopes was analysed in three sections of shallow-marine carbonates from the Pacific and Tethyan realms and one basinal pelagic section from the Tethyan domain. Because the isotopic composition of lithium in seawater is largely controlled by continental silicate weathering and high- and low-temperature alteration of basaltic material, a shift to lighter δ7Li values is expected to characterize OAEs. The studied sections illustrate this phenomenon: δ7Li values decrease to a minimum coincident with the negative carbon-isotope excursion that effectively records the onset of OAE 1a. A second negative δ7Li excursion occurs coeval with the minimum in strontium isotopes after the event. The striking similarity to the strontium-isotope record argues for a common driver. The formation and destruction (weathering) of an oceanic LIP could account for the parallel trend in both isotope systems. The double-spike in lithium isotopes is probably related to a change in weathering congruencies. Such a chemostratigraphy is consistent with the hypothesis that an increase in silicate weathering, in conjunction with organic-carbon burial, led to drawdown of atmospheric CO2 during the early Aptian OAE 1a.

  11. Irregularities in Early Seismic Rupture Propagation for Large Events in a Crustal Earthquake Model

    Science.gov (United States)

    Lapusta, N.; Rice, J. R.; Rice, J. R.

    2001-12-01

    We study early seismic propagation of model earthquakes in a 2-D model of a vertical strike-slip fault with depth-variable rate and state friction properties. Our model earthquakes are obtained in fully dynamic simulations of sequences of instabilities on a fault subjected to realistically slow tectonic loading (Lapusta et al., JGR, 2000). This work is motivated by results of Ellsworth and Beroza (Science, 1995), who observe that for many earthquakes, far-field velocity seismograms during initial stages of dynamic rupture propagation have irregular fluctuations which constitute a "seismic nucleation phase". In our simulations, we find that such irregularities in velocity seismograms can be caused by two factors: (1) rupture propagation over regions of stress concentrations and (2) partial arrest of rupture in neighboring creeping regions. As rupture approaches a region of stress concentration, it sees increasing background stress and its moment acceleration (to which velocity seismographs in the far field are proportional) increases. After the peak in stress concentration, the rupture sees decreasing background stress and moment acceleration decreases. Hence a fluctuation in moment acceleration is created. If rupture starts sufficiently far from a creeping region, then partial arrest of rupture in the creeping region causes a decrease in moment acceleration. As the other parts of rupture continue to develop, moment acceleration then starts to grow again, and a fluctuation again results. Other factors may cause the irregularities in moment acceleration, e.g., phenomena such as branching and/or intermittent rupture propagation (Poliakov et al., submitted to JGR, 2001) which we have not studied here. Regions of stress concentration are created in our model by arrest of previous smaller events as well as by interactions with creeping regions. One such region is deep in the fault zone, and is caused by the temperature-induced transition from seismogenic to creeping

  12. A novel computational method identifies intra- and inter-species recombination events in Staphylococcus aureus and Streptococcus pneumoniae.

    Directory of Open Access Journals (Sweden)

    Lisa Sanguinetti

    Full Text Available Advances in high-throughput DNA sequencing technologies have determined an explosion in the number of sequenced bacterial genomes. Comparative sequence analysis frequently reveals evidences of homologous recombination occurring with different mechanisms and rates in different species, but the large-scale use of computational methods to identify recombination events is hampered by their high computational costs. Here, we propose a new method to identify recombination events in large datasets of whole genome sequences. Using a filtering procedure of the gene conservation profiles of a test genome against a panel of strains, this algorithm identifies sets of contiguous genes acquired by homologous recombination. The locations of the recombination breakpoints are determined using a statistical test that is able to account for the differences in the natural rate of evolution between different genes. The algorithm was tested on a dataset of 75 genomes of Staphylococcus aureus and 50 genomes comprising different streptococcal species, and was able to detect intra-species recombination events in S. aureus and in Streptococcus pneumoniae. Furthermore, we found evidences of an inter-species exchange of genetic material between S. pneumoniae and Streptococcus mitis, a closely related commensal species that colonizes the same ecological niche. The method has been implemented in an R package, Reco, which is freely available from supplementary material, and provides a rapid screening tool to investigate recombination on a genome-wide scale from sequence data.

  13. Risk of Cerebrovascular Events in Elderly Patients After Radiation Therapy Versus Surgery for Early-Stage Glottic Cancer

    International Nuclear Information System (INIS)

    Hong, Julian C.; Kruser, Tim J.; Gondi, Vinai; Mohindra, Pranshu; Cannon, Donald M.; Harari, Paul M.; Bentzen, Søren M.

    2013-01-01

    Purpose: Comprehensive neck radiation therapy (RT) has been shown to increase cerebrovascular disease (CVD) risk in advanced-stage head-and-neck cancer. We assessed whether more limited neck RT used for early-stage (T1-T2 N0) glottic cancer is associated with increased CVD risk, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: We identified patients ≥66 years of age with early-stage glottic laryngeal cancer from SEER diagnosed from 1992 to 2007. Patients treated with combined surgery and RT were excluded. Medicare CPT codes for carotid interventions, Medicare ICD-9 codes for cerebrovascular events, and SEER data for stroke as the cause of death were collected. Similarly, Medicare CPT and ICD-9 codes for peripheral vascular disease (PVD) were assessed to serve as an internal control between treatment groups. Results: A total of 1413 assessable patients (RT, n=1055; surgery, n=358) were analyzed. The actuarial 10-year risk of CVD was 56.5% (95% confidence interval 51.5%-61.5%) for the RT cohort versus 48.7% (41.1%-56.3%) in the surgery cohort (P=.27). The actuarial 10-year risk of PVD did not differ between the RT (52.7% [48.1%-57.3%]) and surgery cohorts (52.6% [45.2%-60.0%]) (P=.89). Univariate analysis showed an increased association of CVD with more recent diagnosis (P=.001) and increasing age (P=.001). On multivariate Cox analysis, increasing age (P<.001) and recent diagnosis (P=.002) remained significantly associated with a higher CVD risk, whereas the association of RT and CVD remained not statistically significant (HR=1.11 [0.91-1.37,] P=.31). Conclusions: Elderly patients with early-stage laryngeal cancer have a high burden of cerebrovascular events after surgical management or RT. RT and surgery are associated with comparable risk for subsequent CVD development after treatment in elderly patients

  14. Risk of Cerebrovascular Events in Elderly Patients After Radiation Therapy Versus Surgery for Early-Stage Glottic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Julian C.; Kruser, Tim J. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Gondi, Vinai [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Central Dupage Hospital Cancer Center, Warrenville, Illinois (United States); Mohindra, Pranshu; Cannon, Donald M.; Harari, Paul M. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Bentzen, Søren M., E-mail: bentzen@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States)

    2013-10-01

    Purpose: Comprehensive neck radiation therapy (RT) has been shown to increase cerebrovascular disease (CVD) risk in advanced-stage head-and-neck cancer. We assessed whether more limited neck RT used for early-stage (T1-T2 N0) glottic cancer is associated with increased CVD risk, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Methods and Materials: We identified patients ≥66 years of age with early-stage glottic laryngeal cancer from SEER diagnosed from 1992 to 2007. Patients treated with combined surgery and RT were excluded. Medicare CPT codes for carotid interventions, Medicare ICD-9 codes for cerebrovascular events, and SEER data for stroke as the cause of death were collected. Similarly, Medicare CPT and ICD-9 codes for peripheral vascular disease (PVD) were assessed to serve as an internal control between treatment groups. Results: A total of 1413 assessable patients (RT, n=1055; surgery, n=358) were analyzed. The actuarial 10-year risk of CVD was 56.5% (95% confidence interval 51.5%-61.5%) for the RT cohort versus 48.7% (41.1%-56.3%) in the surgery cohort (P=.27). The actuarial 10-year risk of PVD did not differ between the RT (52.7% [48.1%-57.3%]) and surgery cohorts (52.6% [45.2%-60.0%]) (P=.89). Univariate analysis showed an increased association of CVD with more recent diagnosis (P=.001) and increasing age (P=.001). On multivariate Cox analysis, increasing age (P<.001) and recent diagnosis (P=.002) remained significantly associated with a higher CVD risk, whereas the association of RT and CVD remained not statistically significant (HR=1.11 [0.91-1.37,] P=.31). Conclusions: Elderly patients with early-stage laryngeal cancer have a high burden of cerebrovascular events after surgical management or RT. RT and surgery are associated with comparable risk for subsequent CVD development after treatment in elderly patients.

  15. Early adverse life events are associated with altered brain network architecture in a sex- dependent manner

    Directory of Open Access Journals (Sweden)

    Arpana Gupta, PhD

    2017-12-01

    Full Text Available Introduction: Early adverse life events (EALs increase the risk for chronic medical and psychiatric disorders by altering early neurodevelopment. The aim of this study was to examine associations between EALs and network properties of core brain regions in the emotion regulation and salience networks, and to test the influence of sex on these associations. Methods: Resting-state functional and diffusion tensor magnetic resonance imaging were obtained in healthy individuals (61 men, 63 women. Functional and anatomical network properties of centrality and segregation were calculated for the core regions of the two networks using graph theory. Moderator analyses were applied to test hypotheses. Results: The type of adversity experienced influences brain wiring differently, as higher general EALs were associated with decreased functional and anatomical centrality in salience and emotion regulation regions, while physical and emotional EALs were associated with increased anatomical centrality and segregation in emotion regulation regions. Sex moderated the associations between EALs and measures of centrality; with decreased centrality of salience and emotion regulation regions with increased general EALs in females, and increased centrality in salience regions with higher physical and emotional EALs in males. Increased segregation of salience regions was associated with increased general EALs in males. Centrality of the amygdala was associated with physical symptoms, and segregation of salience regions was correlated with higher somatization in men only. Conclusions: Emotion regulation and salience regions are susceptible to topological brain restructuring associated with EALs. The male and female brains appear to be differently affected by specific types of EALs. Keywords: Early adverse traumatic life events, Centrality, Segregation, Network metrics, Moderating effects of sex, Emotion regulation network, Salience network

  16. Early events of citrus greening (Huanglongbing) disease development at the ultrastructural level.

    Science.gov (United States)

    Folimonova, Svetlana Y; Achor, Diann S

    2010-09-01

    Citrus greening (Huanglongbing [HLB]) is one of the most destructive diseases of citrus worldwide. The causal agent of HLB in Florida is thought to be 'Candidatus Liberibacter asiaticus'. Understanding of the early events in HLB infection is critical for the development of effective measures to control the disease. In this work, we conducted cytopathological studies by following the development of the disease in citrus trees graft inoculated with 'Ca. L. asiaticus'-containing material under greenhouse conditions to examine the correlation between ultrastructural changes and symptom production, with the main objective of characterizing the early events of infection. Based on our observations, one of the first degenerative changes induced upon invasion of the pathogen appears to be swelling of middle lamella between cell walls surrounding sieve elements. This anatomical aberration was often observed in samples from newly growing flushes in inoculated sweet orange and grapefruit trees at the early "presymptomatic" stage of HLB infection. Development of symptoms and their progression correlated with an increasing degree of microscopic aberrations. Remarkably, the ability to observe the bacterium in the infected tissue also correlated with the degree of the disease progression. Large numbers of bacterial cells were found in phloem sieve tubes in tissue samples from presymptomatic young flushes. In contrast, we did not observe the bacteria in highly symptomatic leaf samples, suggesting a possibility that, at more advanced stages of the disease, a major proportion of 'Ca. L. asiaticus' is present in a nonviable state. We trust that observations reported here advance our understanding of how 'Ca. L. asiaticus' causes disease. Furthermore, they may be an important aid in answering a question: when and where within an infected tree the tissue serves as a better inoculum source for acquisition and transmission of the bacterium by its psyllid vector.

  17. Radiological Emergency Preparedness after the Early Phase of an Accident : Focusing on an Air Contamination Event

    International Nuclear Information System (INIS)

    Jeong, Hyo Joon; Hwang, Won Tae; Kim, Eun Han; Han, Moon Hee

    2010-01-01

    Toxic materials in an urban area can be caused by a variety of events, such as accidental releases on industrial complexes, accidents during the transportation of hazardous materials and intentional explosions. Most governments around the world and their citizens have become increasingly worried about intentional accidents in urban area after the 911 terrorist attack in the United States of America. Even though there have been only a few attempted uses of Radiological Dispersal Devices (RDDs), accidental releases have occurred many times at commercial nuclear power plants and nuclear waste disposal sites. When an intentional release of radioactive materials occurs in an urban area, air quality for radioactive materials in the environment is of great importance to take action for countermeasures and environmental risk assessments. Atmospheric modeling is part of the decision making tasks and that it is particularly important for emergency managers as they often need to take actions quickly on very inadequate information(1). A simple model such as HOTSPOT required wind direction and source term would be enough to support the decision making in the early phase of an accident, but more sophisticated atmospheric modeling is required to adjust decontamination area and relocation etc after the early phase of an accidental event. In this study, we assume an explosion of 137 Cs using RDDs in the metropolitan area of Soul, South Korea. California Puff Model (CALPUFF) is used to calculate an atmospheric dispersion and transport for 137 Cs. Atmospheric dispersion and quantitative radiological risk analysis for 137 Cs were performed assuming an intentional explosion in the metropolitan area of Soul, South Korea after the early phase of emergency. These kinds of atmospheric modeling and risk analysis could provide a means for decision makers to take action on important issues such as the cleanup of the contaminated area and countermeasures to protect the public caused by

  18. Collapse of proteostasis represents an early molecular event in Caenorhabditis elegans aging.

    Science.gov (United States)

    Ben-Zvi, Anat; Miller, Elizabeth A; Morimoto, Richard I

    2009-09-01

    Protein damage contributes prominently to cellular aging. To address whether this occurs at a specific period during aging or accumulates gradually, we monitored the biochemical, cellular, and physiological properties of folding sensors expressed in different tissues of C. elegans. We observed the age-dependent misfolding and loss of function of diverse proteins harboring temperature-sensitive missense mutations in all somatic tissues at the permissive condition. This widespread failure in proteostasis occurs rapidly at an early stage of adulthood, and coincides with a severely reduced activation of the cytoprotective heat shock response and the unfolded protein response. Enhancing stress responsive factors HSF-1 or DAF-16 suppresses misfolding of these metastable folding sensors and restores the ability of the cell to maintain a functional proteome. This suggests that a compromise in the regulation of proteostatic stress responses occurs early in adulthood and tips the balance between the load of damaged proteins and the proteostasis machinery. We propose that the collapse of proteostasis represents an early molecular event of aging that amplifies protein damage in age-associated diseases of protein conformation.

  19. Early decay of Peccei–Quinn fermion and the IceCube neutrino events

    Energy Technology Data Exchange (ETDEWEB)

    Ema, Yohei, E-mail: ema@hep-th.phys.s.u-tokyo.ac.jp; Moroi, Takeo

    2016-11-10

    IceCube observed high-energy neutrino flux in the energy region from TeV to PeV. The decay of a massive long-lived particle in the early universe can be the origin of the IceCube neutrino events, which we call an “early decay scenario.” In this paper, we construct a particle physics model that contains such a massive long-lived particle based on the Peccei–Quinn model. We calculate the present neutrino flux, taking account of realistic initial energy distributions of particles produced by the decay of the massive long-lived particle. We show that the early decay scenario naturally fits into the Peccei–Quinn model, and that the neutrino flux observed by IceCube can be explained in such a framework. We also see that, based on that model, a consistent cosmological history that explains the abundance of the massive long-lived particle is realized.

  20. A Proteomic Approach Identifies Candidate Early Biomarkers to Predict Severe Dengue in Children.

    Directory of Open Access Journals (Sweden)

    Dang My Nhi

    2016-02-01

    Full Text Available Severe dengue with severe plasma leakage (SD-SPL is the most frequent of dengue severe form. Plasma biomarkers for early predictive diagnosis of SD-SPL are required in the primary clinics for the prevention of dengue death.Among 63 confirmed dengue pediatric patients recruited, hospital based longitudinal study detected six SD-SPL and ten dengue with warning sign (DWS. To identify the specific proteins increased or decreased in the SD-SPL plasma obtained 6-48 hours before the shock compared with the DWS, the isobaric tags for relative and absolute quantification (iTRAQ technology was performed using four patients each group. Validation was undertaken in 6 SD-SPL and 10 DWS patients.Nineteen plasma proteins exhibited significantly different relative concentrations (p<0.05, with five over-expressed and fourteen under-expressed in SD-SPL compared with DWS. The individual protein was classified to either blood coagulation, vascular regulation, cellular transport-related processes or immune response. The immunoblot quantification showed angiotensinogen and antithrombin III significantly increased in SD-SPL whole plasma of early stage compared with DWS subjects. Even using this small number of samples, antithrombin III predicted SD-SPL before shock occurrence with accuracy.Proteins identified here may serve as candidate predictive markers to diagnose SD-SPL for timely clinical management. Since the number of subjects are small, so further studies are needed to confirm all these biomarkers.

  1. The Longitudinal Relation Between Accumulation of Adverse Life Events and Body Mass Index From Early Adolescence to Young Adulthood

    NARCIS (Netherlands)

    Elsenburg, Leonie K.; Smidt, Nynke; Liefbroer, Aart C.

    Objective: Stressors, such as adverse life events, can cause weight changes through behavioral and biological mechanisms. Whether the accumulation of adverse life events is related to body mass index (BMI) across multiple time points from early adolescence to young adulthood has not been

  2. The longitudinal relation between accumulation of adverse life events and body mass index from early adolescence to young adulthood

    NARCIS (Netherlands)

    Elsenburg, Leonie K.; Smidt, Nynke; Liefbroer, Aart C.

    2017-01-01

    Objective: Stressors, such as adverse life events, can cause weight changes through behavioral and biological mechanisms. Whether the accumulation of adverse life events is related to body mass index (BMI) across multiple time points from early adolescence to young adulthood has not been

  3. The Longitudinal Relation Between Accumulation of Adverse Life Events and Body Mass Index From Early Adolescence to Young Adulthood

    NARCIS (Netherlands)

    Elsenburg, L.; Smidt, N.; Liefbroer, A.C.

    2017-01-01

    Objective: Stressors, such as adverse life events, can cause weight changes through behavioral and biological mechanisms. Whether the accumulation of adverse life events is related to body mass index (BMI) across multiple time points from early adolescence to young adulthood has not been

  4. Events

    Directory of Open Access Journals (Sweden)

    Igor V. Karyakin

    2016-02-01

    Full Text Available The 9th ARRCN Symposium 2015 was held during 21st–25th October 2015 at the Novotel Hotel, Chumphon, Thailand, one of the most favored travel destinations in Asia. The 10th ARRCN Symposium 2017 will be held during October 2017 in the Davao, Philippines. International Symposium on the Montagu's Harrier (Circus pygargus «The Montagu's Harrier in Europe. Status. Threats. Protection», organized by the environmental organization «Landesbund für Vogelschutz in Bayern e.V.» (LBV was held on November 20-22, 2015 in Germany. The location of this event was the city of Wurzburg in Bavaria.

  5. Seismology-based early identification of dam-formation landquake events.

    Science.gov (United States)

    Chao, Wei-An; Zhao, Li; Chen, Su-Chin; Wu, Yih-Min; Chen, Chi-Hsuan; Huang, Hsin-Hua

    2016-01-12

    Flooding resulting from the bursting of dams formed by landquake events such as rock avalanches, landslides and debris flows can lead to serious bank erosion and inundation of populated areas near rivers. Seismic waves can be generated by landquake events which can be described as time-dependent forces (unloading/reloading cycles) acting on the Earth. In this study, we conduct inversions of long-period (LP, period ≥20 s) waveforms for the landquake force histories (LFHs) of ten events, which provide quantitative characterization of the initiation, propagation and termination stages of the slope failures. When the results obtained from LP waveforms are analyzed together with high-frequency (HF, 1-3 Hz) seismic signals, we find a relatively strong late-arriving seismic phase (dubbed Dam-forming phase or D-phase) recorded clearly in the HF waveforms at the closest stations, which potentially marks the time when the collapsed masses sliding into river and perhaps even impacting the topographic barrier on the opposite bank. Consequently, our approach to analyzing the LP and HF waveforms developed in this study has a high potential for identifying five dam-forming landquake events (DFLEs) in near real-time using broadband seismic records, which can provide timely warnings of the impending floods to downstream residents.

  6. A new index for identifying socioeconomic drought events under climate change over the East River basin in China

    Science.gov (United States)

    Shi, H.; Chen, J.; Wang, K.; Niu, J.

    2017-12-01

    Drought, which means severe water deficiencies, is a complex natural hazard that may have destructive damages on societal properties and lives. Generally, socioeconomic drought occurs when the water resources systems cannot meet the water demands due to a weather-related shortfall in water supply to societies. This paper aims to propose a new index (i.e., socioeconomic drought index (SEDI)) for identifying socioeconomic drought events on different levels (i.e., slight, moderate, severe and extreme) under climate change through considering the gap between water supply and demand. First, the minimum in-stream water requirement (MWR) is determined through comprehensively considering the requirements of water quality, ecology, navigation and water supply. Second, according to the monthly water deficit calculated as the monthly streamflow data minus the MWR, drought month can be identified. Third, according to the cumulative water deficit derived from the monthly water deficit, drought duration (i.e., the number of continuous drought months) can be detected. Fourth, the SEDI of each socioeconomic drought event can be calculated through integrating the impacts of the cumulative water deficit and drought duration. The study area is the East River basin in South China, and the impact of a multi-year reservoir (i.e., the Xinfengjiang Reservoir) on drought is also analyzed. For historical and future drought analysis, it is concluded that the proposed SEDI is feasible to identify socioeconomic drought events. The results show that a number of socioeconomic drought events (including some extreme ones) may occur during 2020-2099, and the appropriate reservoir operation can significantly ease such situation.

  7. Automatically Identifying Fusion Events between GLUT4 Storage Vesicles and the Plasma Membrane in TIRF Microscopy Image Sequences

    Directory of Open Access Journals (Sweden)

    Jian Wu

    2015-01-01

    Full Text Available Quantitative analysis of the dynamic behavior about membrane-bound secretory vesicles has proven to be important in biological research. This paper proposes a novel approach to automatically identify the elusive fusion events between VAMP2-pHluorin labeled GLUT4 storage vesicles (GSVs and the plasma membrane. The differentiation is implemented to detect the initiation of fusion events by modified forward subtraction of consecutive frames in the TIRFM image sequence. Spatially connected pixels in difference images brighter than a specified adaptive threshold are grouped into a distinct fusion spot. The vesicles are located at the intensity-weighted centroid of their fusion spots. To reveal the true in vivo nature of a fusion event, 2D Gaussian fitting for the fusion spot is used to derive the intensity-weighted centroid and the spot size during the fusion process. The fusion event and its termination can be determined according to the change of spot size. The method is evaluated on real experiment data with ground truth annotated by expert cell biologists. The evaluation results show that it can achieve relatively high accuracy comparing favorably to the manual analysis, yet at a small fraction of time.

  8. Archaeal remains dominate marine organic matter from the early Albian oceanic anoxic event 1b

    DEFF Research Database (Denmark)

    Kuypers, M.M.M.; Blokker, P.; Hopmans, E.C.

    2002-01-01

    The sources for both soluble and insoluble organic matter of the early Albian (∼112 Myr) oceanic anoxic event (OAE) 1b black shales of the Ocean Drilling Program (ODP) site 1049C (North Atlantic Ocean off the coast of Florida) and the Ravel section of the Southeast France Basin (SEFB) were...... in C/C ratios was used to estimate that up to ∼40% of the organic matter of the SEFB and up to ∼80% of the organic matter of ODP site 1049C preserved in the black shales is derived from archaea. Furthermore, it is shown that, even though there are apparent similarities (high organic carbon (OC) content......, distinct lamination, C-enrichment of OC) between the black shales of OAE1b and the Cenomanian/Turonian (∼94 Myr) OAE, the origin of the organic matter (archaeal versus phytoplanktonic) and causes for C-enrichment of OC are completely different....

  9. Viral FGARAT ORF75A promotes early events in lytic infection and gammaherpesvirus pathogenesis in mice

    Science.gov (United States)

    Hogan, Chad H.; Oldenburg, Darby G.; Kara, Mehmet

    2018-01-01

    Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen. Intraperitoneal infection rescued splenic latency, but not reactivation. The 75A.stop virus also exhibited defective replication in primary fibroblast and macrophage cells. Viruses produced in the absence of ORF75A were characterized by an increase in the ratio of particles to PFU. In the next round of infection this led to the alteration of early events in lytic replication including the deposition of the ORF75C tegument protein, the accelerated kinetics of viral gene expression, and induction of TNFα release and cell death. Infecting cells to deliver equivalent genomes revealed that ORF75A was required for initiating early events in infection. In contrast with the numerous phenotypes observed in the absence of ORF75A, ORF75B was dispensable for replication and pathogenesis. These studies reveal that murine rhadinovirus vFGARAT family members ORF75A and ORF75C have evolved to perform divergent functions that promote replication and colonization of the host. PMID:29390024

  10. Application of τc*Pd for identifying damaging earthquakes for earthquake early warning

    Science.gov (United States)

    Huang, P. L.; Lin, T. L.; Wu, Y. M.

    2014-12-01

    Earthquake Early Warning System (EEWS) is an effective approach to mitigate earthquake damage. In this study, we used the seismic record by the Kiban Kyoshin network (KiK-net), because it has dense station coverage and co-located borehole strong-motion seismometers along with the free-surface strong-motion seismometers. We used inland earthquakes with moment magnitude (Mw) from 5.0 to 7.3 between 1998 and 2012. We choose 135 events and 10950 strong ground accelerograms recorded by the 696 strong ground accelerographs. Both the free-surface and the borehole data are used to calculate τc and Pd, respectively. The results show that τc*Pd has a good correlation with PGV and is a robust parameter for assessing the potential of damaging earthquake. We propose the value of τc*Pd determined from seconds after the arrival of P wave could be a threshold for the on-site type of EEW.

  11. Glypican1 identifies cancer exosomes and facilitates early detection of cancer

    Science.gov (United States)

    Melo, Sonia A.; Luecke, Linda B.; Kahlert, Christoph; Fernandez, Agustin F.; Gammon, Seth T.; Kaye, Judith; LeBleu, Valerie S.; Mittendorf, Elizabeth A.; Weitz, Juergen; Rahbari, Nuh; Reissfelder, Christoph; Pilarsky, Christian; Fraga, Mario F.; Piwnica-Worms, David; Kalluri, Raghu

    2016-01-01

    Summary Exosomes are lipid bilayer-enclosed extracellular vesicles (EVs) that contain proteins and nucleic acids. They are secreted by all cells and circulate in the blood. Specific detection and isolation of cancer cell-derived exosomes in circulation is currently lacking. Using mass spectrometry analyses, we identified a cell surface proteoglycan, glypican-1 (GPC1), specifically enriched on cancer cell-derived exosomes. GPC1+ circulating exosomes (crExos) were monitored and isolated using flow cytometry from the serum of cancer patients and mice with cancer. GPC1+ crExos were detected in the serum of patients with pancreas cancer with absolute specificity and sensitivity, distinguishing healthy subjects and patients with a benign pancreas disease from patients with early and late stage pancreas cancer. Levels of GPC1+ crExos correlate with tumor burden and survival in patients pre- and post-surgical tumor resection. GPC1+ crExos from patients and from mice with spontaneous pancreas tumors driven by oncogenic KRAS contained RNA with specific KRAS mutation, and it emerges as a reliable biomarker for the detection of PanIN lesions despite negative signal by MRI in mice. GPC1+ crExos may serve as a potential non-invasive diagnostic and screening tool to detect early stages of pancreas cancer to facilitate possible curative surgical therapy. PMID:26106858

  12. Fourier transform infrared microspectroscopy identifies early lineage commitment in differentiating human embryonic stem cells.

    Science.gov (United States)

    Heraud, Philip; Ng, Elizabeth S; Caine, Sally; Yu, Qing C; Hirst, Claire; Mayberry, Robyn; Bruce, Amanda; Wood, Bayden R; McNaughton, Don; Stanley, Edouard G; Elefanty, Andrew G

    2010-03-01

    Human ESCs (hESCs) are a valuable tool for the study of early human development and represent a source of normal differentiated cells for pharmaceutical and biotechnology applications and ultimately for cell replacement therapies. For all applications, it will be necessary to develop assays to validate the efficacy of hESC differentiation. We explored the capacity for FTIR spectroscopy, a technique that rapidly characterises cellular macromolecular composition, to discriminate mesendoderm or ectoderm committed cells from undifferentiated hESCs. Distinct infrared spectroscopic "signatures" readily distinguished hESCs from these early differentiated progeny, with bioinformatic models able to correctly classify over 97% of spectra. These data identify a role for FTIR spectroscopy as a new modality to complement conventional analyses of hESCs and their derivatives. FTIR spectroscopy has the potential to provide low-cost, automatable measurements for the quality control of stem and differentiated cells to be used in industry and regenerative medicine. Crown Copyright 2009. Published by Elsevier B.V. All rights reserved.

  13. Accuracy of episodic autobiographical memory in children with early thyroid hormone deficiency using a staged event

    Directory of Open Access Journals (Sweden)

    Karen A. Willoughby

    2014-07-01

    Full Text Available Autobiographical memory (AM is a highly constructive cognitive process that often contains memory errors. No study has specifically examined AM accuracy in children with abnormal development of the hippocampus, a crucial brain region for AM retrieval. Thus, the present study investigated AM accuracy in 68 typically and atypically developing children using a staged autobiographical event, the Children's Autobiographical Interview, and structural magnetic resonance imaging. The atypically developing group consisted of 17 children (HYPO exposed during gestation to insufficient maternal thyroid hormone (TH, a critical substrate for hippocampal development, and 25 children with congenital hypothyroidism (CH, who were compared to 26 controls. Groups differed significantly in the number of accurate episodic details recalled and proportion accuracy scores, with controls having more accurate recollections of the staged event than both TH-deficient groups. Total hippocampal volumes and anterior hippocampal volumes were positively correlated with proportion accuracy scores, but not total accurate episodic details, in HYPO and CH. In addition, greater severity of TH deficiency predicted lower proportion accuracy scores in both HYPO and CH. Overall, these results indicate that children with early TH deficiency have deficits in AM accuracy and that the anterior hippocampus may play a particularly important role in accurate AM retrieval.

  14. Early notification of the environmental radiation monitoring system to a radioactive event

    International Nuclear Information System (INIS)

    Haquin, G.; Ne'eman, F; Brenner, S.

    1997-01-01

    The National Environmental Radiation Monitoring System managed by the Radiation Safety Division of the Ministry of tile Environment has been completed and is composed of a network of 10 stations; 6 terrestrial stations, 3 waterside stations and one mobile. The system was built by Rotem Co. and the control center is located at the Unit of Environmental Resources of the Ministry of the Environment in Tel Aviv University. Each station consists of a wide range Geiger Mueller detector and ambient dose rate meter that provides the level of the environmental dose rate. Low level radioactive particles are detected by air sampling with devices that collect suspended and settling particles . Each station is connected to the control center through telephone lines and RF communication system providing 24 hour a day the level of the environmental radiation. The background radiation dose rate level depends on the location of the station and varies from 8 - 16 μR/h. The system has proved its efficiency in a 'simulation like event' early detecting an unregistered gamma radiography work in the proximity of two stations performed in June 96 in Ashdod port and in December 96 at Maspenot Israel in Haifa. During the events the radiation level increased up to 20 times above the background level. Survey teams of the Ashdod port and Maspenot Israel were sent to place to check the sources for the radiation level increase. These teams found workers performing radiography work in the area of the stations. (authors)

  15. Excessive Heat Events and National Security: Building Resilience based on Early Warning Systems

    Science.gov (United States)

    Vintzileos, A.

    2017-12-01

    Excessive heat events (EHE) affect security of Nations in multiple direct and indirect ways. EHE are the top cause for morbidity/mortality associated to any atmospheric extremes. Higher energy consumption used for cooling can lead to black-outs and social disorder. EHE affect the food supply chain reducing crop yield and increasing the probability of food contamination during delivery and storage. Distribution of goods during EHE can be severely disrupted due to mechanical failure of transportation equipment. EHE during athletic events e.g., marathons, may result to a high number of casualties. Finally, EHE may also affect military planning by e.g. reducing hours of exercise and by altering combat gear. Early warning systems for EHE allow for building resilience. In this paper we first define EHE as at least two consecutive heat days; a heat day is defined as a day with a maximum heat index with probability of occurrence that exceeds a certain threshold. We then use retrospective forecasts performed with a multitude of operational models and show that it is feasible to forecast EHE at forecast lead of week-2 and week-3 over the contiguous United States. We finally introduce an improved definition of EHE based on an intensity index and investigate forecast skill of the predictive system in the tropics and subtropics.

  16. Constraints on early events in Martian history as derived from the cratering record

    International Nuclear Information System (INIS)

    Barlow, N.G.

    1990-01-01

    The shapes and densities of crater size-frequency distribution curves are used to constrain two major events early in Martian history: termination of high obliteration rates and viability of the multiple impact origin of the crustal dichotomy. Distribution curves of fresh craters superposed on uplands, intercrater plains, and ridged plains display shapes and densities indicative of formation prior to the end of heavy bombardment. This observation correlates with other geologic evidence, suggesting a major change in the erosional regime following the last major basin size impact (i.e., Argrye). In addition, the multisloped nature of the curves supports the idea that the downturn in the crater size-frequency distribution curves reflects the size-frequency distribution of the impactors rather than being the result of erosion. The crustal dichotomy formed prior to the heavy bombardment intermediate epoch based on distribution curves of knobby terrain; if the dichotomy resulted from a single gigantic impact, this observation places constraints on when this event happened. An alternate theory for dichotomy formation, the multiple-impact basin idea, is questioned: since distribution curves of large basins as well as heavy bombardment era units are not represented by a -3 differential power law function, this study finds fewer basins missing on Mars compare to the Moon and Mercury than previously reported. The area covered by these missing basins is less than that covered the northern plains

  17. Relationship between early and late stages of information processing: an event-related potential study

    Directory of Open Access Journals (Sweden)

    Claudio Portella

    2012-11-01

    Full Text Available The brain is capable of elaborating and executing different stages of information processing. However, exactly how these stages are processed in the brain remains largely unknown. This study aimed to analyze the possible correlation between early and late stages of information processing by assessing the latency to, and amplitude of, early and late event-related potential (ERP components, including P200, N200, premotor potential (PMP and P300, in healthy participants in the context of a visual oddball paradigm. We found a moderate positive correlation among the latency of P200 (electrode O2, N200 (electrode O2, PMP (electrode C3, P300 (electrode PZ and the reaction time (RT. In addition, moderate negative correlation between the amplitude of P200 and the latencies of N200 (electrode O2, PMP (electrode C3, P300 (electrode PZ was found. Therefore, we propose that if the secondary processing of visual input (P200 latency occurs faster, the following will also happen sooner: discrimination and classification process of this input (N200 latency, motor response processing (PMP latency, reorganization of attention and working memory update (P300 latency, and RT. N200, PMP, and P300 latencies are also anticipated when higher activation level of occipital areas involved in the secondary processing of visual input rise (P200 amplitude.

  18. Enhanced tocopherol levels during early germination events in Chamaerops humilis var. humilis seeds.

    Science.gov (United States)

    Siles, Laura; Alegre, Leonor; Tijero, Verónica; Munné-Bosch, Sergi

    2015-10-01

    Most angiosperms accumulate vitamin E in the form of tocopherols in seeds, exerting a protective antioxidant role. However, several palm trees principally accumulate tocotrienols, rather than tocopherols, in seeds, as it occurs in other monocots. To unravel the protective role of either tocopherols or tocotrienols against lipid peroxidation during seed germination in Chamaerops humilis var. humilis; seed viability, natural and induced germination capacity, seed water content, malondialdehyde levels (as an indicator of the extent of lipid peroxidation) and vitamin E levels (including both tocopherols and tocotrienols) were examined at various germination phases in a simulated, natural seed bank. At the very early stages of germination (operculum removal), malondialdehyde levels increased 2.8-fold, to decrease later up to 74%, thus indicating a transient lipid peroxidation at early stages of germination. Tocopherol levels were absent in quiescent seeds and did not increase during operculum removal, but increased later presumably dampening malondialdehyde accumulation. Thereafter, tocopherols continued increasing, while lipid peroxidation levels decreased. By contrast, tocotrienols levels remained constant or even decreased as germination progressed, showing no correlation with lipid peroxidation levels. We hypothesize that despite their high tocotrienol content, seeds synthesize tocopherols during germination to protect lipids from peroxidation events. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong

    2015-01-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications. PMID:26265791

  20. Early spring, severe frost events, and drought induce rapid carbon loss in high elevation meadows.

    Directory of Open Access Journals (Sweden)

    Chelsea Arnold

    Full Text Available By the end of the 20th century, the onset of spring in the Sierra Nevada mountain range of California has been occurring on average three weeks earlier than historic records. Superimposed on this trend is an increase in the presence of highly anomalous "extreme" years, where spring arrives either significantly late or early. The timing of the onset of continuous snowpack coupled to the date at which the snowmelt season is initiated play an important role in the development and sustainability of mountain ecosystems. In this study, we assess the impact of extreme winter precipitation variation on aboveground net primary productivity and soil respiration over three years (2011 to 2013. We found that the duration of snow cover, particularly the timing of the onset of a continuous snowpack and presence of early spring frost events contributed to a dramatic change in ecosystem processes. We found an average 100% increase in soil respiration in 2012 and 2103, compared to 2011, and an average 39% decline in aboveground net primary productivity observed over the same time period. The overall growing season length increased by 57 days in 2012 and 61 days in 2013. These results demonstrate the dependency of these keystone ecosystems on a stable climate and indicate that even small changes in climate can potentially alter their resiliency.

  1. Relationship between early and late stages of information processing: an event-related potential study

    Science.gov (United States)

    Portella, Claudio; Machado, Sergio; Arias-Carrión, Oscar; Sack, Alexander T.; Silva, Julio Guilherme; Orsini, Marco; Leite, Marco Antonio Araujo; Silva, Adriana Cardoso; Nardi, Antonio E.; Cagy, Mauricio; Piedade, Roberto; Ribeiro, Pedro

    2012-01-01

    The brain is capable of elaborating and executing different stages of information processing. However, exactly how these stages are processed in the brain remains largely unknown. This study aimed to analyze the possible correlation between early and late stages of information processing by assessing the latency to, and amplitude of, early and late event-related potential (ERP) components, including P200, N200, premotor potential (PMP) and P300, in healthy participants in the context of a visual oddball paradigm. We found a moderate positive correlation among the latency of P200 (electrode O2), N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) and the reaction time (RT). In addition, moderate negative correlation between the amplitude of P200 and the latencies of N200 (electrode O2), PMP (electrode C3), P300 (electrode PZ) was found. Therefore, we propose that if the secondary processing of visual input (P200 latency) occurs faster, the following will also happen sooner: discrimination and classification process of this input (N200 latency), motor response processing (PMP latency), reorganization of attention and working memory update (P300 latency), and RT. N200, PMP, and P300 latencies are also anticipated when higher activation level of occipital areas involved in the secondary processing of visual input rise (P200 amplitude). PMID:23355929

  2. Early Maternal Deprivation Enhances Voluntary Alcohol Intake Induced by Exposure to Stressful Events Later in Life

    Directory of Open Access Journals (Sweden)

    Sara Peñasco

    2015-01-01

    Full Text Available In the present study, we aimed to assess the impact of early life stress, in the form of early maternal deprivation (MD, 24 h on postnatal day, pnd, 9, on voluntary alcohol intake in adolescent male and female Wistar rats. During adolescence, from pnd 28 to pnd 50, voluntary ethanol intake (20%, v/v was investigated using the two-bottle free choice paradigm. To better understand the relationship between stress and alcohol consumption, voluntary alcohol intake was also evaluated following additional stressful events later in life, that is, a week of alcohol cessation and a week of alcohol cessation combined with exposure to restraint stress. Female animals consumed more alcohol than males only after a second episode of alcohol cessation combined with restraint stress. MD did not affect baseline voluntary alcohol intake but increased voluntary alcohol intake after stress exposure, indicating that MD may render animals more vulnerable to the effects of stress on alcohol intake. During adolescence, when animals had free access to alcohol, MD animals showed lower body weight gain but a higher growth rate than control animals. Moreover, the higher growth rate was accompanied by a decrease in food intake, suggesting an altered metabolic regulation in MD animals that may interact with alcohol intake.

  3. A catastrophic event in Lake Geneva region during the Early Bronze Age?

    Science.gov (United States)

    Kremer, Katrina; Yrro, Blé; Marillier, François; Hilbe, Michael; Corboud, Pierre; Rachoud-Schneider, Anne-Marie; Girardclos, Stéphanie

    2013-04-01

    Similarly to steep oceanic continental margins, lake slopes can collapse, producing large sublacustrine landslides and tsunamis. Lake sediments are excellent natural archives of such mass movements and their study allows the reconstructions of these prehistoric events, such as the 563 AD large tsunami over Lake Geneva (Kremer et al, 2012). In Lake Geneva, more than 100 km of high-resolution seismic reflection profiles reveal the late Holocene sedimentation history. The seismic record shows a succession of five large lens-shaped seismic units (A to I), characterized by transparent/chaotic seismic facies with irregular lower boundaries, and interpreted as mass-movement deposits. These units are interbedded with parallel, continuous and strong amplitude reflections, interpreted as the 'background' lake sediments. The oldest dated mass movement (Unit D) covers a surface of 22 km2 in the deep basin, near the city of Lausanne. This deposit has an estimated minimum volume of 0.18 km3 and thus was very likely tsunamigenic (Kremer et al, 2012). A 12-m-long sediment core confirms the seismic interpretation of the mass movement unit and shows that the uppermost 3 m of Unit D are characterized by deformed hemipelagic sediments topped by a 5 cm thick turbidite. This deposit can be classified as a slump whose scar can be interpreted in the seismic data and visualized by multibeam bathymetry. This slump of Lausanne was likely triggered by an earthquake but a spontaneous slope collapse cannot be excluded (Girardclos et al, 2007). Radiocarbon dating of plant macro-remains reveals that the unit D happened during Early Bronze Age. Three other mass wasting deposits occurred during the same time period and may have been triggered during the same event, either by a single earthquake or by a tsunami generated by the slump of Lausanne. Although the exact trigger mechanism of the all these mass-wasting deposits remains unknown, a tsunami likely generated by this event may have affected the

  4. Nonlinear Methodologies for Identifying Seismic Event and Nuclear Explosion Using Random Forest, Support Vector Machine, and Naive Bayes Classification

    Directory of Open Access Journals (Sweden)

    Longjun Dong

    2014-01-01

    Full Text Available The discrimination of seismic event and nuclear explosion is a complex and nonlinear system. The nonlinear methodologies including Random Forests (RF, Support Vector Machines (SVM, and Naïve Bayes Classifier (NBC were applied to discriminant seismic events. Twenty earthquakes and twenty-seven explosions with nine ratios of the energies contained within predetermined “velocity windows” and calculated distance are used in discriminators. Based on the one out cross-validation, ROC curve, calculated accuracy of training and test samples, and discriminating performances of RF, SVM, and NBC were discussed and compared. The result of RF method clearly shows the best predictive power with a maximum area of 0.975 under the ROC among RF, SVM, and NBC. The discriminant accuracies of RF, SVM, and NBC for test samples are 92.86%, 85.71%, and 92.86%, respectively. It has been demonstrated that the presented RF model can not only identify seismic event automatically with high accuracy, but also can sort the discriminant indicators according to calculated values of weights.

  5. SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development

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    Rhys J.P. Skelton

    2014-07-01

    Full Text Available The study of human cardiogenesis would benefit from a detailed cell lineage fate map akin to that established for the haematopoietic lineages. Here we sought to define cell lineage relationships based on the expression of NKX2-5 and the cell surface markers VCAM1, SIRPA and CD34 during human cardiovascular development. Expression of NKX2-5GFP was used to identify cardiac progenitors and cardiomyocytes generated during the differentiation of NKX2-5GFP/w human embryonic stem cells (hESCs. Cardiovascular cell lineages sub-fractionated on the basis of SIRPA, VCAM1 and CD34 expression were assayed for differentiation potential and gene expression. The NKX2-5posCD34pos population gave rise to endothelial cells that rapidly lost NKX2-5 expression in culture. Conversely, NKX2-5 expression was maintained in myocardial committed cells, which progressed from being NKX2-5posSIRPApos to NKX2-5posSIRPAposVCAM1pos. Up-regulation of VCAM1 was accompanied by the expression of myofilament markers and reduced clonal capacity, implying a restriction of cell fate potential. Combinatorial expression of NKX2-5, SIRPA, VCAM1 and CD34 can be used to define discrete stages of cardiovascular cell lineage differentiation. These markers identify specific stages of cardiomyocyte and endothelial lineage commitment and, thus provide a scaffold for establishing a fate map of early human cardiogenesis.

  6. Ophthalmic Vascular Events after Primary Unilateral Intra-arterial Chemotherapy for Retinoblastoma in Early and Recent Eras.

    Science.gov (United States)

    Dalvin, Lauren A; Ancona-Lezama, David; Lucio-Alvarez, J Antonio; Masoomian, Babak; Jabbour, Pascal; Shields, Carol L

    2018-06-16

    To assess risk factors for ophthalmic vascular events after intra-arterial chemotherapy (IAC) for retinoblastoma. Retrospective cohort study. Patients who received unilateral IAC as primary treatment for retinoblastoma from January 1, 2009, to November 30, 2017, at a single center. Records were reviewed for patient demographics, tumor features, IAC parameters, and treatment-related vascular events in the early IAC era (2009-2011) compared with the recent era (2012-2017) using the t test and Fisher exact test. Change in event rates over time was assessed using Poisson regression analysis, with Spearman's rho used to test correlation. Rate of IAC-induced ophthalmic vascular events. There were 243 chemotherapy infusions in 76 eyes of 76 patients, divided into early (22 eyes, 57 infusions) and recent (54 eyes, 186 infusions) eras. Intra-arterial chemotherapy consisted of melphalan (243 infusions), topotecan (124 infusions), and carboplatin (9 infusions). A comparison (early vs. recent era) revealed fewer mean number of infusions (2.6 vs. 3.4, P = 0.02) with similar mean patient age and presenting tumor features. Event rates decreased over time (P early era vs. recent era) in the recent era (59% vs. 9% per eye, 23% vs. 3% per infusion, P age (P = 0.75), tumor diameter (P = 0.32), tumor thickness (P = 0.59), or cumulative dosage of melphalan (P = 0.13) or topotecan (P = 0.59). There were no IAC-induced vascular events in 72 infusions of 21 consecutively treated eyes in 2016 to 2017. Ophthalmic vascular events after IAC have decreased from the early era (2009-2011) through the current era (2012-2017) at this center. Experience performing this highly specialized procedure could be an important factor predicting IAC-related vascular events. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  7. A study looking at the effectiveness of developmental screening in identifying learning disabilities in early childhood.

    Science.gov (United States)

    Flanagan, O; Nualláin, S O

    2001-05-01

    This is a retrospective study of children under six years of age referred to the Brothers of Charity Early Intervention Services in County Galway, a service that caters for children under 6 years with learning disabilities. The aim in doing this study was to assess the value of routine developmental screening in identifying children with learning difficulties. This study also investigates the patterns and sources of referral to the remedial services provided by the Brothers of Charity and highlights possible avoidable delays in referral. The results showed that many children were referred for remedial services late. The reasons for late referral included late identification of some children with problems, insufficient co-ordination of community-based services and a lack of awareness of the importance of early intervention in some cases. As some communication disorders such as autism, autistic spectrum disorders and specific language delay may not express themselves until the later part of the second year of life, the 18-24 month developmental assessment is of vital importance. However identification of these disorders can present difficulties and may call for additional training for professionals involved in the developmental screening of children in that age group. The interval between initial identification and referral for remedial care in many cases was more than twelve months. We propose that, in order to minimize this time, children requiring a more in-depth assessment should be assessed by a community-based multidisciplinary team, enabling integrated assessment by the different disciplines and thus speedier referral to remedial services.

  8. Dynamic CT myocardial perfusion imaging identifies early perfusion abnormalities in diabetes and hypertension : Insights from a multicenter registry

    NARCIS (Netherlands)

    Vliegenthart, Rozemarijn; De Cecco, Carlo N.; Wichmann, Julian L.; Meinel, Felix G.; Pelgrim, Gert Jan; Tesche, Christian; Ebersberger, Ullrich; Pugliese, Francesca; Bamberg, Fabian; Choe, Yeon Hyeon; Wang, Yining; Schoepf, U. Joseph

    2016-01-01

    Background: To identify patients with early signs of myocardial perfusion reduction, a reference base for perfusion measures is needed. Objective: To analyze perfusion parameters derived from dynamic computed tomography perfusion imaging (CTPI) in patients with suspected coronary artery disease

  9. Remedial early numeracy education : Can children identified as having a language deficiency benefit?

    NARCIS (Netherlands)

    Van Luit, Johannes E H; Toll, Sylke W M

    2015-01-01

    Background Growing attention has been paid to the possibility of supporting early numeracy in at-risk kindergartners. Furthermore, it is assumed that language proficiency is an important prerequisite in early maths skills. Aims To examine whether remedial early numeracy education in kindergarten,

  10. Over-expression of 14-3-3zeta is an early event in oral cancer

    International Nuclear Information System (INIS)

    Matta, Ajay; Bahadur, Sudhir; Duggal, Ritu; Gupta, Siddhartha D; Ralhan, Ranju

    2007-01-01

    The functional and clinical significance of 14-3-3 proteins in human cancers remain largely undetermined. Earlier, we have reported differential expression of 14-3-3ζ mRNA in oral squamous cell carcinoma (OSCC) by differential display. The clinical relevance of 14-3-3ζ protein in oral tumorigenesis was determined by immunohistochemistry in paraffin embedded sections of oral pre-malignant lesions (OPLs), OSCCs and histologically normal oral tissues and corroborated by Western Blotting. Co-immunoprecipitation assays were carried out to determine its association with NFκB, β-catenin and Bcl-2. Intense immunostaining of 14-3-3ζ protein was observed in 61/89 (69%) OPLs and 95/120 (79%) OSCCs. Immunohistochemistry showed significant increase in expression of 14-3-3ζ protein from normal mucosa to OPLs to OSCCs (p trend < 0.001). Significant increase in expression of 14-3-3ζ protein was observed as early as in hyperplasia (p = 0.009), with further elevation in moderate and severe dysplasia, that was sustained in OSCCs. These findings were validated by Western blotting. Using Co-immunoprecipitation, we demonstrated that 14-3-3ζ protein binds to NFκB, β-catenin and Bcl-2, suggesting its involvement in cellular signaling, leading to proliferation of oral cancer cells. Our findings suggest that over-expression of 14-3-3ζ is an early event in oral tumorigenesis and may have an important role in its development and progression. Thus, 14-3-3ζ may serve as an important molecular target for designing novel therapy for oral cancer

  11. Gene methylation profiles of normal mucosa, and benign and malignant colorectal tumors identify early onset markers

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    Vatn Morten

    2008-12-01

    Full Text Available Abstract Background Multiple epigenetic and genetic changes have been reported in colorectal tumors, but few of these have clinical impact. This study aims to pinpoint epigenetic markers that can discriminate between non-malignant and malignant tissue from the large bowel, i.e. markers with diagnostic potential. The methylation status of eleven genes (ADAMTS1, CDKN2A, CRABP1, HOXA9, MAL, MGMT, MLH1, NR3C1, PTEN, RUNX3, and SCGB3A1 was determined in 154 tissue samples including normal mucosa, adenomas, and carcinomas of the colorectum. The gene-specific and widespread methylation status among the carcinomas was related to patient gender and age, and microsatellite instability status. Possible CIMP tumors were identified by comparing the methylation profile with microsatellite instability (MSI, BRAF-, KRAS-, and TP53 mutation status. Results The mean number of methylated genes per sample was 0.4 in normal colon mucosa from tumor-free individuals, 1.2 in mucosa from cancerous bowels, 2.2 in adenomas, and 3.9 in carcinomas. Widespread methylation was found in both adenomas and carcinomas. The promoters of ADAMTS1, MAL, and MGMT were frequently methylated in benign samples as well as in malignant tumors, independent of microsatellite instability. In contrast, normal mucosa samples taken from bowels without tumor were rarely methylated for the same genes. Hypermethylated CRABP1, MLH1, NR3C1, RUNX3, and SCGB3A1 were shown to be identifiers of carcinomas with microsatellite instability. In agreement with the CIMP concept, MSI and mutated BRAF were associated with samples harboring hypermethylation of several target genes. Conclusion Methylated ADAMTS1, MGMT, and MAL are suitable as markers for early tumor detection.

  12. The struggling reader: Identifying and addressing reading problems successfully at an early stage

    Directory of Open Access Journals (Sweden)

    Le Cordeur, Michael

    2010-12-01

    Full Text Available The standard of reading of learners in the intermediate phase is cause for considerable concern. In this article, the intermediate phase refers to grades 4, 5 and 6 (roughly ages 10 – 12. According to the 2008 Evaluation Assessment Tests for Reading, only 15% of learners in Grade 6 achieved the required literacy level. Clearly, reading achievement is a problem in South Africa. Although approximately 4% of any given population experience neurological reading problems, the focus of this article is on the significant number of learners in the intermediate phase who experience reading problems and the generic causes of reading problems for learners in general. The intent is to alert teachers and parents to the characteristics of a struggling reader so that the problem can be identified and addressed early. Firstly, ways in which learning problems are manifested are described. Secondly, a discussion of various types of reading problems, of which four, namely poor reading comprehension, inadequate reading fluency, a lack of vocabulary and a negative attitude towards reading, are discussed in depth. Strategies for struggling readers are presented and recommendations are made. The conclusion is that learners who experience reading problems can learn to read successfully when given the necessary support.

  13. Early events associated with infection of Epstein-Barr virus infection of primary B-cells.

    Directory of Open Access Journals (Sweden)

    Sabyasachi Halder

    2009-09-01

    Full Text Available Epstein Barr virus (EBV is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology was used to introduce an expression cassette of green fluorescent protein (GFP by homologous recombination, and the resultant BAC clone, BAC-GFP-EBV was transfected into the HEK 293T epithelial cell line. The resulting recombinant GFP EBV was induced to produce progeny virus by chemical inducer from the stable HEK 293T BAC GFP EBV cell line and the virus was used to immortalize human primary B-cell as monitored by green fluorescence and outgrowth of the primary B cells. The infection, B-cell activation and cell proliferation due to GFP EBV was monitored by the expression of the B-cell surface antigens CD5, CD10, CD19, CD23, CD39, CD40 , CD44 and the intercellular proliferation marker Ki-67 using Flow cytometry. The results show a dramatic increase in Ki-67 which continues to increase by 6-7 days post-infection. Likewise, CD40 signals showed a gradual increase, whereas CD23 signals were increased by 6-12 hours, maximally by 3 days and then decreased. Monitoring the viral gene expression pattern showed an early burst of lytic gene expression. This up-regulation of lytic gene expression prior to latent genes during early infection strongly suggests that EBV infects primary B-cell with an initial burst of lytic gene expression and the resulting progeny virus is competent for infecting new primary B-cells. This process may be critical for establishment of latency prior to cellular transformation. The newly infected primary B-cells can be further analyzed for investigating B cell activation due to EBV infection.

  14. Early Events, Kinetic Intermediates and the Mechanism of Protein Folding in Cytochrome c

    Directory of Open Access Journals (Sweden)

    David S. Kliger

    2009-04-01

    Full Text Available Kinetic studies of the early events in cytochrome c folding are reviewed with a focus on the evidence for folding intermediates on the submillisecond timescale. Evidence from time-resolved absorption, circular dichroism, magnetic circular dichroism, fluorescence energy and electron transfer, small-angle X-ray scattering and amide hydrogen exchange studies on the t £ 1 ms timescale reveals a picture of cytochrome c folding that starts with the ~ 1-ms conformational diffusion dynamics of the unfolded chains. A fractional population of the unfolded chains collapses on the 1 – 100 ms timescale to a compact intermediate IC containing some native-like secondary structure. Although the existence and nature of IC as a discrete folding intermediate remains controversial, there is extensive high time-resolution kinetic evidence for the rapid formation of IC as a true intermediate, i.e., a metastable state separated from the unfolded state by a discrete free energy barrier. Final folding to the native state takes place on millisecond and longer timescales, depending on the presence of kinetic traps such as heme misligation and proline mis-isomerization. The high folding rates observed in equilibrium molten globule models suggest that IC may be a productive folding intermediate. Whether it is an obligatory step on the pathway to the high free energy barrier associated with millisecond timescale folding to the native state, however, remains to be determined.

  15. Visualization of early events in acetic acid denaturation of HIV-1 protease: a molecular dynamics study.

    Directory of Open Access Journals (Sweden)

    Aditi Narendra Borkar

    Full Text Available Protein denaturation plays a crucial role in cellular processes. In this study, denaturation of HIV-1 Protease (PR was investigated by all-atom MD simulations in explicit solvent. The PR dimer and monomer were simulated separately in 9 M acetic acid (9 M AcOH solution and water to study the denaturation process of PR in acetic acid environment. Direct visualization of the denaturation dynamics that is readily available from such simulations has been presented. Our simulations in 9 M AcOH reveal that the PR denaturation begins by separation of dimer into intact monomers and it is only after this separation that the monomer units start denaturing. The denaturation of the monomers is flagged off by the loss of crucial interactions between the α-helix at C-terminal and surrounding β-strands. This causes the structure to transit from the equilibrium dynamics to random non-equilibrating dynamics. Residence time calculations indicate that denaturation occurs via direct interaction of the acetic acid molecules with certain regions of the protein in 9 M AcOH. All these observations have helped to decipher a picture of the early events in acetic acid denaturation of PR and have illustrated that the α-helix and the β-sheet at the C-terminus of a native and functional PR dimer should maintain both the stability and the function of the enzyme and thus present newer targets for blocking PR function.

  16. Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus.

    Science.gov (United States)

    Khositseth, Sookkasem; Uawithya, Panapat; Somparn, Poorichaya; Charngkaew, Komgrid; Thippamom, Nattakan; Hoffert, Jason D; Saeed, Fahad; Michael Payne, D; Chen, Shu-Hui; Fenton, Robert A; Pisitkun, Trairak

    2015-12-17

    Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization, and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.

  17. The geometric preference subtype in ASD: identifying a consistent, early-emerging phenomenon through eye tracking.

    Science.gov (United States)

    Moore, Adrienne; Wozniak, Madeline; Yousef, Andrew; Barnes, Cindy Carter; Cha, Debra; Courchesne, Eric; Pierce, Karen

    2018-01-01

    the new Complex Social GeoPref test), eye tracking of toddlers can accurately identify a specific ASD "GeoPref" subtype with elevated symptom severity. The GeoPref tests are predictive of ASD at the individual subject level and thus potentially useful for various clinical applications (e.g., early identification, prognosis, or development of subtype-specific treatments).

  18. Early Results of Three-Year Monitoring of Red Wood Ants’ Behavioral Changes and Their Possible Correlation with Earthquake Events

    Science.gov (United States)

    Berberich, Gabriele; Berberich, Martin; Grumpe, Arne; Wöhler, Christian; Schreiber, Ulrich

    2013-01-01

    Simple Summary For three years (2009–2012), two red wood ant mounds (Formica rufa-group), located at the seismically active Neuwied Basin (Eifel, Germany), have been monitored 24/7 by high-resolution cameras. Early results show that ants have a well-identifiable standard daily routine. Correlation with local seismic events suggests changes in the ants’ behavior hours before the earthquake: the nocturnal rest phase and daily activity are suppressed, and standard daily routine does not resume until the next day. At present, an automated image evaluation routine is being applied to the video streams. Based on this automated approach, a statistical analysis of the ant behavior will be carried out. Abstract Short-term earthquake predictions with an advance warning of several hours or days are currently not possible due to both incomplete understanding of the complex tectonic processes and inadequate observations. Abnormal animal behaviors before earthquakes have been reported previously, but create problems in monitoring and reliability. The situation is different with red wood ants (RWA; Formica rufa-group (Hymenoptera: Formicidae)). They have stationary mounds on tectonically active, gas-bearing fault systems. These faults may be potential earthquake areas. For three years (2009–2012), two red wood ant mounds (Formica rufa-group), located at the seismically active Neuwied Basin (Eifel, Germany), have been monitored 24/7 by high-resolution cameras with both a color and an infrared sensor. Early results show that ants have a well-identifiable standard daily routine. Correlation with local seismic events suggests changes in the ants’ behavior hours before the earthquake: the nocturnal rest phase and daily activity are suppressed, and standard daily routine does not resume until the next day. At present, an automated image evaluation routine is being applied to the more than 45,000 hours of video streams. Based on this automated approach, a statistical analysis of

  19. Global mapping of protein phosphorylation events identifies novel signalling hubs mediating fatty acid starvation responses in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Pultz, Dennis; Bennetzen, Martin; Rødkær, Steven Vestergaard

    2011-01-01

    Dietary restriction (DR) extends the life span of multiple species, ranging from single-celled organisms like yeast to mammals. This increase in longevity by dietary restriction is coupled to profound beneficial effects on age-related pathology. Despite the number of studies on DR...... and the physiological changes DR induces, only little is known about the genetics and signalling networks, which regulate the DR response. We have recently shown that inhibition of fatty acid synthesis in Saccharomyces cerevisiae induces autophagy mediated by TORC1 signalling and affects life span. In the present study...... in a temporal manner in response to inhibition of fatty acid synthesis by cerulenin. By in silico analysis of these phosphorylation events, we have identified the major downstream regulated processes and signalling networks mediating the cellular response to fatty acid starvation. The analysis further...

  20. Development of an online morbidity, mortality, and near-miss reporting system to identify patterns of adverse events in surgical patients.

    Science.gov (United States)

    Bilimoria, Karl Y; Kmiecik, Thomas E; DaRosa, Debra A; Halverson, Amy; Eskandari, Mark K; Bell, Richard H; Soper, Nathaniel J; Wayne, Jeffrey D

    2009-04-01

    To design a Web-based system to track adverse and near-miss events, to establish an automated method to identify patterns of events, and to assess the adverse event reporting behavior of physicians. A Web-based system was designed to collect physician-reported adverse events including weekly Morbidity and Mortality (M&M) entries and anonymous adverse/near-miss events. An automated system was set up to help identify event patterns. Adverse event frequency was compared with hospital databases to assess reporting completeness. A metropolitan tertiary care center. Identification of adverse event patterns and completeness of reporting. From September 2005 to August 2007, 15,524 surgical patients were reported including 957 (6.2%) adverse events and 34 (0.2%) anonymous reports. The automated pattern recognition system helped identify 4 event patterns from M&M reports and 3 patterns from anonymous/near-miss reporting. After multidisciplinary meetings and expert reviews, the patterns were addressed with educational initiatives, correction of systems issues, and/or intensive quality monitoring. Only 25% of complications and 42% of inpatient deaths were reported. A total of 75.2% of adverse events resulting in permanent disability or death were attributed to the nature of the disease. Interventions to improve reporting were largely unsuccessful. We have developed a user-friendly Web-based system to track complications and identify patterns of adverse events. Underreporting of adverse events and attributing the complication to the nature of the disease represent a problem in reporting culture among surgeons at our institution. Similar systems should be used by surgery departments, particularly those affiliated with teaching hospitals, to identify quality improvement opportunities.

  1. Use of satellite imagery to identify vegetation cover changes following the Waldo Canyon Fire event, Colorado, 2012-2013

    Science.gov (United States)

    Cole, Christopher J.; Friesen, Beverly A.; Wilson, Earl M.

    2014-01-01

    The Waldo Canyon Fire of 2012 was one of the most destructive wildfire events in Colorado history. The fire burned a total of 18,247 acres, claimed 2 lives, and destroyed 347 homes. The Waldo Canyon Fire continues to pose challenges to nearby communities. In a preliminary emergency assessment conducted in 2012, the U.S. Geological Survey (USGS) concluded that drainage basins within and near the area affected by the Waldo Canyon Fire pose a risk for future debris flow events. Rainfall over burned, formerly vegetated surfaces resulted in multiple flood and debris flow events that affected the cities of Colorado Springs and Manitou Springs in 2013. One fatality resulted from a mudslide near Manitou Springs in August 2013. Federal, State, and local governments continue to monitor these hazards and other post-fire effects, along with the region’s ecological recovery. At the request of the Colorado Springs Office of Emergency Management, the USGS Special Applications Science Center developed a geospatial product to identify vegetation cover changes following the 2012 Waldo Canyon Fire event. Vegetation cover was derived from July 2012 WorldView-2 and September 2013 QuickBird multispectral imagery at a spatial resolution of two meters. The 2012 image was collected after the fire had reached its maximum extent. Per-pixel increases and decreases in vegetation cover were identified by measuring spectral changes that occurred between the 2012 and 2013 image dates. A Normalized Difference Vegetation Index (NDVI), and Green-Near Infrared Index (GRNIR) were computed from each image. These spectral indices are commonly used to characterize vegetation cover and health condition, due to their sensitivity to detect foliar chlorophyll content. Vector polygons identifying surface-cover feature boundaries were derived from the 2013 imagery using image segmentation software. This geographic software groups similar image pixels into vector objects based upon their spatial and spectral

  2. The Vallecas Project: a cohort to identify early markers and mechanisms of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Javier eOlazarán

    2015-09-01

    Full Text Available Introduction. Alzheimer’s disease (AD is a major threat for the well-being of an increasingly aged world population. The physiopathological mechanisms of late-onset AD are multiple, possibly heterogeneous, and not well understood. Different combinations of variables from several domains (i.e., clinical, neuropsychological, structural, and biochemical markers may predict dementia conversion, according to distinct physiopathological pathways, in different groups of subjects. Methods. We launched the Vallecas Project (VP, a cohort study of non-demented people aged 70 to 85, to characterize the social, clinical, neuropsychological, structural, and biochemical underpinnings of AD inception. Given the exploratory nature of the VP, multidimensional and machine learning techniques will be applied, in addition to the traditional multivariate statistical methods. Results. A total of 1,169 subjects were recruited between October 2011 and December 2013. Mean age was 74.4 years (SD 3.9, 63.5% of the subjects were women, and 17.9% of the subjects were carriers of at least one ε4 allele of the apolipoprotein E (APOE gene. Cognitive diagnoses at inclusion were as follows: normal cognition 93.0% and mild cognitive impairment (MCI 7.0% (3.1% amnestic MCI, 0.1% non-amnestic MCI, 3.8% mixed MCI. Blood samples were obtained and stored for future determinations in 99.9% of the subjects and 3T magnetic resonance imaging (MRI study was conducted in 89.9% of the volunteers. The cohort is being followed up annually for four years after the baseline. Conclusion. We have established a valuable homogeneous single-center cohort which, by identifying groups of variables associated with high risk of MCI or dementia conversion, should help to clarify the early physiopathological mechanisms of AD and should provide avenues for prompt diagnosis and AD prevention.

  3. Relation between change in blood pressure in acute stroke and risk of early adverse events and poor outcome

    DEFF Research Database (Denmark)

    Sandset, Else C; Murray, Gordon D; Bath, Philip M W

    2012-01-01

    The Scandinavian Candesartan Acute Stroke Trial (SCAST) found no benefits of candesartan in acute stroke. In the present analysis we aim to investigate the effect of change in blood pressure during the first 2 days of stroke on the risk of early adverse events and poor outcome....

  4. Body Mass Index Trajectories from Adolescence to Early Young Adulthood : Do Adverse Life Events Play a Role?

    NARCIS (Netherlands)

    Elsenburg, Leonie K.; Smidt, Nynke; Hoek, Hans W.; Liefbroer, Aart C.

    2017-01-01

    Objective: The aim of this study was to investigate whether there are different classes of body mass index (BMI) development from early adolescence to young adulthood and whether these classes are related to the number of adverse life events children experienced. Methods: Data were from the TRAILS

  5. Developing Fluorescence Sensor Systems for Early Detection of Nitrification Events in Chloraminated Drinking Water Distribution Systems

    Science.gov (United States)

    Detection of nitrification events in chloraminated drinking water distribution systems remains an ongoing challenge for many drinking water utilities, including Dallas Water Utilities (DWU) and the City of Houston (CoH). Each year, these utilities experience nitrification events ...

  6. Identifying cognitive preferences for attractive female faces: an event-related potential experiment using a study-test paradigm.

    Science.gov (United States)

    Zhang, Yan; Kong, Fanchang; Chen, Hong; Jackson, Todd; Han, Li; Meng, Jing; Yang, Zhou; Gao, Jianguo; Najam ul Hasan, Abbasi

    2011-11-01

    In this experiment, sensitivity to female facial attractiveness was examined by comparing event-related potentials (ERPs) in response to attractive and unattractive female faces within a study-test paradigm. Fourteen heterosexual participants (age range 18-24 years, mean age 21.67 years) were required to judge 84 attractive and 84 unattractive face images as either "attractive" or "unattractive." They were then asked whether they had previously viewed each face in a recognition task in which 50% of the images were novel. Analyses indicated that attractive faces elicited more enhanced ERP amplitudes than did unattractive faces in judgment (N300 and P350-550 msec) and recognition (P160 and N250-400 msec and P400-700 msec) tasks on anterior locations. Moreover, longer reaction times and higher accuracy rate were observed in identifying attractive faces than unattractive faces. In sum, this research identified neural and behavioral bases related to cognitive preferences for judging and recognizing attractive female faces. Explanations for the results are that attractive female faces arouse more intense positive emotions in participants than do unattractive faces, and they also represent reproductive fitness and mating value from the evolutionary perspective. Copyright © 2011 Wiley-Liss, Inc.

  7. Retroviral insertional mutagenesis identifies Zeb2 activation as a novel leukemogenic collaborating event in CALM-AF10 transgenic mice.

    Science.gov (United States)

    Caudell, David; Harper, David P; Novak, Rachel L; Pierce, Rachel M; Slape, Christopher; Wolff, Linda; Aplan, Peter D

    2010-02-11

    The t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1. A total of 26% (11 of 42) of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpression of the Zeb2-transcript. A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10 hematopoietic precursors toward B-lineage leukemias. More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations. We searched for Nras, Kras, and Ptpn11 point mutations in the CALM-AF10 leukemic mice. Three mutations were identified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leukemic transformation in concert with CALM-AF10.

  8. TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA.

    Science.gov (United States)

    Wang, Na; Liu, Tiantian; Sofiadis, Anastasios; Juhlin, C Christofer; Zedenius, Jan; Höög, Anders; Larsson, Catharina; Xu, Dawei

    2014-10-01

    The telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have been found in many malignancies, including in thyroid carcinomas. However, it is unclear how early these mutations occur in thyroid tumorigenesis. The study included primary tumors from 58 patients initially diagnosed with follicular thyroid adenoma (FTA), a benign entity, 18 with atypical FTA (AFTA) having an uncertain malignant potential, and 52 with follicular thyroid carcinoma (FTC). Sanger sequencing was used to investigate the mutational status of the TERT promoter. Telomere length and TERT messenger RNA (mRNA) expression were determined using quantitative polymerase chain reaction (PCR). Telomerase activity was assessed using a Telomerase PCR enzyme-linked immunosorbent assay kit. The C228T mutation was identified in 1 of 58 FTA (2%) and 3 of 18 AFTA (17%) samples. These 4 tumors all expressed TERT mRNA and telomerase activity, whereas the majority of C228T-negative adenomas lacked TERT expression (C228T versus wild-type, P = .008). The C228T mutation was associated with NRAS gene mutations (P = .016). The patient with C228T-mutated FTA later developed a scar recurrence and died of FTC, whereas none of the remaining 57 patients with FTA had recurrence. No recurrence occurred in 3 patients with AFTA who carried C228T during the follow-up period (36-285 months). Nine of the 52 FTCs (17%) exhibited the TERT mutation (8 of 9 C228T and 1 of 9 C250T), and the presence of the mutation was associated with shorter patient survival. TERT promoter mutations may occur as an early genetic event in thyroid follicular tumors that have not developed malignant features on routine histopathological workup. © 2014 American Cancer Society.

  9. Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.

    Directory of Open Access Journals (Sweden)

    Jonathan Göke

    2011-12-01

    Full Text Available Transcription factors are proteins that regulate gene expression by binding to cis-regulatory sequences such as promoters and enhancers. In embryonic stem (ES cells, binding of the transcription factors OCT4, SOX2 and NANOG is essential to maintain the capacity of the cells to differentiate into any cell type of the developing embryo. It is known that transcription factors interact to regulate gene expression. In this study we show that combinatorial binding is strongly associated with co-localization of the transcriptional co-activator Mediator, H3K27ac and increased expression of nearby genes in embryonic stem cells. We observe that the same loci bound by Oct4, Nanog and Sox2 in ES cells frequently drive expression in early embryonic development. Comparison of mouse and human ES cells shows that less than 5% of individual binding events for OCT4, SOX2 and NANOG are shared between species. In contrast, about 15% of combinatorial binding events and even between 53% and 63% of combinatorial binding events at enhancers active in early development are conserved. Our analysis suggests that the combination of OCT4, SOX2 and NANOG binding is critical for transcription in ES cells and likely plays an important role for embryogenesis by binding at conserved early developmental enhancers. Our data suggests that the fast evolutionary rewiring of regulatory networks mainly affects individual binding events, whereas "gene regulatory hotspots" which are bound by multiple factors and active in multiple tissues throughout early development are under stronger evolutionary constraints.

  10. Loss of heterozygosity at D8S262: an early genetic event of hepatocarcinogenesis.

    Science.gov (United States)

    Zhu, Qiao; Gong, Li; Liu, Xiaoyan; Wang, Jun; Ren, Pin; Zhang, Wendong; Yao, Li; Han, Xiujuan; Zhu, Shaojun; Lan, Miao; Li, Yanhong; Zhang, Wei

    2015-06-16

    Hepatocellular carcinoma (HCC) is a multi-factor, multi-step, multi-gene and complicated process resulting from the accumulation of sequential genetic and epigenetic alterations. An important change among them is from precancerous lesions to HCC. However, only few studies have been reported about the sequential genetic changes during hepatocarcinogenesis. We observed firstly molecular karyotypes of 10 matched HCC using Affymetrix single-nucleotide polymorphism (SNP) 6.0 arrays, and found chromosomal fragments with high incidence (more than 70%) of loss of heterozygosity (LOH). Then, we selected 28 microsatellite markers at some gene spanning these chromosomal fragments, and examined the frequency of LOH of 128 matched HCC and 43 matched precancerous lesions-dysplastic nodules (DN) by a PCR-based analysis. Finally, we investigated the expression of proteins encoded by these genes in HCC, DN and the surrounding hepatic tissues. The result of Affymetrix SNP6.0 arrays demonstrated that more than 70% (7/10) cases had chromosomal fragment deletion on 4q13.3-35.1, 8p23.2-21.2, 16q11.2-24.3, and 17p13.3-12. Among 28 microsatellite markers selected, LOH frequencies at D8S262 for DN and HCC were found to be the highest, 51.2% and 72.7%, respectively. Immunohistochemically, the positive rate of its adjacent gene CSMD1 in HCC, DN, and the surrounding hepatic tissues were 27.3% (35/128), 75% (33/44), and 82% (105/128), respectively. LOH at D8S262 may be associated with an early genetic event of hepatocarcinogenesis, and a predictor for the monitor and prevention of HCC. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1557074981159099 .

  11. Functional insulin receptors are overexpressed in thyroid tumors: is this an early event in thyroid tumorigenesis?

    Science.gov (United States)

    Frittitta, L; Sciacca, L; Catalfamo, R; Ippolito, A; Gangemi, P; Pezzino, V; Filetti, S; Vigneri, R

    1999-01-15

    Insulin receptor (IR), a member of the receptor tyrosine kinase family, is expressed in normal thyroid cells and affects thyroid cell proliferation and differentiation. The authors measured IR content in benign and malignant thyroid tumors by three independent methods: a specific radioimmunoassay, 125I-insulin binding studies, and immunohistochemistry. The results obtained were compared with the IR content in paired, adjacent, normal thyroid tissue. To assess IR function in thyroid carcinoma cells, glucose uptake responsiveness to insulin was also studied in a human transformed thyroid cell line (B-CPAP) and in follicular carcinoma cells in primary culture. In 9 toxic adenomas, the average IR content was similar to that observed in the 9 paired normal thyroid tissue specimens from the same patients (2.2+/-0.3 vs. 2.1+/-0.3). In 13 benign nonfunctioning, or "cold," adenomas, the average IR content was significantly higher (P thyroid tissue (4.0+/-0.4 vs. 1.6+/-0.2 and 5.6+/-1.0 vs. 1.8+/-0.2, respectively). The finding of a higher IR content in benign "cold" adenomas and in thyroid carcinomas was confirmed by both binding and immunostaining studies. The current studies indicate that 1) IR content is elevated in most follicular and papillary differentiated thyroid carcinomas, and 2) IR content is also elevated in most benign follicular adenomas ("cold" nodules) but not in highly differentiated, hyperfunctioning follicular adenomas ("hot" nodules), which very rarely become malignant. This observation suggests that increased IR expression is not restricted to the thyroid malignant phenotype but is already present in the premalignant "cold" adenomas. It may contribute, therefore, to thyroid tumorigenesis and/or represent an early event that gives a selective growth advantage to transformed thyroid cells.

  12. Shorter exposures to harder X-rays trigger early apoptotic events in Xenopus laevis embryos.

    Directory of Open Access Journals (Sweden)

    JiaJia Dong

    Full Text Available BACKGROUND: A long-standing conventional view of radiation-induced apoptosis is that increased exposure results in augmented apoptosis in a biological system, with a threshold below which radiation doses do not cause any significant increase in cell death. The consequences of this belief impact the extent to which malignant diseases and non-malignant conditions are therapeutically treated and how radiation is used in combination with other therapies. Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems. METHODOLOGY/PRINCIPAL FINDINGS: We explored how the energy of individual X-ray photons and exposure time, both factors that determine the total dose, influence the occurrence of cell death in early Xenopus embryo. Three different experimental scenarios were analyzed and morphological and biochemical hallmarks of apoptosis were evaluated. Initially, we examined cell death events in embryos exposed to increasing incident energies when the exposure time was preset. Then, we evaluated the embryo's response when the exposure time was augmented while the energy value remained constant. Lastly, we studied the incidence of apoptosis in embryos exposed to an equal total dose of radiation that resulted from increasing the incoming energy while lowering the exposure time. CONCLUSIONS/SIGNIFICANCE: Overall, our data establish that the energy of the incident photon is a major contributor to the outcome of the biological system. In particular, for embryos exposed under identical conditions and delivered the same absorbed dose of radiation, the response is significantly increased when shorter bursts of more energetic photons are used. These results suggest that biological organisms display properties similar to the photoelectric effect in physical systems and provide new insights into how radiation-mediated apoptosis should be understood and

  13. Early Results of Three-Year Monitoring of Red Wood Ants’ Behavioral Changes and Their Possible Correlation with Earthquake Events

    Directory of Open Access Journals (Sweden)

    Gabriele Berberich

    2013-02-01

    Full Text Available Short-term earthquake predictions with an advance warning of several hours or days are currently not possible due to both incomplete understanding of the complex tectonic processes and inadequate observations. Abnormal animal behaviors before earthquakes have been reported previously, but create problems in monitoring and reliability. The situation is different with red wood ants (RWA; Formica rufa-group (Hymenoptera: Formicidae. They have stationary mounds on tectonically active, gas-bearing fault systems. These faults may be potential earthquake areas. For three years (2009–2012, two red wood ant mounds (Formica rufa-group, located at the seismically active Neuwied Basin (Eifel, Germany, have been monitored 24/7 by high-resolution cameras with both a color and an infrared sensor. Early results show that ants have a well-identifiable standard daily routine. Correlation with local seismic events suggests changes in the ants’ behavior hours before the earthquake: the nocturnal rest phase and daily activity are suppressed, and standard daily routine does not resume until the next day. At present, an automated image evaluation routine is being applied to the more than 45,000 hours of video streams. Based on this automated approach, a statistical analysis of the ants’ behavior will be carried out. In addition, other parameters (climate, geotectonic and biological, which may influence behavior, will be included in the analysis.

  14. Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia

    Science.gov (United States)

    Lequerré, Thierry; Bansard, Carine; Vittecoq, Olivier; Derambure, Céline; Hiron, Martine; Daveau, Maryvonne; Tron, François; Ayral, Xavier; Biga, Norman; Auquit-Auckbur, Isabelle; Chiocchia, Gilles; Le Loët, Xavier; Salier, Jean-Philippe

    2009-01-01

    Introduction Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia. Methods Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation. Results Three combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA. Conclusions Early and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment. PMID:19563633

  15. Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples

    DEFF Research Database (Denmark)

    den Hoed, M; Luan, J; Langenberg, C

    2013-01-01

    BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes. OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population-based sam......BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes. OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population......, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population....

  16. Early determination of uterine cervical squamous cell carcinoma radioresponse identifies high- and low-response tumors

    International Nuclear Information System (INIS)

    Ohara, Kiyoshi; Oki, Akinori; Tanaka, Yumiko Oishi; Onishi, Kayoko; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Satoh, Toyomi; Tsunoda, Hajime; Hata, Masaharu; Sugahara, Shinji; Tokuuye, Koichi; Akine, Yasuyuki; Yoshikawa, Hiroyuki

    2006-01-01

    Purpose: To investigate whether early-assessed radioresponse of tumors corresponds with late-assessed radioresponse, which is associated with local disease control in radiotherapy (RT) for cervical cancer. Methods and Materials: This prospective study included 12 patients with cervical squamous cell carcinoma treated by RT with or without concurrent cisplatin. Tumor volume was estimated by scheduled magnetic resonance imaging before (preRT), 3 to 4 weeks after (early assessment), and 6 to 7 weeks after (late assessment) RT initiation. Radioresponse was assessed with tumor shrinkage curves based on these volumes. Radioresponse for each tumor was calculated as the slope (day -1 ) of the shrinkage curve by fitting to an exponential equation. Results: Early-assessed radioresponse ranged from 0.001 to 0.106 day -1 (median, 0.021 day -1 ) and late-assessed radioresponse from 0.009 to 0.091 day -1 (median, 0.021 day -1 ), with no significant difference between them (p = 0.1191). The early-assessed radioresponse correlated with the late-assessed radioresponse (R 2 = 0.714, p = 0.0005). Conclusions: Correspondence between early- and late-assessed radioresponse in a series of tumors showing a wide range of radioresponse was not particularly close overall. However, early assessment of radioresponsiveness did seem to be useful for characterizing those tumors with high or low radioresponsiveness

  17. Early Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction event: evidence from a new genus and species, Grimmenodon aureum.

    Science.gov (United States)

    Stumpf, Sebastian; Ansorge, Jörg; Pfaff, Cathrin; Kriwet, Jürgen

    2017-07-04

    A new genus and species of pycnodontiform fishes, Grimmenodon aureum , from marginal marine, marine-brackish lower Toarcian ( Harpoceras exaratum ammonite subzone) clay deposits of Grimmen in northeastern Germany is described. The single specimen represents a diagnostic left prearticular dentition characterized by unique tooth arrangement and ornamentation patterns. Grimmenodon aureum , gen. et sp. nov., is the second unambiguously identified pycnodontiform species from the Early Jurassic, in addition to Eomesodon liassicus from the early Lower Jurassic of western Europe. We also report an indeterminate pycnodontiform tooth crown from the upper Pliensbachian ( Pleuroceras apyrenum ammonite subzone) of the same site. The material expands the Early Jurassic range of pycnodontiforms significantly northwards and confirms their presence before and immediately following the onset of the Toarcian Oceanic Anoxic Event (T-OAE) in the marginal marine ecosystems south of the Fennoscandian Shield. Moreover, the new records indicate that the Early Jurassic diversity of pycnodontiform fishes was greater than previously assumed and probably equaled that of the Late Triassic. Therefore, it is hypothesized that the Triassic-Jurassic mass extinction event did not affect pycnodontiform fishes significantly. Micro-computed tomography was used to study the internal anatomy of the prearticular of Grimmenodon aureum , gen. et sp. nov. Our results show that no replacement teeth were formed within the tooth-bearing bone but rather were added posteriorly to functional teeth. http://zoobank.org/urn:lsid:zoobank.org:pub:A56BDE9C-40C4-4CFA-9C2E-F5FA35A66F2 Citation for this article: Stumpf, S., J. Ansorge, C. Pfaff, and J. Kriwet. 2017. Early Jurassic diversification of pycnodontiform fishes (Actinopterygii, Neopterygii) after the end-Triassic extinction event: Evidence from a new genus and species, Grimmenodon aureum . Journal of Vertebrate Paleontology. DOI: 10.1080/02724634.2017.1344679.

  18. Spot sputum samples are at least as good as early morning samples for identifying Mycobacterium tuberculosis.

    Science.gov (United States)

    Murphy, Michael E; Phillips, Patrick P J; Mendel, Carl M; Bongard, Emily; Bateson, Anna L C; Hunt, Robert; Murthy, Saraswathi; Singh, Kasha P; Brown, Michael; Crook, Angela M; Nunn, Andrew J; Meredith, Sarah K; Lipman, Marc; McHugh, Timothy D; Gillespie, Stephen H

    2017-10-27

    The use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup. However, there is little evidence to support the superiority of EMS over spot sputum samples. In this new analysis of the REMoxTB study, we compare the diagnostic accuracy of EMS with spot samples for identifying Mycobacterium tuberculosis pre- and post-treatment. Patients who were smear positive at screening were enrolled into the study. Paired sputum samples (one EMS and one spot) were collected at each trial visit pre- and post-treatment. Microscopy and culture on solid LJ and liquid MGIT media were performed on all samples; those missing corresponding paired results were excluded from the analyses. Data from 1115 pre- and 2995 post-treatment paired samples from 1931 patients enrolled in the REMoxTB study were analysed. Patients were recruited from South Africa (47%), East Africa (21%), India (20%), Asia (11%), and North America (1%); 70% were male, median age 31 years (IQR 24-41), 139 (7%) co-infected with HIV with a median CD4 cell count of 399 cells/μL (IQR 318-535). Pre-treatment spot samples had a higher yield of positive Ziehl-Neelsen smears (98% vs. 97%, P = 0.02) and LJ cultures (87% vs. 82%, P = 0.006) than EMS, but there was no difference for positivity by MGIT (93% vs. 95%, P = 0.18). Contaminated and false-positive MGIT were found more often with EMS rather than spot samples. Surprisingly, pre-treatment EMS had a higher smear grading and shorter time-to-positivity, by 1 day, than spot samples in MGIT culture (4.5 vs. 5.5 days, P spot samples in those with unfavourable outcomes, there were no differences in smear or culture results, and positive results were not detected earlier in Kaplan-Meier analyses in either EMS or spot samples. Our data do not support the hypothesis that EMS

  19. Early events in speciation: Cryptic species of Drosophila aldrichi.

    Science.gov (United States)

    Castro Vargas, Cynthia; Richmond, Maxi Polihronakis; Ramirez Loustalot Laclette, Mariana; Markow, Therese Ann

    2017-06-01

    Understanding the earliest events in speciation remains a major challenge in evolutionary biology. Thus identifying species whose populations are beginning to diverge can provide useful systems to study the process of speciation. Drosophila aldrichi , a cactophilic fruit fly species with a broad distribution in North America, has long been assumed to be a single species owing to its morphological uniformity. While previous reports either of genetic divergence or reproductive isolation among different D. aldrichi strains have hinted at the existence of cryptic species, the evolutionary relationships of this species across its range have not been thoroughly investigated. Here we show that D. aldrichi actually is paraphyletic with respect to its closest relative, Drosophila wheeleri , and that divergent D. aldrichi lineages show complete hybrid male sterility when crossed. Our data support the interpretation that there are at least two species of D. aldrichi, making these flies particularly attractive for studies of speciation in an ecological and geographical context.

  20. Probing Early Misfolding Events in Prion Protein Mutants by NMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Gregor Ilc

    2013-08-01

    Full Text Available The post-translational conversion of the ubiquitously expressed cellular form of the prion protein, PrPC, into its misfolded and pathogenic isoform, known as prion or PrPSc, plays a key role in prion diseases. These maladies are denoted transmissible spongiform encephalopathies (TSEs and affect both humans and animals. A prerequisite for understanding TSEs is unraveling the molecular mechanism leading to the conversion process whereby most α-helical motifs are replaced by β-sheet secondary structures. Importantly, most point mutations linked to inherited prion diseases are clustered in the C-terminal domain region of PrPC and cause spontaneous conversion to PrPSc. Structural studies with PrP variants promise new clues regarding the proposed conversion mechanism and may help identify “hot spots” in PrPC involved in the pathogenic conversion. These investigations may also shed light on the early structural rearrangements occurring in some PrPC epitopes thought to be involved in modulating prion susceptibility. Here we present a detailed overview of our solution-state NMR studies on human prion protein carrying different pathological point mutations and the implications that such findings may have for the future of prion research.

  1. Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats

    Energy Technology Data Exchange (ETDEWEB)

    Yamazaki, Makoto; Miyake, Manami; Sato, Hiroko; Masutomi, Naoya; Tsutsui, Naohisa [Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba 292-0818 (Japan); Adam, Klaus-Peter; Alexander, Danny C.; Lawton, Kay A.; Milburn, Michael V.; Ryals, John A.; Wulff, Jacob E. [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States); Guo, Lining, E-mail: lguo@metabolon.com [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States)

    2013-04-01

    Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. - Highlights: ► We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ► We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ► The toxins decreased the

  2. Genome characterization of Turkey Rotavirus G strains from the United States identifies potential recombination events with human Rotavirus B strains.

    Science.gov (United States)

    Chen, Fangzhou; Knutson, Todd P; Porter, Robert E; Ciarlet, Max; Mor, Sunil Kumar; Marthaler, Douglas G

    2017-12-01

    Rotavirus G (RVG) strains have been detected in a variety of avian species, but RVG genomes have been published from only a single pigeon and two chicken strains. Two turkey RVG strains were identified and characterized, one in a hatchery with no reported health issues and the other in a hatchery with high embryo/poult mortality. The two turkey RVG strains shared only an 85.3 % nucleotide sequence identity in the VP7 gene while the other genes possessed high nucleotide identity among them (96.3-99.9 %). Low nucleotide percentage identities (31.6-87.3 %) occurred among the pigeon and chicken RVG strains. Interestingly, potential recombination events were detected between our RVG strains and a human RVB strain, in the VP6 and NSP3 segments. The epidemiology of RVG in avian flocks and the pathogenicity of the two different RVG strains should be further investigated to understand the ecology and impact of RVG in commercial poultry flocks.

  3. Early interglacial carbonate-dilution events in the South China Sea: Implications for strengthened typhoon activities over subtropical East Asia

    Science.gov (United States)

    Huang, Enqing; Tian, Jun; Qiao, Peijun; Wan, Sui; Xie, Xin; Yang, Wenguang

    2015-10-01

    A compilation of many late Quaternary marine sediment records from the northern South China Sea (SCS) continental slope confirms 15-50% reductions in sedimentary calcium carbonate concentrations between 11.0 and 8.5 ka BP in the early Holocene. This low carbonate% event occurred at a time when the regional sea level rose from -50 m to -10 m, which drowned large areas of continental shelves especially those near and within the Taiwan Strait. This event is associated with a significant increase in bulk sedimentation rates on the upper continental slope and the relative abundance of fine-grained detritus. Sediment provenance analyses suggest a dominant terrigenous input from Taiwan and a minor contribution from Luzon during the low carbonate% event, similar to the background terrigenous deposition in other periods of the Holocene. Two comparable low carbonate% events, respectively from the beginning of marine isotope stages 5.5 and 7.3, have also been recognized, pointing to similar causal factors. While carbonate dissolution and carbonate accumulation rate should not have been responsible, increased terrigenous input and dilution is considered as the main cause for the recurrent low carbonate% events in early interglacials. We further hypothesize that, during early interglacials, fluvial sediment discharge from Taiwan and Luzon intensified due to stronger typhoon activities, and massive fine-grained sediments from these two end members may have been transported to the northern SCS continental slope via surface and deep ocean currents. The conjecture of strengthened typhoon activities over East Asia during the early Holocene is supported by high ocean heat contents in the West Pacific Warm Pool area with the prevailing La Niña-like conditions.

  4. Predictive values of diagnostic codes for identifying serious hypocalcemia and dermatologic adverse events among women with postmenopausal osteoporosis in a commercial health plan database.

    Science.gov (United States)

    Wang, Florence T; Xue, Fei; Ding, Yan; Ng, Eva; Critchlow, Cathy W; Dore, David D

    2018-04-10

    Post-marketing safety studies of medicines often rely on administrative claims databases to identify adverse outcomes following drug exposure. Valid ascertainment of outcomes is essential for accurate results. We aim to quantify the validity of diagnostic codes for serious hypocalcemia and dermatologic adverse events from insurance claims data among women with postmenopausal osteoporosis (PMO). We identified potential cases of serious hypocalcemia and dermatologic events through ICD-9 diagnosis codes among women with PMO within claims from a large US healthcare insurer (June 2005-May 2010). A physician adjudicated potential hypocalcemic and dermatologic events identified from the primary position on emergency department (ED) or inpatient claims through medical record review. Positive predictive values (PPVs) and 95% confidence intervals (CIs) quantified the fraction of potential cases that were confirmed. Among 165,729 patients with PMO, medical charts were obtained for 40 of 55 (73%) potential hypocalcemia cases; 16 were confirmed (PPV 40%, 95% CI 25-57%). The PPV was higher for ED than inpatient claims (82 vs. 24%). Among 265 potential dermatologic events (primarily urticaria or rash), we obtained 184 (69%) charts and confirmed 128 (PPV 70%, 95% CI 62-76%). The PPV was higher for ED than inpatient claims (77 vs. 39%). Diagnostic codes for hypocalcemia and dermatologic events may be sufficient to identify events giving rise to emergency care, but are less accurate for identifying events within hospitalizations.

  5. Early phase drug discovery: cheminformatics and computational techniques in identifying lead series.

    Science.gov (United States)

    Duffy, Bryan C; Zhu, Lei; Decornez, Hélène; Kitchen, Douglas B

    2012-09-15

    Early drug discovery processes rely on hit finding procedures followed by extensive experimental confirmation in order to select high priority hit series which then undergo further scrutiny in hit-to-lead studies. The experimental cost and the risk associated with poor selection of lead series can be greatly reduced by the use of many different computational and cheminformatic techniques to sort and prioritize compounds. We describe the steps in typical hit identification and hit-to-lead programs and then describe how cheminformatic analysis assists this process. In particular, scaffold analysis, clustering and property calculations assist in the design of high-throughput screening libraries, the early analysis of hits and then organizing compounds into series for their progression from hits to leads. Additionally, these computational tools can be used in virtual screening to design hit-finding libraries and as procedures to help with early SAR exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Identifying the factors that affect the job satisfaction of early career Notre Dame graduate physiotherapists.

    Science.gov (United States)

    Bacopanos, Eleni; Edgar, Susan

    2016-11-01

    Objective Previous studies have highlighted the short career intentions and high attrition rates of physiotherapists from the profession. The aim of the present study was to examine the job satisfaction and attrition rates of early career physiotherapists graduating from one Western Australian university. Methods A self-administered online survey was conducted of 157 Notre Dame physiotherapy graduates (2006-2012), incorporating a job satisfaction rating scale. Results Results showed that lowered job satisfaction was related to working in the cardiorespiratory area of physiotherapy and working in multiple jobs since graduation. The majority of graduates did not predict a long-term career in physiotherapy, highlighting a lack of career progression and limited scope of practice as influential factors. Conclusions Job satisfaction in early career physiotherapists varies across different clinical areas of practice related to several factors, including challenge and flexibility. New roles in the profession, including extended scope roles, may impact on the future job satisfaction of physiotherapists. Further studies are needed to explore the effect of these roles on workforce trends, including attrition rates. What is known about the topic? Physiotherapists predict careers of 10 years or less on entry into the profession. No previous studies have explored the individual factors influencing job satisfaction in early career physiotherapists across different clinical settings. What does this paper add? This study highlights specific factors influencing the job satisfaction of early career physiotherapists, including clinical area of practice. Physiotherapists working in the cardiorespiratory area were less satisfied, as were physiotherapists undertaking multiple positions since graduation. What are the implications for practitioners? This study informs employers and workforce planners on the factors affecting job satisfaction in early career physiotherapists. In addition

  7. Breast Cancer Awareness and Prevention Behavior Among Women of Delhi, India: Identifying Barriers to Early Detection

    OpenAIRE

    Dey, Subhojit; Sharma, Surabhi; Mishra, Arti; Krishnan, Suneeta; Govil, Jyotsna; Dhillon, Preet K.

    2016-01-01

    Background Globally, breast cancer (BC) has become the leading cause of mortality in women. Awareness and early detection can curb the growing burden of BC and are the first step in the battle against BC. The aim of this qualitative study was to explore the awareness and perceived barriers concerning the early detection of BC. Methods A total of 20 focus group discussions (FGDs) were conducted during May 2013–March 2014. Pre-existing themes were used to conduct FGDs; each FGD group consisted ...

  8. Organic geochemistry of the early Toarcian oceanic anoxic event in Hawsker Bottoms, Yorkshire, England

    Science.gov (United States)

    French, K. L.; Sepúlveda, J.; Trabucho-Alexandre, J.; Gröcke, D. R.; Summons, R. E.

    2014-03-01

    A comprehensive organic geochemical investigation of the Hawsker Bottoms outcrop section in Yorkshire, England has provided new insights about environmental conditions leading into and during the Toarcian oceanic anoxic event (T-OAE; ∼183 Ma). Rock-Eval and molecular analyses demonstrate that the section is uniformly within the early oil window. Hydrogen index (HI), organic petrography, polycyclic aromatic hydrocarbon (PAH) distributions, and tricyclic terpane ratios mark a shift to a lower relative abundance of terrigenous organic matter supplied to the sampling locality during the onset of the T-OAE and across a lithological transition. Unlike other ancient intervals of anoxia and extinction, biomarker indices of planktonic community structure do not display major changes or anomalous values. Depositional environment and redox indicators support a shift towards more reducing conditions in the sediment porewaters and the development of a seasonally stratified water column during the T-OAE. In addition to carotenoid biomarkers for green sulfur bacteria (GSB), we report the first occurrence of okenane, a marker of purple sulfur bacteria (PSB), in marine samples younger than ∼1.64 Ga. Based on modern observations, a planktonic source of okenane's precursor, okenone, would require extremely shallow photic zone euxinia (PZE) and a highly restricted depositional environment. However, due to coastal vertical mixing, the lack of planktonic okenone production in modern marine sulfidic environments, and building evidence of okenone production in mat-dwelling Chromatiaceae, we propose a sedimentary source of okenone as an alternative. Lastly, we report the first parallel compound-specific δC13 record in marine- and terrestrial-derived biomarkers across the T-OAE. The δC13 records of short-chain n-alkanes, acyclic isoprenoids, and long-chain n-alkanes all encode negative carbon isotope excursions (CIEs), and together, they support an injection of isotopically light

  9. Circulating mutational portrait of cancer: manifestation of aggressive clonal events in both early and late stages

    Directory of Open Access Journals (Sweden)

    Meng Yang

    2017-05-01

    Full Text Available Abstract Background Solid tumors residing in tissues and organs leave footprints in circulation through circulating tumor cells (CTCs and circulating tumor DNAs (ctDNA. Characterization of the ctDNA portraits and comparison with tumor DNA mutational portraits may reveal clinically actionable information on solid tumors that is traditionally achieved through more invasive approaches. Methods We isolated ctDNAs from plasma of patients of 103 lung cancer and 74 other solid tumors of different tissue origins. Deep sequencing using the Guardant360 test was performed to identify mutations in 73 clinically actionable genes, and the results were associated with clinical characteristics of the patient. The mutation profiles of 37 lung cancer cases with paired ctDNA and tumor genomic DNA sequencing were used to evaluate clonal representation of tumor in circulation. Five lung cancer cases with longitudinal ctDNA sampling were monitored for cancer progression or response to treatments. Results Mutations in TP53, EGFR, and KRAS genes are most prevalent in our cohort. Mutation rates of ctDNA are similar in early (I and II and late stage (III and IV cancers. Mutation in DNA repair genes BRCA1, BRCA2, and ATM are found in 18.1% (32/177 of cases. Patients with higher mutation rates had significantly higher mortality rates. Lung cancer of never smokers exhibited significantly higher ctDNA mutation rates as well as higher EGFR and ERBB2 mutations than ever smokers. Comparative analysis of ctDNA and tumor DNA mutation data from the same patients showed that key driver mutations could be detected in plasma even when they were present at a minor clonal population in the tumor. Mutations of key genes found in the tumor tissue could remain in circulation even after frontline radiotherapy and chemotherapy suggesting these mutations represented resistance mechanisms. Longitudinal sampling of five lung cancer cases showed distinct changes in ctDNA mutation portraits that

  10. Direct and indirect costs for adverse drug events identified in medical records across care levels, and their distribution among payers.

    Science.gov (United States)

    Natanaelsson, Jennie; Hakkarainen, Katja M; Hägg, Staffan; Andersson Sundell, Karolina; Petzold, Max; Rehnberg, Clas; Jönsson, Anna K; Gyllensten, Hanna

    2017-11-01

    Adverse drug events (ADEs) cause considerable costs in hospitals. However, little is known about costs caused by ADEs outside hospitals, effects on productivity, and how the costs are distributed among payers. To describe the direct and indirect costs caused by ADEs, and their distribution among payers. Furthermore, to describe the distribution of patient out-of-pocket costs and lost productivity caused by ADEs according to socio-economic characteristics. In a random sample of 5025 adults in a Swedish county, prevalence-based costs for ADEs were calculated. Two different methods were used: 1) based on resource use judged to be caused by ADEs, and 2) as costs attributable to ADEs by comparing costs among individuals with ADEs to costs among matched controls. Payers of costs caused by ADEs were identified in medical records among those with ADEs (n = 596), and costs caused to individual patients were described by socio-economic characteristics. Costs for resource use caused by ADEs were €505 per patient with ADEs (95% confidence interval €345-665), of which 38% were indirect costs. Compared to matched controls, the costs attributable to ADEs were €1631, of which €410 were indirect costs. The local health authorities paid 58% of the costs caused by ADEs. Women had higher productivity loss than men (€426 vs. €109, p = 0.018). Out-of-pocket costs displaced a larger proportion of the disposable income among low-income earners than higher income earners (0.7% vs. 0.2%-0.3%). We used two methods to identify costs for ADEs, both identifying indirect costs as an important component of the overall costs for ADEs. Although the largest payers of costs caused by ADEs were the local health authorities responsible for direct costs, employers and patients costs for lost productivity contributed substantially. Our results indicate inequalities in costs caused by ADEs, by sex and income. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Early thromboembolic events ≤1week after fast-track total hip and knee arthroplasty

    DEFF Research Database (Denmark)

    Jørgensen, Christoffer C; Kehlet, Henrik

    2016-01-01

    characteristics, complete follow-up through the Danish National Patient Register, and detailed evaluation on disposing factors and consequences of "early" TEEs through review of medical records. RESULTS: In 13,775 procedures with a median LOS of 2days, 43 (0.32%; 95% CI: 0.23-0.42) "early" and 90 (0.65%; 95% CI...... reduced by improving perioperative treatment of anemia. Further research is needed regarding interventions for prevention of "early" TEE in disposed patients....

  12. Gender Differences in Early Mother-Child Interactions: Talking about an Imminent Event.

    Science.gov (United States)

    Eisenmann, Barbara

    1997-01-01

    Examines maternal modes of organizing an imminent emotional event, a brief separation from the child. Finds that the mothers displayed two ways of structuring the future event, and these different modes were related statistically to the gender of the child. Investigates how the mother directs the child's mental processes by using augments of…

  13. Early events triggering delayed vasoconstrictor receptor upregulation and cerebral ischemia after subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Povlsen, Gro Klitgaard; Johansson, Sara Ellinor; Larsen, Carl Christian

    2013-01-01

    shown to be mediated by intracellular signalling via the mitogen activated protein kinase kinase (MEK1/2)--extracellular regulated kinase 1/2 (ERK1/2) pathway. However, it is not known what event(s) that trigger MEK-ERK1/2 activation and vasoconstrictor receptor upregulation after SAH.We hypothesise...

  14. How Much and What Kind? Identifying an Adequate Technology Infrastructure for Early Childhood Education. Policy Brief

    Science.gov (United States)

    Daugherty, Lindsay; Dossani, Rafiq; Johnson, Erin-Elizabeth; Wright, Cameron

    2014-01-01

    To realize the potential benefits of technology use in early childhood education (ECE), and to ensure that technology can help to address the digital divide, providers, families of young children, and young children themselves must have access to an adequate technology infrastructure. The goals for technology use in ECE that a technology…

  15. Identifying Early Links between Temperament, Short-Term and Working Memory in Preschoolers

    Science.gov (United States)

    Visu-Petra, Laura; Cheie, Lavinia; Câmpan, Maria; Scutelnicu, Ioana; Benga, Oana

    2018-01-01

    The present study aimed to investigate early interrelationships between temperament, short-term memory (STM) and working memory (WM), while also relating them to incipient anxious traits in a sample of 4-7-year-olds. Preschoolers were evaluated using verbal and visuospatial STM and WM tasks, while parental reports were used to assess children's…

  16. SNIPE: A New Method to Identify Imaging Biomarker for Early Detection of Alzheimer’s Disease

    DEFF Research Database (Denmark)

    Coupé, Pierrick; Eskildsen, Simon Fristed; Manjón, José V.

    , from a clinical point of view the prediction of AD is the key question since it is in that moment when treatment is possible. The potential use of structural MRI as imaging biomarker for Alzheimer’s disease (AD) for early detection has become generally accepted, especially the use of atrophy...

  17. Getting on the Same Page: Identifying Goals for Technology Use in Early Childhood Education. Policy Brief

    Science.gov (United States)

    Daugherty, Lindsay; Dossani, Rafiq; Johnson, Erin-Elizabeth; Wright, Cameron

    2014-01-01

    Technology use among young children is increasingly a fact of life, and establishing a clear set of goals that are broadly accepted by stakeholders is critical to planning for the successful integration of technology into early childhood education (ECE). However, debates about the role of technology in ECE settings are ongoing, with some…

  18. Identifying Local Benefits of Early Childhood Development Programs Using Regional Modeling

    Science.gov (United States)

    Temple, Judy A.; Rolnick, Arthur J.

    2012-01-01

    This article presents a review of "Investing in Kids: Early Childhood Programs and Local Economic Development" by Timothy J. Bartik. Timothy Bartik's timely book contributes to an important conversation about the role of government in promoting investments in children in the years before traditional public schooling typically begins. Until…

  19. Demographic clusters identified within the northern Gulf of Mexico common bottlenose dolphin (Tursiops truncates unusual mortality event: January 2010-June 2013.

    Directory of Open Access Journals (Sweden)

    Stephanie Venn-Watson

    Full Text Available A multi-year unusual mortality event (UME involving primarily common bottlenose dolphins (Tursiops truncates was declared in the northern Gulf of Mexico (GoM with an initial start date of February 2010 and remains ongoing as of August 2014. To examine potential changing characteristics of the UME over time, we compared the number and demographics of dolphin strandings from January 2010 through June 2013 across the entire GoM as well as against baseline (1990-2009 GoM stranding patterns. Years 2010 and 2011 had the highest annual number of stranded dolphins since Louisiana's record began, and 2011 was one of the years with the highest strandings for both Mississippi and Alabama. Statewide, annual numbers of stranded dolphins were not elevated for GoM coasts of Florida or Texas during the UME period. Demographic, spatial, and temporal clusters identified within this UME included increased strandings in northern coastal Louisiana and Mississippi (March-May 2010; Barataria Bay, Louisiana (August 2010-December 2011; Mississippi and Alabama (2011, including a high prevalence and number of stranded perinates; and multiple GoM states during early 2013. While the causes of the GoM UME have not been determined, the location and magnitude of dolphin strandings during and the year following the 2010 Deepwater Horizon oil spill, including the Barataria Bay cluster from August 2010 to December 2011, overlap in time and space with locations that received heavy and prolonged oiling. There are, however, multiple known causes of previous GoM dolphin UMEs, including brevetoxicosis and dolphin morbillivirus. Additionally, increased dolphin strandings occurred in northern Louisiana and Mississippi before the Deepwater Horizon oil spill. Identification of spatial, temporal, and demographic clusters within the UME suggest that this mortality event may involve different contributing factors varying by location, time, and bottlenose dolphin populations that will be

  20. Remedial early numeracy education: can children identified as having a language deficiency benefit?

    Science.gov (United States)

    Van Luit, Johannes E H; Toll, Sylke W M

    2015-01-01

    Growing attention has been paid to the possibility of supporting early numeracy in at-risk kindergartners. Furthermore, it is assumed that language proficiency is an important prerequisite in early maths skills. To examine whether remedial early numeracy education in kindergarten, which has been proven to be effective in general, is also beneficial for children with a language deficiency. Based on intensive selection, four different conditions were included: two groups received remedial education, one consisting of children being language proficient (N = 86) and one of children with a language deficiency (N = 26), and two groups followed the regular curriculum, one consisting of children being language proficient (N = 51) and one of children with a language deficiency (N = 24). Remedial education was for 1.5 school years (90 sessions, 30 min per session, twice per week), following the programme 'The Road to Mathematics'. During this period, the children receiving remedial education did not attend the regular maths lessons in the classroom, which were offered for at least 1 h per week. Effects were assessed for early numeracy and mathematical skills (operationalized as basic calculation fluency) in kindergarten and first grade. Three analyses of covariance (ANCOVAs) revealed that, when accounting for achievement at pre-test, children with a language deficiency who received remedial numeracy education performed better on early numeracy skills in kindergarten and first grade than kindergartners with a language deficiency that followed the regular curriculum. Furthermore, they were able to catch up with their language proficient peers in early numeracy. However, children with a language deficiency who received remedial numeracy education did not differ from children who followed the regular curriculum on mathematical skills, suggesting that benefits for numeracy did not generalize to more advanced skills of addition and subtraction. Since, in general, it can be

  1. Stability of Early Identified Aggressive Victim Status in Elementary School and Associations with Later Mental Health Problems and Functional Impairments

    Science.gov (United States)

    Burk, Linnea R.; Armstrong, Jeffrey M.; Park, Jong-Hyo; Zahn-Waxler, Carolyn; Klein, Marjorie H.; Essex, Marilyn J.

    2011-01-01

    Aggressive victims--children who are both perpetrators and victims of peer aggression--experience greater concurrent mental health problems and impairments than children who are only aggressive or only victimized. The stability of early identified aggressive victim status has not been evaluated due to the fact that most studies of aggressor/victim…

  2. Performance of Earthquake Early Warning Systems during the Major Events of the 2016-2017 Central Italy Seismic Sequence.

    Science.gov (United States)

    Festa, G.; Picozzi, M.; Alessandro, C.; Colombelli, S.; Cattaneo, M.; Chiaraluce, L.; Elia, L.; Martino, C.; Marzorati, S.; Supino, M.; Zollo, A.

    2017-12-01

    Earthquake early warning systems (EEWS) are systems nowadays contributing to the seismic risk mitigation actions, both in terms of losses and societal resilience, by issuing an alert promptly after the earthquake origin and before the ground shaking impacts the targets to be protected. EEWS systems can be grouped in two main classes: network based and stand-alone systems. Network based EEWS make use of dense seismic networks surrounding the fault (e.g. Near Fault Observatory; NFO) generating the event. The rapid processing of the P-wave early portion allows for the location and magnitude estimation of the event then used to predict the shaking through ground motion prediction equations. Stand-alone systems instead analyze the early P-wave signal to predict the ground shaking carried by the late S or surface waves, through empirically calibrated scaling relationships, at the recording site itself. We compared the network-based (PRESTo, PRobabilistic and Evolutionary early warning SysTem, www.prestoews.org, Satriano et al., 2011) and the stand-alone (SAVE, on-Site-Alert-leVEl, Caruso et al., 2017) systems, by analyzing their performance during the 2016-2017 Central Italy sequence. We analyzed 9 earthquakes having magnitude 5.0 security actions. PRESTo also evaluated the accuracy of location and magnitude. Both systems well predict the ground shaking nearby the event source, with a success rate around 90% within the potential damage zone. The lead-time is significantly larger for the network based system, increasing to more than 10s at 40 km from the event epicentre. The stand-alone system better performs in the near-source region showing a positive albeit small lead-time (operational in Italy, based on the available acceleration networks, by improving the capability of reducing the lead-time related to data telemetry.

  3. Energy dependence of identified hadron spectra and event-by-event fluctuations in p+p interactions from NA61/SHINE at the CERN SPS

    CERN Document Server

    Rybczynski, Maciej; Aduszkiewicz, A.; Ali, Y.; Anticic, T.; Antoniou, N.; Argyriades, J.; Baatar, B.; Blondel, A.; Blumer, J.; Bogomilov, M.; Bravar, A.; Brooks, W.; Brzychczyk, J.; Bubak, A.; Bunyatov, S.A.; Busygina, O.; Christakoglou, P.; Czopowicz, T.; Davis, N.; Debieux, S.; Dembinski, H.; Diakonos, F.; Di Luise, S.; Dominik, W.; Drozhzhova, T.; Dumarchez, J.; Dynowski, K.; Engel, R.; Ereditato, A.; Esposito, L.S.; Feofilov, G.A.; Fodor, Z.; Ferrero, A.; Fulop, A.; Gazdzicki, M.; Golubeva, M.; Grabez, B.; Grebieszkow, K.; Grzeszczuk, A.; Guber, F.; Hakobyan, H.; Hasegawa, T.; Hierholzer, M.; Idczak, R.; Igolkin, S.; Ivanov, Y.; Ivashkin, A.; Jakovic, D.; Kadija, K.; Kapoyannis, A.; Katrynska, N.; Kaptur, E.; Kielczewska, D.; Kikola, D.; Kirejczyk, M.; Kisiel, J.; Kiss, T.; Kleinfelder, S.; Kobayashi, T.; Kolesnikov, V.I.; Kolev, D.; Kondratiev, V.P.; Korzenev, A.; Kowalski, S.; Krasnoperov, A.; Kuleshov, S.; Kurepin, A.; Larsen, D.; Laszlo, A.; Lyubushkin, V.V.; Mackowiak-Pawlowska, M.; Majka, Z.; Maksiak, B.; Malakhov, A.I.; Maletic, D.; Marchionni, A.; Marcinek, A.; Marin, V.; Marton, K.; Mathes, H.J.; Matulewicz, T.; Matveev, V.; Melkumov, G.L.; Mrowczynski, St.; Murphy, S.; Nakadaira, T.; Nirkko, M.; Nishikawa, K.; Palczewski, T.; Palla, G.; Panagiotou, A.D.; Paul, T.; Pistillo, C.; Redij, A.; Peryt, W.; Petukhov, O.; Planeta, R.; Pluta, J.; Popov, B.A.; Posiadala, M.; Pulawski, S.; Puzovic, J.; Rauch, W.; Ravonel, M.; Renfordt, R.; Robert, A.; Röhrich, D.; Rondio, E.; Roth, M.; Rubbia, A.; Rustamov, A.; Rybczynski, M.; Sadovsky, A.; Sakashita, K.; Savic, M.; Sekiguchi, T.; Seyboth, P.; Shibata, M.; Sipos, M.; Skrzypczak, E.; Slodkowski, M.; Staszel, P.; Stefanek, G.; Stepaniak, J.; Stroebele, H.; Susa, T.; Szuba, M.; Tada, M.; Tereshchenko, V.; Tolyhi, T.; Tsenov, R.; Turko, L.; Ulrich, R.; Unger, M.; Vassiliou, M.; Veberic, D.; Vechernin, V.V.; Vesztergombi, G.; Vinogradov, L.; Wilczek, A.; Wlodarczyk, Z.; Wojtaszek, A.; Wyszynski, O.; Zambelli, L.; Zipper, W.

    2013-01-01

    NA61/SHINE at the CERN SPS is a fixed-target experiment pursuing a rich physics program including measurements for heavy ion, neutrino and cosmic ray physics. The main goal of the ion program is to explore the most interesting $T, mu_{B}$ region of the phase diagram of strongly interacting matter. We plan to study the properties of the onset of deconfinement and to search for the signatures of the critical point. The search is performed by varying collision energy (13A-158A GeV/c) and system size (p+p, Be+Be, Ar+Ca, Xe+La). Thanks to its large acceptance and excellent particle identification capability NA61/SHINE is well suited for performing high-precision particle production measurements as well as for studying event-by-event fluctuations in p+p, p+nucleus and nucleus+nucleus collisions. Preliminary results on p+p interactions at 20, 31, 40, 80 and 158 GeV/c are presented. They include inclusive spectra of pi+, pi-, K- and protons as a function of transverse momentum/mass and rapidity as well as event-by-ev...

  4. Breast Cancer Awareness and Prevention Behavior among Women of Delhi, India: Identifying Barriers to Early Detection

    Directory of Open Access Journals (Sweden)

    Subhojit Dey

    2016-01-01

    Full Text Available Background Globally, breast cancer (BC has become the leading cause of mortality in women. Awareness and early detection can curb the growing burden of BC and are the first step in the battle against BC. The aim of this qualitative study was to explore the awareness and perceived barriers concerning the early detection of BC. Methods A total of 20 focus group discussions (FGDs were conducted during May 2013–March 2014. Pre-existing themes were used to conduct FGDs; each FGD group consisted of an average of ~10 women (aged ≥18–70 years who came to participate in a BC awareness workshop. All FGDs were audio taped and transcribed verbatim. The transcripts were inductively analyzed using ATLAS.ti. Based on emerged codes and categories, thematic analysis was done, and theory was developed using the grounded theory approach. Results Data were analyzed in three major themes: i knowledge and perception about BC; ii barriers faced by women in the early presentation of BC; and iii healthcare-seeking behavior. The findings revealed that shyness, fear, and posteriority were the major behavioral barriers in the early presentation of BC. Erroneously, pain was considered as an initial symptom of BC by most women. Financial constraint was also mentioned as a cause for delay in accessing treatment. Social stigma that breast problems reflect bad character of women also contributed in hiding BC symptoms. Conclusions Lack of BC awareness was prevalent, especially in low socioeconomic class. Women's ambivalence in prioritizing their own health and social and behavioral hurdles should be addressed by BC awareness campaigns appropriately suited for various levels of social class.

  5. Breast Cancer Awareness and Prevention Behavior Among Women of Delhi, India: Identifying Barriers to Early Detection.

    Science.gov (United States)

    Dey, Subhojit; Sharma, Surabhi; Mishra, Arti; Krishnan, Suneeta; Govil, Jyotsna; Dhillon, Preet K

    2016-01-01

    Globally, breast cancer (BC) has become the leading cause of mortality in women. Awareness and early detection can curb the growing burden of BC and are the first step in the battle against BC. The aim of this qualitative study was to explore the awareness and perceived barriers concerning the early detection of BC. A total of 20 focus group discussions (FGDs) were conducted during May 2013-March 2014. Pre-existing themes were used to conduct FGDs; each FGD group consisted of an average of ~10 women (aged ≥18-70 years) who came to participate in a BC awareness workshop. All FGDs were audio taped and transcribed verbatim. The transcripts were inductively analyzed using ATLAS.ti. Based on emerged codes and categories, thematic analysis was done, and theory was developed using the grounded theory approach. Data were analyzed in three major themes: i) knowledge and perception about BC; ii) barriers faced by women in the early presentation of BC; and iii) healthcare-seeking behavior. The findings revealed that shyness, fear, and posteriority were the major behavioral barriers in the early presentation of BC. Erroneously, pain was considered as an initial symptom of BC by most women. Financial constraint was also mentioned as a cause for delay in accessing treatment. Social stigma that breast problems reflect bad character of women also contributed in hiding BC symptoms. Lack of BC awareness was prevalent, especially in low socioeconomic class. Women's ambivalence in prioritizing their own health and social and behavioral hurdles should be addressed by BC awareness campaigns appropriately suited for various levels of social class.

  6. A new commelinid monocot seed fossil from the early Eocene previously identified as Solanaceae.

    Science.gov (United States)

    Särkinen, Tiina; Kottner, Sören; Stuppy, Wolfgang; Ahmed, Farah; Knapp, Sandra

    2018-01-01

    Fossils provide minimum age estimates for extant lineages. Here we critically evaluate Cantisolanum daturoides Reid & Chandler and two other early putative seed fossils of Solanaceae, an economically important plant family in the Asteridae. Three earliest seed fossil taxa of Solanaceae from the London Clay Formation (Cantisolanum daturoides) and the Poole and Branksome Sand Formations (Solanum arnense Chandler and Solanispermum reniforme Chandler) were studied using x-ray microcomputed tomography (MCT) and scanning electron microscopy (SEM). The MCT scans of Cantisolanum daturoides revealed a high level of pyrite preservation at the cellular level. Cantisolanum daturoides can be clearly excluded from Solanaceae and has more affinities to the commelinid monocots based on a straight longitudinal axis, a prominent single layer of relatively thin-walled cells in the testa, and a clearly differentiated micropyle surrounded by radially elongated and inwardly curved testal cells. While the MCT scans show no internal preservation in Solanum arnense and Solanispermum reniforme, SEM images show the presence of several characteristics that allow the placement of these taxa at the stem node of Solanaceae. Cantisolanum daturoides is likely a member of commelinid monocots and not Solanaceae as previously suggested. The earliest fossil record of Solanaceae is revised to consist of fruit fossil with inflated calyces from the early Eocene of Patagonia (52 Ma) and fossilized seeds from the early to mid-Eocene of Europe (48-46 Ma). The new identity for Cantisolanum daturoides does not alter a late Cretaceous minimum age for commelinids. © 2018 Botanical Society of America.

  7. Modeling Temporal Processes in Early Spacecraft Design: Application of Discrete-Event Simulations for Darpa's F6 Program

    Science.gov (United States)

    Dubos, Gregory F.; Cornford, Steven

    2012-01-01

    While the ability to model the state of a space system over time is essential during spacecraft operations, the use of time-based simulations remains rare in preliminary design. The absence of the time dimension in most traditional early design tools can however become a hurdle when designing complex systems whose development and operations can be disrupted by various events, such as delays or failures. As the value delivered by a space system is highly affected by such events, exploring the trade space for designs that yield the maximum value calls for the explicit modeling of time.This paper discusses the use of discrete-event models to simulate spacecraft development schedule as well as operational scenarios and on-orbit resources in the presence of uncertainty. It illustrates how such simulations can be utilized to support trade studies, through the example of a tool developed for DARPA's F6 program to assist the design of "fractionated spacecraft".

  8. Slow Earthquake Hunters: A New Citizen Science Project to Identify and Catalog Slow Slip Events in Geodetic Data

    Science.gov (United States)

    Bartlow, N. M.

    2017-12-01

    Slow Earthquake Hunters is a new citizen science project to detect, catalog, and monitor slow slip events. Slow slip events, also called "slow earthquakes", occur when faults slip too slowly to generate significant seismic radiation. They typically take between a few days and over a year to occur, and are most often found on subduction zone plate interfaces. While not dangerous in and of themselves, recent evidence suggests that monitoring slow slip events is important for earthquake hazards, as slow slip events have been known to trigger damaging "regular" earthquakes. Slow slip events, because they do not radiate seismically, are detected with a variety of methods, most commonly continuous geodetic Global Positioning System (GPS) stations. There is now a wealth of GPS data in some regions that experience slow slip events, but a reliable automated method to detect them in GPS data remains elusive. This project aims to recruit human users to view GPS time series data, with some post-processing to highlight slow slip signals, and flag slow slip events for further analysis by the scientific team. Slow Earthquake Hunters will begin with data from the Cascadia subduction zone, where geodetically detectable slow slip events with a duration of at least a few days recur at regular intervals. The project will then expand to other areas with slow slip events or other transient geodetic signals, including other subduction zones, and areas with strike-slip faults. This project has not yet rolled out to the public, and is in a beta testing phase. This presentation will show results from an initial pilot group of student participants at the University of Missouri, and solicit feedback for the future of Slow Earthquake Hunters.

  9. Brain urea increase is an early Huntington's disease pathogenic event observed in a prodromal transgenic sheep model and HD cases.

    Science.gov (United States)

    Handley, Renee R; Reid, Suzanne J; Brauning, Rudiger; Maclean, Paul; Mears, Emily R; Fourie, Imche; Patassini, Stefano; Cooper, Garth J S; Rudiger, Skye R; McLaughlan, Clive J; Verma, Paul J; Gusella, James F; MacDonald, Marcy E; Waldvogel, Henry J; Bawden, C Simon; Faull, Richard L M; Snell, Russell G

    2017-12-26

    The neurodegenerative disorder Huntington's disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the Huntingtin ( HTT ) gene, translating to an elongated glutamine tract in the huntingtin protein. The pathogenic mechanism resulting in cell dysfunction and death beyond the causative mutation is not well defined. To further delineate the early molecular events in HD, we performed RNA-sequencing (RNA-seq) on striatal tissue from a cohort of 5-y-old OVT73 -line sheep expressing a human CAG-expansion HTT cDNA transgene. Our HD OVT73 sheep are a prodromal model and exhibit minimal pathology and no detectable neuronal loss. We identified significantly increased levels of the urea transporter SLC14A1 in the OVT73 striatum, along with other important osmotic regulators. Further investigation revealed elevated levels of the metabolite urea in the OVT73 striatum and cerebellum, consistent with our recently published observation of increased urea in postmortem human brain from HD cases. Extending that finding, we demonstrate that postmortem human brain urea levels are elevated in a larger cohort of HD cases, including those with low-level neuropathology (Vonsattel grade 0/1). This elevation indicates increased protein catabolism, possibly as an alternate energy source given the generalized metabolic defect in HD. Increased urea and ammonia levels due to dysregulation of the urea cycle are known to cause neurologic impairment. Taken together, our findings indicate that aberrant urea metabolism could be the primary biochemical disruption initiating neuropathogenesis in HD.

  10. Shortened telomeres in serous tubal intraepithelial carcinoma: an early event in ovarian high-grade serous carcinogenesis.

    Science.gov (United States)

    Kuhn, Elisabetta; Meeker, Alan; Wang, Tian-Li; Sehdev, Ann Smith; Kurman, Robert J; Shih, Ie-Ming

    2010-06-01

    Short telomeres are one of the main genetic manifestations in human cancer, as they have been shown to play an important role in inducing chromosomal instability and in contributing to tumor progression. The purpose of this study was to determine if changes in telomere length occur in serous tubal intraepithelial carcinoma (STIC), the putative precursor of "ovarian" high-grade serous carcinoma (HGSC). Twenty-two STICs from 15 patients with concurrent but discrete HGSCs were analyzed for telomere length on formalin-fixed, paraffin-embedded sections by conducting p53 immunofluorescence to assist in identifying STICs and telomere-specific FISH. Telomere length (short, long, or no change) in STICs was compared with HGSCs using normal fallopian tube epithelium and stromal cells as controls. We found that STICs had the shortest telomeres, as 18 (82%) of 22 STICs had short telomeres, whereas only 2 (9%) showed no change and 2 (9%) had long telomeres compared with the normal-looking tubal epithelium. In contrast, among 12 paired HGSCs and STICs, 6 HGSCs showed an increase in telomere length, one showed a decrease in length and 5 did not show any change when compared with their matched STICs, although, such as STICs, the majority of HGSCs had shorter telomeres than the associated normal tubal epithelial cells. These differences in telomere length between normal tubal epithelial cells and STICs, and between STICs and HGSCs were statisticaly significant (PSTICs provides further support to the proposal that STICs are precursors of HGSC and opens new areas of research in elucidating the early events of ovarian high-grade serous carcinogenesis.

  11. Massive Expansion of Marine Archaea During The Early Albian Oceanic Anoxic Event 1B

    Science.gov (United States)

    Kuypers, M. M.; Kuypers, M. M.; Blokker, P.; Erbacher, J.; Kinkel, H.; Pancost, R. D.; Pancost, R. D.; Schouten, S.; Sinninghe Damsté, J. S.

    2001-12-01

    Oceanic anoxic events (OAEs), periods of globally enhanced burial of organic matter (OM) in the marine realm, played an important role in the mid-Cretaceous `greenhouse climate' by effectively reducing atmospheric carbon dioxide concentrations. It is generally believed that these OAEs were caused either by decreased remineralisation or increased production of phytoplanktonic OM. Here we show that enhanced organic carbon (OC) burial during the early Albian OAE1b (~112 My) was caused by a different process. Combined biogeochemical and stable carbon isotopic analyses indicate that black shales from this period contain up to 80% of OC derived from archaea. Archaea-derived isoprenoidal tetraether membrane lipids and free and macromolecularly bound isoprenoid alkanes are abundantly present in these black shales. More specifically the presence of certain ether lipids (cyclic biphytane tetraethers) indicates representatives of the pelagic archaea. To the best of our knowledge this is the earliest fossil evidence for marine planktonic archaea, extending their geological record by more than 60 million years. The diversity of archaeal lipids recovered from the OAE1b black shales suggests that they derive from a multitude of archaeal species. However, the specific 13C enrichment of all such lipids indicates a common `heavy' (13C-rich) carbon source for the archaea and/or a common pathway of carbon-fixation with a reduced 13C fractionation effect compared to the Calvin cycle used by algae, cyanobacteria and higher plants. The large differences (up to 12%) in 13C/12C ratios between the algal biomarkers and the much more abundant archaeal molecular fossils suggest that the latter were not living heterotrophically on photoautotrophic biomass. It seems likely that the archaea present during OAE1b used a chemical energy source (possibly ammonium) for carbon fixation since photoautotrophy within the domain of the Archaea is restricted to only a few species from hypersaline

  12. [Eventful life stories. Members of student fraternities persecuted in Silesia in the early 19th century].

    Science.gov (United States)

    Schmidt, Walter

    2003-01-01

    This study supplemented by three charts and a list of biographies, is, for the first time, encompassing their life-data, their resumés and even their professional careers as well as political commitments shown by more than 200 Silesian students. They, at the University of Breslau, but also at other German universities, had joined the student fraternities in the 20-ies and early 30-ies of the 19th century and, in consequence, were persecuted by state authorities, notably in Prussia and, in the majority of cases, had been sentenced to prison terms of varying degrees. The first demagogic persecution, which happened in the first half of the twenties, culminating in 1822 in the Breslau Arminen Trail and ending up with the staging of the Youth-Association-Trail in 1826, had implicated about 100 Silesians, with a smaller portion of them - apart from teh three Youth-Association Silesians who were sentenced to five years imprisonment in a fortress - getting away with a relatively short "political fortress imprisonment". Later a considerable part of them made a career in the prussian judicial authority, in the institutions of higher learning, as parish priests, physicians and scientists, whereas any political engagement remained a rare exception. Out of the 137 Silesian members of the student fraternities affected by the second wave of persecution, the overwhelming majority of them being Protestants and originating partly from the middle classes, mostly artisans, and from intellectual background, with about a hundred of them being given essentially higher sentences ranging from six years up to capital punishment and, in the event of reprieves, they had to serve their sentences between six months and four-to-six years in a fortress. The majority of them made a medium-level professional career, never exceeding the medium ranks, as judicial officers, lawyers in state or communal services, parish priests, teachers or physicians. However, from this group of persecuted persons, a

  13. Managing the surge in demand for blood following mass casualty events: Early automatic restocking may preserve red cell supply.

    Science.gov (United States)

    Glasgow, Simon; Vasilakis, Christos; Perkins, Zane; Brundage, Susan; Tai, Nigel; Brohi, Karim

    2016-07-01

    Traumatic hemorrhage is a leading preventable cause of mortality following mass casualty events (MCEs). Improving outcomes requires adequate in-hospital provision of high-volume red blood cell (RBC) transfusions. This study investigated strategies for optimizing RBC provision to casualties in MCEs using simulation modeling. A computerized simulation model of a UK major trauma center (TC) transfusion system was developed. The model used input data from past MCEs and civilian and military trauma registries. We simulated the effect of varying on-shelf RBC stock hold and the timing of externally restocking RBC supplies on TC treatment capacity across increasing loads of priority one (P1) and two (P2) casualties from an event. Thirty-five thousand simulations were performed. A casualty load of 20 P1s and P2s under standard TC RBC stock conditions left 35% (95% confidence interval, 32-38%) of P1s and 7% (4-10%) of P2s inadequately treated for hemorrhage. Additionally, exhaustion of type O emergency RBC stocks (a surrogate for reaching surge capacity) occurred in a median of 10 hours (IQR, 5 to >12 hours). Doubling casualty load increased this to 60% (57-63%) and 30% (26-34%), respectively, with capacity reached in 2 hours (1-3 hours). The model identified a minimum requirement of 12 U of on-shelf RBCs per P1/P2 casualty received to prevent surge capacity being reached. Restocking supplies in an MCE versus greater permanent on-shelf RBC stock holds was considered at increasing hourly intervals. T-test analysis showed no difference between stock hold versus supply restocking with regard to overall outcomes for MCEs up to 80 P1s and P2s in size (p < 0.05), provided the restock occurred within 6 hours. Even limited-sized MCEs threaten to overwhelm TC transfusion systems. An early-automated push approach to restocking RBCs initiated by central suppliers can produce equivocal outcomes compared with holding excess stock permanently at TCs. Therapeutic/care management study

  14. Early Holocene hydroclimate of Baffin Bay: Understanding the interplay between abrupt climate change events and ice sheet fluctuations

    Science.gov (United States)

    Corcoran, M. C.; Thomas, E. K.; Castañeda, I. S.; Briner, J. P.

    2017-12-01

    Understanding the causes of ice sheet fluctuations resulting in sea level rise is essential in today's warming climate. In high-latitude ice-sheet-proximal environments such as Baffin Bay, studying both the cause and the rate of ice sheet variability during past abrupt climate change events aids in predictions. Past climate reconstructions are used to understand ice sheet responses to changes in temperature and precipitation. The 9,300 and 8,200 yr BP events are examples of abrupt climate change events in the Baffin Bay region during which there were multiple re-advances of the Greenland and Laurentide ice sheets. High-resolution (decadal-scale) hydroclimate variability near the ice sheet margins during these abrupt climate change events is still unknown. We will generate a decadal-scale record of early Holocene temperature and precipitation using leaf wax hydrogen isotopes, δ2Hwax, from a lake sediment archive on Baffin Island, western Baffin Bay, to better understand abrupt climate change in this region. Shifts in temperature and moisture source result in changes in environmental water δ2H, which in turn is reflected in δ2Hwax, allowing for past hydroclimate to be determined from these compound-specific isotopes. The combination of terrestrial and aquatic δ2Hwax is used to determine soil evaporation and is ultimately used to reconstruct moisture variability. We will compare our results with a previous analysis of δ2Hwax and branched glycerol dialkyl glycerol tetraethers, a temperature and pH proxy, in lake sediment from western Greenland, eastern Baffin Bay, which indicates that cool and dry climate occurred in response to freshwater forcing events in the Labrador Sea. Reconstructing and comparing records on both the western and eastern sides of Baffin Bay during the early Holocene will allow for a spatial understanding of temperature and moisture balance changes during abrupt climate events, aiding in ice sheet modeling and predictions of future sea level

  15. Identifying economic hurdles to early adoption of preventative practices: The case of trunk diseases in California winegrape vineyards

    Directory of Open Access Journals (Sweden)

    Jonathan Kaplan

    2016-12-01

    Full Text Available Despite the high likelihood of infection and substantial yield losses from trunk diseases, many California practitioners wait to adopt field-tested, preventative practices (delayed pruning, double pruning, and application of pruning-wound protectants until after disease symptoms appear in the vineyard at around 10 years old. We evaluate net benefits from adoption of these practices before symptoms appear in young Cabernet Sauvignon vineyards and after they become apparent in mature vineyards to identify economic hurdles to early adoption. We simulate winegrape production in select counties of California and find widespread benefits from early adoption, increasing vineyard profitable lifespans, in some cases, by close to 50%. However, hurdles may result from uncertainty about the cost and returns from adoption, labor constraints, long time lags in benefits from early adoption, growers’ perceived probabilities of infection, and their discount rate. Development of extension resources communicating benefits and potential hurdles to growers likely reduces uncertainty, increasing early adoption. Improvements in efficacy of preventative practices, perhaps by detecting when pathogen spores are released into the vineyard, will increase early adoption. Lastly, practice cost reductions will increase early adoption too, especially when the time it takes for adoption to payoff and infection uncertainty are influential in adoption decisions.

  16. Depletion of Key Meiotic Genes and Transcriptome-Wide Abiotic Stress Reprogramming Mark Early Preparatory Events Ahead of Apomeiotic Transition

    Directory of Open Access Journals (Sweden)

    Jubin N Shah

    2016-10-01

    Full Text Available Molecular dissection of apomixis - an asexual reproductive mode - is anticipated to solve the enigma of loss of meiotic sex, and to help fixing elite agronomic traits. The Brassicaceae genus Boechera comprises of both sexual and apomictic species, permitting comparative analyses of meiotic circumvention (apomeiosis and parthenogenesis. Whereas previous studies reported local transcriptome changes during these events, it remained unclear whether global changes associated with hybridization, polyploidy and environmental adaptation that arose during evolution of Boechera might hint as (epigenetic regulators of early development prior apomictic initiation. To identify these signatures during vegetative stages, we compared seedling RNA-seq transcriptomes of an obligate triploid apomict and a diploid sexual, both isolated from a drought-prone habitat. Uncovered were several genes differentially expressed between sexual and apomictic seedlings, including homologues of meiotic genes ASYNAPTIC 1 (ASY1 and MULTIPOLAR SPINDLE 1 (MPS1 that were down-regulated in apomicts. An intriguing class of apomict-specific deregulated genes included several NAC transcription factors, homologues of which are known to be transcriptionally reprogrammed during abiotic stress in other plants. Deregulation of both meiotic and stress-response genes during seedling stages might possibly be important in preparation for meiotic circumvention, as similar transcriptional alteration was discernible in apomeiotic floral buds too. Furthermore, we noted that the apomict showed better tolerance to osmotic stress in vitro than the sexual, in conjunction with significant upregulation of a subset of NAC genes. In support of the current model that DNA methylation epigenetically regulates stress, ploidy, hybridization and apomixis, we noted that ASY1, MPS1 and NAC019 homologues were deregulated in Boechera seedlings upon DNA demethylation, and ASY1 in particular seems to be repressed by

  17. Is epigenetics an important link between early life events and adult disease?

    Science.gov (United States)

    Epigenetic mechanisms provide one potential explanation for how environmental influences in early life cause long-term changes in chronic disease susceptibility. Whereas epigenetic dysregulation is increasingly implicated in various rare developmental syndromes and cancer, the role of epigenetics in...

  18. Identifying autism early: The Toddlers at Risk of Autism Clinic model.

    Science.gov (United States)

    Davis, Tessa; Clifton, Deirdre; Papadopoulos, Con

    2015-07-01

    This paper describes the Toddlers at Risk of Autism Clinic (TRAC), which utilises the Social Attention and Communication Study (SACS) and/or Autism Detection in Early Childhood (ADEC) play-based assessments to facilitate the early diagnosis of autism. A retrospective audit was conducted of all 42 children assessed over a 3-year period in the TRAC. A semi-structured interview and play-based assessment (SACS and ADEC) were used to aid experienced clinicians in diagnosing autism. Intervention was recommended, and families were routinely followed up. Analysis was conducted on the tools used, the outcomes of assessment, diagnosis and stability of diagnosis on follow-up. During this period, 35 boys and 7 girls were assessed, with a mean age of 25 months. The average waiting time for clinic was 11.6 weeks. Twenty-five patients were diagnosed with autism; 90.5% of toddlers given an initial diagnosis retained that diagnosis at follow-up. Out of the 17 children who were not diagnosed with autism in the TRAC, one child was later diagnosed with autism. Experienced clinicians can use the SACS and/or ADEC to assist with a Diagnostic and Statistical Manual diagnosis of autism in toddlers. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

  19. Using association rule mining to identify risk factors for early childhood caries.

    Science.gov (United States)

    Ivančević, Vladimir; Tušek, Ivan; Tušek, Jasmina; Knežević, Marko; Elheshk, Salaheddin; Luković, Ivan

    2015-11-01

    Early childhood caries (ECC) is a potentially severe disease affecting children all over the world. The available findings are mostly based on a logistic regression model, but data mining, in particular association rule mining, could be used to extract more information from the same data set. ECC data was collected in a cross-sectional analytical study of the 10% sample of preschool children in the South Bačka area (Vojvodina, Serbia). Association rules were extracted from the data by association rule mining. Risk factors were extracted from the highly ranked association rules. Discovered dominant risk factors include male gender, frequent breastfeeding (with other risk factors), high birth order, language, and low body weight at birth. Low health awareness of parents was significantly associated to ECC only in male children. The discovered risk factors are mostly confirmed by the literature, which corroborates the value of the methods. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Identifying Disruptive Technologies in Design: Horizon Scanning in the Early Stages of Design

    DEFF Research Database (Denmark)

    Ernstsen, Sidsel Katrine; Thuesen, Christian; Larsen, Laurids Rolighed

    context to anticipate disruption of construction. By means of a 3-step horizon scan, we identify 133 potentially disruptive technologies from across industries. We find that when preparing for disruption, design may benefit from the future-oriented and technology-focused features of horizon scanning....

  1. The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA.

    Science.gov (United States)

    Rao, Zilong; Zheng, Huaguang; Wang, Fei; Wang, Anxin; Liu, Liping; Dong, Kehui; Zhao, Xingquan; Wang, Yilong; Cao, Yibin

    2017-08-01

    To evaluate the role of HTPR in predicting early recurrence of ischemic events in patients with minor ischemic stroke or high-risk TIA. From January 2014 to September 2014, a single center continuously enrolled patients with minor ischemic stroke or high-risk TIA and gave them antiplatelet therapy consisting of aspirin with clopidogrel. HTPR was assessed by TEG after 7 days of antiplatelet therapy and detected CYP2C19 genotype. The incidence of recurrent ischemic events was assessed 3 months after onset. The incidence of recurrent ischemic events was compared between the HTPR and NTPR groups with the Kaplan-Meier method, and multivariate Cox proportional hazards models were used to determine the risk factors associated with recurrent ischemic events. We enrolled 278 eligible patients with minor ischemic stroke or high-risk TIA. Through TEG testing, patients with HTPR were 22.7%, and carriers were not associated with HTPR to ADP by TEG-ADP(%) (p = 0.193). A total of 265 patients completed 3 months of follow-up, and Kaplan-Meier analysis showed that patients with HTPR had a higher percentage of recurrent ischemic events compared with patients with NTPR (p = 0.002). In multivariate Cox proportional hazards models, history of ischemic stroke or TIA (HR 4.45, 95% CI 1.77-11.16, p = 0.001) and HTPR (HR 3.34, 95% CI 1.41-7.91, p = 0.006) was independently associated with recurrent ischemic events. In patients with minor stroke or TIA, the prevalence of HTPR was 22.7%, and HTPR was independently associated with recurrent ischemic events.

  2. REANALYSES OF ANOMALOUS GRAVITATIONAL MICROLENSING EVENTS IN THE OGLE-III EARLY WARNING SYSTEM DATABASE WITH COMBINED DATA

    International Nuclear Information System (INIS)

    Jeong, J.; Park, H.; Han, C.; Gould, A.; Poleski, R.; Udalski, A.; Szymański, M. K.; Pietrzyński, G.; Soszyński, I.; Ulaczyk, K.; Wyrzykowski, Ł.; Abe, F.; Fukunaga, D.; Itow, Y.; Bennett, D. P.; Bond, I. A.; Botzler, C. S.; Freeman, M.; Fukui, A.; Koshimoto, N.

    2015-01-01

    We reanalyze microlensing events in the published list of anomalous events that were observed from the Optical Gravitational Lensing Experiment (OGLE) lensing survey conducted during the 2004–2008 period. In order to check the existence of possible degenerate solutions and extract extra information, we conduct analyses based on combined data from other survey and follow-up observation and consider higher-order effects. Among the analyzed events, we present analyses of eight events for which either new solutions are identified or additional information is obtained. We find that the previous binary-source interpretations of five events are better interpreted by binary-lens models. These events include OGLE-2006-BLG-238, OGLE-2007-BLG-159, OGLE-2007-BLG-491, OGLE-2008-BLG-143, and OGLE-2008-BLG-210. With additional data covering caustic crossings, we detect finite-source effects for six events including OGLE-2006-BLG-215, OGLE-2006-BLG-238, OGLE-2006-BLG-450, OGLE-2008-BLG-143, OGLE-2008-BLG-210, and OGLE-2008-BLG-513. Among them, we are able to measure the Einstein radii of three events for which multi-band data are available. These events are OGLE-2006-BLG-238, OGLE-2008-BLG-210, and OGLE-2008-BLG-513. For OGLE-2008-BLG-143, we detect higher-order effects induced by the changes of the observer’s position caused by the orbital motion of the Earth around the Sun. In addition, we present degenerate solutions resulting from the known close/wide or ecliptic degeneracy. Finally, we note that the masses of the binary companions of the lenses of OGLE-2006-BLG-450 and OGLE-2008-BLG-210 are in the brown-dwarf regime

  3. REANALYSES OF ANOMALOUS GRAVITATIONAL MICROLENSING EVENTS IN THE OGLE-III EARLY WARNING SYSTEM DATABASE WITH COMBINED DATA

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, J.; Park, H.; Han, C. [Department of Physics, Institute for Astrophysics, Chungbuk National University, Cheongju 361-763 (Korea, Republic of); Gould, A.; Poleski, R. [Department of Astronomy, Ohio State University, 140 W. 18th Ave., Columbus, OH 43210 (United States); Udalski, A.; Szymański, M. K.; Pietrzyński, G.; Soszyński, I.; Ulaczyk, K.; Wyrzykowski, Ł. [Warsaw University Observatory, Al. Ujazdowskie 4, 00-478 Warszawa (Poland); Abe, F.; Fukunaga, D.; Itow, Y. [Solar-Terrestrial Environment Laboratory, Nagoya University, Nagoya, 464-8601 (Japan); Bennett, D. P. [Department of Physics, University of Notre Dame, 225 Nieuwland Science Hall, Notre Dame, IN 46556-5670 (United States); Bond, I. A. [Institute of Information and Mathematical Sciences, Massey University, Private Bag 102-904, North Shore Mail Centre, Auckland (New Zealand); Botzler, C. S.; Freeman, M. [Department of Physics, University of Auckland, Private Bag 92-019, Auckland 1001 (New Zealand); Fukui, A. [Okayama Astrophysical Observatory, National Astronomical Observatory of Japan, Asakuchi, Okayama 719-0232 (Japan); Koshimoto, N. [Department of Earth and Space Science, Osaka University, Osaka 560-0043 (Japan); Collaboration: (The OGLE Collaboration); (The MOA Collaboration); (The PLANET Collaboration); (The μFUN Collaboration); (The RoboNet Collaboration); and others

    2015-05-01

    We reanalyze microlensing events in the published list of anomalous events that were observed from the Optical Gravitational Lensing Experiment (OGLE) lensing survey conducted during the 2004–2008 period. In order to check the existence of possible degenerate solutions and extract extra information, we conduct analyses based on combined data from other survey and follow-up observation and consider higher-order effects. Among the analyzed events, we present analyses of eight events for which either new solutions are identified or additional information is obtained. We find that the previous binary-source interpretations of five events are better interpreted by binary-lens models. These events include OGLE-2006-BLG-238, OGLE-2007-BLG-159, OGLE-2007-BLG-491, OGLE-2008-BLG-143, and OGLE-2008-BLG-210. With additional data covering caustic crossings, we detect finite-source effects for six events including OGLE-2006-BLG-215, OGLE-2006-BLG-238, OGLE-2006-BLG-450, OGLE-2008-BLG-143, OGLE-2008-BLG-210, and OGLE-2008-BLG-513. Among them, we are able to measure the Einstein radii of three events for which multi-band data are available. These events are OGLE-2006-BLG-238, OGLE-2008-BLG-210, and OGLE-2008-BLG-513. For OGLE-2008-BLG-143, we detect higher-order effects induced by the changes of the observer’s position caused by the orbital motion of the Earth around the Sun. In addition, we present degenerate solutions resulting from the known close/wide or ecliptic degeneracy. Finally, we note that the masses of the binary companions of the lenses of OGLE-2006-BLG-450 and OGLE-2008-BLG-210 are in the brown-dwarf regime.

  4. Identifying and Overcoming Barriers to Effective Consideration of Human and Organisational Factors in Event Analysis and Root Cause Analysis. Workshop Proceedings, September 21-22, 2009, Paris, France

    International Nuclear Information System (INIS)

    2011-01-01

    Nuclear licensees must have effective processes for learning from operating experience in order to manage safety, secure continuous improvement and defend against the potential for repeat events. These processes include root cause analysis (RCA) to identify the underlying causes of events and mechanisms to learn from these analyses and to implement improvements. Correctly identifying and correcting the causes of events will allow lessons to be learned and shared with others in the industry. The treatment of Human and Organisational Factors (HOF) in RCA is of special interest to WGHOF. It is estimated that approximately 60-80% of events in the nuclear industry can be attributed to human and organisational factors. Although the importance of correctly identifying the HOF causes is understood, there is still a tendency for the analysis to focus solely on the technical issues of the event. The history of prominent events across the major hazards sector shows that HOF lessons often fail to be learned. A NEA/CSNI special experts meeting entitled 'Identification of Barriers to Analyzing and Identifying Human and Organisational Factors in Root Cause Analysis' was held at the NEA Headquarters in Paris, France on September 21-22, 2009. A total of 17 participants from 10 countries representing licensee organisations, regulators, international organisations and an independent consultant attended the meeting. The meeting was structured to allow for small group discussions during which a number of themes were explored, followed by plenary discussion. There were also four papers presented which complemented the discussion themes. As set out in the objectives of this work, the participants identified barriers to the effective treatment of HOF in RCA and recommendations to mitigate the effects of these barriers. Many of the barriers and recommendations identified relate to the RCA process in general, not specifically to the treatment of HOF in the RCA process. This is logical, for

  5. A study on method to identify actual causes and conditions of safety rule deviations through analyzing events due to unsafe acts of workers

    International Nuclear Information System (INIS)

    Hirotsu, Yuko; Takeda, Daisuke

    2010-01-01

    The purpose of this study is to establish a method to understand actual causes and condition of intentional deviation from safety rules (including norm and written rules that has developed to anticipate, prevent, detect and recover human errors) in an organization by analyzing events due to unsafe acts of workers (human factor events) and to propose effective measures. Firstly, by reviewing literature regarding safety violations, the following two advantages of investigating actual condition of safety rule deviation through human factor event analysis were extracted, such as (a) being able to clarify relationships between deviations, human errors, and events, and (b) being able to identify specific causal factors that influenced the decision to deviate, including acts of people concerned, problems with rules, task demands, environment and management. Next, through the analysis of human factor event data in accordance with existing human error analysis method on the basis of advantages above, the following three requirements for analyzing event data were extracted, such as (a) gathering information such as rules concerning to the work activities related to the human factor events, and whether there are intentional deviations of the rules, (b) gathering information and identify interrelations among causal factors of the intentional deviations, and (c) gathering information on general condition of deviations and the causal factors. (author)

  6. Insights into the early dissolution events of amlodipine using UV imaging and Raman spectroscopy

    DEFF Research Database (Denmark)

    Boetker, Johan P; Savolainen, Marja; Koradia, Vishal

    2011-01-01

    Traditional dissolution testing determines drug release to the bulk, but does not enable an understanding of the events happening close to the surface of a solid or a tablet. UV imaging is a new imaging approach that can be used to study the dissolution behavior of chemical compounds. The UV imag...

  7. Risk Factors for Preschool Depression: The Mediating Role of Early Stressful Life Events

    Science.gov (United States)

    Luby, Joan L.; Belden, Andy C.; Spitznagel, Edward

    2006-01-01

    Background: Family history of mood disorders and stressful life events are both established risk factors for childhood depression. However, the role of mediators in risk trajectories, which are potential targets for intervention, remains understudied. To date, there have been no investigations of mediating relationships between risk factors and…

  8. Early referential context effects in sentence processing: Evidence from event-related brain potentials

    NARCIS (Netherlands)

    Berkum, J.J.A. van; Brown, C.M.; Hagoort, P.

    1999-01-01

    An event-related brain potentials experiment was carried out to examine the interplay of referential and structural factors during sentence processing in discourse. Subjects read (Dutch) sentences beginning like “David told the girl that … ” in short story contexts that had introduced either one or

  9. Skin carcinomas in organ-transplant recipients : from early oncogenic events to therapy

    NARCIS (Netherlands)

    Graaf, Ymke Grete Leontien de

    2008-01-01

    Skin carcinomas develop at a high rate in organ-transplant recipients who are kept on immune suppressive drugs to prevent graft rejection. The present study dealt with a broad range of aspects of this elevated carcinoma risk, starting from the earliest oncogenic events to the ultimate therapy.

  10. Identifying high-functioning dyslexics: is self-report of early reading problems enough?

    Science.gov (United States)

    Deacon, S Hélène; Cook, Kathryn; Parrila, Rauno

    2012-07-01

    We used a questionnaire to identify university students with self-reported difficulties in reading acquisition during elementary school (self-report; n=31). The performance of the self-report group on standardized measures of word and non-word reading and fluency, passage comprehension and reading rate, and phonological awareness was compared to that of two other groups of university students: one with a recent diagnosis (diagnosed; n=20) and one with no self-reported reading acquisition problems (comparison group; n=33). The comparison group outperformed both groups with a history of reading difficulties (self-report and diagnosed) on almost all measures. The self-report and diagnosed groups performed similarly on most tasks, with the exception of untimed reading comprehension (better performance for diagnosed) and reading rate (better performance for self-report). The two recruitment methods likely sample from the same underlying population but identify individuals with different adaptive strategies.

  11. Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

    Science.gov (United States)

    Berghella, Libera; Ferraro, Elisabetta

    2012-01-01

    Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

  12. Early Healing Events around Titanium Implant Devices with Different Surface Microtopography: A Pilot Study in an In Vivo Rabbit Model

    Directory of Open Access Journals (Sweden)

    Ester Orsini

    2012-01-01

    Full Text Available In the present pilot study, the authors morphologically investigated sandblasted, acid-etched surfaces (SLA at very early experimental times. The tested devices were titanium plate-like implants with flattened wide lateral sides and jagged narrow sides. Because of these implant shape and placement site, the device gained a firm mechanical stability but the largest portion of the implant surface lacked direct contact with host bone and faced a wide peri-implant space rich in marrow tissue, intentionally created in order to study the interfacial interaction between metal surface and biological microenvironment. The insertion of titanium devices into the proximal tibia elicited a sequence of healing events. Newly formed bone proceeded through an early distance osteogenesis, common to both surfaces, and a delayed contact osteogenesis which seemed to follow different patterns at the two surfaces. In fact, SLA devices showed a more osteoconductive behavior retaining a less dense blood clot, which might be earlier and more easily replaced, and leading to a surface-conditioning layer which promotes osteogenic cell differentiation and appositional new bone deposition at the titanium surface. This model system is expected to provide a starting point for further investigations which clarify the early cellular and biomolecular events occurring at the metal surface.

  13. Astrochronology of extreme global warming events during the early Eocene greenhouse climate

    NARCIS (Netherlands)

    Lauretano, V.

    2016-01-01

    The early Eocene represents an ideal case study to analyse the impact of enhanced global warming on the ocean-atmosphere system and the relationship between carbon cycling and climate. During this time interval, the Earth’s surface experienced a long-term warming trend that culminated in a period of

  14. Spiders do not evoke greater early posterior negativity in the event-related potential as snakes.

    Science.gov (United States)

    He, Hongshen; Kubo, Kenta; Kawai, Nobuyuki

    2014-09-10

    It has been long believed that both snakes and spiders are archetypal fear stimuli for humans. Furthermore, snakes have been assumed as stronger threat cues for nonhuman primates. However, it is still unclear whether spiders hold a special status in human perception. The current study explored to what extent spider pictures draw early visual attention [as assessed with early posterior negativity (EPN)] when compared with insects similar to spiders. To measure the EPN, participants watched a random rapid serial presentation of pictures, which consisted of two conditions: spider condition (spider, wasp, bumblebee, beetle) and snake condition (snake, bird). EPN amplitudes revealed no significant difference between spider, wasp, bumblebee, and beetle pictures, whereas EPN amplitudes were significantly larger for snake pictures relative to bird pictures. In addition, EPN amplitudes were significantly larger for snake pictures relative to spider pictures. These results suggest that the early visual attentional capture of animate objects is stronger for snakes, whereas spiders do not appear to hold special early attentional value.

  15. Ostracods and facies of the Early and Middle Frasnian at Devils Gate in Nevada: Relationship to the Alamo Event

    Science.gov (United States)

    Casier, J.-G.; Berra, I.; Olempska, Ewa; Sandberg, C.; Preat, A.

    2006-01-01

    In order to document the Alamo Event and to investigate its influence on shallow-marine environments, we undertook a study of ostracods, conodonts, and analysis of the sedimentology of the lower member of the type Devils Gate Limestone, Six major carbonate microfacies (MF1-MF6) ranging from open-marine environments below storm wave base to pre-evaporitic supratidal lagoons were recognized. The sedimentological study detected no important sedimentological changes during the Alamo Event; only an influx of detrital material and lithoclasts indicate that an unusual event had occurred. Ostracods are generally rare or absent in the lower member of the Devils Gate Limestone, and only 2,000 carapaces, valves and fragments were extracted; from these some 26 taxa were identified. Two new species, Voronina? eureka and Serenida dorsoplicata are proposed. The ostracods belong to the Eifelian Mega-Assemblage and their distribution was influenced by strong salinity variations. Because of the rarity and low diversity of ostracods and conodonts in samples collected from the lower part of the lower member of the Devils Gate Limestone it is not adequate to demonstrate conclusively an extinction event close to the Alamo Event Bed. Nevertheless the greater abundance and diversity of ostracods above this bed seems to indicate that the Alamo Event did not result in significant extinction of ostracod taxa in this shallow water setting. The ostracod fauna present in the lower member of the Devils Gate Limestone suggests faunal exchanges between Nevada and the Russian Platform via the Western Canadian platform.

  16. Economics of Early Warning Scores for identifying clinical deterioration-a systematic review.

    Science.gov (United States)

    Murphy, A; Cronin, J; Whelan, R; Drummond, F J; Savage, E; Hegarty, J

    2018-02-01

    In 2013, a National Early Warning System (EWS) was implemented in Ireland. Whilst evidence exists to support the clinical effectiveness of EWS in the acute health care setting, there is a paucity of information on their cost and cost effectiveness. The objective of this systematic literature review was to critically evaluate the economic literature on the use of EWS in adult patients in acute health care settings for the timely detection of physiological deterioration. A systematic literature review was conducted to accumulate the economic evidence on the use of EWS in adult patients in acute health care settings. The search yielded one health technology assessment, two budget impact analyses and two cost descriptions. Three of the studies were Irish, and considered the national EWS system. A Dutch study reported financial consequences of a single parameter EWS, as part of a rapid response system, in a surgical ward. The fifth study examined an advanced triage system in a medical emergency admission unit in Wales. The economic evidence on the use of EWS amongst adult patients in acute health care settings for the timely detection of physiological deterioration is limited. Further research is required to investigate the cost effectiveness of EWS, and the appropriateness of using standard methods to do so. The recent implementation of a national EWS in Ireland offers a unique opportunity to bridge this gap in the literature to examine the costs and cost effectiveness of a nationally implemented EWS system.

  17. Identifying deliberate attempts to fake memory impairment through the combined use of reaction time and event-related potential measures

    NARCIS (Netherlands)

    van Hooff, Johanna C.; Sargeant, Elizabeth; Foster, Jonathan K.; Schmand, Ben A.

    2009-01-01

    The central aim of this study was to evaluate the value of reaction time (RT) measures and event-related potentials (ERPs) for the assessment of simulated memory impairment. In two identical experiments (N = 24), healthy volunteers carried out an adapted version of the Amsterdam Short-Term Memory

  18. Bagging grey swans : A supply network approach to identifying and managing low-probability high-impact supply chain events

    NARCIS (Netherlands)

    Rossetti, Christian; Akkermans, Henk; Bhakoo, Vikram; Carnovale, Steven

    Over the past decade practitioners and researchers have become increasingly focused on managing risks in extended supply chains. Whether these risks involve supply disruptions, financial liabilities for a supplier’s actions, or large market shifts; Grey Swan events, defined as unforeseen

  19. Identifying Disruptive Technologies in Design: Horizon Scanning in the Early Stages of Design

    DEFF Research Database (Denmark)

    Ernstsen, Sidsel Katrine; Thuesen, Christian; Larsen, Laurids Rolighed

    Technology development is accelerating, driving disruption. Design is seen as key differentiator in creating innovative offerings but few design methods consider future technologies explicitly. In this article, we explore how a foresight method, namely horizon scanning, may be applied in a design...... context to anticipate disruption of construction. By means of a 3-step horizon scan, we identify 133 potentially disruptive technologies from across industries. We find that when preparing for disruption, design may benefit from the future-oriented and technology-focused features of horizon scanning....

  20. Stressful life events and neuroticism as predictors of late-life versus early-life depression.

    Science.gov (United States)

    Weber, Kerstin; Giannakopoulos, Panteleimon; Herrmann, François R; Bartolomei, Javier; Digiorgio, Sergio; Ortiz Chicherio, Nadia; Delaloye, Christophe; Ghisletta, Paolo; Lecerf, Thierry; De Ribaupierre, Anik; Canuto, Alessandra

    2013-12-01

    The occurrence of depression in younger adults is related to the combination of long-standing factors such as personality traits (neuroticism) and more acute factors such as the subjective impact of stressful life events. Whether an increase in physical illnesses changes these associations in old age depression remains a matter of debate. We compared 79 outpatients with major depression and 102 never-depressed controls; subjects included both young (mean age: 35 years) and older (mean age: 70 years) adults. Assessments included the Social Readjustment Rating Scale, NEO Personality Inventory and Cumulative Illness Rating Scale. Logistic regression models analyzed the association between depression and subjective impact of stressful life events while controlling for neuroticism and physical illness. Patients and controls experienced the same number of stressful life events in the past 12 months. However, in contrast to the controls, patients associated the events with a subjective negative emotional impact. Negative stress impact and levels of neuroticism, but not physical illness, significantly predicted depression in young age. In old age, negative stress impact was weakly associated with depression. In this age group, depressive illness was also determined by physical illness burden and neuroticism. Our data suggest that the subjective impact of life stressors, although rated as of the same magnitude, plays a less important role in accounting for depression in older age compared to young age. They also indicate an increasing weight of physical illness burden in the prediction of depression occurrence in old age. © 2013 The Authors. Psychogeriatrics © 2013 Japanese Psychogeriatric Society.

  1. Early elevation of soluble CD14 may help identify trauma patients at high risk for infection.

    Science.gov (United States)

    Carrillo, E H; Gordon, L; Goode, E; Davis, E; Polk, H C

    2001-05-01

    Elevated levels of soluble CD14 (sCD14) have been implicated in both gram-positive and gram-negative sepsis, and it has been associated with high mortality in trauma patients who become infected. Eleven healthy volunteers and 25 adult trauma patients with multiple injuries and a mean Injury Severity Score of 32 participated. Whole blood was obtained at intervals. Immunohistochemistry was used to quantify membrane CD14 (mCD14), by flow cytometry and plasma levels of sCD14 by enzyme-linked immunosorbent assay. Analysis of variance and Student's T test with Mann-Whitney posttest were used to determine significance at p < 0.05. On posttrauma day 1, sCD14 was significantly different in the plasma of infected patients compared with normal controls (7.16 +/- 1.87 microg/mL vs. 4.4 +/- 0.92 microg/mL, p < 0.01), but not significantly different from noninfected patients. The percentage of monocytes expressing mCD14 in trauma patients did not differentiate them from normal controls; however, mCD14 receptor density did demonstrate significance in septic trauma patients (n = 15) versus normal controls on posttrauma day 3 (p = 0.0065). On the basis of our data, mCD14 did not differentiate infected and noninfected trauma patients, although trauma in general reduced mCD14 and elevated sCD14. Interestingly, 100% of patients who exceeded plasma levels of 8 microg/mL of sCD14 on day 1 after injury developed infections. Therefore, early high expressers of sCD14 may be at higher risk for infectious complications after trauma.

  2. Indirect Effects of Attributional Style for Positive Events on Depressive Symptoms Through Self-Esteem During Early Adolescence.

    Science.gov (United States)

    Rueger, Sandra Yu; George, Rachel

    2017-04-01

    Research on adolescent depression has overwhelmingly focused on risk factors, such as stressful negative events and cognitive vulnerabilities, but much important information can be gained by focusing on protective factors. Thus, the current study aimed to broaden understanding on adolescent depression by considering the role of two positive elements as protective factors, attributional style for positive events and self-esteem, in a model of depression. The sample included 491 middle school students (52 % female; n = 249) with an age range from 12 to 15 years (M = 13.2, SD = .70). The sample was ethnically/racially diverse, with 55 % White, 22 % Hispanic, 10 % Asian American, 3 % African American, and 10 % Biracial/Other. Correlational analyses indicated significant cross-sectional and longitudinal associations between an enhancing attributional style (internal, stable, global attributions for positive events), self-esteem and depressive symptoms. Further, prospective analyses using bootstrapping methodology demonstrated significant indirect effects of an enhancing attributional style on decreases in depressive symptoms through its effects on self-esteem. These findings highlight the importance of considering attributional style for positive events as a protective factor in the developmental course of depressive symptoms during early adolescence.

  3. Identifying differences in early literacy skills across subgroups of language-minority children: A latent profile analysis.

    Science.gov (United States)

    Lonigan, Christopher J; Goodrich, J Marc; Farver, JoAnn M

    2018-04-01

    Despite acknowledgment that language-minority children come from a wide variety of home language backgrounds and have a wide range of proficiency in their first (L1) and second (L2) languages, it is unknown whether differences across language-minority children in relative and absolute levels of proficiency in L1 and L2 predict subsequent development of literacy-related skills. The purpose of this study was to identify subgroups of language-minority children and evaluate whether differences in level and rate of growth of early literacy skills differed across subgroups. Five-hundred and twenty-six children completed measures of Spanish and English language and early literacy skills at the beginning, middle, and end of the preschool year. Latent growth models indicated that children's early literacy skills were increasing over the course of the preschool year. Latent profile analysis indicated that language-minority children could be classified into nine distinct groups, each with unique patterns of absolute and relative levels of proficiency in L1 and L2. Results of three-step mixture models indicated that profiles were closely associated with level of early literacy skills at the beginning of the preschool year. Initial level of early literacy skills was positively associated with growth in code-related skills (i.e., print knowledge, phonological awareness) and inversely associated with growth in language skills. These findings suggest that language-minority children are a diverse group with regard to their L1 and L2 proficiencies and that growth in early literacy skills is most associated with level of proficiency in the same language. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  4. High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.

    Science.gov (United States)

    de Masson, Adele; O'Malley, John T; Elco, Christopher P; Garcia, Sarah S; Divito, Sherrie J; Lowry, Elizabeth L; Tawa, Marianne; Fisher, David C; Devlin, Phillip M; Teague, Jessica E; Leboeuf, Nicole R; Kirsch, Ilan R; Robins, Harlan; Clark, Rachael A; Kupper, Thomas S

    2018-05-09

    Mycosis fungoides (MF), the most common cutaneous T cell lymphoma (CTCL) is a malignancy of skin-tropic memory T cells. Most MF cases present as early stage (stage I A/B, limited to the skin), and these patients typically have a chronic, indolent clinical course. However, a small subset of early-stage cases develop progressive and fatal disease. Because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. We evaluated the use of next-generation high-throughput DNA sequencing of the T cell receptor β gene ( TCRB ) in lesional skin biopsies to predict progression and survival in a discovery cohort of 208 patients with CTCL (177 with MF) from a 15-year longitudinal observational clinical study. We compared these data to the results in an independent validation cohort of 101 CTCL patients (87 with MF). The tumor clone frequency (TCF) in lesional skin, measured by high-throughput sequencing of the TCRB gene, was an independent prognostic factor of both progression-free and overall survival in patients with CTCL and MF in particular. In early-stage patients, a TCF of >25% in the skin was a stronger predictor of progression than any other established prognostic factor (stage IB versus IA, presence of plaques, high blood lactate dehydrogenase concentration, large-cell transformation, or age). The TCF therefore may accurately predict disease progression in early-stage MF. Early identification of patients at high risk for progression could help identify candidates who may benefit from allogeneic hematopoietic stem cell transplantation before their disease becomes treatment-refractory. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  5. Early events in speciation: polymorphism for hybrid male sterility in Drosophila.

    Science.gov (United States)

    Reed, Laura K; Markow, Therese A

    2004-06-15

    Capturing the process of speciation early enough to determine the initial genetic causes of reproductive isolation remains a major challenge in evolutionary biology. We have found, to our knowledge, the first example of substantial intraspecific polymorphism for genetic factors contributing to hybrid male sterility. Specifically, we show that the occurrence of hybrid male sterility in crosses between Drosophila mojavensis and its sister species, Drosophila arizonae, is controlled by factors present at different frequencies in different populations of D. mojavensis. In addition, we show that hybrid male sterility is a complex phenotype; some hybrid males with motile sperm still cannot sire offspring. Because male sterility factors in hybrids between these species are not yet fixed within D. mojavensis, this system provides an invaluable opportunity to characterize the genetics of reproductive isolation at an early stage.

  6. Bridging the gap: academic and practitioner perspectives to identify early career competencies needed in healthcare management.

    Science.gov (United States)

    Shewchuk, Richard M; O'Connor, Stephen J; Fine, David J

    2006-01-01

    Healthcare organizations, health management professional associations, and educational institutions have begun to examine carefully what it means to be a fully competent healthcare executive. As a result, an upsurge in interest in healthcare management competencies has been observed recently. The present study uses two critically important groups of informants as participants: health management practitioners and faculty. Using the nominal group process, health administrators identified critical environmental issues perceived to have an impact on healthcare executives today. These issues were employed in a card-sort assessment and a survey was administered to a nationwide sample of health administrators. These data were used to create a map and five clusters of the environmental landscape of healthcare management. These clusters of environmental issues provided a framework for having groups of administrators and faculty members generate and rank perceived behavioral competencies relative to each cluster. Implications for healthcare management practice, education, and research are discussed.

  7. Early Events in Populus Hybrid and Fagus sylvatica Leaves Exposed to Ozone

    Directory of Open Access Journals (Sweden)

    R. Desotgiu

    2010-01-01

    Full Text Available This paper aims to investigate early responses to ozone in leaves of Fagus sylvatica (beech and Populus maximowiczii x Populus berolinensis (poplar. The experimental setup consisted of four open-air (OA plots, four charcoal-filtered (CF open-top chambers (OTCs, and four nonfiltered (NF OTCs. Qualitative and quantitative analyses were carried out on nonsymptomatic (CF and symptomatic (NF and OA leaves of both species. Qualitative analyses were performed applying microscopic techniques: Evans blue staining for detection of cell viability, CeCl3 staining of transmission electron microscope (TEM samples to detect the accumulation of H2O2, and multispectral fluorescence microimaging and microspectrofluorometry to investigate the accumulation of fluorescent phenolic compounds in the walls of the damaged cells. Quantitative analyses consisted of the analysis of the chlorophyll a fluorescence transients (fast kinetics. The early responses to ozone were demonstrated by the Evans blue and CeCl3 staining techniques that provided evidence of plant responses in both species 1 month before foliar symptoms became visible. The fluorescence transients analysis, too, demonstrated the breakdown of the oxygen evolving system and the inactivation of the end receptors of electrons at a very early stage, both in poplar and in beech. The accumulation of phenolic compounds in the cell walls, on the other hand, was a species-specific response detected in poplar, but not in beech. Evans blue and CeCl3 staining, as well as the multispectral fluorescence microimaging and microspectrofluorometry, can be used to support the field diagnosis of ozone injury, whereas the fast kinetics of chlorophyll fluorescence provides evidence of early physiological responses.

  8. Early events in speciation: Polymorphism for hybrid male sterility in Drosophila

    OpenAIRE

    Reed, Laura K.; Markow, Therese A.

    2004-01-01

    Capturing the process of speciation early enough to determine the initial genetic causes of reproductive isolation remains a major challenge in evolutionary biology. We have found, to our knowledge, the first example of substantial intraspecific polymorphism for genetic factors contributing to hybrid male sterility. Specifically, we show that the occurrence of hybrid male sterility in crosses between Drosophila mojavensis and its sister species, Drosophila arizonae, is controlled by factors p...

  9. Radiation and chemotherapy bystander effects induce early genomic instability events: telomere shortening and bridge formation coupled with mitochondrial dysfunction.

    LENUS (Irish Health Repository)

    Gorman, Sheeona

    2012-02-01

    The bridge breakage fusion cycle is a chromosomal instability mechanism responsible for genomic changes. Radiation bystander effects induce genomic instability; however, the mechanism driving this instability is unknown. We examined if radiation and chemotherapy bystander effects induce early genomic instability events such as telomere shortening and bridge formation using a human colon cancer explant model. We assessed telomere lengths, bridge formations, mitochondrial membrane potential and levels of reactive oxygen species in bystander cells exposed to medium from irradiated and chemotherapy-treated explant tissues. Bystander cells exposed to media from 2Gy, 5Gy, FOLFOX treated tumor and matching normal tissue showed a significant reduction in telomere lengths (all p values <0.018) and an increase in bridge formations (all p values <0.017) compared to bystander cells treated with media from unirradiated tissue (0Gy) at 24h. There was no significant difference between 2Gy and 5Gy treatments, or between effects elicited by tumor versus matched normal tissue. Bystander cells exposed to media from 2Gy irradiated tumor tissue showed significant depolarisation of the mitochondrial membrane potential (p=0.012) and an increase in reactive oxygen species levels. We also used bystander cells overexpressing a mitochondrial antioxidant manganese superoxide dismutase (MnSOD) to examine if this antioxidant could rescue the mitochondrial changes and subsequently influence nuclear instability events. In MnSOD cells, ROS levels were reduced (p=0.02) and mitochondrial membrane potential increased (p=0.04). These events were coupled with a decrease in percentage of cells with anaphase bridges and a decrease in the number of cells undergoing telomere length shortening (p values 0.01 and 0.028 respectively). We demonstrate that radiation and chemotherapy bystander responses induce early genomic instability coupled with defects in mitochondrial function. Restoring mitochondrial

  10. End-Binding Protein 1 (EB1) Up-regulation is an Early Event in Colorectal Carcinogenesis

    Science.gov (United States)

    Stypula-Cyrus, Yolanda; Mutyal, Nikhil N.; Cruz, Mart Angelo Dela; Kunte, Dhananjay P.; Radosevich, Andrew J.; Wali, Ramesh; Roy, Hemant K.; Backman, Vadim

    2014-01-01

    End-binding protein (EB1) is a microtubule protein that binds to the tumor suppressor adenomatous polyposis coli (APC). While EB1 is implicated as a potential oncogene, its role in cancer progression is unknown. Therefore, we analyzed EB1/APC expression at the earliest stages of colorectal carcinogenesis and in the uninvolved mucosa ("field effect") of human and animal tissue. We also performed siRNA-knockdown in colon cancer cell lines. EB1 is up-regulated in early and field carcinogenesis in the colon, and the cellular/nano-architectural effect of EB1 knockdown depended on the genetic context. Thus, dysregulation of EB1 is an important early event in colon carcinogenesis. PMID:24492008

  11. Stressful Life Events and Predictors of Post-traumatic Growth among High-Risk Early Emerging Adults.

    Science.gov (United States)

    Arpawong, Thalida E; Rohrbach, Louise A; Milam, Joel E; Unger, Jennifer B; Land, Helen; Sun, Ping; Spruijt-Metz, Donna; Sussman, Steve

    2016-01-01

    Stressful life events (SLEs) may elicit positive psychosocial change among youth, referred to as Post-traumatic Growth (PTG). We assessed types of SLEs experienced, degree to which participants reported PTG, and variables predicting PTG across 24 months among a sample of high risk, ethnically diverse early emerging adults. Participants were recruited from alternative high schools ( n = 564; mean age=16.8; 65% Hispanic). Multi-level regression models were constructed to examine the impact of environmental (SLE quantity, severity) and personal factors (hedonic ability, perceived stress, developmental stage, future time orientation) on a composite score of PTG. The majority of participants reported positive changes resulted from their most life-altering SLE of the past two years. Predictors of PTG included fewer SLEs, less general stress, having a future time perspective, and greater identification with the developmental stage of Emerging Adulthood. Findings suggest intervention targets to foster positive adaptation among early emerging adults who experience frequent SLEs.

  12. Parental Substance Abuse As an Early Traumatic Event. Preliminary Findings on Neuropsychological and Personality Functioning in Young Drug Addicts Exposed to Drugs Early.

    Science.gov (United States)

    Parolin, Micol; Simonelli, Alessandra; Mapelli, Daniela; Sacco, Marianna; Cristofalo, Patrizia

    2016-01-01

    Parental substance use is a major risk factor for child development, heightening the risk of drug problems in adolescence and young adulthood, and exposing offspring to several types of traumatic events. First, prenatal drug exposure can be considered a form of trauma itself, with subtle but long-lasting sequelae at the neuro-behavioral level. Second, parents' addiction often entails a childrearing environment characterized by poor parenting skills, disadvantaged contexts and adverse childhood experiences (ACEs), leading to dysfunctional outcomes. Young adults born from/raised by parents with drug problems and diagnosed with a Substance Used Disorder (SUD) themselves might display a particularly severe condition in terms of cognitive deficits and impaired personality function. This preliminary study aims to investigate the role of early exposure to drugs as a traumatic event, capable of affecting the psychological status of young drug addicts. In particular, it intends to examine the neuropsychological functioning and personality profile of young adults with severe SUDs who were exposed to drugs early in their family context. The research involved three groups, each consisting of 15 young adults (aged 18-24): a group of inpatients diagnosed with SUDs and exposed to drugs early, a comparison group of non-exposed inpatients and a group of non-exposed youth without SUDs. A neuropsychological battery (Esame Neuropsicologico Breve-2), an assessment procedure for personality disorders (Shedler-Westen Assessment Procedure-200) and the Symptom CheckList-90-Revised were administered. According to present preliminary results, young drug addicts exposed to drugs during their developmental age were characterized by elevated rates of neuropsychological impairments, especially at the expense of attentive and executive functions (EF); personality disorders were also common but did not differentiate them from non-exposed youth with SUDs. Alternative multi-focused prevention and

  13. Identifying early pathways of risk and resilience: The codevelopment of internalizing and externalizing symptoms and the role of harsh parenting.

    Science.gov (United States)

    Wiggins, Jillian Lee; Mitchell, Colter; Hyde, Luke W; Monk, Christopher S

    2015-11-01

    Psychological disorders co-occur often in children, but little has been done to document the types of conjoint pathways internalizing and externalizing symptoms may take from the crucial early period of toddlerhood or how harsh parenting may overlap with early symptom codevelopment. To examine symptom codevelopment trajectories, we identified latent classes of individuals based on internalizing and externalizing symptoms across ages 3-9 and found three symptom codevelopment classes: normative symptoms (low), severe-decreasing symptoms (initially high but rapidly declining), and severe symptoms (high) trajectories. Next, joint models examined how parenting trajectories overlapped with internalizing and externalizing symptom trajectories. These trajectory classes demonstrated that, normatively, harsh parenting increased after toddlerhood, but the severe symptoms class was characterized by a higher level and a steeper increase in harsh parenting and the severe-decreasing class by high, stable harsh parenting. In addition, a transactional model examined the bidirectional relationships among internalizing and externalizing symptoms and harsh parenting because they may cascade over time in this early period. Harsh parenting uniquely contributed to externalizing symptoms, controlling for internalizing symptoms, but not vice versa. In addition, internalizing symptoms appeared to be a mechanism by which externalizing symptoms increase. Results highlight the importance of accounting for both internalizing and externalizing symptoms from an early age to understand risk for developing psychopathology and the role harsh parenting plays in influencing these trajectories.

  14. Knockin' on pollen's door: live cell imaging of early polarization events in germinating Arabidopsis pollen

    Science.gov (United States)

    Vogler, Frank; Konrad, Sebastian S. A.; Sprunck, Stefanie

    2015-01-01

    Pollen tubes are an excellent system for studying the cellular dynamics and complex signaling pathways that coordinate polarized tip growth. Although several signaling mechanisms acting in the tip-growing pollen tube have been described, our knowledge on the subcellular and molecular events during pollen germination and growth site selection at the pollen plasma membrane is rather scarce. To simultaneously track germinating pollen from up to 12 genetically different plants we developed an inexpensive and easy mounting technique, suitable for every standard microscope setup. We performed high magnification live-cell imaging during Arabidopsis pollen activation, germination, and the establishment of pollen tube tip growth by using fluorescent marker lines labeling either the pollen cytoplasm, vesicles, the actin cytoskeleton or the sperm cell nuclei and membranes. Our studies revealed distinctive vesicle and F-actin polarization during pollen activation and characteristic growth kinetics during pollen germination and pollen tube formation. Initially, the germinating Arabidopsis pollen tube grows slowly and forms a uniform roundish bulge, followed by a transition phase with vesicles heavily accumulating at the growth site before switching to rapid tip growth. Furthermore, we found the two sperm cells to be transported into the pollen tube after the phase of rapid tip growth has been initiated. The method presented here is suitable to quantitatively study subcellular events during Arabidopsis pollen germination and growth, and for the detailed analysis of pollen mutants with respect to pollen polarization, bulging, or growth site selection at the pollen plasma membrane. PMID:25954283

  15. Altered lysosome distribution is an early neuropathological event in neurological forms of Gaucher disease.

    Science.gov (United States)

    Zigdon, Hila; Meshcheriakova, Anna; Farfel-Becker, Tamar; Volpert, Giora; Sabanay, Helena; Futerman, Anthony H

    2017-03-01

    In the lysosomal storage disorder Gaucher disease (GD), glucosylceramide (GlcCer) accumulates due to the defective activity of glucocerebrosidase. A subset of GD patients develops neuropathology. We now show mislocalization of Limp2-positive puncta and a large reduction in the number of Lamp1-positive puncta, which are associated with impaired tubulin. These changes occur at an early stage in animal models of GD, prior to development of overt symptoms and considerably earlier than neuronal loss. Altered lysosomal localization and cytoskeleton disruption precede the neuroinflammatory pathways, axonal dystrophy and neuronal loss previously characterized in neuronal forms of GD. © 2017 Federation of European Biochemical Societies.

  16. Quantifying risk of early relapse in patients with first demyelinating events: Prediction in clinical practice.

    Science.gov (United States)

    Spelman, Tim; Meyniel, Claire; Rojas, Juan Ignacio; Lugaresi, Alessandra; Izquierdo, Guillermo; Grand'Maison, Francois; Boz, Cavit; Alroughani, Raed; Havrdova, Eva; Horakova, Dana; Iuliano, Gerardo; Duquette, Pierre; Terzi, Murat; Grammond, Pierre; Hupperts, Raymond; Lechner-Scott, Jeannette; Oreja-Guevara, Celia; Pucci, Eugenio; Verheul, Freek; Fiol, Marcela; Van Pesch, Vincent; Cristiano, Edgardo; Petersen, Thor; Moore, Fraser; Kalincik, Tomas; Jokubaitis, Vilija; Trojano, Maria; Butzkueven, Helmut

    2017-09-01

    Characteristics at clinically isolated syndrome (CIS) examination assist in identification of patient at highest risk of early second attack and could benefit the most from early disease-modifying drugs (DMDs). To examine determinants of second attack and validate a prognostic nomogram for individualised risk assessment of clinical conversion. Patients with CIS were prospectively followed up in the MSBase Incident Study. Predictors of clinical conversion were analysed using Cox proportional hazards regression. Prognostic nomograms were derived to calculate conversion probability and validated using concordance indices. A total of 3296 patients from 50 clinics in 22 countries were followed up for a median (inter-quartile range (IQR)) of 1.92 years (0.90, 3.71). In all, 1953 (59.3%) patients recorded a second attack. Higher Expanded Disability Status Scale (EDSS) at baseline, first symptom location, oligoclonal bands and various brain and spinal magnetic resonance imaging (MRI) metrics were all predictors of conversion. Conversely, older age and DMD exposure post-CIS were associated with reduced rates. Prognostic nomograms demonstrated high concordance between estimated and observed conversion probabilities. This multinational study shows that age at CIS onset, DMD exposure, EDSS, multiple brain and spinal MRI criteria and oligoclonal bands are associated with shorter time to relapse. Nomogram assessment may be useful in clinical practice for estimating future clinical conversion.

  17. Identifying at-risk profiles and protective factors for problem gambling: A longitudinal study across adolescence and early adulthood.

    Science.gov (United States)

    Allami, Youssef; Vitaro, Frank; Brendgen, Mara; Carbonneau, René; Tremblay, Richard E

    2018-05-01

    Past studies have identified various risk and protective factors for problem gambling (PG). However, no study has examined the interplay between these factors using a combination of person-centered and variable-centered approaches embedded within a longitudinal design. The present study aimed to (a) identify distinct profiles in early adolescence based on a set of risk factors commonly associated with PG (impulsivity, depression, anxiety, drug-alcohol use, aggressiveness, and antisociality), (b) explore the difference in reported gambling problems between these profiles during midadolescence and early adulthood, and (c) identify family- and peer-related variables that could operate as protective or compensatory factors in this context. Two samples were used: (a) a population sample (N = 1,033) living in low socioeconomic-status neighborhoods and (b) a population sample (N = 3,017) representative of students attending Quebec schools. Latent profile analyses were conducted to identify at-risk profiles based on individual risk factors measured at age 12 years. Negative binomial regression models were estimated to compare profiles in terms of their reported gambling problems at ages 16 and 23. Finally, family- and peer-related variables measured at age 14 were included to test their protective or compensatory role with respect to the link between at-risk profiles and gambling problems. Four profiles were identified: well-adjusted, internalizing, externalizing, and comorbid. Compared to the well-adjusted profile, the externalizing and comorbid profiles reported more gambling problems at ages 16 and 23, but the internalizing profile did not differ significantly. Various protective and compensatory factors emerged for each profile at both time points. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  18. Initiatives on early detection and intervention to proactively identify health and social problems in older people: experiences from the Netherlands.

    Science.gov (United States)

    Lette, Manon; Baan, Caroline A; van den Berg, Matthijs; de Bruin, Simone R

    2015-10-30

    Over the last years, several initiatives on early detection and intervention have been put in place to proactively identify health and social problems in (frail) older people. An overview of the initiatives currently available in the Netherlands is lacking, and it is unknown whether they meet the preferences and needs of older people. Therefore, the objectives of this study were threefold: 1. To identify initiatives on early detection and intervention for older people in the Netherlands and compare their characteristics; 2. To explore the experiences of professionals with these initiatives; and 3. To explore to what extent existing initiatives meet the preferences and needs of older people. We performed a qualitative descriptive study in which we conducted semi-structured interviews with seventeen experts in preventive elderly care and three group interviews with volunteer elderly advisors. Data were analysed using the framework analysis method. We identified eight categories of initiatives based on the setting (e.g. general practitioner practice, hospital, municipality) in which they were offered. Initiatives differed in their aims and target groups. The utilization of peers to identify problems and risks, as was done by some initiatives, was seen as a strength. Difficulties were experienced with identifying the target group that would benefit from proactive delivery of care and support most, and with addressing prevalent issues among older people (e.g. psychosocial issues, self-reliance issues). Although there is a broad array of initiatives available, there is a discrepancy between supply and demand. Current initiatives insufficiently address needs of (frail) older people. More insight is needed in "what should be done by whom, for which target group and at what moment", in order to improve current practice in preventive elderly care.

  19. Modeling long recovery early events (LOREs) produced by lightning-induced ionization of the nighttime upper mesosphere

    Science.gov (United States)

    Kotovsky, D. A.; Moore, R. C.

    2017-07-01

    We present results of a cylindrically symmetric, coupled electrodynamic, and photochemical model which simulates diffuse ionization of the middle atmosphere induced by strong lightning discharges (peak currents >150 kA). Scattering of subionospherically propagating, very low frequency radio waves is then evaluated using the Long-Wave Propagation Capability code. Some modeled sprite halos exhibit continued electron density growth up to timescales of seconds due to O- detachment, though it is not yet clear how this might relate to the slower onset durations (>20 ms) of some early VLF events. Modeled electron density enhancements in sprite halos, capable of strong VLF scattering, can persist for long periods of time (greater than hundreds of seconds) even at lower altitudes where their recovery is initially controlled by fast attachment processes. Consequently, our modeling results indicate that both typical recovery (20 to 240 s) and long recovery (LOREs, >300 s) VLF scattering events can be explained by scattering from conductivity changes associated with sprite halos. In contrast, modeled scattered fields resulting from elve-associated conductivity changes, though exhibiting long recovery times, are too weak to sufficiently explain typical LORE observations. Theoretical scattering from structured ionization events (e.g., sprites columns and gigantic jets) is not considered in this work.

  20. Riding the Wave to Reach the Masses: Natural Events in Early Twentieth Century Portuguese Daily Press

    Science.gov (United States)

    Simões, Ana; Carneiro, Ana; Diogo, Maria Paula

    2012-03-01

    This paper brings together science communicated in newspapers in Portugal by looking at how news on natural events were communicated in two different newspapers—the capital newspaper Diário de Notícias ( Daily News) and the Diário dos Açores ( Azores Daily). In particular, we look at how the 1900 solar eclipse, a hot topic throughout Europe, was reported by the capital newspaper, and how news on seismology were conveyed in the period 1907-1910 in the newspaper published in Azores, an archipelago with a significant seismic and volcanic activity. We argue that the importance conceded to these scientific news was related to their overwhelming features, that their dissimilar presentation stemmed from their local relevance allied to their different nature, predictable in the case of eclipses, and unpredictable in the case of earthquakes, and that behind these two instances of science journalism laid an attempt by the scientific and political communities to gain the support of the general public to such an extent that these two specific instances of science journalism transcended their usual features to become successful forms of expository science.

  1. A Possible Late Paleocene-Early Eocene Ocean Acidification Event Recoded in the Adriatic Carbonate Platform

    Science.gov (United States)

    Weiss, A.; Martindale, R. C.; Kosir, A.; Oefinger, J.

    2017-12-01

    The Paleocene-Eocene Thermal Maximum (PETM) event ( 56.3 Ma) was a period of massive carbon release into the Earth system, resulting in significant shifts in ocean chemistry. It has been proposed that ocean acidification - a decrease in the pH and carbonate saturation state of the water as a result of dissolved carbon dioxide in sea water - occurred in both the shallow and deep marine realms. Ocean acidification would have had a devastating impact on the benthic ecosystem, and has been proposed as the cause of decreased carbonate deposition in marine sections and coral reef collapse during the late Paleocene. To date, however, the only physical evidence of Paleocene-Eocene ocean acidification has been shown for offshore sites (i.e., a shallow carbonate compensation depth), but isotope analysis (i.e. B, I/Ca) suggests that acidification occurred in the shallow shelves as well. Several sites in the Kras region of Slovenia, has been found to contain apparent erosion surfaces coeval with the Paleocene-Eocene Boundary. We have investigated these potentially acidified horizons using petrography, stable carbon isotopes, cathodoluminescence, and elemental mapping. These datasets will inform whether the horizons formed by seafloor dissolution in an acidified ocean, or are due to subaerial exposure, or burial diagenesis (i.e. stylotization). Physical erosion and diagenesis can easily be ruled out based on field relationships and petrography, but the other potential causes must be analyzed more critically.

  2. Astronomy in the ancient world early and modern views on celestial events

    CERN Document Server

    McLeod, Alexus

    2016-01-01

    Alexus McLeod explores every aspect of the lesser-known history of astronomy in the Americas (Mesoamerica and North America), China and India, each through the frame of a particular astronomical phenomena. Part One considers the development of astronomy in the Americas as a response, in part, to the Supernova of 1054, which may have led to a cultural renaissance in astronomy. He then goes on to explore the contemporary understanding of supernovae, contrasting it with that of the ancient Americas.  Part Two is framed through the appearances of great comets, which had major divinatory significance in early China. The author discusses the advancement of observational astronomy in China, its influence on politics and its role in the survival or failure of empires.  Furthermore, the contemporary understanding of comets is also discussed for comparison.  Part Three, on India, considers the magnificent observatories of the Rajput king Jai Singh II, and the question of their purpose. The origins of Indian ast...

  3. Eco-Efficient Process Improvement at the Early Development Stage: Identifying Environmental and Economic Process Hotspots for Synergetic Improvement Potential.

    Science.gov (United States)

    Piccinno, Fabiano; Hischier, Roland; Seeger, Stefan; Som, Claudia

    2018-05-15

    We present here a new eco-efficiency process-improvement method to highlight combined environmental and costs hotspots of the production process of new material at a very early development stage. Production-specific and scaled-up results for life cycle assessment (LCA) and production costs are combined in a new analysis to identify synergetic improvement potentials and trade-offs, setting goals for the eco-design of new processes. The identified hotspots and bottlenecks will help users to focus on the relevant steps for improvements from an eco-efficiency perspective and potentially reduce their associated environmental impacts and production costs. Our method is illustrated with a case study of nanocellulose. The results indicate that the production route should start with carrot pomace, use heat and solvent recovery, and deactivate the enzymes with bleach instead of heat. To further improve the process, the results show that focus should be laid on the carrier polymer, sodium alginate, and the production of the GripX coating. Overall, the method shows that the underlying LCA scale-up framework is valuable for purposes beyond conventional LCA studies and is applicable at a very early stage to provide researchers with a better understanding of their production process.

  4. Targeted next generation sequencing identifies functionally deleterious germline mutations in novel genes in early-onset/familial prostate cancer.

    Directory of Open Access Journals (Sweden)

    Paula Paulo

    2018-04-01

    Full Text Available Considering that mutations in known prostate cancer (PrCa predisposition genes, including those responsible for hereditary breast/ovarian cancer and Lynch syndromes, explain less than 5% of early-onset/familial PrCa, we have sequenced 94 genes associated with cancer predisposition using next generation sequencing (NGS in a series of 121 PrCa patients. We found monoallelic truncating/functionally deleterious mutations in seven genes, including ATM and CHEK2, which have previously been associated with PrCa predisposition, and five new candidate PrCa associated genes involved in cancer predisposing recessive disorders, namely RAD51C, FANCD2, FANCI, CEP57 and RECQL4. Furthermore, using in silico pathogenicity prediction of missense variants among 18 genes associated with breast/ovarian cancer and/or Lynch syndrome, followed by KASP genotyping in 710 healthy controls, we identified "likely pathogenic" missense variants in ATM, BRIP1, CHEK2 and TP53. In conclusion, this study has identified putative PrCa predisposing germline mutations in 14.9% of early-onset/familial PrCa patients. Further data will be necessary to confirm the genetic heterogeneity of inherited PrCa predisposition hinted in this study.

  5. CISN ShakeAlert: Faster Warning Information Through Multiple Threshold Event Detection in the Virtual Seismologist (VS) Early Warning Algorithm

    Science.gov (United States)

    Cua, G. B.; Fischer, M.; Caprio, M.; Heaton, T. H.; Cisn Earthquake Early Warning Project Team

    2010-12-01

    The Virtual Seismologist (VS) earthquake early warning (EEW) algorithm is one of 3 EEW approaches being incorporated into the California Integrated Seismic Network (CISN) ShakeAlert system, a prototype EEW system that could potentially be implemented in California. The VS algorithm, implemented by the Swiss Seismological Service at ETH Zurich, is a Bayesian approach to EEW, wherein the most probable source estimate at any given time is a combination of contributions from a likehihood function that evolves in response to incoming data from the on-going earthquake, and selected prior information, which can include factors such as network topology, the Gutenberg-Richter relationship or previously observed seismicity. The VS codes have been running in real-time at the Southern California Seismic Network since July 2008, and at the Northern California Seismic Network since February 2009. We discuss recent enhancements to the VS EEW algorithm that are being integrated into CISN ShakeAlert. We developed and continue to test a multiple-threshold event detection scheme, which uses different association / location approaches depending on the peak amplitudes associated with an incoming P pick. With this scheme, an event with sufficiently high initial amplitudes can be declared on the basis of a single station, maximizing warning times for damaging events for which EEW is most relevant. Smaller, non-damaging events, which will have lower initial amplitudes, will require more picks to initiate an event declaration, with the goal of reducing false alarms. This transforms the VS codes from a regional EEW approach reliant on traditional location estimation (and the requirement of at least 4 picks as implemented by the Binder Earthworm phase associator) into an on-site/regional approach capable of providing a continuously evolving stream of EEW information starting from the first P-detection. Real-time and offline analysis on Swiss and California waveform datasets indicate that the

  6. Signal transduction by FcεRI: Analysis of the early molecular events

    Directory of Open Access Journals (Sweden)

    Henry Metzger

    1999-01-01

    Full Text Available We are analysing the initial molecular events stimulated by the high-affinity receptor for IgE, FcεRI. Earlier studies have shown that the first response when the receptor-bound IgE interacts with a multivalent antigen is a transphosphorylation of receptor tyrosines, induced by the approximation of two or more receptors by a constitutively associated src-family kinase (Lyn. The amount of weakly associated kinase regulates the intensity of the response. Several aspects are being analyzed: (i the sites on Lyn and the receptor that account for the constitutive interaction; (ii how the intrinsic affinity of a ligand for the receptor-bound IgE influences the responses; and (iii the mechanism(s by which low-affinity ligands can act as antagonists. In the latter studies, mast cell responses were followed by monitoring the phosphorylation of tyrosines on several proteins and secretion. At equivalent levels of receptor phosphorylation, a ligand with high affinity stimulated vigorous phosphorylation of downstream components, whereas a low-affinity ligand was unable to stimulate phosphorylation of the same components effectively. Cells stimulated with a mixture of high- and low-affinity ligands, under a protocol where simple displacement of one by the other was prevented, remarkably showed that excess low-affinity ligand inhibited the phosphorylation as well as degranulation by the high-affinity ligand. This antagonism results from a competition for the limiting amount of the constitutive initiating kinase. Related receptors that depend on recruitment of initiating kinases may be subject to similar regulatory mechanisms.

  7. The Early Toarcian oceanic anoxic event: Paleoenvironmental and paleoclimatic change across the Alpine Tethys (Switzerland)

    Science.gov (United States)

    Fantasia, Alicia; Föllmi, Karl B.; Adatte, Thierry; Spangenberg, Jorge E.; Montero-Serrano, Jean-Carlos

    2018-03-01

    Paleoenvironmental and paleoclimatic change associated with the Toarcian oceanic anoxic event (T-OAE) was evaluated in five successions located in Switzerland. They represent different paleogeographic settings across the Alpine Tethys: the northern shelf (Gipf, Riniken and Rietheim), the Sub-Briançonnais basin (Creux de l'Ours), and the Lombardian basin (Breggia). The multi-proxy approach chosen (whole-rock and clay mineralogy, phosphorus, major and trace elements) shows that local environmental conditions modulated the response to the T-OAE across the Alpine Tethys. On the northern shelf and in the Sub-Briançonnais basin, high kaolinite contents and detrital proxies (detrital index, Ti, Zr, Si) in the T-OAE interval suggest a change towards a warmer and more humid climate coupled with an increase in the chemical weathering rates. In contrast, low kaolinite content in the Lombardian basin is likely related to a more arid climate along the southern Tethys margin and/or to a deeper and more distal setting. Redox-sensitive trace-element (V, Mo, Cu, Ni) enrichments in the T-OAE intervals reveal that dysoxic to anoxic conditions developed on the northern shelf, whereas reducing conditions were less severe in the Sub-Briançonnais basin. In the Lombardian basin well-oxygenated bottom water conditions prevailed. Phosphorus (P) speciation analysis was performed at Riniken and Creux de l'Ours. This is the first report of P speciation data for T-OAE sections, clearly suggesting that high P contents during this time interval are mainly linked to the presence of an authigenic phases and fish remains. The development of oxygen-depleted conditions during the T-OAE seems to have promoted the release of the organic-bound P back into the water column, thereby further sustaining primary productivity in a positive feedback loop.

  8. The PRESSCA operational early warning system for landslide forecasting: the 11-12 November 2013 rainfall event in Central Italy.

    Science.gov (United States)

    Ciabatta, Luca; Brocca, Luca; Ponziani, Francesco; Berni, Nicola; Stelluti, Marco; Moramarco, Tommaso

    2014-05-01

    The Umbria Region, located in Central Italy, is one of the most landslide risk prone area in Italy, almost yearly affected by landslides events at different spatial scales. For early warning procedures aimed at the assessment of the hydrogeological risk, the rainfall thresholds represent the main tool for the Italian Civil Protection System. As shown in previous studies, soil moisture plays a key-role in landslides triggering. In fact, acting on the pore water pressure, soil moisture influences the rainfall amount needed for activating a landslide. In this work, an operational physically-based early warning system, named PRESSCA, that takes into account soil moisture for the definition of rainfall thresholds is presented. Specifically, the soil moisture conditions are evaluated in PRESSCA by using a distributed soil water balance model that is recently coupled with near real-time satellite soil moisture product obtained from ASCAT (Advanced SCATterometer) and from in-situ monitoring data. The integration of three different sources of soil moisture information allows to estimate the most accurate possible soil moisture condition. Then, both observed and forecasted rainfall data are compared with the soil moisture-based thresholds in order to obtain risk indicators over a grid of ~ 5 km. These indicators are then used for the daily hydrogeological risk evaluation and management by the Civil Protection regional service, through the sharing/delivering of near real-time landslide risk scenarios (also through an open source web platform: www.cfumbria.it). On the 11th-12th November, 2013, Umbria Region was hit by an exceptional rainfall event with up to 430mm/72hours that resulted in significant economic damages, but fortunately no casualties among the population. In this study, the results during the rainfall event of PRESSCA system are described, by underlining the model capability to reproduce, two days in advance, landslide risk scenarios in good spatial and temporal

  9. The Center for the Study of Early Events in Photosynthesis. Final report, September 1, 1988--August 31, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Orr, L.A.

    1994-12-31

    The ASU Center for the Study of Early Events in Photosynthesis was established in 1988 with funding through a five-year grant from the USDA/DOE/NSF Plant Science Center program and a grant from the NSF Biological Facilities program. Its scientific objective is to elucidate the basic principles that govern photosynthetic energy collection and storage. Understanding these principles is vital to mankind, as photosynthesis provides most of our food, fiber and energy needs. The Center attempts to fulfill this objective through research of the highest standard, coupled inextricably with quality education at the undergraduate, graduate and postdoctoral levels. These goals are met via a network of collaborative, interdisciplinary research groups comprising 100 personnel within the Department of Chemistry and Biochemistry, the Department of Botany, and the Department of Physics and Astronomy. The work of these research groups is facilitated by the Center through a variety of important infrastructural functions.

  10. Baseline HbA1c to Identify High-Risk Gestational Diabetes: Utility in Early vs Standard Gestational Diabetes.

    Science.gov (United States)

    Sweeting, Arianne N; Ross, Glynis P; Hyett, Jon; Molyneaux, Lynda; Tan, Kris; Constantino, Maria; Harding, Anna Jane; Wong, Jencia

    2017-01-01

    The increasing prevalence of gestational diabetes mellitus (GDM) necessitates risk stratification directing limited antenatal resources to those at greatest risk. Recent evidence demonstrates that an early pregnancy glycated hemoglobin (HbA1c ≥5.9% (41 mmol/mol) predicts adverse pregnancy outcomes. To determine the optimal HbA1c threshold for adverse pregnancy outcomes in GDM in a treated multiethnic cohort and whether this differs in women diagnosed HbA1c (single-laboratory) measurement at the time of GDM diagnosis. Maternal clinical and pregnancy outcome data were collected prospectively. The association between baseline HbA1c and adverse pregnancy outcomes in early vs standard GDM. HbA1c was measured at a median of 17.6 ± 3.3 weeks' gestation in early GDM (n = 844) and 29.4 ± 2.6 weeks' gestation in standard GDM (n = 2254). In standard GDM, HbA1c >5.9% (41 mmol/mol) was associated with the greatest risk of large-for-gestational-age (odds ratio [95% confidence interval] = 2.7 [1.5-4.9]), macrosomia (3.5 [1.4-8.6]), cesarean section (3.6 [2.1-6.2]), and hypertensive disorders (2.6 [1.1-5.8]). In early GDM, similar HbA1c associations were seen; however, lower HbA1c correlated with the greatest risk of small-for-gestational-age (P trend = 0.004) and prevalence of neonatal hypoglycemia. Baseline HbA1c >5.9% (41 mmol/mol) identifies an increased risk of large-for-gestational-age, macrosomia, cesarean section, and hypertensive disorders in standard GDM. Although similar associations are seen in early GDM, higher HbA1c levels do not adequately capture risk-limiting utility as a triage tool in this cohort. Copyright © 2017 by the Endocrine Society

  11. The Intense Arctic Cyclone of Early August 2012: A Dynamically Driven Cyclogenesis Event

    Science.gov (United States)

    Bosart, L. F.; Turchioe, A.; Adamchcik, E.

    2013-12-01

    A series of surface cyclones formed along an anomalously strong northeast-southwest oriented baroclinic zone over north-central Russia on 1-3 August 2012. These cyclones moved northeastward, intensified slowly, and crossed the coast of Russia by 4 August. The last cyclone in the series strengthened rapidly as it moved poleward over the Arctic Ocean on 5-6 August, achieved a minimum sea level pressure of life cycle of this Arctic Ocean cyclone from a multiscale perspective. Anticyclonic wave breaking in the upper troposphere across Russia in late July and very early August 2012 created an anomalously strong baroclinic zone across northern Asia between 60-80°N. During 1-5 August, negative 850 hPa temperature anomalies between -2° and -4°C were found poleward of 70-75°N between 90°E and the Dateline over the Arctic Ocean while positive 850 hPa temperature anomalies of 8-9°C were found over eastern Russia near 60°N. The associated anomalously strong 850 hPa meridional temperature gradient of ~10°C (2000 km)-1 helped to sustain an anomalously strong (20-30 m s-1) 250 hPa jet along the coast of northeastern Russia. A local wind speed maximum (~50 m s-1 ) embedded in this 250 hPa jet corridor contributed to the extreme intensity of the trailing (last) surface cyclone in the series. Although the dominant surface cyclone in the series of surface cyclones intensified most rapidly over the relatively ice free Arctic Ocean, the impact of surface heat and moisture fluxes appeared to be secondary to jet-driven dynamical processes in the deepening process. Anomalously high observed 1000-500 hPa thickness values between 564-570 dam, precipitable water values between 30-40 mm, and CAPE values between 500-1000 J kg-1 in the warm sector of the developing cyclone over north-central Russia were indicative of the enhanced baroclinicity and instability in the cyclone warm sector and the ability of lower tropospheric warm-air advection to sustain deep ascent in the intensifying

  12. Multiple-Threshold Event Detection and Other Enhancements to the Virtual Seismologist (VS) Earthquake Early Warning Algorithm

    Science.gov (United States)

    Fischer, M.; Caprio, M.; Cua, G. B.; Heaton, T. H.; Clinton, J. F.; Wiemer, S.

    2009-12-01

    The Virtual Seismologist (VS) algorithm is a Bayesian approach to earthquake early warning (EEW) being implemented by the Swiss Seismological Service at ETH Zurich. The application of Bayes’ theorem in earthquake early warning states that the most probable source estimate at any given time is a combination of contributions from a likelihood function that evolves in response to incoming data from the on-going earthquake, and selected prior information, which can include factors such as network topology, the Gutenberg-Richter relationship or previously observed seismicity. The VS algorithm was one of three EEW algorithms involved in the California Integrated Seismic Network (CISN) real-time EEW testing and performance evaluation effort. Its compelling real-time performance in California over the last three years has led to its inclusion in the new USGS-funded effort to develop key components of CISN ShakeAlert, a prototype EEW system that could potentially be implemented in California. A significant portion of VS code development was supported by the SAFER EEW project in Europe. We discuss recent enhancements to the VS EEW algorithm. We developed and continue to test a multiple-threshold event detection scheme, which uses different association / location approaches depending on the peak amplitudes associated with an incoming P pick. With this scheme, an event with sufficiently high initial amplitudes can be declared on the basis of a single station, maximizing warning times for damaging events for which EEW is most relevant. Smaller, non-damaging events, which will have lower initial amplitudes, will require more picks to be declared an event to reduce false alarms. This transforms the VS codes from a regional EEW approach reliant on traditional location estimation (and it requirement of at least 4 picks as implemented by the Binder Earthworm phase associator) to a hybrid on-site/regional approach capable of providing a continuously evolving stream of EEW

  13. Resolving Early Signaling Events in T-Cell Activation Leading to IL-2 and FOXP3 Transcription

    Directory of Open Access Journals (Sweden)

    Jeffrey P. Perley

    2014-11-01

    Full Text Available Signal intensity and feedback regulation are known to be major factors in the signaling events stemming from the T-cell receptor (TCR and its various coreceptors, but the exact nature of these relationships remains in question. We present a mathematical model of the complex signaling network involved in T-cell activation with cross-talk between the Erk, calcium, PKC and mTOR signaling pathways. The model parameters are adjusted to fit new and published data on TCR trafficking, Zap70, calcium, Erk and Isignaling. The regulation of the early signaling events by phosphatases, CD45 and SHP1, and the TCR dynamics are critical to determining the behavior of the model. Additional model corroboration is provided through quantitative and qualitative agreement with experimental data collected under different stimulating and knockout conditions. The resulting model is analyzed to investigate how signal intensity and feedback regulation affect TCR- and coreceptor-mediated signal transduction and their downstream transcriptional profiles to predict the outcome for a variety of stimulatory and knockdown experiments. Analysis of the model shows that: (1 SHP1 negative feedback is necessary for preventing hyperactivity in TCR signaling; (2 CD45 is required for TCR signaling, but also partially suppresses it at high expression levels; and (3 elevated FOXP3 and reduced IL-2 signaling, an expression profile often associated with T regulatory cells (Tregs, is observed when the system is subjected to weak TCR and CD28 costimulation or a severe reduction in CD45 activity.

  14. Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study.

    Science.gov (United States)

    Duarte, João V; Pereira, João M S; Quendera, Bruno; Raimundo, Miguel; Moreno, Carolina; Gomes, Leonor; Carrilho, Francisco; Castelo-Branco, Miguel

    2015-10-01

    Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.

  15. Genome-wide allelotyping of a new in vitro model system reveals early events in breast cancer progression.

    Science.gov (United States)

    Li, Zheng; Meng, Zhen Hang; Sayeed, Aejaz; Shalaby, Refaat; Ljung, Britt-Marie; Dairkee, Shanaz H

    2002-10-15

    Toward the goal of identifying early genetic losses, which mediate the release of human breast epithelium from replicative suppression leading to cellular immortalization, we have used a newly developed in vitro model system. This system consists of epithelial cultures derived from noncancerous breast tissue, treated with the chemical carcinogen N-ethyl-N-nitrosourea, and continuously passaged to yield cell populations culminating in the immortal phenotype. Genome-wide allelotyping of early passage N-ethyl-N-nitrosourea-exposed cell populations revealed aberrations at >10% (18 of 169) loci examined. Allelic losses encompassing chromosomes 6q24-6q27, implicating immortalization-associated candidate genes, hZAC and SEN6, occurred in two independently derived cell lines before the Hayflick limit. Additional LOH sites were present in one cell line at 3p11-3p26, 11p15, and 20p12-13. Allelic losses reported in this cell line preceded detectable levels of telomerase activity and the occurrence of p53-related aberrations. Information gained from the search for early immortalization-associated genetic deletions in cultured cells was applied in a novel approach toward the analysis of morphologically normal terminal ductal lobular units microdissected from 20 cases of ductal carcinoma in situ. Notably, clonal allelic losses at chromosome 3p24 and 6q24 were an early occurrence in adjoining terminal ductal lobular units of a proportion of primary tumors, which displayed loss of heterozygosity (3 of 11 and 3 of 6, respectively). The biological insights provided by the new model system reported here strongly suggest that early allelic losses delineated in immortalized cultures and validated in vivo could serve as surrogate endpoints to assist in the identification and intervention of high-risk benign breast tissue, which sustains the potential for continuous proliferation.

  16. Early psychosocial interventions after disasters, terrorism and other shocking events: is there a gap between norms and practice in Europe?

    Science.gov (United States)

    Te Brake, Hans

    2013-01-01

    Background Internationally, several initiatives exist to describe standards for post-disaster psychosocial care. Objective This study explored the level of consensus of experts within Europe on a set of recommendations on early psychosocial intervention after shocking events (Dutch guidelines), and to what degree these standards are implemented into mental health care practice. Methods Two hundred and six (mental) health care professionals filled out a questionnaire to assess the extent to which they consider the guidelines’ scope and recommendations relevant and part of the regular practice in their own country. Forty-five European experts from 24 EU countries discussed the guidelines at an international seminar. Results The data suggest overall agreement on the standards although many of the recommendations appear not (yet) to be embedded in everyday practice. Conclusions Although large consensus exists on standards for early psychosocial care, a chasm between norms and practice appears to exist throughout the EU, stressing the general need for investments in guideline development and implementation. PMID:23393613

  17. Timing of the Toarcian Ocean Anoxic Event (Early Jurassic) from correlation of astronomically forced global stratigraphic sections

    Science.gov (United States)

    Huang, C.; Hinnov, L. A.; Hesselbo, S. P.

    2012-12-01

    The Early Toarcian Oceanic Anoxic Event (OAE) in the Early Jurassic Period is associated with a major negative carbon isotope excursion (CIE), mass extinction, marine transgression and global warming. The Toarcian OAE is thought to have been caused by flood basalt magmatism, and may have been a trigger for mass extinction. However, these proposed causes of the Toarcian OAE and associated biotic crisis are not adequately resolved by a precise chronology. The duration of the Toarcian OAE has been estimated to be anywhere from ~0.12 to ~0.9 Myr, most recently 0.74 to 3.26 Myr from U-Pb dating. The CIE associated with the Toarcian OAE has a similar pattern at numerous localities, and there is evidence for astronomical forcing of marine carbon isotopes. Here we estimate a duration of ~625 kyr for the main negative CIE, ~860 kyr for the polymorphum zone and >1.58 Myr for the levisoni zone based on 405-kyr astronomical eccentricity tuning of the marine section at Peniche (Portugal). This 405-kyr tuned series provides a ~2.5 Myr continuous high-resolution chronology through the Early Toarcian. There are 6, or possibly 7 short eccentricity cycles in the main CIE interval at Peniche. To confirm this astronomically based estimate, we analyzed five other sections at Yorkshire (UK), Dotternhausen (Germany), Valdorbia (Italy), Mechowo (Poland) and Serrucho, Neuquén (Argentina), from marine and terrestrial carbon isotopic series. These six stratigraphic sections from Early Jurassic western Tethys and eastern Panthalassa record the Toarcian OAE with ~6 prominent carbon isotope cycles in the CIE that provide us a 600 ± 100 kyr duration. The Peniche 405 kyr-tuned series indicates that the pre- and post-CIE intervals experienced strong precession-eccentricity-forced climate change, whereas the CIE interval is marked by dominant obliquity forcing. These dramatic and abrupt changes in astronomical response in the carbon isotopes point to fundamental shifting in the Early Toarcian

  18. Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota.

    Science.gov (United States)

    Martin, Rocio; Makino, Hiroshi; Cetinyurek Yavuz, Aysun; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan

    2016-01-01

    Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the

  19. Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota.

    Directory of Open Access Journals (Sweden)

    Rocio Martin

    Full Text Available Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to

  20. Inhibition of Rho kinase regulates specification of early differentiation events in P19 embryonal carcinoma stem cells.

    Directory of Open Access Journals (Sweden)

    Roman J Krawetz

    Full Text Available The Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK play pivotal roles in cell migration, apoptosis (membrane blebbing, cell proliferation/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma stem cells, however, the effect of ROCK inhibition on mesoderm and ectoderm specification has not been fully examined. In this study, the role of ROCK within the specification and differentiation of all three germ layers was examined.P19 cells were treated with the specific ROCK inhibitor Y-27623, and increase in differentiation efficiency into neuro-ectodermal and mesodermal lineages was observed. However, as expected a dramatic decrease in early endodermal markers was observed when ROCK was inhibited. Interestingly, within these ROCK-inhibited RA treated cultures, increased levels of mesodermal or ectodermal markers were not observed, instead it was found that the pluripotent markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in undifferentiated cultures. Using standard and widely accepted methods for reproducible P19 differentiation into all three germ layers, an enhancement of mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage specification was observed with Y-27632 treatment. Evidence would suggest that this effect is in part mediated through TGF-β and SMAD signaling as ROCK-inhibited cells displayed aberrant SMAD activation and did not return to a 'ground' state after the inhibition had been removed.Given this data and the fact that only a partial rescue of normal differentiation capacity occurred when ROCK inhibition was alleviated, the effect of ROCK inhibition on the differentiation capacity of pluripotent cell populations should be further examined to elucidate the

  1. RADAR study: protocol for an observational cohort study to identify early warning signals on the pathways to alcohol use disorder.

    Science.gov (United States)

    Slade, Tim; Swift, Wendy; Mewton, Louise; Kypri, Kypros; Lynskey, Michael T; Butterworth, Peter; Tibbetts, Joel; McCraw, Stacey; Upton, Emily

    2017-08-21

    Harmful alcohol consumption, particularly alcohol use disorder (AUD), is a worldwide health priority, contributing substantially to global morbidity and mortality. The peak age of onset of AUD is 18-24, thus a deeper understanding of the young adult experience is vital if we are to identify modifiable risk factors and intervene early in the developmental course of this disabling disorder. Critical unanswered questions include: How soon after drinking initiation do AUD symptoms begin to emerge? Which symptoms come first? Do the symptoms unfold in a predictable pattern? In what ways do the emerging symptoms interact with individual, peer, family and environmental risk factors to impact on the transition to disorder? The proposed RADAR study will examine the prospective development of AUD symptoms over the young adulthood (18-24) years. We will capitalise on an existing cohort of 1911 community-based adolescents who were recruited at age 13 and have completed a baseline and five annual follow-up assessments as part of an observational cohort study. We will interview these adolescents every 6 months between the ages of 19 and 23 to derive monthly histories of both alcohol use and AUD symptomatology, along with a comprehensive battery of risk and protective factor scales hypothesised to predict the emergence and course of AUD. The results of this study will inform the natural history of AUD and will be used to identify specific targets for prevention and early intervention of AUD. Ethical approval has already been granted for the study (UNSW HREC 10144). We will disseminate the results of the study through published manuscripts, conferences and seminar presentations. Data used in published manuscripts will be made available through a suitable online repository (eg, Dryad-datadryad.org). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly

  2. Identifying and quantifying proteolytic events and the natural N terminome by terminal amine isotopic labeling of substrates.

    Science.gov (United States)

    Kleifeld, Oded; Doucet, Alain; Prudova, Anna; auf dem Keller, Ulrich; Gioia, Magda; Kizhakkedathu, Jayachandran N; Overall, Christopher M

    2011-09-22

    Analysis of the sequence and nature of protein N termini has many applications. Defining the termini of proteins for proteome annotation in the Human Proteome Project is of increasing importance. Terminomics analysis of protease cleavage sites in degradomics for substrate discovery is a key new application. Here we describe the step-by-step procedures for performing terminal amine isotopic labeling of substrates (TAILS), a 2- to 3-d (depending on method of labeling) high-throughput method to identify and distinguish protease-generated neo-N termini from mature protein N termini with all natural modifications with high confidence. TAILS uses negative selection to enrich for all N-terminal peptides and uses primary amine labeling-based quantification as the discriminating factor. Labeling is versatile and suited to many applications, including biochemical and cell culture analyses in vitro; in vivo analyses using tissue samples from animal and human sources can also be readily performed. At the protein level, N-terminal and lysine amines are blocked by dimethylation (formaldehyde/sodium cyanoborohydride) and isotopically labeled by incorporating heavy and light dimethylation reagents or stable isotope labeling with amino acids in cell culture labels. Alternatively, easy multiplex sample analysis can be achieved using amine blocking and labeling with isobaric tags for relative and absolute quantification, also known as iTRAQ. After tryptic digestion, N-terminal peptide separation is achieved using a high-molecular-weight dendritic polyglycerol aldehyde polymer that binds internal tryptic and C-terminal peptides that now have N-terminal alpha amines. The unbound naturally blocked (acetylation, cyclization, methylation and so on) or labeled mature N-terminal and neo-N-terminal peptides are recovered by ultrafiltration and analyzed by tandem mass spectrometry (MS/MS). Hierarchical substrate winnowing discriminates substrates from the background proteolysis products and

  3. The Role of Difficulty in Identifying and Describing Feelings in Non-Suicidal Self-Injury Behavior (NSSI): Associations With Perceived Attachment Quality, Stressful Life Events, and Suicidal Ideation.

    Science.gov (United States)

    Cerutti, Rita; Zuffianò, Antonio; Spensieri, Valentina

    2018-01-01

    Objective: Core alexithymic features, such as the difficulty in identifying and describing feelings, are associated with poor attachment styles and emotional trauma, which influence the capacity to regulate affect. Additionally, emotional regulation has been found to be the most commonly identified function associated with non-suicidal self-injury behavior (NSSI) in adolescents as they attempt to modulate strong emotions. However, few studies have examined the link between difficulty in identifying and describing feelings (core components of alexithymia), NSSI behaviors, quality of attachment, life stressors and suicidal ideation in healthy early adolescents. Consequently, this study aims to investigate these constructs and the relationship among them in a large non-clinical sample of adolescents. Methods: Seven hundred and nine middle school students (50.4% males), aged 10-15 years ( M = 12.6; SD = 1.06) were involved in this study. In order to investigate the variables considered in the study, the following measures were administered: the Deliberate Self-Harm Inventory exploring non-suicidal self-injurious behaviors; the Alexithymia Questionnaire for Children examining difficulty in identifying and describing feelings; the Inventory of Parent and Peer Attachment assessing the quality of parental and peer attachment; the Life Stressor Checklist-Revised outlining stressful/traumatic events and the Children's Depression Inventory evaluating suicidal ideation. Results: We found significantly positive relationships among difficulty in identifying and describing feelings, NSSI behaviors, stressful events, and suicidal ideation. Data indicated a significant negative association of difficulty in identifying and describing feelings with quality of attachment to parents and peers. Further findings highlighted that difficulty in identifying and describing feelings significantly mediated the effect of quality of attachment (parent and peer) on NSSI and suicidal ideation

  4. Exome Sequencing Identified a Recessive RDH12 Mutation in a Family with Severe Early-Onset Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Bo Gong

    2015-01-01

    Full Text Available Retinitis pigmentosa (RP is the most important hereditary retinal disease caused by progressive degeneration of the photoreceptor cells. This study is to identify gene mutations responsible for autosomal recessive retinitis pigmentosa (arRP in a Chinese family using next-generation sequencing technology. A Chinese family with 7 members including two individuals affected with severe early-onset RP was studied. All patients underwent a complete ophthalmic examination. Exome sequencing was performed on a single RP patient (the proband of this family and direct Sanger sequencing on other family members and normal controls was followed to confirm the causal mutations. A homozygous mutation c.437Tidentified as being related to the phenotype of this arRP family. This homozygous mutation was detected in the two affected patients, but not present in other family members and 600 normal controls. Another three normal members in the family were found to carry this heterozygous missense mutation. Our results emphasize the importance of c.437T

  5. Early markers of autism spectrum disorders in infants and toddlers prospectively identified in the Social Attention and Communication Study.

    Science.gov (United States)

    Barbaro, Josephine; Dissanayake, Cheryl

    2013-01-01

    The Social Attention and Communication Study involved the successful implementation of developmental surveillance of the early markers of autism spectrum disorders in a community-based setting. The objective in the current study was to determine the most discriminating and predictive markers of autism spectrum disorders used in the Social Attention and Communication Study at 12, 18 and 24 months of age, so that these could be used to identify children with autism spectrum disorders with greater accuracy. The percentage of 'yes/no' responses for each behavioural marker was compared between children with autistic disorder (n = 39), autism spectrum disorder (n = 50) and developmental and/or language delay (n = 20) from 12 to 24 months, with a logistic regression also conducted at 24 months. Across all ages, the recurring key markers of both autistic disorder and autism spectrum disorder were deficits in eye contact and pointing, and from 18 months, deficits in showing became an important marker. In combination, these behaviours, along with pretend play, were found to be the best group of predictors for a best estimate diagnostic classification of autistic disorder/autism spectrum disorder at 24 months. It is argued that the identified markers should be monitored repeatedly during the second year of life by community health-care professionals.

  6. Demonstration of a Novel Synchrophasor-based Situational Awareness System: Wide Area Power System Visualization, On-line Event Replay and Early Warning of Grid Problems

    Energy Technology Data Exchange (ETDEWEB)

    Rosso, A.

    2012-12-31

    Since the large North Eastern power system blackout on August 14, 2003, U.S. electric utilities have spent lot of effort on preventing power system cascading outages. Two of the main causes of the August 14, 2003 blackout were inadequate situational awareness and inadequate operator training In addition to the enhancements of the infrastructure of the interconnected power systems, more research and development of advanced power system applications are required for improving the wide-area security monitoring, operation and planning in order to prevent large- scale cascading outages of interconnected power systems. It is critically important for improving the wide-area situation awareness of the operators or operational engineers and regional reliability coordinators of large interconnected systems. With the installation of large number of phasor measurement units (PMU) and the related communication infrastructure, it will be possible to improve the operators’ situation awareness and to quickly identify the sequence of events during a large system disturbance for the post-event analysis using the real-time or historical synchrophasor data. The purpose of this project was to develop and demonstrate a novel synchrophasor-based comprehensive situational awareness system for control centers of power transmission systems. The developed system named WASA (Wide Area Situation Awareness) is intended to improve situational awareness at control centers of the power system operators and regional reliability coordinators. It consists of following main software modules: • Wide-area visualizations of real-time frequency, voltage, and phase angle measurements and their contour displays for security monitoring. • Online detection and location of a major event (location, time, size, and type, such as generator or line outage). • Near-real-time event replay (in seconds) after a major event occurs. • Early warning of potential wide-area stability problems. The system has been

  7. HCN4 ion channel function is required for early events that regulate anatomical left-right patterning in a nodal and lefty asymmetric gene expression-independent manner.

    Science.gov (United States)

    Pai, Vaibhav P; Willocq, Valerie; Pitcairn, Emily J; Lemire, Joan M; Paré, Jean-François; Shi, Nian-Qing; McLaughlin, Kelly A; Levin, Michael

    2017-10-15

    Laterality is a basic characteristic of all life forms, from single cell organisms to complex plants and animals. For many metazoans, consistent left-right asymmetric patterning is essential for the correct anatomy of internal organs, such as the heart, gut, and brain; disruption of left-right asymmetry patterning leads to an important class of birth defects in human patients. Laterality functions across multiple scales, where early embryonic, subcellular and chiral cytoskeletal events are coupled with asymmetric amplification mechanisms and gene regulatory networks leading to asymmetric physical forces that ultimately result in distinct left and right anatomical organ patterning. Recent studies have suggested the existence of multiple parallel pathways regulating organ asymmetry. Here, we show that an isoform of the hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels (hyperpolarization-activated cyclic nucleotide-gated channel 4, HCN4) is important for correct left-right patterning. HCN4 channels are present very early in Xenopus embryos. Blocking HCN channels ( I h currents) with pharmacological inhibitors leads to errors in organ situs. This effect is only seen when HCN4 channels are blocked early (pre-stage 10) and not by a later block (post-stage 10). Injections of HCN4-DN (dominant-negative) mRNA induce left-right defects only when injected in both blastomeres no later than the 2-cell stage. Analysis of key asymmetric genes' expression showed that the sidedness of Nodal , Lefty , and Pitx2 expression is largely unchanged by HCN4 blockade, despite the randomization of subsequent organ situs, although the area of Pitx2 expression was significantly reduced. Together these data identify a novel, developmental role for HCN4 channels and reveal a new Nodal-Lefty-Pitx2 asymmetric gene expression-independent mechanism upstream of organ positioning during embryonic left-right patterning. © 2017. Published by The Company of Biologists Ltd.

  8. The AFFORD clinical decision aid to identify emergency department patients with atrial fibrillation at low risk for 30-day adverse events.

    Science.gov (United States)

    Barrett, Tyler W; Storrow, Alan B; Jenkins, Cathy A; Abraham, Robert L; Liu, Dandan; Miller, Karen F; Moser, Kelly M; Russ, Stephan; Roden, Dan M; Harrell, Frank E; Darbar, Dawood

    2015-03-15

    There is wide variation in the management of patients with atrial fibrillation (AF) in the emergency department (ED). We aimed to derive and internally validate the first prospective, ED-based clinical decision aid to identify patients with AF at low risk for 30-day adverse events. We performed a prospective cohort study at a university-affiliated tertiary-care ED. Patients were enrolled from June 9, 2010, to February 28, 2013, and followed for 30 days. We enrolled a convenience sample of patients in ED presenting with symptomatic AF. Candidate predictors were based on ED data available in the first 2 hours. The decision aid was derived using model approximation (preconditioning) followed by strong bootstrap internal validation. We used an ordinal outcome hierarchy defined as the incidence of the most severe adverse event within 30 days of the ED evaluation. Of 497 patients enrolled, stroke and AF-related death occurred in 13 (3%) and 4 (aid included the following: age, triage vitals (systolic blood pressure, temperature, respiratory rate, oxygen saturation, supplemental oxygen requirement), medical history (heart failure, home sotalol use, previous percutaneous coronary intervention, electrical cardioversion, cardiac ablation, frequency of AF symptoms), and ED data (2 hours heart rate, chest radiograph results, hemoglobin, creatinine, and brain natriuretic peptide). The decision aid's c-statistic in predicting any 30-day adverse event was 0.7 (95% confidence interval 0.65, 0.76). In conclusion, in patients with AF in the ED, Atrial Fibrillation and Flutter Outcome Risk Determination provides the first evidence-based decision aid for identifying patients who are at low risk for 30-day adverse events and candidates for safe discharge. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Regional variation in identified cancer care needs of early-career oncologists in China, India, and Pakistan.

    Science.gov (United States)

    Lyerly, H Kim; Fawzy, Maria R; Aziz, Zeba; Nair, Reena; Pramesh, C S; Parmar, Vani; Parikh, Purvish M; Jamal, Rozmin; Irumnaz, Azizunissa; Ren, Jun; Stockler, Martin R; Abernethy, Amy P

    2015-05-01

    Cancer incidence and mortality is increasing in the developing world. Inequities between low-, middle-, and high-income countries affect disease burden and the infrastructure needs in response to cancer. We surveyed early-career oncologists attending workshops in clinical research in three countries with emerging economies about their perception of the evolving cancer burden. A cross-sectional survey questionnaire was distributed at clinical trial concept development workshops held in Beijing, Lahore, Karachi, and Mumbai at major hospitals to acquire information regarding home-country health conditions and needs. A total of 100 respondents participated in the workshops held at major hospitals in the region (India = 29, China = 25, Pakistan = 42, and other = 4). Expected consensus on many issues (e.g., emergence of cancer as a significant health issue) was balanced with significant variation in priorities, opportunities, and challenges. Chinese respondents prioritized improvements in cancer-specific care and palliative care, Indian respondents favored improved cancer detection and advancing research in cancer care, and Pakistani respondents prioritized awareness of cancer and improvements in disease detection and cancer care research. For all, the most frequently cited opportunity was help in improving professional cancer education and training. Predominantly early-career oncologists attending clinical research workshops (in China, India, and Pakistan) identified needs for increasing clinical cancer research, professional education, and public awareness of cancer. Decision makers supporting efforts to reduce the burden of cancer worldwide will need to factor the specific needs and aspirations of health care providers in their country in prioritizing health policies and budgets. ©AlphaMed Press.

  10. Early onset of disc degeneration in SM/J mice is associated with changes in ion transport systems and fibrotic events.

    Science.gov (United States)

    Zhang, Ying; Xiong, Chi; Kudelko, Mateusz; Li, Yan; Wang, Cheng; Wong, Yuk Lun; Tam, Vivian; Rai, Muhammad Farooq; Cheverud, James; Lawson, Heather A; Sandell, Linda; Chan, Wilson C W; Cheah, Kathryn S E; Sham, Pak C; Chan, Danny

    2018-04-09

    Intervertebral disc degeneration (IDD) causes back pain and sciatica, affecting quality of life and resulting in high economic/social burden. The etiology of IDD is not well understood. Along with aging and environmental factors, genetic factors also influence the onset, progression and severity of IDD. Genetic studies of risk factors for IDD using human cohorts are limited by small sample size and low statistical power. Animal models amenable to genetic and functional studies of IDD provide desirable alternatives. Despite differences in size and cellular content as compared to human intervertebral discs (IVDs), the mouse is a powerful model for genetics and assessment of cellular changes relevant to human biology. Here, we provide evidence for early onset disc degeneration in SM/J relative to LG/J mice with poor and good tissue healing capacity respectively. In the first few months of life, LG/J mice maintain a relatively constant pool of notochordal-like cells in the nucleus pulposus (NP) of the IVD. In contrast, chondrogenic events are observed in SM/J mice beginning as early as one-week-old, with progressive fibrotic changes. Further, the extracellular matrix changes in the NP are consistent with IVD degeneration. Leveraging on the genomic data of two parental and two recombinant inbred lines, we assessed the genetic contribution to the NP changes and identified processes linked to the regulation of ion transport systems. Significantly, "transport" system is also in the top three gene ontology (GO) terms from a comparative proteomic analysis of the mouse NP. These findings support the potential of the SM/J, LG/J and their recombinant inbred lines for future genetic and biological analysis in mice and validation of candidate genes and biological relevance in human cohort studies. The proteomic data has been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD008784. Copyright © 2017. Published by

  11. Early molecular events involved in Pinus pinaster Ait. somatic embryo development under reduced water availability: transcriptomic and proteomic analyses.

    Science.gov (United States)

    Morel, Alexandre; Teyssier, Caroline; Trontin, Jean-François; Eliášová, Kateřina; Pešek, Bedřich; Beaufour, Martine; Morabito, Domenico; Boizot, Nathalie; Le Metté, Claire; Belal-Bessai, Leila; Reymond, Isabelle; Harvengt, Luc; Cadene, Martine; Corbineau, Françoise; Vágner, Martin; Label, Philippe; Lelu-Walter, Marie-Anne

    2014-09-01

    Maritime pine somatic embryos (SEs) require a reduction in water availability (high gellan gum concentration in the maturation medium) to reach the cotyledonary stage. This key switch, reported specifically for pine species, is not yet well understood. To facilitate the use of somatic embryogenesis for mass propagation of conifers, we need a better understanding of embryo development. Comparison of both transcriptome (Illumina RNA sequencing) and proteome [two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis with mass spectrometry (MS) identification] of immature SEs, cultured on either high (9G) or low (4G) gellan gum concentration, was performed, together with analysis of water content, fresh and dry mass, endogenous abscisic acid (ABA; gas chromatography-MS), soluble sugars (high-pressure liquid chromatography), starch and confocal laser microscope observations. This multiscale, integrated analysis was used to unravel early molecular and physiological events involved in SE development. Under unfavorable conditions (4G), the glycolytic pathway was enhanced, possibly in relation to cell proliferation that may be antagonistic to SE development. Under favorable conditions (9G), SEs adapted to culture constraint by activating specific protective pathways, and ABA-mediated molecular and physiological responses promoting embryo development. Our results suggest that on 9G, germin-like protein and ubiquitin-protein ligase could be used as predictive markers of SE development, whereas protein phosphatase 2C could be a biomarker for culture adaptive responses. This is the first characterization of early molecular mechanisms involved in the development of pine SEs following an increase in gellan gum concentration in the maturation medium, and it is also the first report on somatic embryogenesis in conifers combining transcriptomic and proteomic datasets. © 2014 Scandinavian Plant Physiology Society.

  12. Definition of herpes simplex virus type 1 helper activities for adeno-associated virus early replication events.

    Directory of Open Access Journals (Sweden)

    Nathalie Alazard-Dany

    2009-03-01

    Full Text Available The human parvovirus Adeno-Associated Virus (AAV type 2 can only replicate in cells co-infected with a helper virus, such as Adenovirus or Herpes Simplex Virus type 1 (HSV-1; whereas, in the absence of a helper virus, it establishes a latent infection. Previous studies demonstrated that the ternary HSV-1 helicase/primase (HP complex (UL5/8/52 and the single-stranded DNA-Binding Protein (ICP8 were sufficient to induce AAV-2 replication in transfected cells. We independently showed that, in the context of a latent AAV-2 infection, the HSV-1 ICP0 protein was able to activate rep gene expression. The present study was conducted to integrate these observations and to further explore the requirement of other HSV-1 proteins during early AAV replication steps, i.e. rep gene expression and AAV DNA replication. Using a cellular model that mimics AAV latency and composite constructs coding for various sets of HSV-1 genes, we first confirmed the role of ICP0 for rep gene expression and demonstrated a synergistic effect of ICP4 and, to a lesser extent, ICP22. Conversely, ICP27 displayed an inhibitory effect. Second, our analyses showed that the effect of ICP0, ICP4, and ICP22 on rep gene expression was essential for the onset of AAV DNA replication in conjunction with the HP complex and ICP8. Third, and most importantly, we demonstrated that the HSV-1 DNA polymerase complex (UL30/UL42 was critical to enhance AAV DNA replication to a significant level in transfected cells and that its catalytic activity was involved in this process. Altogether, this work represents the first comprehensive study recapitulating the series of early events taking place during HSV-1-induced AAV replication.

  13. Using machine learning to identify air pollution exposure profiles associated with early cognitive skills among U.S. children

    International Nuclear Information System (INIS)

    Stingone, Jeanette A.; Pandey, Om P.; Claudio, Luz; Pandey, Gaurav

    2017-01-01

    Data-driven machine learning methods present an opportunity to simultaneously assess the impact of multiple air pollutants on health outcomes. The goal of this study was to apply a two-stage, data-driven approach to identify associations between air pollutant exposure profiles and children's cognitive skills. Data from 6900 children enrolled in the Early Childhood Longitudinal Study, Birth Cohort, a national study of children born in 2001 and followed through kindergarten, were linked to estimated concentrations of 104 ambient air toxics in the 2002 National Air Toxics Assessment using ZIP code of residence at age 9 months. In the first-stage, 100 regression trees were learned to identify ambient air pollutant exposure profiles most closely associated with scores on a standardized mathematics test administered to children in kindergarten. In the second-stage, the exposure profiles frequently predicting lower math scores were included within linear regression models and adjusted for confounders in order to estimate the magnitude of their effect on math scores. This approach was applied to the full population, and then to the populations living in urban and highly-populated urban areas. Our first-stage results in the full population suggested children with low trichloroethylene exposure had significantly lower math scores. This association was not observed for children living in urban communities, suggesting that confounding related to urbanicity needs to be considered within the first-stage. When restricting our analysis to populations living in urban and highly-populated urban areas, high isophorone levels were found to predict lower math scores. Within adjusted regression models of children in highly-populated urban areas, the estimated effect of higher isophorone exposure on math scores was −1.19 points (95% CI −1.94, −0.44). Similar results were observed for the overall population of urban children. This data-driven, two-stage approach can be

  14. The influence of deficient retro-aortic rim on technical success and early adverse events following device closure of secundum atrial septal defects: An Analysis of the IMPACT Registry®.

    Science.gov (United States)

    O'Byrne, Michael L; Gillespie, Matthew J; Kennedy, Kevin F; Dori, Yoav; Rome, Jonathan J; Glatz, Andrew C

    2017-01-01

    Concern regarding aortic erosion has focused attention on the retro-aortic rim in patients undergoing device closure of atrial septal defects (ASD), but its effect on early outcomes is not well studied. A multicenter retrospective cohort study of patients undergoing device occlusion of ASD between 1/2011-10/2014 was performed, using data from the IMproving Pediatric and Adult Congenital Treatment Registry. Subjects were divided between those with retro-aortic rim technical failure and major early adverse events. Case times were measured as surrogates of technical complexity. The effect of deficient retro-aortic rim on primary outcomes was assessed using hierarchical logistic regression, adjusting for other suspected covariates and assessing whether they represent independent risk factors RESULTS: 1,564 subjects (from 77 centers) were included, with deficient retro-aortic rim present in 40%. Technical failure occurred in 91 subjects (5.8%) and a major early adverse event in 64 subjects (4.1%). Adjusting for known covariates, the presence of a deficient retro-aortic rim was not significantly associated with technical failure (OR: 1.3, 95% CI: 0.9-2.1) or major early adverse event (OR: 0.7, 95% CI: 0.4-1. 2). Total case (P = 0.01) and fluoroscopy time (P = 0.02) were greater in subjects with deficient rim, but sheath time was not significantly different (P = 0.07). Additional covariates independently associated with these outcomes were identified. Deficient retro-aortic rim was highly prevalent but not associated with increased risk of technical failure or early adverse events. Studies with longer follow-up are necessary to assess other outcomes, including device erosion. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Whole genome analysis of selected human and animal rotaviruses identified in Uganda from 2012 to 2014 reveals complex genome reassortment events between human, bovine, caprine and porcine strains.

    Science.gov (United States)

    Bwogi, Josephine; Jere, Khuzwayo C; Karamagi, Charles; Byarugaba, Denis K; Namuwulya, Prossy; Baliraine, Frederick N; Desselberger, Ulrich; Iturriza-Gomara, Miren

    2017-01-01

    Rotaviruses of species A (RVA) are a common cause of diarrhoea in children and the young of various other mammals and birds worldwide. To investigate possible interspecies transmission of RVAs, whole genomes of 18 human and 6 domestic animal RVA strains identified in Uganda between 2012 and 2014 were sequenced using the Illumina HiSeq platform. The backbone of the human RVA strains had either a Wa- or a DS-1-like genetic constellation. One human strain was a Wa-like mono-reassortant containing a DS-1-like VP2 gene of possible animal origin. All eleven genes of one bovine RVA strain were closely related to those of human RVAs. One caprine strain had a mixed genotype backbone, suggesting that it emerged from multiple reassortment events involving different host species. The porcine RVA strains had mixed genotype backbones with possible multiple reassortant events with strains of human and bovine origin.Overall, whole genome characterisation of rotaviruses found in domestic animals in Uganda strongly suggested the presence of human-to animal RVA transmission, with concomitant circulation of multi-reassortant strains potentially derived from complex interspecies transmission events. However, whole genome data from the human RVA strains causing moderate and severe diarrhoea in under-fives in Uganda indicated that they were primarily transmitted from person-to-person.

  16. Abnormalities of Early “Memory-Scanning” Event-Related Potentials in Patients with Temporal Lobe Epilepsy

    Directory of Open Access Journals (Sweden)

    A. Grippo

    1994-01-01

    Full Text Available We have recorded auditory event-related potentials (ERPs evoked by the “memory-scanning” (digit-probe identification/matching paradigm that was originally described by Sternberg (1966, in 17 patients with complex partial seizures (temporal lobe epilepsy and in 17 matched healthy control subjects. The patients, who had all complained spontaneously of memory difficulties, had significantly reduced scores on psychological tests of memory with relatively intact digit span and cognition. Their performance of the memory-scanning task was characterized by a higher error rate, longer reaction times and an increased slope of the reaction time/set size relationship. The associated ERPs in both patients and controls showed there were significant effects of memory load on several major components, but only a reduced amplitude of the N170 and a prolonged latency of the N290 waves distinguished the patients. In addition, the N170 wave in the patients decreased further as memory load increased. The prolonged N290 latency in the patients appeared to reflect the slowed processing time. This study has shown that ERPs generated by a short-term memory task are abnormal in patients with temporal lobe epilepsy who have neuropsychologically documented cognitive and memory deficits. Some of the significant waveform alterations occur earlier than those reported in previous ERP studies and provide electrophysiological support for the hypothesis that abnormalities of the early stages of short-term memory processing may contribute to the memory difficulties experienced by patients with temporal lobe epilepsy.

  17. Early and late HIV-1 membrane fusion events are impaired by sphinganine lipidated peptides that target the fusion site.

    Science.gov (United States)

    Klug, Yoel A; Ashkenazi, Avraham; Viard, Mathias; Porat, Ziv; Blumenthal, Robert; Shai, Yechiel

    2014-07-15

    Lipid-conjugated peptides have advanced the understanding of membrane protein functions and the roles of lipids in the membrane milieu. These lipopeptides modulate various biological systems such as viral fusion. A single function has been suggested for the lipid, binding to the membrane and thus elevating the local concentration of the peptide at the target site. In the present paper, we challenged this argument by exploring in-depth the antiviral mechanism of lipopeptides, which comprise sphinganine, the lipid backbone of DHSM (dihydrosphingomyelin), and an HIV-1 envelope-derived peptide. Surprisingly, we discovered a partnership between the lipid and the peptide that impaired early membrane fusion events by reducing CD4 receptor lateral diffusion and HIV-1 fusion peptide-mediated lipid mixing. Moreover, only the joint function of sphinganine and its conjugate peptide disrupted HIV-1 fusion protein assembly and folding at the later fusion steps. Via imaging techniques we revealed for the first time the direct localization of these lipopeptides to the virus-cell and cell-cell contact sites. Overall, the findings of the present study may suggest lipid-protein interactions in various biological systems and may help uncover a role for elevated DHSM in HIV-1 and its target cell membranes.

  18. Early life events carry over to influence pre-migratory condition in a free-living songbird.

    Directory of Open Access Journals (Sweden)

    Greg W Mitchell

    Full Text Available Conditions experienced during development can have long-term consequences for individual success. In migratory songbirds, the proximate mechanisms linking early life events and survival are not well understood because tracking individuals across stages of the annual cycle can be extremely challenging. In this paper, we first use a 13 year dataset to demonstrate a positive relationship between 1(st year survival and nestling mass in migratory Savannah sparrows (Passerculus sandwichensis. We also use a brood manipulation experiment to show that nestlings from smaller broods have higher mass in the nest relative to individuals from larger broods. Having established these relationships, we then use three years of field data involving multiple captures of individuals throughout the pre-migratory period and a multi-level path model to examine the hypothesis that conditions during development limit survival during migration by affecting an individual's ability to accumulate sufficient lean tissue and fat mass prior to migration. We found a positive relationship between fat mass during the pre-migratory period (Sept-Oct and nestling mass and a negative indirect relationship between pre-migratory fat mass and fledging date. Our results provide the first evidence that conditions during development limit survival during migration through their effect on fat stores. These results are particularly important given recent evidence showing that body condition of songbirds at fledging is affected by climate change and anthropogenic changes to landscape structure.

  19. Inflammatory Reaction as Determinant of Foreign Body Reaction Is an Early and Susceptible Event after Mesh Implantation

    Directory of Open Access Journals (Sweden)

    Holger Gerullis

    2014-01-01

    Full Text Available Purpose. To investigate and relate the ultrashort-term and long-term courses of determinants for foreign body reaction as biocompatibility predictors for meshes in an animal model. Materials and Methods. Three different meshes (TVT, UltraPro, and PVDF were implanted in sheep. Native and plasma coated meshes were placed bilaterally: (a interaperitoneally, (b as fascia onlay, and (c as muscle onlay (fascia sublay. At 5 min, 20 min, 60 min, and 120 min meshes were explanted and histochemically investigated for inflammatory infiltrate, macrophage infiltration, vessel formation, myofibroblast invasion, and connective tissue accumulation. The results were related to long-term values over 24 months. Results. Macrophage invasion reached highest extents with up to 60% in short-term and decreased within 24 months to about 30%. Inflammatory infiltrate increased within the first 2 hours, the reached levels and the different extents and ranking among the investigated meshes remained stable during long-term follow up. For myofibroblasts, connective tissue, and CD31+ cells, no activity was detected during the first 120 min. Conclusion. The local inflammatory reaction is an early and susceptible event after mesh implantation. It cannot be influenced by prior plasma coating and does not depend on the localisation of implantation.

  20. The dimerization of the yeast cytochrome bc1 complex is an early event and is independent of Rip1.

    Science.gov (United States)

    Conte, Annalea; Papa, Benedetta; Ferramosca, Alessandra; Zara, Vincenzo

    2015-05-01

    In Saccharomyces cerevisiae the mature cytochrome bc1 complex exists as an obligate homo-dimer in which each monomer consists of ten distinct protein subunits inserted into or bound to the inner mitochondrial membrane. Among them, the Rieske iron-sulfur protein (Rip1), besides its catalytic role in electron transfer, may be implicated in the bc1 complex dimerization. Indeed, Rip1 has the globular domain containing the catalytic center in one monomer while the transmembrane helix interacts with the adjacent monomer. In addition, the lack of Rip1 leads to the accumulation of an immature bc1 intermediate, only loosely associated with cytochrome c oxidase. In this study we have investigated the biogenesis of the yeast cytochrome bc1 complex using epitope tagged proteins to purify native assembly intermediates. We showed that the dimerization process is an early event during bc1 complex biogenesis and that the presence of Rip1, differently from previous proposals, is not essential for this process. We also investigated the multi-step model of bc1 assembly thereby lending further support to the existence of bona fide subcomplexes during bc1 maturation in the inner mitochondrial membrane. Finally, a new model of cytochrome bc1 complex assembly, in which distinct intermediates sequentially interact during bc1 maturation, has been proposed. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. A proteomic analysis identifies candidate early biomarkers to predict ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients.

    Science.gov (United States)

    Wu, Lan; Sun, Yazhou; Wan, Jun; Luan, Ting; Cheng, Qing; Tan, Yong

    2017-07-01

    Ovarian hyperstimulation syndrome (OHSS) is a potentially life‑threatening, iatrogenic complication that occurs during assisted reproduction. Polycystic ovarian syndrome (PCOS) significantly increases the risk of OHSS during controlled ovarian stimulation. Therefore, a more effective early prediction technique is required in PCOS patients. Quantitative proteomic analysis of serum proteins indicates the potential diagnostic value for disease. In the present study, the authors revealed the differentially expressed proteins in OHSS patients with PCOS as new diagnostic biomarkers. The promising proteins obtained from liquid chromatography‑mass spectrometry were subjected to ELISA and western blotting assay for further confirmation. A total of 57 proteins were identified with significant difference, of which 29 proteins were upregulated and 28 proteins were downregulated in OHSS patients. Haptoglobin, fibrinogen and lipoprotein lipase were selected as candidate biomarkers. Receiver operating characteristic curve analysis demonstrated all three proteins may have potential as biomarkers to discriminate OHSS in PCOS patients. Haptoglobin, fibrinogen and lipoprotein lipase have never been reported as a predictive marker of OHSS in PCOS patients, and their potential roles in OHSS occurrence deserve further studies. The proteomic results reported in the present study may gain deeper insights into the pathophysiology of OHSS.

  2. Using Remote Sensing and High-Resolution Digital Elevation Models to Identify Potential Erosional Hotspots Along River Channels During High Discharge Storm Events

    Science.gov (United States)

    Orland, E. D.; Amidon, W. H.

    2017-12-01

    As global warming intensifies, large precipitation events and associated floods are becoming increasingly common. Channel adjustments during floods can occur by both erosion and deposition of sediment, often damaging infrastructure in the process. There is thus a need for predictive models that can help managers identify river reaches that are most prone to adjustment during storms. Because rivers in post-glacial landscapes often flow over a mixture of bedrock and alluvial substrates, the identification of bedrock vs. alluvial channel reaches is an important first step in predicting vulnerability to channel adjustment during flood events, especially because bedrock channels are unlikely to adjust significantly, even during floods. This study develops a semi-automated approach to predicting channel substrate using a high-resolution LiDAR-derived digital elevation model (DEM). The study area is the Middlebury River in Middlebury, VT-a well-studied watershed with a wide variety of channel substrates, including reaches with documented channel adjustments during recent flooding events. Multiple metrics were considered for reference—such as channel width and drainage area—but the study utilized channel slope as a key parameter for identifying morphological variations within the Middlebury River. Using data extracted from the DEM, a power law was fit to selected slope and drainage area values for each branch in order to model idealized slope-drainage area relationships, which were then compared with measured slope-drainage area relationships. Differences in measured slope minus predicted slope (called delta-slope) are shown to help predict river channel substrate. Compared with field observations, higher delta-slope values correlate with more stable, boulder rich channels or bedrock gorges; conversely the lowest delta-slope values correlate with flat, sediment rich alluvial channels. The delta-slope metric thus serves as a reliable first-order predictor of channel

  3. Identifying MRI markers to evaluate early treatment-related changes post-laser ablation for cancer pain management

    Science.gov (United States)

    Tiwari, Pallavi; Danish, Shabbar; Madabhushi, Anant

    2014-03-01

    by correcting for intensity drift in order to examine tissue-specific response, and (3) quantification of MRI maps via texture and intensity features to evaluate changes in MR markers pre- and post-LITT. A total of 78 texture features comprising of non-steerable and steerable gradient and second order statistical features were extracted from pre- and post-LITT MP-MRI on a per-voxel basis. Quantitative, voxel-wise comparison of the changes in MRI texture features between pre-, and post-LITT MRI indicate that (a) steerable and non-steerable gradient texture features were highly sensitive as well as specific in predicting subtle micro-architectural changes within and around the ablation zone pre- and post-LITT, (b) FLAIR was identified as the most sensitive MRI protocol in identifying early treatment changes yielding a normalized percentage change of 360% within the ablation zone relative to its pre-LITT value, and (c) GRE was identified as the most sensitive MRI protocol in quantifying changes outside the ablation zone post-LITT. Our preliminary results thus indicate great potential for non-invasive computerized MRI features in determining localized micro-architectural focal treatment related changes post-LITT.

  4. Evaluation of early healing events around mesenchymal stem cell-seeded collagen-glycosaminoglycan scaffold. An experimental study in Wistar rats.

    LENUS (Irish Health Repository)

    Alhag, Mohamed

    2011-03-01

    Tissue engineering using cell-seeded biodegradable scaffolds offers a new bone regenerative approach that might circumvent many of the limitations of current therapeutic modalities. The aim of this experiment was to study the early healing events around mesenchymal stem cell-seeded collagen-glycosaminoglycan scaffolds.

  5. Size-resolved aerosol chemical analysis of extreme haze pollution events during early 2013 in urban Beijing, China

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Shili; Pan, Yuepeng, E-mail: panyuepeng@mail.iap.ac.cn; Liu, Zirui; Wen, Tianxue; Wang, Yuesi, E-mail: wys@mail.iap.ac.cn

    2014-08-30

    Highlights: • Anthropogenic species substantially accumulated in both fine and coarse particles. • Secondary organic carbon in PM{sub 1.1} decreased from clear to haze days. • The mass peak shifted to larger particles from clear to haze days. • The NO{sub 3}{sup −}/SO{sub 4}{sup 2−} ratio decreased with enhanced haze pollution. • Both mobile local and stationary regional sources were vital for haze formation. - Abstract: Using size-resolved filter sampling and chemical characterization, high concentrations of water-soluble ions, carbonaceous species and heavy metals were found in both fine (PM{sub 2.1}) and coarse (PM{sub 2.1–9}) particles in Beijing during haze events in early 2013. Even on clear days, average mass concentration of submicron particles (PM{sub 1.1}) was several times higher than that previously measured in most of abroad urban areas. A high concentration of particulate matter on haze days weakens the incident solar radiation, which reduces the generation rate of secondary organic carbon in PM{sub 1.1}. We show that the peak mass concentration of particles shifted from 0.43–0.65 μm on clear days to 0.65–1.1 μm on lightly polluted days and to 1.1–2.1 μm on heavily polluted days. The peak shifts were also found for the following species: organic carbon, elemental carbon, NH{sub 4}{sup +}, SO{sub 4}{sup 2−}, NO{sub 3}{sup −}, K, Cu, Zn, Cd and Pb. Our findings demonstrate that secondary inorganic aerosols (36%) and organic matter (26%) dominated the fine particle mass on heavily polluted days, while their contribution reduced to 29% and 18%, respectively, on clear days. Besides fine particles, anthropogenic chemical species also substantially accumulated in the coarse mode, which suggests that particles with aerodynamic diameter larger than 2.1 μm cannot be neglected during severe haze events.

  6. Evaluation of epidemic intelligence systems integrated in the early alerting and reporting project for the detection of A/H5N1 influenza events.

    Directory of Open Access Journals (Sweden)

    Philippe Barboza

    Full Text Available The objective of Web-based expert epidemic intelligence systems is to detect health threats. The Global Health Security Initiative (GHSI Early Alerting and Reporting (EAR project was launched to assess the feasibility and opportunity for pooling epidemic intelligence data from seven expert systems. EAR participants completed a qualitative survey to document epidemic intelligence strategies and to assess perceptions regarding the systems performance. Timeliness and sensitivity were rated highly illustrating the value of the systems for epidemic intelligence. Weaknesses identified included representativeness, completeness and flexibility. These findings were corroborated by the quantitative analysis performed on signals potentially related to influenza A/H5N1 events occurring in March 2010. For the six systems for which this information was available, the detection rate ranged from 31% to 38%, and increased to 72% when considering the virtual combined system. The effective positive predictive values ranged from 3% to 24% and F1-scores ranged from 6% to 27%. System sensitivity ranged from 38% to 72%. An average difference of 23% was observed between the sensitivities calculated for human cases and epizootics, underlining the difficulties in developing an efficient algorithm for a single pathology. However, the sensitivity increased to 93% when the virtual combined system was considered, clearly illustrating complementarities between individual systems. The average delay between the detection of A/H5N1 events by the systems and their official reporting by WHO or OIE was 10.2 days (95% CI: 6.7-13.8. This work illustrates the diversity in implemented epidemic intelligence activities, differences in system's designs, and the potential added values and opportunities for synergy between systems, between users and between systems and users.

  7. The functional organization of trial-related activity in lexical processing after early left hemispheric brain lesions: An event-related fMRI study.

    Science.gov (United States)

    Fair, Damien A; Choi, Alexander H; Dosenbach, Yannic B L; Coalson, Rebecca S; Miezin, Francis M; Petersen, Steven E; Schlaggar, Bradley L

    2010-08-01

    Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon is accepted, its neurobiological mechanisms are not well characterized. In this paper we examined the functional neuroanatomy of lexical processing in 13 children/adolescents with perinatal left hemispheric damage. In contrast to many previous perinatal infarct fMRI studies, we used an event-related design, which allowed us to isolate trial-related activity and examine correct and error trials separately. Using both group and single subject analysis techniques we attempt to address several methodological factors that may contribute to some discrepancies in the perinatal lesion literature. These methodological factors include making direct statistical comparisons, using common stereotactic space, using both single subject and group analyses, and accounting for performance differences. Our group analysis, investigating correct trial-related activity (separately from error trials), showed very few statistical differences in the non-involved right hemisphere between patients and performance matched controls. The single subject analysis revealed atypical regional activation patterns in several patients; however, the location of these regions identified in individual patients often varied across subjects. These results are consistent with the idea that alternative functional organization of trial-related activity after left hemisphere lesions is in large part unique to the individual. In addition, reported differences between results obtained with event-related designs and blocked designs may suggest diverging organizing principles for sustained and trial-related activity after early childhood brain injuries. 2009 Elsevier Inc. All rights reserved.

  8. Evaluation of Epidemic Intelligence Systems Integrated in the Early Alerting and Reporting Project for the Detection of A/H5N1 Influenza Events

    Science.gov (United States)

    Barboza, Philippe; Vaillant, Laetitia; Mawudeku, Abla; Nelson, Noele P.; Hartley, David M.; Madoff, Lawrence C.; Linge, Jens P.; Collier, Nigel; Brownstein, John S.; Yangarber, Roman; Astagneau, Pascal; on behalf of the Early Alerting, Reporting Project of the Global Health Security Initiative

    2013-01-01

    The objective of Web-based expert epidemic intelligence systems is to detect health threats. The Global Health Security Initiative (GHSI) Early Alerting and Reporting (EAR) project was launched to assess the feasibility and opportunity for pooling epidemic intelligence data from seven expert systems. EAR participants completed a qualitative survey to document epidemic intelligence strategies and to assess perceptions regarding the systems performance. Timeliness and sensitivity were rated highly illustrating the value of the systems for epidemic intelligence. Weaknesses identified included representativeness, completeness and flexibility. These findings were corroborated by the quantitative analysis performed on signals potentially related to influenza A/H5N1 events occurring in March 2010. For the six systems for which this information was available, the detection rate ranged from 31% to 38%, and increased to 72% when considering the virtual combined system. The effective positive predictive values ranged from 3% to 24% and F1-scores ranged from 6% to 27%. System sensitivity ranged from 38% to 72%. An average difference of 23% was observed between the sensitivities calculated for human cases and epizootics, underlining the difficulties in developing an efficient algorithm for a single pathology. However, the sensitivity increased to 93% when the virtual combined system was considered, clearly illustrating complementarities between individual systems. The average delay between the detection of A/H5N1 events by the systems and their official reporting by WHO or OIE was 10.2 days (95% CI: 6.7–13.8). This work illustrates the diversity in implemented epidemic intelligence activities, differences in system's designs, and the potential added values and opportunities for synergy between systems, between users and between systems and users. PMID:23472077

  9. Evaluation of epidemic intelligence systems integrated in the early alerting and reporting project for the detection of A/H5N1 influenza events.

    Science.gov (United States)

    Barboza, Philippe; Vaillant, Laetitia; Mawudeku, Abla; Nelson, Noele P; Hartley, David M; Madoff, Lawrence C; Linge, Jens P; Collier, Nigel; Brownstein, John S; Yangarber, Roman; Astagneau, Pascal

    2013-01-01

    The objective of Web-based expert epidemic intelligence systems is to detect health threats. The Global Health Security Initiative (GHSI) Early Alerting and Reporting (EAR) project was launched to assess the feasibility and opportunity for pooling epidemic intelligence data from seven expert systems. EAR participants completed a qualitative survey to document epidemic intelligence strategies and to assess perceptions regarding the systems performance. Timeliness and sensitivity were rated highly illustrating the value of the systems for epidemic intelligence. Weaknesses identified included representativeness, completeness and flexibility. These findings were corroborated by the quantitative analysis performed on signals potentially related to influenza A/H5N1 events occurring in March 2010. For the six systems for which this information was available, the detection rate ranged from 31% to 38%, and increased to 72% when considering the virtual combined system. The effective positive predictive values ranged from 3% to 24% and F1-scores ranged from 6% to 27%. System sensitivity ranged from 38% to 72%. An average difference of 23% was observed between the sensitivities calculated for human cases and epizootics, underlining the difficulties in developing an efficient algorithm for a single pathology. However, the sensitivity increased to 93% when the virtual combined system was considered, clearly illustrating complementarities between individual systems. The average delay between the detection of A/H5N1 events by the systems and their official reporting by WHO or OIE was 10.2 days (95% CI: 6.7-13.8). This work illustrates the diversity in implemented epidemic intelligence activities, differences in system's designs, and the potential added values and opportunities for synergy between systems, between users and between systems and users.

  10. T cell receptor sequencing of early-stage breast cancer tumors identifies altered clonal structure of the T cell repertoire.

    Science.gov (United States)

    Beausang, John F; Wheeler, Amanda J; Chan, Natalie H; Hanft, Violet R; Dirbas, Frederick M; Jeffrey, Stefanie S; Quake, Stephen R

    2017-11-28

    Tumor-infiltrating T cells play an important role in many cancers, and can improve prognosis and yield therapeutic targets. We characterized T cells infiltrating both breast cancer tumors and the surrounding normal breast tissue to identify T cells specific to each, as well as their abundance in peripheral blood. Using immune profiling of the T cell beta-chain repertoire in 16 patients with early-stage breast cancer, we show that the clonal structure of the tumor is significantly different from adjacent breast tissue, with the tumor containing ∼2.5-fold greater density of T cells and higher clonality compared with normal breast. The clonal structure of T cells in blood and normal breast is more similar than between blood and tumor, and could be used to distinguish tumor from normal breast tissue in 14 of 16 patients. Many T cell sequences overlap between tissue and blood from the same patient, including ∼50% of T cells between tumor and normal breast. Both tumor and normal breast contain high-abundance "enriched" sequences that are absent or of low abundance in the other tissue. Many of these T cells are either not detected or detected with very low frequency in the blood, suggesting the existence of separate compartments of T cells in both tumor and normal breast. Enriched T cell sequences are typically unique to each patient, but a subset is shared between many different patients. We show that many of these are commonly generated sequences, and thus unlikely to play an important role in the tumor microenvironment. Copyright © 2017 the Author(s). Published by PNAS.

  11. Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syndromes.

    Science.gov (United States)

    Chow, Clara K; Jolly, Sanjit; Rao-Melacini, Purnima; Fox, Keith A A; Anand, Sonia S; Yusuf, Salim

    2010-02-16

    Although preventive drug therapy is a priority after acute coronary syndrome, less is known about adherence to behavioral recommendations. The aim of this study was to examine the influence of adherence to behavioral recommendations in the short term on risk of cardiovascular events. The study population included 18 809 patients from 41 countries enrolled in the Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS) 5 randomized clinical trial. At the 30-day follow-up, patients reported adherence to diet, physical activity, and smoking cessation. Cardiovascular events (myocardial infarction, stroke, cardiovascular death) and all-cause mortality were documented to 6 months. About one third of smokers persisted in smoking. Adherence to neither diet nor exercise recommendations was reported by 28.5%, adherence to either diet or exercise by 41.6%, and adherence to both by 29.9%. In contrast, 96.1% of subjects reported antiplatelet use, 78.9% reported statin use, and 72.4% reported angiotensin-converting enzyme/angiotensin receptor blocker use. Quitting smoking was associated with a decreased risk of myocardial infarction compared with persistent smoking (odds ratio, 0.57; 95% confidence interval, 0.36 to 0.89). Diet and exercise adherence was associated with a decreased risk of myocardial infarction compared with nonadherence (odds ratio, 0.52; 95% confidence interval, 0.4 to 0.69). Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold (95% confidence interval, 2.5 to 5.9) increased risk of myocardial infarction/stroke/death compared with never smokers who modified diet and exercise. Adherence to behavioral advice (diet, exercise, and smoking cessation) after acute coronary syndrome was associated with a substantially lower risk of recurrent cardiovascular events. These findings suggest that behavioral modification should be given priority similar to other preventive medications immediately after acute coronary

  12. Plasma membrane potential depolarization and cytosolic calcium flux are early events involved in tomato (Solanum lycopersicon) plant-to-plant communication.

    Science.gov (United States)

    Zebelo, Simon A; Matsui, Kenji; Ozawa, Rika; Maffei, Massimo E

    2012-11-01

    Tomato plants respond to herbivory by emitting volatile organic compounds (VOCs), which are released into the surrounding atmosphere. We analyzed the tomato herbivore-induced VOCs and tested the ability of tomato receiver plants to detect tomato donor volatiles by analyzing early responses, including plasma membrane potential (V(m)) variations and cytosolic calcium ([Ca²⁺](cyt)) fluxes. Receiver tomato plants responded within seconds to herbivore-induced VOCs with a strong V(m) depolarization, which was only partly recovered by fluxing receiver plants with clean air. Among emitted volatiles, we identified by GC-MS some green leaf volatiles (GLVs) such as (E)-2-hexenal, (Z)-3-hexenal, (Z)-3-hexenyl acetate, the monoterpene α-pinene, and the sesquiterpene β-caryophyllene. GLVs were found to exert the stronger V(m) depolarization, when compared to α-pinene and β-caryophyllene. Furthermore, V(m) depolarization was found to increase with increasing GLVs concentration. GLVs were also found to induce a strong [Ca²⁺](cyt) increase, particularly when (Z)-3-hexenyl acetate was tested both in solution and with a gas. On the other hand, α-pinene and β-caryophyllene, which also induced a significant V(m) depolarization with respect to controls, did not exert any significant effect on [Ca²⁺](cyt) homeostasis. Our results show for the first time that plant perception of volatile cues (especially GLVs) from the surrounding environment is mediated by early events, occurring within seconds and involving the alteration of the plasma membrane potential and the [Ca²⁺](cyt) flux. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Combined oxygen- and carbon-isotope records through the Early Jurassic: multiple global events and two modes of carbon-cycle/temperature coupling

    DEFF Research Database (Denmark)

    Hesselbo, Stephen P.; Korte, Christoph

    2010-01-01

    , to the extent that meaningful comparisons between these events can begin to be made. Here we present new carbon and oxygen isotope data from mollusks (bivalves and belemnites) and brachiopods collected through the marine Early Jurassic succession of NE England, including the Sinemurian-Plienbachian boundary...... GSSP. All materials have been screened by chemical analysis and scanning electron microscopy to check for diagenetic alteration. Analysis of carbon isotopes from marine calcite is supplemented by analysis of carbon-isotope values from fossil wood collected through the same section. It is demonstrated...... that both long-term and short-term carbon-isotope shifts from the UK Early Jurassic represent global changes in carbon cycle balances. The Sinemurian-Pliensbachian boundary event is an event of global significance and shows several similarities to the Toarcian OAE (relative sea-level change, carbon-isotope...

  14. Using machine learning to identify air pollution exposure profiles associated with early cognitive skills among U.S. children.

    Science.gov (United States)

    Stingone, Jeanette A; Pandey, Om P; Claudio, Luz; Pandey, Gaurav

    2017-11-01

    Data-driven machine learning methods present an opportunity to simultaneously assess the impact of multiple air pollutants on health outcomes. The goal of this study was to apply a two-stage, data-driven approach to identify associations between air pollutant exposure profiles and children's cognitive skills. Data from 6900 children enrolled in the Early Childhood Longitudinal Study, Birth Cohort, a national study of children born in 2001 and followed through kindergarten, were linked to estimated concentrations of 104 ambient air toxics in the 2002 National Air Toxics Assessment using ZIP code of residence at age 9 months. In the first-stage, 100 regression trees were learned to identify ambient air pollutant exposure profiles most closely associated with scores on a standardized mathematics test administered to children in kindergarten. In the second-stage, the exposure profiles frequently predicting lower math scores were included within linear regression models and adjusted for confounders in order to estimate the magnitude of their effect on math scores. This approach was applied to the full population, and then to the populations living in urban and highly-populated urban areas. Our first-stage results in the full population suggested children with low trichloroethylene exposure had significantly lower math scores. This association was not observed for children living in urban communities, suggesting that confounding related to urbanicity needs to be considered within the first-stage. When restricting our analysis to populations living in urban and highly-populated urban areas, high isophorone levels were found to predict lower math scores. Within adjusted regression models of children in highly-populated urban areas, the estimated effect of higher isophorone exposure on math scores was -1.19 points (95% CI -1.94, -0.44). Similar results were observed for the overall population of urban children. This data-driven, two-stage approach can be applied to other

  15. Comprehensive Analysis of Cancer-Proteogenome to Identify Biomarkers for the Early Diagnosis and Prognosis of Cancer.

    Science.gov (United States)

    Shukla, Hem D

    2017-10-25

    data, are indispensable to glean into the cancer genome and proteome and these approaches have generated multidimensional universal studies of genes and proteins (OMICS) data which has the potential to facilitate precision medicine. However, due to slow progress in computational technologies, the translation of big omics data into their clinical aspects have been slow. In this review, attempts have been made to describe the role of high-throughput genomic and proteomic technologies in identifying a panel of biomarkers which could be used for the early diagnosis and prognosis of cancer.

  16. Comprehensive Analysis of Cancer-Proteogenome to Identify Biomarkers for the Early Diagnosis and Prognosis of Cancer

    Directory of Open Access Journals (Sweden)

    Hem D. Shukla

    2017-10-01

    , and pharmacogenomics data, are indispensable to glean into the cancer genome and proteome and these approaches have generated multidimensional universal studies of genes and proteins (OMICS data which has the potential to facilitate precision medicine. However, due to slow progress in computational technologies, the translation of big omics data into their clinical aspects have been slow. In this review, attempts have been made to describe the role of high-throughput genomic and proteomic technologies in identifying a panel of biomarkers which could be used for the early diagnosis and prognosis of cancer.

  17. Distribution of Early, Middle, and Late Noachian cratered surfaces in the Martian highlands: Implications for resurfacing events and processes

    Science.gov (United States)

    Irwin, Rossman P.; Tanaka, Kenneth L.; Robbins, Stuart J.

    2013-02-01

    Most of the geomorphic changes on Mars occurred during the Noachian Period, when the rates of impact crater degradation and valley network incision were highest. Fluvial erosion around the Noachian/Hesperian transition is better constrained than the longer-term landscape evolution throughout the Noachian Period, when the highland intercrater geomorphic surfaces developed. We interpret highland resurfacing events and processes using a new global geologic map of Mars (at 1:20,000,000 scale), a crater data set that is complete down to 1 km in diameter, and Mars Orbiter Laser Altimeter topography. The Early Noachian highland (eNh) unit is nearly saturated with craters of 32-128 km diameter, the Middle Noachian highland (mNh) unit has a resurfacing age of ~4 Ga, and the Late Noachian highland unit (lNh) includes younger composite surfaces of basin fill and partially buried cratered terrain. These units have statistically distinct ages, and their distribution varies with elevation. The eNh unit is concentrated in the high-standing Hellas basin annulus and in highland terrain that was thinly mantled by basin ejecta near 180° longitude. The mNh unit includes most of Arabia Terra, the Argyre vicinity, highland plateau areas between eNh outcrops, and the Thaumasia range. The lNh unit mostly occurs within highland basins. Crater depth/diameter ratios do not vary strongly between the eNh and mNh units, although crater losses to Noachian resurfacing appear greater in lower lying areas. Noachian resurfacing was spatially non-uniform, long-lived, and gravity-driven, more consistent with arid-zone fluvial and aeolian erosion and volcanism than with air fall mantling or mass wasting.

  18. Loss of co-ordinate expression of progesterone receptors A and B is an early event in breast carcinogenesis.

    Science.gov (United States)

    Mote, P A; Bartow, S; Tran, N; Clarke, C L

    2002-03-01

    Progesterone receptor (PR) mediates the effects of progesterone in mammary tissues and plays a crucial role in normal breast development and in breast cancer. PR proteins are expressed as two isoforms, PRA and PRB, that have different capacities to activate target genes, yet it is unknown whether progesterone action in normal and malignant breast is mediated by PRA and/or PRB. This study determines the relative expression of PRA and PRB in normal breast and in benign, premalignant and malignant archival breast lesions by dual immunofluorescent histochemistry. In normal breast and in proliferative disease without atypia (PDWA) PRA and PRB were co-expressed within the same cells in comparable amounts, implicating both isoforms in progesterone action. In atypical lesions, however, there was a significant increase in predominant expression of PRA or PRB, with lesion progression from the normal state to malignancy. PR isoform predominance, especially PRA predominance, was evident in a high proportion of ductal carcinomas in situ (DCIS) and invasive breast lesions. In the normal breast and in PDWA, the relative expression of PRA and PRB in adjacent cells was homogenous. There was a significant increase in cell-to-cell heterogeneity of PR isoform expression in ADH and DCIS lesions and in the majority of breast cancers. Heterogeneous cell-to-cell expression of PR isoforms occurred prior to overall predominant expression of one isoform in premalignant breast lesions, demonstrating that loss of control of relative PRA:PRB expression is an early event in the development of breast cancer. PRA:PRB ratios within a breast lesion are likely to be important as both markers and effectors of tumor growth and development, and progressively aberrant PR isoform expression may play a role in the etiology of breast cancer.

  19. Prospects of a cross section ratio measurement of W and Z events as a function of the jet multiplicity with early ATLAS data

    CERN Document Server

    Sandhoff, Marisa

    The production of W and Z bosons in association with jets plays an important role at the ATLAS experiment at the "Large Hadron Collider (LHC)" situated at the "European Organization for Nuclear Research" CERN (Geneva, Switzerland). The work presented in this thesis prepared the measurement of the cross section ratio of W and Z events as a function of the jet multiplicity. This cross section ratio is needed to improve the W+jets normalization for top quark analyses and to test Monte Carlo generator and QCD predictions. It focused on a measurement using early ATLAS data. The idea of this analysis is to use the compatible event structures of W+jets and Z+jets events to estimate W+jets events from the easy selectable Z+jets event. Hence, first the event structures of W and Z events were compared proving that the event structures are very similar. Then a measurement of the cross section ratio was prepared. The consequences of systematic uncertainties on the measurement were also tested. In a final step the W+jets ...

  20. Application of the RES methodology for identifying features, events and processes (FEPs) for near-field analysis of copper-steel canister

    International Nuclear Information System (INIS)

    Vieno, T.; Hautojaervi, A.; Raiko, H.; Ahonen, L.; Salo, J.P.

    1994-12-01

    Rock Engineering Systems (RES) is an approach to discover the important characteristics and interactions of a complex problem. Recently RES has been applied to identify features, events and processes (FEPs) for performance analysis of nuclear waste repositories. The RES methodology was applied to identify FEPs for the near-field analysis of the copper-steel canister for spent fuel disposal. The aims of the exercise were to learn and test the RES methodology and, secondly, to find out how much the results differ when RES is applied by two different groups on the same problem. A similar exercise was previously carried out by a SKB group. A total of 90 potentially significant FEPs were identified. The exercise showed that the RES methodology is a practicable tool to get a comprehensive and transparent picture of a complex problem. The approach is easy to learn and use. It reveals the important characteristics and interactions and organizes them in a format easy to understand. (9 refs., 5 figs., 3 tabs.)

  1. Intra-event correlations and the statistical moments of the identified particle multiplicity distributions in the RHIC beam energy scan data collected by STAR

    Science.gov (United States)

    Llope, W. J.; STAR Collaboration

    2013-10-01

    Specific products of the statistical moments of the multiplicity distributions of identified particles can be directly compared to susceptibility ratios obtained from lattice QCD calculations. They may also diverge for nuclear systems formed close to a possible QCD critical point due to the phenomenon of critical opalescence. Of particular interest are the moments products for net-protons, net-kaons, and net-charge, as these are considered proxies for conserved quantum numbers. The moments products have been measured by the STAR experiment for Au+Au collisions at seven beam energies ranging from 7.7 to 200 GeV. In this presentation, the experimental results are compared to data-based calculations in which the intra-event correlations of the numbers of positive and negative particles are broken by construction. The importance of intra-event correlations to the moments products values for net-protons, net-kaons, and net-charge can thus be evaluated. Work supported by the U.S. Dept of Energy under grant DE-PS02-09ER09.

  2. Search for charged Higgs bosons and measurement of |V sub c sub s | in quark and lepton flavour identified events at LEP2

    CERN Document Server

    Kiiskinen, A P

    1999-01-01

    A search for pair produced charged Higgs bosons was performed on the high energy data collected by DELPHI at LEP2. All three major final states, tau nu tau nu, cs tau nu and cscs were searched for. The analyses used a combination of event shape variables, di-jet masses and jet flavour tagging. The jet flavours were identified by using life time tagging and particle identification based on the RICH detector complemented by ionisation energy loss measurements. A similar type of jet flavour tagging was also used in extracting the |V sub c sub s | element of the Cabibbo-Kobayashi-Maskawa (CKM) matrix in hadronic decays of the W sup+- boson.

  3. Identifying early pathways of risk and resilience: The co-development of internalizing and externalizing symptoms and the role of harsh parenting

    OpenAIRE

    Wiggins, Jillian Lee; Mitchell, Colter; Hyde, Luke W.; Monk, Christopher S.

    2015-01-01

    Psychological disorders co-occur often in children, but little has been done to document the types of conjoint pathways internalizing and externalizing symptoms may take from the crucial early period of toddlerhood or how harsh parenting may overlap with early symptom co-development. To examine symptom co-development trajectories, we identified latent classes of individuals based on internalizing and externalizing symptoms across ages 3–9 and found three symptom co-development classes: normat...

  4. Evaluation of the feasibility and performance of early warning scores to identify patients at risk of adverse outcomes in a low-middle income country setting

    Science.gov (United States)

    Beane, Abi; De Silva, Ambepitiyawaduge Pubudu; De Silva, Nirodha; Sujeewa, Jayasingha A; Rathnayake, R M Dhanapala; Sigera, P Chathurani; Athapattu, Priyantha Lakmini; Mahipala, Palitha G; Rashan, Aasiyah; Munasinghe, Sithum Bandara; Jayasinghe, Kosala Saroj Amarasiri; Dondorp, Arjen M; Haniffa, Rashan

    2018-01-01

    Objective This study describes the availability of core parameters for Early Warning Scores (EWS), evaluates the ability of selected EWS to identify patients at risk of death or other adverse outcome and describes the burden of triggering that front-line staff would experience if implemented. Design Longitudinal observational cohort study. Setting District General Hospital Monaragala. Participants All adult (age >17 years) admitted patients. Main outcome measures Existing physiological parameters, adverse outcomes and survival status at hospital discharge were extracted daily from existing paper records for all patients over an 8-month period. Statistical analysis Discrimination for selected aggregate weighted track and trigger systems (AWTTS) was assessed by the area under the receiver operating characteristic (AUROC) curve. Performance of EWS are further evaluated at time points during admission and across diagnostic groups. The burden of trigger to correctly identify patients who died was evaluated using positive predictive value (PPV). Results Of the 16 386 patients included, 502 (3.06%) had one or more adverse outcomes (cardiac arrests, unplanned intensive care unit admissions and transfers). Availability of physiological parameters on admission ranged from 90.97% (95% CI 90.52% to 91.40%) for heart rate to 23.94% (95% CI 23.29% to 24.60%) for oxygen saturation. Ability to discriminate death on admission was less than 0.81 (AUROC) for all selected EWS. Performance of the best performing of the EWS varied depending on admission diagnosis, and was diminished at 24 hours prior to event. PPV was low (10.44%). Conclusion There is limited observation reporting in this setting. Indiscriminate application of EWS to all patients admitted to wards in this setting may result in an unnecessary burden of monitoring and may detract from clinician care of sicker patients. Physiological parameters in combination with diagnosis may have a place when applied on admission to

  5. Identifying early dehydration risk with home-based sensors during radiation treatment: a feasibility study on patients with head and neck cancer.

    Science.gov (United States)

    Peterson, Susan K; Shinn, Eileen H; Basen-Engquist, Karen; Demark-Wahnefried, Wendy; Prokhorov, Alexander V; Baru, Chaitanya; Krueger, Ingolf H; Farcas, Emilia; Rios, Philip; Garden, Adam S; Beadle, Beth M; Lin, Kai; Yan, Yan; Martch, Stephanie L; Patrick, Kevin

    2013-12-01

    Systems that enable remote monitoring of patients' symptoms and other health-related outcomes may optimize cancer care outside of the clinic setting. CYCORE (CYberinfrastructure for COmparative effectiveness REsearch) is a software-based prototype for a user-friendly cyberinfrastructure supporting the comprehensive collection and analyses of data from multiple domains using a suite of home-based and mobile sensors. This study evaluated the feasibility of using CYCORE to address early at-home identification of dehydration risk in head and neck cancer patients undergoing radiation therapy. Head and neck cancer patients used home-based sensors to capture weight, blood pressure, pulse, and patient-reported outcomes for two 5-day periods during radiation therapy. Data were sent to the radiation oncologist of each head and neck cancer patient, who viewed them online via a Web-based interface. Feasibility outcomes included study completion rate, acceptability and perceived usefulness of the intervention, and adherence to the monitoring protocol. We also evaluated whether sensor data could identify dehydration-related events. Fifty patients consented to participate, and 48 (96%) completed the study. More than 90% of patients rated their ease, self-efficacy, and satisfaction regarding use of the sensor suite as extremely favorable, with minimal concerns expressed regarding data privacy issues. Patients highly valued the ability to have immediate access to objective, self-monitoring data related to personal risk for dehydration. Clinician assessments indicated a high degree of satisfaction with the ease of using the CYCORE system and the resulting ability to monitor their patients remotely. Implementing CYCORE in a clinical oncology care setting is feasible and highly acceptable to both patients and providers.

  6. A potential approach for monitoring drinking water quality from groundwater systems using organic matter fluorescence as an early warning for contamination events.

    Science.gov (United States)

    Stedmon, Colin A; Seredyńska-Sobecka, Bożena; Boe-Hansen, Rasmus; Le Tallec, Nicolas; Waul, Christopher K; Arvin, Erik

    2011-11-15

    The fluorescence characteristics of natural organic matter in a groundwater based drinking water supply plant were studied with the aim of applying it as a technique to identify contamination of the water supply. Excitation-emission matrices were measured and modeled using parallel factor analysis (PARAFAC) and used to identify which wavelengths provide the optimal signal for monitoring contamination events. The fluorescence was characterized by four components: three humic-like and one amino acid-like. The results revealed that the relative amounts of two of the humic-like components were very stable within the supply plant and distribution net and changed in a predictable fashion depending on which wells were supplying the water. A third humic-like component and an amino acid-like component did not differ between wells. Laboratory contamination experiments with wastewater revealed that combined they could be used as an indicator of microbial contamination. Their fluorescence spectra did not overlap with the other components and therefore the raw broadband fluorescence at the wavelengths specific to their fluorescence could be used to detect contamination. Contamination could be detected at levels equivalent to the addition of 60 μg C/L in drinking water with a TOC concentration of 3.3 mg C/L. The results of this study suggest that these types of drinking water systems, which are vulnerable to microbial contamination due to the lack of disinfectant treatment, can be easily monitored using online organic matter fluorescence as an early warning system to prompt further intensive sampling and appropriate corrective measures. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Putative alternative polyadenylation (APA) events in the early interaction of Salmonella enterica Typhimurium and human host cells.

    Science.gov (United States)

    Afonso-Grunz, Fabian

    2015-12-01

    The immune response of epithelial cells upon infection is mediated by changing activity levels of a variety of proteins along with changes in mRNA, and also ncRNA abundance. Alternative polyadenylation (APA) represents a mechanism that diversifies gene expression similar to alternative splicing. T-cell activation, neuronal activity, development and several human diseases including viral infections involve APA, but at present it remains unclear if this mechanism is also implicated in the response to bacterial infections. Our recently published study of interacting Salmonella enterica Typhimurium and human host cells includes genome-wide expression profiles of human epithelial cells prior and subsequent to infection with the invasive pathogen. The generated dataset (GEO accession number: GSE61730) covers several points of time post infection, and one of these interaction stages was additionally profiled with MACE-based dual 3'Seq, which allows for identification of polyadenylation (PA) sites. The present study features the polyadenylation landscape in early interacting cells based on this data, and provides a comparison of the identified PA sites with those of a corresponding 3P-Seq dataset of non-interacting cells. Differential PA site usage of FTL , PRDX1 and VAPA results in transcription of mRNA isoforms with distinct sets of miRNA and protein binding sites that influence processing, localization, stability, and translation of the respective mRNA. APA of these candidate genes consequently harbors the potential to modulate the host cell response to bacterial infection.

  8. Putative alternative polyadenylation (APA events in the early interaction of Salmonella enterica Typhimurium and human host cells

    Directory of Open Access Journals (Sweden)

    Fabian Afonso-Grunz

    2015-12-01

    Full Text Available The immune response of epithelial cells upon infection is mediated by changing activity levels of a variety of proteins along with changes in mRNA, and also ncRNA abundance. Alternative polyadenylation (APA represents a mechanism that diversifies gene expression similar to alternative splicing. T-cell activation, neuronal activity, development and several human diseases including viral infections involve APA, but at present it remains unclear if this mechanism is also implicated in the response to bacterial infections. Our recently published study of interacting Salmonella enterica Typhimurium and human host cells includes genome-wide expression profiles of human epithelial cells prior and subsequent to infection with the invasive pathogen. The generated dataset (GEO accession number: GSE61730 covers several points of time post infection, and one of these interaction stages was additionally profiled with MACE-based dual 3'Seq, which allows for identification of polyadenylation (PA sites. The present study features the polyadenylation landscape in early interacting cells based on this data, and provides a comparison of the identified PA sites with those of a corresponding 3P-Seq dataset of non-interacting cells. Differential PA site usage of FTL, PRDX1 and VAPA results in transcription of mRNA isoforms with distinct sets of miRNA and protein binding sites that influence processing, localization, stability, and translation of the respective mRNA. APA of these candidate genes consequently harbors the potential to modulate the host cell response to bacterial infection.

  9. Fast events in protein folding: structural volume changes accompanying the early events in the N-->I transition of apomyoglobin induced by ultrafast pH jump.

    OpenAIRE

    Abbruzzetti, S; Crema, E; Masino, L; Vecli, A; Viappiani, C; Small, J R; Libertini, L J; Small, E W

    2000-01-01

    Ultrafast, laser-induced pH jump with time-resolved photoacoustic detection has been used to investigate the early protonation steps leading to the formation of the compact acid intermediate (I) of apomyoglobin (ApoMb). When ApoMb is in its native state (N) at pH 7.0, rapid acidification induced by a laser pulse leads to two parallel protonation processes. One reaction can be attributed to the binding of protons to the imidazole rings of His24 and His119. Reaction with imidazole leads to an u...

  10. Evolution of GHF5 endoglucanase gene structure in plant-parasitic nematodes: no evidence for an early domain shuffling event.

    Science.gov (United States)

    Kyndt, Tina; Haegeman, Annelies; Gheysen, Godelieve

    2008-11-03

    the whole gene cassette, i.e. the GHF5 catalytic domain and the CBM2, rather than that it evolved by domain shuffling. Our evolutionary model for the gene structure in PPN GHF5 endoglucanases implies the occurrence of an early duplication event, and more recent gene duplications at genus or species level.

  11. Evolution of GHF5 endoglucanase gene structure in plant-parasitic nematodes: no evidence for an early domain shuffling event

    Directory of Open Access Journals (Sweden)

    Gheysen Godelieve

    2008-11-01

    PPN GHF5 endoglucanase gene most probably consisted of the whole gene cassette, i.e. the GHF5 catalytic domain and the CBM2, rather than that it evolved by domain shuffling. Our evolutionary model for the gene structure in PPN GHF5 endoglucanases implies the occurrence of an early duplication event, and more recent gene duplications at genus or species level.

  12. Early-life risk factors identified for owner-reported feline overweight and obesity at around two years of age.

    Science.gov (United States)

    Rowe, E C; Browne, W J; Casey, R A; Gruffydd-Jones, T J; Murray, J K

    2017-08-01

    Obesity is considered the second most common health problem in pet cats in developed countries. This study used prospective data from a longitudinal study of pet cats ('C.L.A.W.S.', www.bristol.ac.uk/vetscience/claws) to identify early-life risk factors for feline overweight/obesity occurring at around two years of age. Data were collected via five owner-completed questionnaires (for cats aged two-six months, six months, 12 months, 18 months and two years respectively) completed between May 2011 and April 2015. Owner-reported body condition scores (BCS) of cats at age two years, assessed using images from the 9-point BCS system (Laflamme, 1997), were categorised into a dichotomous variable: overweight/obese (BCS 6-9) and not overweight (BCS 1-5) and used as the dependent variable. Of the 375 cats with owner-reported BCS, 25.3% were overweight or obese at two years of age. Multivariable logistic regression models were built using stepwise forward-selection. To account for potential hierarchical clustering due to multi-cat households two-level random intercept models were considered but clustering had no impact on the analysis. Models were compared using Wald tests. Six factors were significantly associated with overweight/obesity at two years of age: being overweight or obese at one year of age (OR=10.6, 95%CI 4.4-25.3); owner belief that BCS 7 was the ideal weight (OR=33.2, 95%CI 8.5-129.4), or that BCS represented overweight cats but they would not be concerned if their cat were classified in this category (OR=2.7, 95%CI 1.2-6.2), at questionnaire five completion; vets advising owners that the cat should lose weight, or making no comment on their weight, between one and two years of age (OR=12.1, 95%CI 3.2-44.9 and OR=3.9, 95%CI 1.5-10.3 respectively); owners giving their cat treats when they "felt happy" with them at 18 months of age (OR=2.7, 95%CI 1.0 - 7.3); feeding ≥250g wet food daily between two and six months of age (OR=2.7, 95%CI 1.2-5.9), and feeding

  13. Early Markers of Autism Spectrum Disorders in Infants and Toddlers Prospectively Identified in the Social Attention and Communication Study

    Science.gov (United States)

    Barbaro, Josephine; Dissanayake, Cheryl

    2013-01-01

    The Social Attention and Communication Study involved the successful implementation of developmental surveillance of the early markers of autism spectrum disorders in a community-based setting. The objective in the current study was to determine the most discriminating and predictive markers of autism spectrum disorders used in the Social…

  14. Ability of spectral domain optical coherence tomography peripapillary retinal nerve fiber layer thickness measurements to identify early glaucoma

    Directory of Open Access Journals (Sweden)

    Tarannum Mansoori

    2011-01-01

    Full Text Available Purpose : To evaluate the ability of spectral domain optical coherence tomography (OCT peripapillary retinal nerve fiber layer thickness (RNFLT parameters to distinguish normal eyes from those with early glaucoma in Asian Indian eyes. Design : Observational cross-sectional study. Materials and Methods : One hundred and seventy eight eyes (83 glaucoma patients and 95 age matched healthy subjects of subjects more than 40 years of age were included in the study. All subjects underwent RNFLT measurement with spectral OCT/ scanning laser ophthalmoscope (SLO after dilatation. Sensitivity, specificity and area under the receiving operating characteristic curve (AROC were calculated for various OCT peripapillary RNFL parameters. Results: The mean RNFLT in healthy subjects and patients with early glaucoma were 105.7 ± 5.1 μm and 90.7 ± 7.5 μm, respectively. The largest AROC was found for 12 o′clock- hour (0.98, average (0.96 and superior quadrant RNFLT (0.9. When target specificity was set at ≥ 90% and ≥ 80%, the parameters with highest sensitivity were 12 o′clock -hour (91.6%, average RNFLT (85.3% and 12 o′ clock- hour (96.8 %, average RNFLT (94.7% respectively. Conclusion : Our study showed good ability of spectral OCT/ SLO to differentiate normal eyes from patients with early glaucoma and hence it may serve as an useful adjunct for early diagnosis of glaucoma.

  15. The relation of early experienced negative life events and current itch. A longitudinal study among adolescents in Oslo, Norway.

    Science.gov (United States)

    Lien, Lars; Halvorsen, Jon Anders; Haavet, Ole Rikard; Dalgard, Florence

    2012-03-01

    Negative life events have impact on mental health and skin diseases among adults. Itch is a common, disabling skin symptom. The aim was to describe negative life events associated with current itch and to analyze the impact of number of negative life events on symptoms of itch, controlling for possible confounders. This school-based longitudinal survey was conducted among 15 and 18 years old high-school students in Oslo, Norway. From a baseline cohort of 3811 students, 2489 (65%) participants were followed-up after three years later. They completed questionnaires at baseline and follow-up. Current itch was measured with a validated instrument asking for symptoms on a four point Likert scale at follow-up. More girls than boys reported itch. There were no gender differences in number of negative life events. Death among close relative/friend was the most common negative life event among boys and girls. All negative life experiences before 15 years of age were statistically significantly associated with itch, but after 15 years only half of the negative life events were associated with itch. The bivariate association between number of negative life events and itch was statistically significant, and only when adjusting for mental distress at baseline there was a considerable drop in the Odds Ratio. There is a clear association between number of negative life events at baseline and itch at follow-up three years later among adolescents. It is therefore important to discuss possible adverse experiences with adolescents presenting with severe symptoms of itch. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. SRBreak: A read-depth and split-read framework to identify breakpoints of different events inside simple copy-number variable regions

    Directory of Open Access Journals (Sweden)

    HOANG T NGUYEN

    2016-09-01

    Full Text Available Copy-number variation (CNV has been associated with increased risk of complex diseases. High throughput sequencing (HTS technologies facilitate the detection of copy-number variable regions (CNVRs and their breakpoints. This helps in understanding genome structures of genomes as well as their evolution process. Various approaches have been proposed for detecting CNV breakpoints, but currently it is still challenging for tools based on a single analysis method to identify breakpoints of CNVs. It has been shown, however, that pipelines which integrate multiple approaches are able to report more reliable breakpoints. Here, based on HTS data, we have developed a pipeline to identify approximate breakpoints (±10 bp relating to different ancestral events within a specific CNVR. The pipeline combines read-depth and split-read information to infer breakpoints, using information from multiple samples to allow an imputation approach to be taken. The main steps involve using a normal mixture model to cluster samples into different groups, followed by simple kernel-based approaches to maximise information obtained from read-depth and split-read approaches, after which common breakpoints of groups are inferred. The pipeline uses split-read information directly from CIGAR strings of BAM files, without using a re-alignment step. On simulated data sets, it was able to report breakpoints for very low-coverage samples including those for which only single-end reads were available. When applied to three loci from existing human resequencing data sets (NEGR1, LCE3, IRGM the pipeline obtained good concordance with results from the 1000 Genomes Project (92%, 100% and 82%, respectively.The package is available at https://github.com/hoangtn/SRBreak, and also as a docker-based application at https://registry.hub.docker.com/u/hoangtn/srbreak/.

  17. Impact of sirolimus-eluting stent fractures without early cardiac events on long-term clinical outcomes: A multislice computed tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Tsuyoshi [Toyohashi Heart Center, Oyama-cho, Toyohashi (Japan); Nagoya City University Graduate School of Medical Sciences, Department of Cardio-Renal Medicine and Hypertension, Nagoya (Japan); Kimura, Masashi; Ehara, Mariko; Terashima, Mitsuyasu; Nasu, Kenya; Kinoshita, Yoshihisa; Habara, Maoto; Tsuchikane, Etsuo; Suzuki, Takahiko [Toyohashi Heart Center, Oyama-cho, Toyohashi (Japan)

    2014-05-15

    This study sought to evaluate the impact of sirolimus-eluting stent (SES) fractures on long-term clinical outcomes using multislice computed tomography (MSCT). In this study, 528 patients undergoing 6- to 18-month follow-up 64-slice MSCT after SES implantation without early clinical events were followed clinically (the median follow-up interval was 4.6 years). A CT-detected stent fracture was defined as a complete gap with Hounsfield units (HU) <300 at the site of separation. The major adverse cardiac events (MACEs), including cardiac death, stent thrombosis, and target lesion revascularisation, were compared according to the presence of stent fracture. Stent fractures were observed in 39 patients (7.4 %). MACEs were more common in patients with CT-detected stent fractures than in those without (46 % vs. 7 %, p < 0.01). Univariate Cox regression analysis indicated a significant relationship between MACE and stent fracture [hazard ratio (HR) 7.65; p < 0.01], age (HR 1.03; p = 0.04), stent length (HR 1.03; p < 0.01), diabetes mellitus (HR 1.77; p = 0.04), and chronic total occlusion (HR 2.54; p = 0.01). In the multivariate model, stent fracture (HR 5.36; p < 0.01) and age (HR 1.03; p = 0.04) remained significant predictors of MACE. An SES fracture detected by MSCT without early clinical events was associated with long-term clinical adverse events. (orig.)

  18. Modeling Retention at a Large Public University: Can At-Risk Students Be Identified Early Enough to Treat?

    Science.gov (United States)

    Singell, Larry D.; Waddell, Glen R.

    2010-01-01

    We examine the extent to which readily available data at a large public university can be used to a priori identify at-risk students who may benefit from targeted retention efforts. Although it is possible to identify such students, there remains an inevitable tradeoff in any resource allocation between not treating the students who are likely to…

  19. Early traumatic life events, parental attitudes, family history, and birth risk factors in patients with depressive disorder and healthy controls.

    Science.gov (United States)

    Bandelow, Borwin; Gutermann, Julia; Peter, Helmut; Wedekind, Dirk

    2013-02-01

    Only few studies have compared the frequency of traumatic life events during childhood in inpatients with depression with a healthy control group. Consecutively admitted inpatients with depression (n = 79), most of whom belonged to the melancholic subtype (n = 73; 92.4%), and healthy controls (n = 110) were investigated using a comprehensive retrospective interview with 203 questions regarding childhood traumatic life events, parental attitudes, family history of psychiatric disorders and birth risk factors. Depressed patients had significantly more severe traumatic events (mean score 1.33; SD 1.4) than control subjects (0.85; SD 1.2) on a 0-10 point "severe trauma scale". 70.9% (n = 56) of the depressed patients, but only 48.2% (n = 53) of the controls reported at least one severe traumatic event. When looking at single events, only few differences were found between patients and controls. Compared to controls, patients described significantly higher rates of psychiatric disorders in their families, in particular depression. Parental rearing styles were rated as more unfavorable in the patient group. In a logistic regression model, of all possible etiological factors examined, only a family history of psychiatric disorders showed a significant influence (OR = 3.6). Melancholic depression seems to be less associated with traumatic events than other psychiatric disorders.

  20. Monitoring early hydration of reinforced concrete structures using structural parameters identified by piezo sensors via electromechanical impedance technique

    Science.gov (United States)

    Talakokula, Visalakshi; Bhalla, Suresh; Gupta, Ashok

    2018-01-01

    Concrete is the most widely used material in civil engineering construction. Its life begins when the hydration process is activated after mixing the cement granulates with water. In this paper, a non-dimensional hydration parameter, obtained from piezoelectric ceramic (PZT) patches bonded to rebars embedded inside concrete, is employed to monitor the early age hydration of concrete. The non-dimensional hydration parameter is derived from the equivalent stiffness determined from the piezo-impedance transducers using the electro-mechanical impedance (EMI) technique. The focus of the study is to monitor the hydration process of cementitious materials commencing from the early hours and continue till 28 days using single non-dimensional parameter. The experimental results show that the proposed piezo-based non-dimensional hydration parameter is very effective in monitoring the early age hydration, as it has been derived from the refined structural impedance parameters, obtained by eliminating the PZT contribution, and using both the real and imaginary components of the admittance signature.

  1. A major 2.1 Ga event of mafic magmatism in west Africa: An Early stage of crustal accretion

    Science.gov (United States)

    Abouchami, Wafa; Boher, Muriel; Michard, Annie; Albarede, Francis

    1990-10-01

    environments. Back-arc or low-Ti continental flood basalts provide a marginally good agreement but still face some difficulties. Oceanic flood basalts similar to those which form oceanic plateaus (e.g. in the Nauru basin) and later accreted to continents as allochtonous terranes represent the most acceptable modern analogue of many Proterozoic basalts. It is suggested that deep plumes piercing young lithosphere can generate huge amounts of tholeiites in a short time. Birimian basalts, like many Early Proterozoic basalts, may also be viewed as recent equivalents of the Archean greenstone belts. The modern komatiite of Gorgona Island is suggested to fit this model of intraplate volcanism. Although the 2.1 Ga magmatic event in West Africa has gone virtually unnoticed in the literature, it extends over several thousand kilometers and compares with the distribution of mantle-derived magmatic activity in other major orogenic provinces (e.g. Superior). It shows that the growth rate of continents cannot be extrapolated from the data obtained solely from the best studied continents (North America, Europe, Australia). If such large crustal segments were overlooked, a spurious pattern of episodic activity of the mantle could arise.

  2. Fast events in protein folding: structural volume changes accompanying the early events in the N-->I transition of apomyoglobin induced by ultrafast pH jump.

    Science.gov (United States)

    Abbruzzetti, S; Crema, E; Masino, L; Vecli, A; Viappiani, C; Small, J R; Libertini, L J; Small, E W

    2000-01-01

    Ultrafast, laser-induced pH jump with time-resolved photoacoustic detection has been used to investigate the early protonation steps leading to the formation of the compact acid intermediate (I) of apomyoglobin (ApoMb). When ApoMb is in its native state (N) at pH 7.0, rapid acidification induced by a laser pulse leads to two parallel protonation processes. One reaction can be attributed to the binding of protons to the imidazole rings of His24 and His119. Reaction with imidazole leads to an unusually large contraction of -82 +/- 3 ml/mol, an enthalpy change of 8 +/- 1 kcal/mol, and an apparent bimolecular rate constant of (0.77 +/- 0.03) x 10(10) M(-1) s(-1). Our experiments evidence a rate-limiting step for this process at high ApoMb concentrations, characterized by a value of (0. 60 +/- 0.07) x 10(6) s(-1). The second protonation reaction at pH 7. 0 can be attributed to neutralization of carboxylate groups and is accompanied by an apparent expansion of 3.4 +/- 0.2 ml/mol, occurring with an apparent bimolecular rate constant of (1.25 +/- 0.02) x 10(11) M(-1) s(-1), and a reaction enthalpy of about 2 kcal/mol. The activation energy for the processes associated with the protonation of His24 and His119 is 16.2 +/- 0.9 kcal/mol, whereas that for the neutralization of carboxylates is 9.2 +/- 0.9 kcal/mol. At pH 4.5 ApoMb is in a partially unfolded state (I) and rapid acidification experiments evidence only the process assigned to carboxylate protonation. The unusually large contraction and the high energetic barrier observed at pH 7.0 for the protonation of the His residues suggests that the formation of the compact acid intermediate involves a rate-limiting step after protonation.

  3. Molecular evolution of glutamine synthetase II: Phylogenetic evidence of a non-endosymbiotic gene transfer event early in plant evolution

    Directory of Open Access Journals (Sweden)

    Tartar Aurélien

    2010-06-01

    Full Text Available Abstract Background Glutamine synthetase (GS is essential for ammonium assimilation and the biosynthesis of glutamine. The three GS gene families (GSI, GSII, and GSIII are represented in both prokaryotic and eukaryotic organisms. In this study, we examined the evolutionary relationship of GSII from eubacterial and eukaryotic lineages and present robust phylogenetic evidence that GSII was transferred from γ-Proteobacteria (Eubacteria to the Chloroplastida. Results GSII sequences were isolated from four species of green algae (Trebouxiophyceae, and additional green algal (Chlorophyceae and Prasinophytae and streptophyte (Charales, Desmidiales, Bryophyta, Marchantiophyta, Lycopodiophyta and Tracheophyta sequences were obtained from public databases. In Bayesian and maximum likelihood analyses, eubacterial (GSIIB and eukaryotic (GSIIE GSII sequences formed distinct clades. Both GSIIB and GSIIE were found in chlorophytes and early-diverging streptophytes. The GSIIB enzymes from these groups formed a well-supported sister clade with the γ-Proteobacteria, providing evidence that GSIIB in the Chloroplastida arose by horizontal gene transfer (HGT. Bayesian relaxed molecular clock analyses suggest that GSIIB and GSIIE coexisted for an extended period of time but it is unclear whether the proposed HGT happened prior to or after the divergence of the primary endosymbiotic lineages (the Archaeplastida. However, GSIIB genes have not been identified in glaucophytes or red algae, favoring the hypothesis that GSIIB was gained after the divergence of the primary endosymbiotic lineages. Duplicate copies of the GSIIB gene were present in Chlamydomonas reinhardtii, Volvox carteri f. nagariensis, and Physcomitrella patens. Both GSIIB proteins in C. reinhardtii and V. carteri f. nagariensis had N-terminal transit sequences, indicating they are targeted to the chloroplast or mitochondrion. In contrast, GSIIB proteins of P. patens lacked transit sequences, suggesting

  4. High-resolution carbonate isotopic study of the Mural Formation (Cerro Pimas section), Sonora, México: Implications for early Albian oceanic anoxic events

    Science.gov (United States)

    Madhavaraju, J.; Lee, Yong Il; Scott, R. W.; González-León, C. M.; Jenkyns, H. C.; Saucedo-Samaniego, J. C.; Ramasamy, S.

    2018-03-01

    The 420-m thick stratigraphic section of the Mural Formation that is exposed in the Cerro Pimas area of northern Sonora, Mexico, is composed of limestone lithofacies ranging from bioclastic wackestone to boundstone, whose biota is characterized by low diversity. Prominent age-diagnostic fossils are benthic foraminifera and long-ranging calcareous algae that indicate the Aptian/Albian boundary is close to the base of the Los Coyotes Member. The carbonates of this formation have negative to positive δ13C values (-4.63 to +2.6‰) and highly depleted δ18O values that range from -12.74 to -8.34‰. The absence of correlation between δ13C and δ18O values supports a primary marine origin for the δ13C values of these limestones. The carbon-isotopic curve of the Cerro Pimas stratigraphic section has well-defined δ13C segments (C8 - C15) that compare with published curves of similar age. In the lower part of the early Albian Los Coyotes Member, the presence of OAE 1b is indicated by an increase followed by a decrease in δ13C values, suggesting correlation with the Kilian Event. The middle part of the Los Coyotes Member has a significant negative carbon-isotope excursion correlated with the globally recognizable early Albian Paquier event. Moreover, another significant negative carbon-isotope shift is observed in the upper part of the Los Coyotes Member, which can be correlated with the Leenhardt Event. The occurrence of the Kilian, Paquier and Leenhardt Events (OAE 1b cluster) in the Cerro Pimas stratigraphy confirms the global nature of these early Albian disturbances of the carbon cycle.

  5. Weighted cumulative exposure models helped identify an association between early knee-pain consultations and future knee OA diagnosis.

    Science.gov (United States)

    Yu, Dahai; Peat, George; Bedson, John; Edwards, John J; Turkiewicz, Aleksandra; Jordan, Kelvin P

    2016-08-01

    To establish the association between prior knee-pain consultations and early diagnosis of knee osteoarthritis (OA) by weighted cumulative exposure (WCE) models. Data were from an electronic health care record (EHR) database (Consultations in Primary Care Archive). WCE functions for modeling the cumulative effect of time-varying knee-pain consultations weighted by recency were derived as a predictive tool in a population-based case-control sample and validated in a prospective cohort sample. Two WCE functions ([i] weighting of the importance of past consultations determined a priori; [ii] flexible spline-based estimation) were comprehensively compared with two simpler models ([iii] time since most recent consultation; total number of past consultations) on model goodness of fit, discrimination, and calibration both in derivation and validation phases. People with the most recent and most frequent knee-pain consultations were more likely to have high WCE scores that were associated with increased risk of knee OA diagnosis both in derivation and validation phases. Better model goodness of fit, discrimination, and calibration were observed for flexible spline-based WCE models. WCE functions can be used to model prediagnostic symptoms within routine EHR data and provide novel low-cost predictive tools contributing to early diagnosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Bayesian phylogenetic analysis of Semitic languages identifies an Early Bronze Age origin of Semitic in the Near East.

    Science.gov (United States)

    Kitchen, Andrew; Ehret, Christopher; Assefa, Shiferaw; Mulligan, Connie J

    2009-08-07

    The evolution of languages provides a unique opportunity to study human population history. The origin of Semitic and the nature of dispersals by Semitic-speaking populations are of great importance to our understanding of the ancient history of the Middle East and Horn of Africa. Semitic populations are associated with the oldest written languages and urban civilizations in the region, which gave rise to some of the world's first major religious and literary traditions. In this study, we employ Bayesian computational phylogenetic techniques recently developed in evolutionary biology to analyse Semitic lexical data by modelling language evolution and explicitly testing alternative hypotheses of Semitic history. We implement a relaxed linguistic clock to date language divergences and use epigraphic evidence for the sampling dates of extinct Semitic languages to calibrate the rate of language evolution. Our statistical tests of alternative Semitic histories support an initial divergence of Akkadian from ancestral Semitic over competing hypotheses (e.g. an African origin of Semitic). We estimate an Early Bronze Age origin for Semitic approximately 5750 years ago in the Levant, and further propose that contemporary Ethiosemitic languages of Africa reflect a single introduction of early Ethiosemitic from southern Arabia approximately 2800 years ago.

  7. Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study.

    Science.gov (United States)

    Paciaroni, Maurizio; Agnelli, Giancarlo; Caso, Valeria; Tsivgoulis, Georgios; Furie, Karen L; Tadi, Prasanna; Becattini, Cecilia; Falocci, Nicola; Zedde, Marialuisa; Abdul-Rahim, Azmil H; Lees, Kennedy R; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo; Mosconi, Maria Giulia; Cimini, Ludovica Anna; Procopio, Antonio; Bovi, Paolo; Carletti, Monica; Rigatelli, Alberto; Cappellari, Manuel; Putaala, Jukka; Tomppo, Liisa; Tatlisumak, Turgut; Bandini, Fabio; Marcheselli, Simona; Pezzini, Alessandro; Poli, Loris; Padovani, Alessandro; Masotti, Luca; Vannucchi, Vieri; Sohn, Sung-Il; Lorenzini, Gianni; Tassi, Rossana; Guideri, Francesca; Acampa, Maurizio; Martini, Giuseppe; Ntaios, George; Karagkiozi, Efstathia; Athanasakis, George; Makaritsis, Kostantinos; Vadikolias, Kostantinos; Liantinioti, Chrysoula; Chondrogianni, Maria; Mumoli, Nicola; Consoli, Domenico; Galati, Franco; Sacco, Simona; Carolei, Antonio; Tiseo, Cindy; Corea, Francesco; Ageno, Walter; Bellesini, Marta; Colombo, Giovanna; Silvestrelli, Giorgio; Ciccone, Alfonso; Scoditti, Umberto; Denti, Licia; Mancuso, Michelangelo; Maccarrone, Miriam; Orlandi, Giovanni; Giannini, Nicola; Gialdini, Gino; Tassinari, Tiziana; De Lodovici, Maria Luisa; Bono, Giorgio; Rueckert, Christina; Baldi, Antonio; D'Anna, Sebastiano; Toni, Danilo; Letteri, Federica; Giuntini, Martina; Lotti, Enrico Maria; Flomin, Yuriy; Pieroni, Alessio; Kargiotis, Odysseas; Karapanayiotides, Theodore; Monaco, Serena; Baronello, Mario Maimone; Csiba, Laszló; Szabó, Lilla; Chiti, Alberto; Giorli, Elisa; Del Sette, Massimo; Imberti, Davide; Zabzuni, Dorjan; Doronin, Boris; Volodina, Vera; Michel, Patrik; Vanacker, Peter; Barlinn, Kristian; Pallesen, Lars-Peder; Kepplinger, Jessica; Bodechtel, Ulf; Gerber, Johannes; Deleu, Dirk; Melikyan, Gayane; Ibrahim, Faisal; Akhtar, Naveed; Gourbali, Vanessa; Yaghi, Shadi

    2017-03-01

    This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P =0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P =0.10) for major bleedings. The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P =0.009) for ischemic outcome events and 0.407 (0.275-0.540; P =0.14) for hemorrhagic outcome events. In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. © 2017 American Heart Association, Inc.

  8. Microaerophilic conditions permit to mimic in vitro events occurring during in vivo Helicobacter pylori infection and to identify Rho/Ras-associated proteins in cellular signaling.

    Science.gov (United States)

    Cottet, Sandra; Corthésy-Theulaz, Irène; Spertini, François; Corthésy, Blaise

    2002-09-13

    Molecular dissection of the mechanisms underlying Helicobacter pylori infection suffers from the lack of in vitro systems mimicking in vivo observations. A system was developed whereby human epithelial cells (Caco-2) grown as polarized monolayers and bacteria can communicate with each other under culture conditions optimal for each partner. Caco-2 cells grown on filter supports were inserted in a vertical position into diffusion chambers equilibrated with air and 5% CO(2) at their basolateral surface (aerophilic conditions) and 5% CO(2), 5% O(2), 90% N(2) (microaerophilic conditions) in the apical compartment. Remarkably, the epithelial polarized layer was stable under these asymmetric culture conditions for at least 24 h, and the presence of Caco-2 cells was necessary to maintain H. pylori growth. In contrast to previous studies conducted with non-polarized Caco-2 cells and other cell lines kept under aerophilic conditions, we found H. pylori-dependent stimulation of cytokine secretion (MCP-1 (monocyte chemoattractant protein-1), GRO-alpha (growth-regulated oncogene-alpha), RANTES (regulated on activation normal T cell expressed and secreted)). This correlated with nuclear translocation of NF-kappaB p50 and p65 subunits. Tyrosine phosphorylation of nine cellular proteins was induced or enhanced; we identified p120(RasGAP), p190(RhoGAP), p62dok (downstream of tyrosine kinases), and cortactin as H. pylori-inducible targets. Moreover, reduction of H. pylori urease expression was observed in adherent bacteria as compared with bacteria in suspension. In addition to mimicking several observations seen in the inflamed gastric mucosa, the novel in vitro system was allowed to underscore complex cellular events not seen in classical in vitro analyses of microaerophilic bacteria-epithelial cell cross-talk.

  9. ABA Inhibits Embryo Cell Expansion and Early Cell Division Events During Coffee (Coffea arabica 'Rubi') Seed Germination

    NARCIS (Netherlands)

    Silva, da E.A.A.; Toorop, P.E.; Lammeren, van A.A.M.; Hilhorst, H.W.M.

    2008-01-01

    Background and Aims: Coffee seed germination represents an interplay between the embryo and the surrounding endosperm. A sequence of events in both parts of the seed determines whether germination will be successful or not. Following previous studies, the aim here was to further characterize the

  10. The Early Ludfordian leintwardinensis graptolite Event and the Gorstian-Ludfordian boundary in Bohemia (Silurian, Czech Republic)

    Czech Academy of Sciences Publication Activity Database

    Štorch, Petr; Manda, Š.; Loydell, D. K.

    2014-01-01

    Roč. 57, č. 5 (2014), s. 1003-1043 ISSN 0031-0239 R&D Projects: GA ČR GA205/09/0703 Institutional support: RVO:67985831 Keywords : biostratigraphy * extinction * Gorstian-Ludfordian boundary * graptolites * leintwardinensis Event * Silurian Subject RIV: DB - Geology ; Mineralogy Impact factor: 2.240, year: 2014

  11. Analysis of early events in the interaction between Fusarium graminearum and the susceptible barley (Hordeum vulgare) cultivar Scarlett

    DEFF Research Database (Denmark)

    Yang, Fen; Jensen, J.D.; Svensson, Birte

    2010-01-01

    A proteomic analysis was conducted to map the events during the initial stages of the interaction between the fungal pathogen Fusarium graminearum and the susceptible barley cultivar Scarlett. Quantification of fungal DNA demonstrated a sharp increase in fungal biomass in barley spikelets at 3 da...

  12. Identifying Early Childhood Personality Dimensions Using the California Child Q-Set and Prospective Associations With Behavioral and Psychosocial Development.

    Science.gov (United States)

    Wilson, Sylia; Schalet, Benjamin D; Hicks, Brian M; Zucker, Robert A

    2013-08-01

    The present study used an empirical, "bottom-up" approach to delineate the structure of the California Child Q-Set (CCQ), a comprehensive set of personality descriptors, in a sample of 373 preschool-aged children. This approach yielded two broad trait dimensions, Adaptive Socialization (emotional stability, compliance, intelligence) and Anxious Inhibition (emotional/behavioral introversion). Results demonstrate the value of using empirical derivation to investigate the structure of personality in young children, speak to the importance of early-evident personality traits for adaptive development, and are consistent with a growing body of evidence indicating that personality structure in young children is similar, but not identical to, that in adults, suggesting a model of broad personality dimensions in childhood that evolve into narrower traits in adulthood.

  13. Identifying Domains of Ideas to Influence Early Childhood Teachers' Beliefs in Globalisation: A Mixed-Method Study

    Science.gov (United States)

    Tzuo, Pei-Wen; Tan, Liang See; Yang, Chien-Hui

    2013-01-01

    In the age of globalisation, it has been understood that teachers' beliefs revolve between old--new and local--foreign ideas of teaching and learning. The purpose of this study is to identify the domains of the various ideas that influence teachers' beliefs in globalisation, compare them to the strengths of influence, and explore the meanings of…

  14. Spatiotemporal proteomic analyses during pancreas cancer progression identifies serine/threonine stress kinase 4 (STK4) as a novel candidate biomarker for early stage disease.

    Science.gov (United States)

    Mirus, Justin E; Zhang, Yuzheng; Hollingsworth, Michael A; Solan, Joell L; Lampe, Paul D; Hingorani, Sunil R

    2014-12-01

    Pancreas cancer, or pancreatic ductal adenocarcinoma, is the deadliest of solid tumors, with a five-year survival rate of pancreas cancer. Mouse models that accurately recapitulate the human condition allow disease tracking from inception to invasion and can therefore be useful for studying early disease stages in which surgical resection is possible. Using a highly faithful mouse model of pancreas cancer in conjunction with a high-density antibody microarray containing ∼2500 antibodies, we interrogated the pancreatic tissue proteome at preinvasive and invasive stages of disease. The goal was to discover early stage tissue markers of pancreas cancer and follow them through histologically defined stages of disease using cohorts of mice lacking overt clinical signs and symptoms and those with end-stage metastatic disease, respectively. A panel of seven up-regulated proteins distinguishing pancreas cancer from normal pancreas was validated, and their levels were assessed in tissues collected at preinvasive, early invasive, and moribund stages of disease. Six of the seven markers also differentiated pancreas cancer from an experimental model of chronic pancreatitis. The levels of serine/threonine stress kinase 4 (STK4) increased between preinvasive and invasive stages, suggesting its potential as a tissue biomarker, and perhaps its involvement in progression from precursor pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma. Immunohistochemistry of STK4 at different stages of disease revealed a dynamic expression pattern further implicating it in early tumorigenic events. Immunohistochemistry of a panel of human pancreas cancers confirmed that STK4 levels were increased in tumor epithelia relative to normal tissue. Overall, this integrated approach yielded several tissue markers that could serve as signatures of disease stage, including early (resectable), and therefore clinically meaningful, stages. © 2014 by The American Society for

  15. Impacts of a water stress followed by an early frost event on beech (Fagus sylvatica L.) susceptibility to Scolytine ambrosia beetles - Research strategy and first results

    Science.gov (United States)

    La Spina, Sylvie; de Cannière, Charles; Molenberg, Jean-Marc; Vincke, Caroline; Deman, Déborah; Grégoire, Jean-Claude

    2010-05-01

    Climate change tends to induce more frequent abiotic and biotic extreme events, having large impacts on tree vitality. Weakened trees are then more susceptible to secondary insect outbreaks, as it happened in Belgium in the early 2000s: after an early frost event, secondary Scolytine ambrosia beetles attacks were observed on beech trees. In this study, we test if a combination of stress, i.e. a soil water deficit preceding an early frost, could render trees more attractive to beetles. An experimental study was set in autumn 2008. Two parcels of a beech forest were covered with plastic tents to induce a water stress by rain interception. The parcels were surrounded by 2-meters depth trenches to avoid water supply by streaming. Soil water content and different indicators of tree water use (sap flow, predawn leaf water potential, tree radial growth) were followed. In autumn 2010, artificial frost injuries will be inflicted to trees using dry ice. Trees attractivity for Scolytine insects, and the success of insect colonization will then be studied. The poster will focus on experiment setting and first results (impacts of soil water deficit on trees).

  16. Early-Life events, including mode of delivery and type of feeding, siblings and gender, shape the developing gut microbiota

    NARCIS (Netherlands)

    Martin, Rocio; Makino, Hiroshi; Yavuz, Aysun Cetinyurek; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan

    2016-01-01

    Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with

  17. Clay mineralogical constraints on weathering in response to early Eocene hyperthermal events in the Bighorn Basin, Wyoming (Western Interior, USA)

    NARCIS (Netherlands)

    Wang, Chaowen; Adriaens, Rieko; Hong, Hanlie; Elsen, Jan; Vandenberghe, Noël; Lourens, Lucas J.|info:eu-repo/dai/nl/125023103; Gingerich, Philip D.; Abels, Hemmo A.|info:eu-repo/dai/nl/304848018

    2017-01-01

    Series of transient greenhouse warming intervals in the early Eocene provide an opportunity to study the response of rock weathering and erosion to changes in temperature and precipitation. During greenhouse warming, chemical weathering is thought to increase the uptake of carbon from the

  18. Proteomics Mapping of Cord Blood Identifies Haptoglobin ?Switch-On? Pattern as Biomarker of Early-Onset Neonatal Sepsis in Preterm Newborns

    OpenAIRE

    Buhimschi, Catalin S.; Bhandari, Vineet; Dulay, Antonette T.; Nayeri, Unzila A.; Abdel-Razeq, Sonya S.; Pettker, Christian M.; Thung, Stephen; Zhao, Guomao; Han, Yiping W.; Bizzarro, Matthew; Buhimschi, Irina A.

    2011-01-01

    Background Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns. Methodology/Principal Findings We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A prote...

  19. Early prosthetic aortic valve infection identified with the use of positron emission tomography in a patient with lead endocarditis.

    Science.gov (United States)

    Amraoui, Sana; Tlili, Ghoufrane; Sohal, Manav; Bordenave, Laurence; Bordachar, Pierre

    2016-12-01

    18-Fluorodeoxyglucose positron emission tomography/computerized tomography (FDG PET/CT) scanning has recently been proposed as a diagnostic tool for lead endocarditis (LE). FDG PET/CT might be also useful to localize associated septic emboli in patients with LE. We report an interesting case of a LE patient with a prosthetic aortic valve in whom a trans-esophageal echocardiogram did not show associated aortic endocarditis. FDG PET/CT revealed prosthetic aortic valve infection. A second TEE performed 2 weeks after identified aortic vegetation. A longer duration of antimicrobial therapy with serial follow-up echocardiography was initiated. There was also increased uptake in the sigmoid colon, corresponding to focal polyps resected during a colonoscopy. FDG PET/CT scanning seems to be highly sensitive for prosthetic aortic valve endocarditis diagnosis. This promising diagnostic tool may be beneficial in LE patients, by identifying septic emboli and potential sites of pathogen entry.

  20. Early data from project engage: a program to identify and transition medically hospitalized patients into addictions treatment

    OpenAIRE

    Pecoraro, Anna; Horton, Terry; Ewen, Edward; Becher, Julie; Wright, Patricia A; Silverman, Basha; McGraw, Patty; Woody, George E

    2012-01-01

    Background Patients with untreated substance use disorders (SUDs) are at risk for frequent emergency department visits and repeated hospitalizations. Project Engage, a US pilot program at Wilmington Hospital in Delaware, was conducted to facilitate entry of these patients to SUD treatment after discharge. Patients identified as having hazardous or harmful alcohol consumption based on results of the Alcohol Use Disorders Identification Test-Primary Care (AUDIT-PC), administered to all patients...

  1. Ultrasonography and radiography to identify early post traumatic myosistis ossificans in an 18-year-old male: a case report.

    Science.gov (United States)

    Yochum, Alicia M; Reckelhoff, Kenneth; Kaeser, Martha; Kettner, Norman W

    2014-06-01

    The purpose of this case report is to describe a patient with post traumatic myositis ossificans (PTMO) of the anterior thigh following blunt trauma and discuss the incidence, clinical presentation, management, and imaging findings. An 18-year-old male presented to a chiropractic clinic with a chief complaint of left knee pain and reduced range of motion after an impact injury to his left anterior thigh during hurdling 6 weeks earlier. Immediately after the injury, he presented to the emergency department where radiography of the left knee was negative and he was diagnosed with a muscle sprain. Follow-up radiography and ultrasonography of the left knee in a chiropractic radiology department revealed ossification consistent with PTMO within his vastus intermedius. The patient underwent a course of rehabilitation for 2 months including ice, class IV cold laser and vibration applied to his anterior thigh, and myofascial release of his quadriceps musculature with targeted and progressive rehabilitative exercises. His left knee pain resolved within 2 weeks of care. He resumed sports participation (American football) pain-free, while wearing protective padding over the affected thigh, 1 month after presentation, which was approximately 2 1/2 months following his injury. This case demonstrates that ultrasonography may have the capability to detect early phases of PTMO approximately 2 weeks prior to radiographic evidence and to monitor progression throughout its course.

  2. Correlating carbon and oxygen isotope events in early to middle Miocene shallow marine carbonates in the Mediterranean region using orbitally tuned chemostratigraphy and lithostratigraphy

    Science.gov (United States)

    Auer, Gerald; Piller, Werner E.; Reuter, Markus; Harzhauser, Mathias

    2015-04-01

    During the Miocene prominent oxygen isotope events (Mi-events) reflect major changes in glaciation, while carbonate isotope maxima (CM-events) reflect changes in organic carbon burial, particularly during the Monterey carbon isotope excursion. However, despite their importance to the global climate history they have never been recorded in shallow marine carbonate successions. The Decontra section on the Maiella Platform (central Apennines, Italy), however, allows to resolve them for the first time in such a setting during the early to middle Miocene. The present study improves the stratigraphic resolution of parts of the Decontra section via orbital tuning of high-resolution gamma ray (GR) and magnetic susceptibility data to the 405 kyr eccentricity metronome. The tuning allows, within the established biostratigraphic, sequence stratigraphic, and isotope stratigraphic frameworks, a precise correlation of the Decontra section with pelagic records of the Mediterranean region, as well as the global paleoclimatic record and the global sea level curve. Spectral series analyses of GR data further indicate that the 405 kyr orbital cycle is particularly well preserved during the Monterey Event. Since GR is a direct proxy for authigenic uranium precipitation during increased burial of organic carbon in the Decontra section, it follows the same long-term orbital pacing as observed in the carbon isotope records. The 405 kyr GR beat is thus correlated with the carbon isotope maxima observed during the Monterey Event. Finally, the Mi-events can now be recognized in the δ18O record and coincide with plankton-rich, siliceous, or phosphatic horizons in the lithology of the section.

  3. High resolution chronology of late Cretaceous-early Tertiary events determined from 21,000 yr orbital-climatic cycles in marine sediments

    Science.gov (United States)

    Herbert, Timothy D.; Dhondt, Steven

    1988-01-01

    A number of South Atlantic sites cored by the Deep Sea Drilling Project (DSDP) recovered late Cretaceous and early Tertiary sediments with alternating light-dark, high-low carbonate content. The sedimentary oscillations were turned into time series by digitizing color photographs of core segments at a resolution of about 5 points/cm. Spectral analysis of these records indicates prominent periodicity at 25 to 35 cm in the Cretaceous intervals, and about 15 cm in the early Tertiary sediments. The absolute period of the cycles that is determined from paleomagnetic calibration at two sites is 20,000 to 25,000 yr, and almost certainly corresponds to the period of the earth's precessional cycle. These sequences therefore contain an internal chronometer to measure events across the K/T extinction boundary at this scale of resolution. The orbital metronome was used to address several related questions: the position of the K/T boundary within magnetic chron 29R, the fluxes of biogenic and detrital material to the deep sea immediately before and after the K/T event, the duration of the Sr anomaly, and the level of background climatic variability in the latest Cretaceous time. The carbonate/color cycles that were analyzed contain primary records of ocean carbonate productivity and chemistry, as evidenced by bioturbational mixing of adjacent beds and the weak lithification of the rhythmic sequences. It was concluded that sedimentary sequences that contain orbital cyclicity are capable of providing resolution of dramatic events in earth history with much greater precision than obtainable through radiometric methods. The data show no evidence for a gradual climatic deterioration prior to the K/T extinction event, and argue for a geologically rapid revolution at this horizon.

  4. Complementary standoff chemical imaging to map and identify artist materials in an early Italian Renaissance panel painting.

    Science.gov (United States)

    Dooley, Kathryn A; Conover, Damon M; Glinsman, Lisha Deming; Delaney, John K

    2014-12-08

    Two imaging modalities based on molecular and elemental spectroscopy were used to characterize a painting by Cosimo Tura. Visible-to-near-infrared (400-1680 nm) reflectance imaging spectroscopy (RIS) and X-ray fluorescence (XRF) imaging spectroscopy were employed to identify pigments and determine their spatial distribution with higher confidence than from either technique alone. For example, Mary's red robe was modeled through the distribution of an insect-derived red lake (RIS map) and lead white (XRF lead map), rather than a layer of red lake on vermilion. The RIS image cube was also used to isolate the preparatory design by mapping the reflectance spectra associated with it. In conjunction with results from an earlier RIS study (1650-2500 nm) to map and identify the binding media, a more thorough understanding was gained of the materials and techniques used in the painting. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Deciphering early events involved in hyperosmotic stress-induced programmed cell death in tobacco BY-2 cells.

    Science.gov (United States)

    Monetti, Emanuela; Kadono, Takashi; Tran, Daniel; Azzarello, Elisa; Arbelet-Bonnin, Delphine; Biligui, Bernadette; Briand, Joël; Kawano, Tomonori; Mancuso, Stefano; Bouteau, François

    2014-03-01

    Hyperosmotic stresses represent one of the major constraints that adversely affect plants growth, development, and productivity. In this study, the focus was on early responses to hyperosmotic stress- (NaCl and sorbitol) induced reactive oxygen species (ROS) generation, cytosolic Ca(2+) concentration ([Ca(2+)]cyt) increase, ion fluxes, and mitochondrial potential variations, and on their links in pathways leading to programmed cell death (PCD). By using BY-2 tobacco cells, it was shown that both NaCl- and sorbitol-induced PCD seemed to be dependent on superoxide anion (O2·(-)) generation by NADPH-oxidase. In the case of NaCl, an early influx of sodium through non-selective cation channels participates in the development of PCD through mitochondrial dysfunction and NADPH-oxidase-dependent O2·(-) generation. This supports the hypothesis of different pathways in NaCl- and sorbitol-induced cell death. Surprisingly, other shared early responses, such as [Ca(2+)]cyt increase and singlet oxygen production, do not seem to be involved in PCD.

  6. Early Solar System Alkali Fractionation Events Recorded by K-Ca Isotopes in the Yamato-74442 LL-Chondritic Breccia

    Science.gov (United States)

    Tatsunori, T.; Misawa, K.; Okano, O.; Shih, C.-Y.; Nyquist, L. E.; Simon, J. I.; Tappa, M. J.; Yoneda, S.

    2015-01-01

    Radiogenic ingrowth of Ca-40 due to decay of K-40 occurred early in the solar system history causing the Ca-40 abundance to vary within different early-former reservoirs. Marshall and DePaolo ] demonstrated that the K-40/Ca-40 decay system could be a useful radiogenic tracer for studies of terrestrial rocks. Shih et al. [3,4] determined 40K/40Ca ages of lunar granitic rock fragments and discussed the chemical characteristics of their source materials. Recently, Yokoyama et al. [5] showed the application of the K-40/Ca-40 chronometer for high K/Ca materials in ordinary chondrites (OCs). High-precision calcium isotopic data are needed to constrain mixing processes among early solar system materials and the time of planetesimal formation. To better constrain the solar system calcium isotopic compositions among astromaterials, we have determined the calcium isotopic compositions of OCs and an angrite. We further estimated a source K/Ca ratio for alkali-rich fragments in a chondritic breccia using the estimated solar system initial Ca-40/Ca-44.

  7. Prediction of early recurrent thromboembolic event and major bleeding in patients with acute stroke and atrial fibrillation by a risk stratification schema: the ALESSA score study

    OpenAIRE

    Paciaroni, Maurizio; Agnelli, Giancarlo; Caso, Valeria; Tsivgoulis, Georgios; Furie, Karen L; Tadi, Prasanna; Becattini, Cecilia; Falocci, Nicola; Zedde, Marialuisa; Abdul-Rahim, Azmil H.; Lees, Kennedy R.; Alberti, Andrea; Venti, Michele; Acciarresi, Monica; D'Amore, Cataldo

    2017-01-01

    Background and Purposes—This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation.\\ud \\ud Methods—The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlar...

  8. Observations of an early Agulhas current retroflection event in 2001: a temporary cessation of inter-ocean exchange south of Africa?

    CSIR Research Space (South Africa)

    Van Aken, HM

    2013-02-01

    Full Text Available -1 Deep-Sea Research Part 1: Oceanographic Research Papers February 2013/Vol. 72, pp 1-8 Observations of an early Agulhas current retroflection event in 2001: A temporary cessation of inter-ocean exchange south of Africa? H.M. van Akena,*, J.R.E.... Lutjeharms b, M. Rouault b,c, C. Whittle d,b, W.P.M. de Ruijter e aNIOZ Royal Netherlands Institute for Sea Research, PO Box 59, Den Burg, Texel, The Netherlands bDepartment of Oceanography, Mare Institute, University of Cape Town, Rondebosch, South...

  9. Analysis of dental erosion induced by different beverages and validity of equipment for identifying early dental erosion, in vitro study.

    Science.gov (United States)

    Jameel, Rafey Ahmad; Khan, Shah Salman; Abdul Rahim, Zubaidah Hj; Bakri, Marina Mohd; Siddiqui, Saima

    2016-07-01

    To understand early dental erosion induced by different beverages and the equipment for its detection. The study was conducted at the University Malaya Medical Centre, Kuala Lumpur, Malaysia, from June to September 2014, and comprised single-rooted, unpolished teeth divided into six groups. Electron micrographs and other baseline readings for further analyses were taken before and after the exposure to different beverages. The teeth were exposed to the beverages using a modified Nordini's artificial mouth model. The positioning of the teeth on the motorised stage of the equipment was standardised. Of the several beverages used, CocaCola had the lowest pH value of 2.53, while tap water had the highest pH of 5.4. Deionised distilled water, which was used as a reference, had a pH near to neutral /alkaline of 7.3. The fluoride content ranged between 9.38ppm in tea and 0.005ppm in orange juice. Teeth exposed to beverages with low pH and considerably high fluoride underwent slight remineralisation (roughness increase 8% from tea), while beverages with no fluoride content and low pH roughened the enamel surface (Coca Cola roughened upto 37%). Quantitative analyses of tooth erosion, micro-hardness, surface-roughness, and surface-height showed that all beverages exhibited positive erosive effect on the tooth enamel surface (pCocaCola was found to be the most erosive agent among both hot and cold beverages (37%), while coffee was more erosive among the hot beverages (29%).

  10. Identifying early pathways of risk and resilience: The co-development of internalizing and externalizing symptoms and the role of harsh parenting

    Science.gov (United States)

    Wiggins, Jillian Lee; Mitchell, Colter; Hyde, Luke W.; Monk, Christopher S.

    2016-01-01

    Psychological disorders co-occur often in children, but little has been done to document the types of conjoint pathways internalizing and externalizing symptoms may take from the crucial early period of toddlerhood or how harsh parenting may overlap with early symptom co-development. To examine symptom co-development trajectories, we identified latent classes of individuals based on internalizing and externalizing symptoms across ages 3–9 and found three symptom co-development classes: normative symptoms (low), severe-decreasing symptoms (initially high but rapidly declining) and severe symptoms (high) trajectories. Next, joint models examined how parenting trajectories overlapped with internalizing and externalizing symptom trajectories. These trajectory classes demonstrated that, normatively, harsh parenting increased after toddlerhood, but the severe symptoms class was characterized by a higher level and steeper increase in harsh parenting and the severe-decreasing class by high, stable harsh parenting. Additionally, a transactional model examined the bi-directional relationships among internalizing and externalizing symptoms and harsh parenting as they may cascade over time in this early period. Harsh parenting uniquely contributed to externalizing symptoms, controlling for internalizing symptoms, but not vice versa. Also, internalizing symptoms appeared to be a mechanism by which externalizing symptoms increase. Results highlight the importance accounting for both internalizing and externalizing symptoms from an early age to understand risk for developing psychopathology and the role harsh parenting plays in influencing these trajectories. PMID:26439075

  11. Ancient DNA from South-East Europe Reveals Different Events during Early and Middle Neolithic Influencing the European Genetic Heritage.

    Science.gov (United States)

    Hervella, Montserrat; Rotea, Mihai; Izagirre, Neskuts; Constantinescu, Mihai; Alonso, Santos; Ioana, Mihai; Lazăr, Cătălin; Ridiche, Florin; Soficaru, Andrei Dorian; Netea, Mihai G; de-la-Rua, Concepcion

    2015-01-01

    The importance of the process of Neolithization for the genetic make-up of European populations has been hotly debated, with shifting hypotheses from a demic diffusion (DD) to a cultural diffusion (CD) model. In this regard, ancient DNA data from the Balkan Peninsula, which is an important source of information to assess the process of Neolithization in Europe, is however missing. In the present study we show genetic information on ancient populations of the South-East of Europe. We assessed mtDNA from ten sites from the current territory of Romania, spanning a time-period from the Early Neolithic to the Late Bronze Age. mtDNA data from Early Neolithic farmers of the Starčevo Criş culture in Romania (Cârcea, Gura Baciului and Negrileşti sites), confirm their genetic relationship with those of the LBK culture (Linienbandkeramik Kultur) in Central Europe, and they show little genetic continuity with modern European populations. On the other hand, populations of the Middle-Late Neolithic (Boian, Zau and Gumelniţa cultures), supposedly a second wave of Neolithic migration from Anatolia, had a much stronger effect on the genetic heritage of the European populations. In contrast, we find a smaller contribution of Late Bronze Age migrations to the genetic composition of Europeans. Based on these findings, we propose that permeation of mtDNA lineages from a second wave of Middle-Late Neolithic migration from North-West Anatolia into the Balkan Peninsula and Central Europe represent an important contribution to the genetic shift between Early and Late Neolithic populations in Europe, and consequently to the genetic make-up of modern European populations.

  12. Knockin’ on pollen’s door: live cell imaging of early polarization events in germinating Arabidopsis pollen

    Directory of Open Access Journals (Sweden)

    Frank eVogler

    2015-04-01

    Full Text Available Pollen tubes are an excellent system for studying the cellular dynamics and complex signaling pathways that coordinate polarized tip growth. Although several signaling mechanisms acting in the tip-growing pollen tube have been described, our knowledge on the subcellular and molecular events during pollen germination and growth site selection at the pollen plasma membrane is rather scarce. To simultaneously track germinating pollen from up to 12 genetically different plants we developed an inexpensive and easy mounting technique, suitable for every standard microscope setup. We performed high magnification live-cell imaging during Arabidopsis pollen activation, germination, and the establishment of pollen tube tip growth by using fluorescent marker lines labeling either the pollen cytoplasm, vesicles, the actin cytoskeleton or the sperm cell nuclei and membranes. Our studies revealed distinctive vesicle and F-actin polarization during pollen activation and characteristic growth kinetics during pollen germination and pollen tube formation. Initially, the germinating Arabidopsis pollen tube grows slowly and forms a uniform roundish bulge, followed by a transition phase with vesicles heavily accumulating at the growth site before switching to rapid tip growth. Furthermore, we found the two sperm cells to be transported into the pollen tube after the phase of rapid tip growth has been initiated. The method presented here is suitable to quantitatively study subcellular events during Arabidopsis pollen germination and growth, and for the detailed analysis of pollen mutants with respect to pollen polarization, bulging, or growth site selection at the pollen plasma membrane.

  13. Bridging the Faraoni and Selli oceanic anoxic events: late Hauterivian to early Aptian dysaerobic to anaerobic phases in the Tethys

    Science.gov (United States)

    Föllmi, K. B.; Bôle, M.; Jammet, N.; Froidevaux, P.; Godet, A.; Bodin, S.; Adatte, T.; Matera, V.; Fleitmann, D.; Spangenberg, J. E.

    2012-01-01

    A detailed geochemical analysis was performed on the upper part of the Maiolica Formation in the Breggia (southern Switzerland) and Capriolo sections (northern Italy). The analysed sediments consist of well-bedded, partly siliceous, pelagic carbonate, which lodges numerous thin, dark and organic-rich layers. Stable-isotope, phosphorus, organic-carbon and a suite of redox-sensitive trace-element contents (RSTE: Mo, U, Co, V and As) were measured. The RSTE pattern and Corg:Ptot ratios indicate that most organic-rich layers were deposited under dysaerobic rather than anaerobic conditions and that latter conditions were likely restricted to short intervals in the latest Hauterivian, the early Barremian and the pre-Selli early Aptian. Correlations are both possible with organic-rich intervals in central Italy (the Gorgo a Cerbara section) and the Boreal Lower Saxony Basin, as well as with the facies and drowning pattern in the Helvetic segment of the northern Tethyan carbonate platform. Our data and correlations suggest that the latest Hauterivian witnessed the progressive installation of dysaerobic conditions in the Tethys, which went along with the onset in sediment condensation, phosphogenesis and platform drowning on the northern Tethyan margin, and which culminated in the Faraoni anoxic episode. This episode is followed by further episodes of dysaerobic conditions in the Tethys and the Lower Saxony Basin, which became more frequent and progressively stronger in the late early Barremian. Platform drowning persisted and did not halt before the latest early Barremian. The late Barremian witnessed diminishing frequencies and intensities in dysaerobic conditions, which went along with the progressive installation of the Urgonian carbonate platform. Near the Barremian-Aptian boundary, the increasing density in dysaerobic episodes in the Tethyan and Lower Saxony Basins is paralleled by a change towards heterozoan carbonate production on the northern Tethyan shelf. The

  14. Bridging the Faraoni and Selli oceanic anoxic events: late Hauterivian to early Aptian dysaerobic to anaerobic phases in the Tethys

    Directory of Open Access Journals (Sweden)

    K. B. Föllmi

    2012-01-01

    Full Text Available A detailed geochemical analysis was performed on the upper part of the Maiolica Formation in the Breggia (southern Switzerland and Capriolo sections (northern Italy. The analysed sediments consist of well-bedded, partly siliceous, pelagic carbonate, which lodges numerous thin, dark and organic-rich layers. Stable-isotope, phosphorus, organic-carbon and a suite of redox-sensitive trace-element contents (RSTE: Mo, U, Co, V and As were measured. The RSTE pattern and Corg:Ptot ratios indicate that most organic-rich layers were deposited under dysaerobic rather than anaerobic conditions and that latter conditions were likely restricted to short intervals in the latest Hauterivian, the early Barremian and the pre-Selli early Aptian.

    Correlations are both possible with organic-rich intervals in central Italy (the Gorgo a Cerbara section and the Boreal Lower Saxony Basin, as well as with the facies and drowning pattern in the Helvetic segment of the northern Tethyan carbonate platform. Our data and correlations suggest that the latest Hauterivian witnessed the progressive installation of dysaerobic conditions in the Tethys, which went along with the onset in sediment condensation, phosphogenesis and platform drowning on the northern Tethyan margin, and which culminated in the Faraoni anoxic episode. This episode is followed by further episodes of dysaerobic conditions in the Tethys and the Lower Saxony Basin, which became more frequent and progressively stronger in the late early Barremian. Platform drowning persisted and did not halt before the latest early Barremian. The late Barremian witnessed diminishing frequencies and intensities in dysaerobic conditions, which went along with the progressive installation of the Urgonian carbonate platform. Near the Barremian-Aptian boundary, the increasing density in dysaerobic episodes in the Tethyan and Lower Saxony Basins is paralleled by a change towards heterozoan carbonate

  15. Early T Cell Recognition of B Cells following Epstein-Barr Virus Infection: Identifying Potential Targets for Prophylactic Vaccination.

    Directory of Open Access Journals (Sweden)

    Jill M Brooks

    2016-04-01

    Full Text Available Epstein-Barr virus, a B-lymphotropic herpesvirus, is the cause of infectious mononucleosis, has strong aetiologic links with several malignancies and has been implicated in certain autoimmune diseases. Efforts to develop a prophylactic vaccine to prevent or reduce EBV-associated disease have, to date, focused on the induction of neutralising antibody responses. However, such vaccines might be further improved by inducing T cell responses capable of recognising and killing recently-infected B cells. In that context, EBNA2, EBNA-LP and BHRF1 are the first viral antigens expressed during the initial stage of B cell growth transformation, yet have been poorly characterised as CD8+ T cell targets. Here we describe CD8+ T cell responses against each of these three "first wave" proteins, identifying target epitopes and HLA restricting alleles. While EBNA-LP and BHRF1 each contained one strong CD8 epitope, epitopes within EBNA2 induced immunodominant responses through several less common HLA class I alleles (e.g. B*3801 and B*5501, as well as subdominant responses through common class I alleles (e.g. B7 and C*0304. Importantly, such EBNA2-specific CD8+ T cells recognised B cells within the first day post-infection, prior to CD8+ T cells against well-characterised latent target antigens such as EBNA3B or LMP2, and effectively inhibited outgrowth of EBV-transformed B cell lines. We infer that "first wave" antigens of the growth-transforming infection, especially EBNA2, constitute potential CD8+ T cell immunogens for inclusion in prophylactic EBV vaccine design.

  16. Commissioning with low-intensity beams helps prepare CMS for this year’s physics run. This event is one of the first low-intensity collisions recorded in the CMS detector, during the early hours of 23 April 2016

    CERN Multimedia

    AUTHOR|(CDS)2068005

    2016-01-01

    Commissioning with low-intensity beams helps prepare CMS for this year’s physics run. This event is one of the first low-intensity collisions recorded in the CMS detector, during the early hours of 23 April 2016

  17. Evaluation of hygiene practices in catering premises at large-scale events in the UK: identifying risks for the Olympics 2012.

    Science.gov (United States)

    Willis, C; Elviss, N; Aird, H; Fenelon, D; McLauchlin, J

    2012-08-01

    To investigate hygiene practices of caterers at large events in order to: support the production of guidance on catering at such events; to compare hygiene standards at weekends with other times in the week; and to learn lessons in preparation for the London Olympics in 2012. UK-wide study of caterers at large events, including questionnaires on hygiene procedures and microbiological examination of food, water and environmental samples. In total, 1364 samples of food, water, surface swabs and cloths were collected at 139 events, by local authority sampling officers, and transported to laboratories for microbiological analysis. Eight percent of food samples were of an unsatisfactory quality, and a further 2% contained potentially hazardous levels of Bacillus spp. A significantly higher proportion of unsatisfactory food samples were taken from vendors without adequate food safety procedures in place. Fifty-two percent of water samples, 38% of swabs and 71% of cloths were also unsatisfactory. The majority of samples (57%) were collected on Saturdays, Sundays or bank holidays. Environmental swab results were significantly poorer at weekends compared with other days of the week. This study reinforces the fact that food hygiene is a continuing cause for concern in mobile vendors, and indicates a need for an ongoing programme of training and monitoring of caterers in preparation for the London Olympics. Copyright © 2012 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  18. Structure of proton-proton events at high center-of-mass energy with an identified particle of large transverse momentum

    International Nuclear Information System (INIS)

    Hanke, P.

    1977-01-01

    At the CERN-ISR events of pp-collisions, in which particles of large transverse momentum psub(T) are produced, were studied at √S = 52 GeV center-of-mass energy, using the 'Split-Field'-magnetspectrometer. The lorentz-invariant production cross-section of positive particles with high psub(T) was measured in the fragmentation region (average* approximately 20 0 ). In the same kinematical region the pion-fraction of produced particles for both charges was determined. In these events the effect of 'strangeness'-conservation on the dynamics of additionally produced particles was investigated. The comparison of events with negative pions and events with heavier particles - mainly kaons - at high psub(T) indicates, that the compensation of transverse momentum does not depend on the 'strangeness' of the particle at high psub(T). The quantum-number conservation rather influences the particle-content from the hadronic rest inside longitudinal phase-space. This was shown by reconstruction of decay-vertices of neutral kaons. The results obtained can be interpreted by 'constituent'-models of the proton-structure. (orig.) [de

  19. Readiness of the ATLAS Spanish Federated Tier-2 for the Physics Analysis of the early collision events at the LHC

    Energy Technology Data Exchange (ETDEWEB)

    Oliver, E; Amoros, G; Fassi, F; Fernandez, A; Gonzalez, S; Kaci, M; Lamas, A; Salt, J; Sanchez, J [Instituto de Fisica Corpuscular (IFIC) (centro mixto CSIC - University Valencia), E-46071 Valencia (Spain); Nadal, J; Borrego, C; Campos, M; Pacheco, A [Institut de Fisica d' Altes Energies (IFAE) Facultat de Ciencies UAB, E-08193 Bellaterra, Barcelona (Spain); Pardo, J; Del Cano, L; Peso, J Del; Fernandez, P; March, L; Munoz, L [Universidad Autonoma de Madrid (UAM) Dpto. de Fisica Teorica, 28049 Madrid (Spain); Espinal, X, E-mail: elena.oliver@ific.uv.e [Port d' Informacio CientIfica (PIC) Campus UAB Edifici D E-08193 Bellaterra, Barcelona (Spain)

    2010-04-01

    In this contribution an evaluation of the readiness parameters for the Spanish ATLAS Federated Tier-2 is presented, regarding the ATLAS data taking which is expected to start by the end of the year 2009. Special attention will be paid to the Physics Analysis from different points of view: Data Management, Simulated events Production and Distributed Analysis Tests. Several use cases of Distributed Analysis in GRID infrastructures and local interactive analysis in non-Grid farms, are provided, in order to evaluate the interoperability between both environments, and to compare the different performances. The prototypes for local computing infrastructures for data analysis are described. Moreover, information about a local analysis facilities, called Tier-3, is given.

  20. Early data from Project Engage: a program to identify and transition medically hospitalized patients into addictions treatment.

    Science.gov (United States)

    Pecoraro, Anna; Horton, Terry; Ewen, Edward; Becher, Julie; Wright, Patricia A; Silverman, Basha; McGraw, Patty; Woody, George E

    2012-09-25

    Patients with untreated substance use disorders (SUDs) are at risk for frequent emergency department visits and repeated hospitalizations. Project Engage, a US pilot program at Wilmington Hospital in Delaware, was conducted to facilitate entry of these patients to SUD treatment after discharge. Patients identified as having hazardous or harmful alcohol consumption based on results of the Alcohol Use Disorders Identification Test-Primary Care (AUDIT-PC), administered to all patients at admission, received bedside assessment with motivational interviewing and facilitated referral to treatment by a patient engagement specialist (PES). This program evaluation provides descriptive information on self-reported rates of SUD treatment initiation of all patients and health-care utilization and costs for a subset of patients. Program-level data on treatment entry after discharge were examined retrospectively. Insurance claims data for two small cohorts who entered treatment after discharge (2009, n = 18, and 2010, n = 25) were reviewed over a six-month period in 2009 (three months pre- and post-Project Engage), or over a 12-month period in 2010 (six months pre- and post-Project Engage). These data provided descriptive information on health-care utilization and costs. (Data on those who participated in Project Engage but did not enter treatment were unavailable). Between September 1, 2008, and December 30, 2010, 415 patients participated in Project Engage, and 180 (43%) were admitted for SUD treatment. For a small cohort who participated between June 1, 2009, and November 30, 2009 (n = 18), insurance claims demonstrated a 33% ($35,938) decrease in inpatient medical admissions, a 38% ($4,248) decrease in emergency department visits, a 42% ($1,579) increase in behavioral health/substance abuse (BH/SA) inpatient admissions, and a 33% ($847) increase in outpatient BH/SA admissions, for an overall decrease of $37,760. For a small cohort who participated between June 1

  1. Early use of orthographic information in spoken word recognition: Event-related potential evidence from the Korean language.

    Science.gov (United States)

    Kwon, Youan; Choi, Sungmook; Lee, Yoonhyoung

    2016-04-01

    This study examines whether orthographic information is used during prelexical processes in spoken word recognition by investigating ERPs during spoken word processing for Korean words. Differential effects due to orthographic syllable neighborhood size and sound-to-spelling consistency on P200 and N320 were evaluated by recording ERPs from 42 participants during a lexical decision task. The results indicate that P200 was smaller for words whose orthographic syllable neighbors are large in number rather than those that are small. In addition, a word with a large orthographic syllable neighborhood elicited a smaller N320 effect than a word with a small orthographic syllable neighborhood only when the word had inconsistent sound-to-spelling mapping. The results provide support for the assumption that orthographic information is used early during the prelexical spoken word recognition process. © 2015 Society for Psychophysiological Research.

  2. Changes in ultraviolet resistance and photoproduct formation as early events in spore germination of Bacillus cereus T

    International Nuclear Information System (INIS)

    Irie, R.

    1978-01-01

    In order to determine the timing of the change in the state of DNA in bacterial spores during the course of germination, L-alanine-induced germination of Bacillus cereus spores was interrupted by 0.3M CaCl 2 as an inhibitor, and the resulting semi-refractive spores (spores at the end of the first phase of germination) were examined for UV-resistance and photoproduct formation. Upon UV-irradiation, these spores, still having a semi-refractile core as observed under a phase-contrast microscope, gave rise to mainly the cyclobutane-type thymine dimer. It was concluded that change in the stats of the spore DNA occurs early in the process of germination, i.e. before the refractility of the core is lost. It was also found that CaCl 2 markedly prolonged the duration of the transient UV-resistant stage. (author)

  3. Muscle Tissue Damage Induced by the Venom of Bothrops asper: Identification of Early and Late Pathological Events through Proteomic Analysis.

    Directory of Open Access Journals (Sweden)

    Cristina Herrera

    2016-04-01

    Full Text Available The time-course of the pathological effects induced by the venom of the snake Bothrops asper in muscle tissue was investigated by a combination of histology, proteomic analysis of exudates collected in the vicinity of damaged muscle, and immunodetection of extracellular matrix proteins in exudates. Proteomic assay of exudates has become an excellent new methodological tool to detect key biomarkers of tissue alterations for a more integrative perspective of snake venom-induced pathology. The time-course analysis of the intracellular proteins showed an early presence of cytosolic and mitochondrial proteins in exudates, while cytoskeletal proteins increased later on. This underscores the rapid cytotoxic effect of venom, especially in muscle fibers, due to the action of myotoxic phospholipases A2, followed by the action of proteinases in the cytoskeleton of damaged muscle fibers. Similarly, the early presence of basement membrane (BM and other extracellular matrix (ECM proteins in exudates reflects the rapid microvascular damage and hemorrhage induced by snake venom metalloproteinases. The presence of fragments of type IV collagen and perlecan one hour after envenoming suggests that hydrolysis of these mechanically/structurally-relevant BM components plays a key role in the genesis of hemorrhage. On the other hand, the increment of some ECM proteins in the exudate at later time intervals is likely a consequence of the action of endogenous matrix metalloproteinases (MMPs or of de novo synthesis of ECM proteins during tissue remodeling as part of the inflammatory reaction. Our results offer relevant insights for a more integrative and systematic understanding of the time-course dynamics of muscle tissue damage induced by B. asper venom and possibly other viperid venoms.

  4. Adenomatous polyposis coli is required for early events in the normal growth and differentiation of the developing cerebral cortex

    Directory of Open Access Journals (Sweden)

    Price David J

    2009-01-01

    Full Text Available Abstract Background Adenomatous polyposis coli (Apc is a large multifunctional protein known to be important for Wnt/β-catenin signalling, cytoskeletal dynamics, and cell polarity. In the developing cerebral cortex, Apc is expressed in proliferating cells and its expression increases as cells migrate to the cortical plate. We examined the consequences of loss of Apc function for the early development of the cerebral cortex. Results We used Emx1Cre to inactivate Apc specifically in proliferating cerebral cortical cells and their descendents starting from embryonic day 9.5. We observed reduction in the size of the mutant cerebral cortex, disruption to its organisation, and changes in the molecular identity of its cells. Loss of Apc leads to a decrease in the size of the proliferative pool, disrupted interkinetic nuclear migration, and increased apoptosis. β-Catenin, pericentrin, and N-cadherin proteins no longer adopt their normal high concentration at the apical surface of the cerebral cortical ventricular zone, indicating that cell polarity is disrupted. Consistent with enhanced Wnt/β-catenin signalling resulting from loss of Apc we found increased levels of TCF/LEF-dependent transcription and expression of endogenous Wnt/β-catenin target genes (Axin2 (conductin, Lef1, and c-myc in the mutant cerebral cortex. In the Apc mutant cerebral cortex the expression of transcription factors Foxg1, Pax6, Tbr1, and Tbr2 is drastically reduced compared to normal and many cells ectopically express Pax3, Wnt1, and Wt1 (but not Wnt2b, Wnt8b, Ptc, Gli1, Mash1, Olig2, or Islet1. This indicates that loss of Apc function causes cerebral cortical cells to lose their normal identity and redirect to fates normally found in more posterior-dorsal regions of the central nervous system. Conclusion Apc is required for multiple aspects of early cerebral cortical development, including the regulation of cell number, interkinetic nuclear migration, cell polarity, and

  5. Inhibition of MHC-I by Brucella abortus is an early event during infection and involves EGFR pathway.

    Science.gov (United States)

    Velásquez, Lis N; Milillo, M Ayelén; Delpino, M Victoria; Trotta, Aldana; Mercogliano, M Florencia; Pozner, Roberto G; Schillaci, Roxana; Elizalde, Patricia V; Giambartolomei, Guillermo H; Barrionuevo, Paula

    2017-04-01

    Brucella abortus is able to persist inside the host despite the development of potent CD8 + T-cell responses. We have recently reported the ability of B. abortus to inhibit the interferon-γ-induced major histocompatibility complex (MHC)-I cell surface expression on human monocytes. This phenomenon was due to the B. abortus-mediated retention of MHC-I molecules within the Golgi apparatus and was dependent on bacterial viability. However, the implications of bacterial virulence or replicative capacity and the signaling pathways remained unknown. Here we demonstrated that the B. abortus mutant strains RB51 and virB10 - are able to inhibit MHC-I expression in the same manner as wild-type B. abortus, even though they are unable to persist inside human monocytes for a long period of time. Consistent with this, the phenomenon was triggered early in time and could be observed at 8 h postinfection. At 24 and 48 h, it was even stronger. Regarding the signaling pathway, targeting epidermal growth factor (EGF) receptor (EGFR), ErbB2 (HER2) or inhibition of tumor necrosis factor-α-converting enzyme, one of the enzymes which generates soluble EGF-like ligands, resulted in partial recovery of MHC-I surface expression. Moreover, recombinant EGF and transforming growth factor-α as well as the combination of both were also able to reproduce the B. abortus-induced MHC-I downmodulation. Finally, when infection was performed in the presence of an extracellular signal-regulated kinase 1/2 (Erk1/2) inhibitor, MHC-I surface expression was significantly recovered. Overall, these results describe how B. abortus evades CD8 + T-cell responses early during infection and exploits the EGFR-ERK signaling pathway to escape from the immune system and favor chronicity.

  6. Meaning in meaninglessness: The propensity to perceive meaningful patterns in coincident events and randomly arranged stimuli is linked to enhanced attention in early sensory processing.

    Science.gov (United States)

    Rominger, Christian; Schulter, Günter; Fink, Andreas; Weiss, Elisabeth M; Papousek, Ilona

    2018-05-01

    Perception of objectively independent events or stimuli as being significantly connected and the associated proneness to perceive meaningful patterns constitute part of the positive symptoms of schizophrenia, which are associated with altered attentional processes in lateralized speech perception. Since perceiving meaningful patterns is to some extent already prevalent in the general population, the aim of the study was to investigate whether the propensity to experience meaningful patterns in co-occurring events and random stimuli may be associated with similar altered attentional processes in lateralized speech perception. Self-reported and behavioral indicators of the perception of meaningful patterns were assessed in non-clinical individuals, along with EEG auditory evoked potentials during the performance of an attention related lateralized speech perception task (Dichotic Listening Test). A greater propensity to perceive meaningful patterns was associated with higher N1 amplitudes of the evoked potentials to the onset of the dichotically presented consonant-vowel syllables, indicating enhanced automatic attention in early sensory processing. The study suggests that more basic mechanisms in how people associate events may play a greater role in the cognitive biases that are manifest in personality expressions such as positive schizotypy, rather than that positive schizotypy moderates these cognitive biases directly. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Brachial-ankle pulse wave velocity predicts decline in renal function and cardiovascular events in early stages of chronic kidney disease.

    Science.gov (United States)

    Yoon, Hye Eun; Shin, Dong Il; Kim, Sung Jun; Koh, Eun Sil; Hwang, Hyeon Seok; Chung, Sungjin; Shin, Seok Joon

    2013-01-01

    In this study, we investigated the predictive capacity of the brachial-ankle aortic pulse wave velocity (baPWV), a marker of arterial stiffness, for the decline in renal function and for cardiovascular events in the early stages of chronic kidney disease (CKD). Two hundred forty-one patients who underwent a comprehensive check-up were included and were divided into two groups according to their estimated glomerular filtration rates (eGFR): patients with CKD categories G2, G3a and G3b (30 ≤ eGFR function, the eGFR change, was determined by the slope of eGFR against time. We analysed whether baPWV was associated with eGFR change or predicted cardiovascular events. baPWV was independently associated with eGFR change in a multivariate analysis of the total patients (β=-0.011, p=0.011) and remained significantly associated with eGFR change in a subgroup analysis of the eGFR function and short-term cardiovascular events.

  8. Early protection events in swine immunized with an experimental live attenuated classical swine fever marker vaccine, FlagT4G.

    Directory of Open Access Journals (Sweden)

    Lauren G Holinka

    Full Text Available Prophylactic vaccination using live attenuated classical swine fever (CSF vaccines has been a very effective method to control the disease in endemic regions and during outbreaks in previously disease-free areas. These vaccines confer effective protection against the disease at early times post-vaccination although the mechanisms mediating the protection are poorly characterized. Here we present the events occurring after the administration of our in-house developed live attenuated marker vaccine, FlagT4Gv. We previously reported that FlagT4Gv intramuscular (IM administered conferred effective protection against intranasal challenge with virulent CSFV (BICv as early as 7 days post-vaccination. Here we report that FlagT4Gv is able to induce protection against disease as early as three days post-vaccination. Immunohistochemical testing of tissues from FlagT4Gv-inoculated animals showed that tonsils were colonized by the vaccine virus by day 3 post-inoculation. There was a complete absence of BICv in tonsils of FlagT4Gv-inoculated animals which had been intranasal (IN challenged with BICv 3 days after FlagT4Gv infection, confirming that FlagT4Gv inoculation confers sterile immunity. Analysis of systemic levels of 19 different cytokines in vaccinated animals demonstrated an increase of IFN-α three days after FlagT4Gv inoculation compared with mock infected controls.

  9. The attitude of the Church towards the social and political events in Poland in the early 1980’s

    Directory of Open Access Journals (Sweden)

    Zdzisław Gogola

    2014-12-01

    Full Text Available In Polish historiography the martial law period is still an issue that causes a lot of controversy. It also seems that even growing period of time and psychological distance do not automatically facilitate developing clear and objective assessment of the dramatic events of the years 1981–1983. The difference between presented opinions is strongly influenced by current trends of political correctness as well as inaccessibility of classified documents still kept in the Polish and Russian archives. An attempt to conduct a thorough and multifaceted evaluation of the martial law period seems impossible without analysing tense sociopolitical situation as well as difficult economic situation of Poland at the end of 1970s and the beginning of 1980s. It is also necessary to take into account an important factor – the Solidarity movement that was founded in 1980. It was the first post-war mass opposition movement, rooted firmly on the ground of Christian ideas. Thus, it seems impossible to ignore the role of the Polish Catholic Church during the period of the martial law. It was within the framework of the Church structures – due to suspension of almost every social organization – that the victims of repression and their families were granted physical, legal, and spiritual support. The attitude presented by the hierarchy and numerous representatives of the clergy (e.g. Primate J. Glemp, Archbishop B. Dąbrowski, Fr. J. Popiełuszko or Fr. K. Jancarz clearly proved that numerous cases of violating the law, in particular arresting and detaining the members of the Solidarity movement, were strongly condemned. The ideas and conclusions presented in the article, although still imperfect and probably premature, enable the reader to assume that the events of 1981–1983 were caused by the lack of both authority of the government as well as fundamental social freedom rather than insufficient supply of food, economic crisis or a threat of a military

  10. The QT dispersion and QTc dispersion in patients presenting with acute neurological events and its impact on early prognosis

    Directory of Open Access Journals (Sweden)

    Kailash Kumar Rahar

    2016-01-01

    Full Text Available Aims: To find out and investigate whether the QT dispersion and QTc dispersion is related to type and prognosis of the acute stroke in patients presenting within 24 h of the onset of stroke. Settings and Design: This was a observational study conducted at Mahatma Gandhi Hospital, Dr. SN. Medical College, Jodhpur, during January 2014 to January 2015. Subjects and Methods: The patients presented within 24 h of onset of acute stroke (hemorrhagic, infarction, or transient ischemic event were included in the study. The stroke was confirmed by computed tomography scan and magnetic resonance imaging. Patients with (i altered sensorium because of metabolic, infective, seizures, trauma, or tumor; (ii prior history of cardiovascular disease, electrocardiographic abnormalities' because of dyselectrolytemia; and (iii and patients who were on drugs (antiarrhythmic drugs, antipsychotic drugs, erythromycin, theophylline, etc., which known to cause electrocardiogram changes, were excluded from the study. National Institute of Health Stroke Score (NIHSS was calculated at the time of admission and Modified Rankin Scale (MRS at the time of discharge. Fifty age- and sex-matched healthy controls included. Statistical Analysis Used: Student's t-test, ANOVA, and area under curve for sensitivity and specificity for the test. Results: We included 52 patients (male/female: 27/25 and 50 controls (26/24. The mean age of patients was 63.17 ± 08.90 years. Of total patients, infarct was found in 32 (61.53%, hemorrhage in 18 (34.61%, transient ischemic attack (TIA in 1 (1.9%, and subarachnoid hemorrhage in 1 (1.9% patient. The QT dispersion and QTc dispersion were significantly higher in cases as compare to controls. (87.30 ± 24.42 vs. 49.60 ± 08.79 ms; P < 0.001 and (97.53 ± 27.36 vs. 56.28 ± 09.86 ms; P < 0.001. Among various types of stroke, the mean QT dispersion and QTc dispersion were maximum and significantly higher in hemorrhagic stroke as compared to infarct and

  11. Non-Verbal Reasoning Ability and Academic Achievement as Moderators of the Relation between Adverse Life Events and Emotional and Behavioural Problems in Early Adolescence: The Importance of Moderator and Outcome Specificity

    Science.gov (United States)

    Flouri, Eirini; Tzavidis, Nikos

    2011-01-01

    This study was carried out to model the functional form of the effect of contextual risk (number of adverse life events) on emotional and behavioural problems in early adolescence, and to test how intelligence and academic achievement compare as moderators of this effect. The effect of number of adverse life events on emotional and behavioural…

  12. Exercise electrocardiogram in middle-aged and older leisure time sportsmen: 100 exercise tests would be enough to identify one silent myocardial ischemia at risk for cardiac event.

    Science.gov (United States)

    Hupin, David; Edouard, Pascal; Oriol, Mathieu; Laukkanen, Jari; Abraham, Pierre; Doutreleau, Stéphane; Guy, Jean-Michel; Carré, François; Barthélémy, Jean-Claude; Roche, Frédéric; Chatard, Jean-Claude

    2018-04-15

    The importance of exercise electrocardiogram (ECG) has been controversial in the prevention of cardiac events among sportsmen. The aim of this study was to determine the frequency of silent myocardial ischemia (SMI) from an exercise ECG and its relationship with induced coronary angiographic assessment and potentially preventable cardiac events. This prospective cohort study included leisure time asymptomatic sportsmen over 35years old, referred from 2011 to 2014 in the Sports Medicine Unit of the University Hospital of Saint-Etienne. Of the cohort of 1500 sportsmen (1205 men; mean age 50.7±9.4years; physical activity level 32.8±26.8MET-h/week), 951 (63%) had at least one cardiovascular disease (CVD) risk factor. Family history, medical examination and standard resting 12-lead were collected. A total of 163 exercise ECGs (10.9%) were defined as positive, most of them due to SMI (n=129, 8.6%). SMI was an indication for coronary angiography in 23 cases, leading to 17 documented SMIs (1.1%), including 11 significant stenoses requiring revascularization. In multivariate logistic regression analysis, a high risk of CVD (OR=2.65 [CI 95%: 1.33-5.27], p=0.005) and an age >50years (OR=2.71 [CI 95%: 1.65-4.44], p<0.0001) were independently associated with confirmed SMI. The association of positive exercise ECG with significant coronary stenosis was stronger among sportsmen with CVD risk factors and older than 50years. Screening by exercise ECG can lower the risk of cardiac events in middle-aged and older sportsmen. One hundred tests would be enough to detect one silent myocardial ischemia at risk for cardiac event. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Mutations altering the gammaretrovirus endoproteolytic motif affect glycosylation of the envelope glycoprotein and early events of the virus life cycle

    Energy Technology Data Exchange (ETDEWEB)

    Argaw, Takele; Wilson, Carolyn A., E-mail: carolyn.wilson@fda.hhs.gov

    2015-01-15

    Previously, we found that mutation of glutamine to proline in the endoproteolytic cleavage signal of the PERV-C envelope (RQKK to RPKK) resulted in non-infectious vectors. Here, we show that RPKK results in a non-infectious vector when placed in not only a PERV envelope, but also the envelope of a related gammaretrovirus, FeLV-B. The amino acid substitutions do not prevent envelope precursor cleavage, viral core and genome assembly, or receptor binding. Rather, the mutations result in the formation of hyperglycosylated glycoprotein and a reduction in the reverse transcribed minus strand synthesis and undetectable 2-LTR circular DNA in cells exposed to vectors with these mutated envelopes. Our findings suggest novel functions associated with the cleavage signal sequence that may affect trafficking through the glycosylation machinery of the cell. Further, the glycosylation status of the envelope appears to impact post-binding events of the viral life cycle, either membrane fusion, internalization, or reverse transcription. - Highlights: • Env cleavage signal impacts infectivity of gammaretroviruses. • Non-infectious mutants have hyper-glycosylated envelope that bind target cells. • Non-infectious mutants have defects in the formation of the double-stranded DNA. • Env cleavage motif has functions beyond cleavage of the env precursor.

  14. Sedimentary evidence for enhanced hydrological cycling in response to rapid carbon release during the early Toarcian oceanic anoxic event

    Science.gov (United States)

    Izumi, Kentaro; Kemp, David B.; Itamiya, Shoma; Inui, Mutsuko

    2018-01-01

    A pronounced excursion in the carbon-isotope composition of biospheric carbon and coeval seawater warming during the early Toarcian (∼183 Ma) has been linked to the large-scale transfer of 12C-enriched carbon to the oceans and atmosphere. A European bias in the distribution of available data means that the precise pattern, tempo and global expression of this carbon cycle perturbation, and the associated environmental responses, remain uncertain. Here, we present a new cm-scale terrestrial-dominated carbon-isotope record through an expanded lower Toarcian section from Japan that displays a negative excursion pattern similar to marine and terrestrial carbon-isotope records documented from Europe. These new data suggest that 12C-enriched carbon was added to the biosphere in at least one rapid, millennial-scale pulse. Sedimentological analysis indicates a close association between the carbon-isotope excursion and high-energy sediment transport and enhanced fluvial discharge. Together, these data support the hypothesis that a sudden strengthening of the global hydrological cycle occurred in direct and immediate response to rapid carbon release and atmospheric warming.

  15. Adiposity, post-diagnosis weight change, and risk of cardiovascular events among early-stage breast cancer survivors.

    Science.gov (United States)

    Cespedes Feliciano, Elizabeth M; Kwan, Marilyn L; Kushi, Lawrence H; Weltzien, Erin K; Castillo, Adrienne L; Caan, Bette J

    2017-04-01

    Little research examines whether adiposity or post-diagnosis weight changes influence Cardiovascular disease (CVD) among breast cancer patients for whom effects may differ due to treatment and recovery. We studied Stage I-III breast cancer survivors 18 to  diagnosis and weight and waist circumference (WC) around 24 months post diagnosis. Using Cox models for time to incident coronary artery disease, heart failure, valve abnormality, arrhythmia, stroke, or CVD death, we examined at-diagnosis body mass index (BMI, n = 3109) and post-diagnosis WC (n = 1898) and weight change (n = 1903, stable, ±5 to  diagnosis, 25% of women gained and 14% lost ≥10-lbs; mean (SD) WC was 90 (15) cm. Over a median of 8.28 years, 915 women developed CVD. BMI 25-30-kg/m 2 (vs. BMI diagnosis weight change had no association with CVD. Extreme adiposity and any elevation in WC increased risk of CVD among breast cancer survivors; however, changes in weight in the early post-diagnosis period were not associated with CVD. Survivors with high WC and existing CVD risk factors should be monitored.

  16. Neurotensin receptor 1 gene activation by the Tcf/beta-catenin pathway is an early event in human colonic adenomas.

    Science.gov (United States)

    Souazé, Frédérique; Viardot-Foucault, Véronique; Roullet, Nicolas; Toy-Miou-Leong, Mireille; Gompel, Anne; Bruyneel, Erik; Comperat, Eva; Faux, Maree C; Mareel, Marc; Rostène, William; Fléjou, Jean-François; Gespach, Christian; Forgez, Patricia

    2006-04-01

    Alterations in the Wnt/APC (adenomatous polyposis coli) signalling pathway, resulting in beta-catenin/T cell factor (Tcf)-dependent transcriptional gene activation, are frequently detected in familial and sporadic colon cancers. The neuropeptide neurotensin (NT) is widely distributed in the gastrointestinal tract. Its proliferative and survival effects are mediated by a G-protein coupled receptor, the NT1 receptor. NT1 receptor is not expressed in normal colon epithelial cells, but is over expressed in a number of cancer cells and tissues suggesting a link to the outgrowth of human colon cancer. Our results demonstrate that the upregulation of NT1 receptor occurring in colon cancer is the result of Wnt/APC signalling pathway activation. We first established the functionality of the Tcf response element within the NT1 receptor promoter. Consequently, we observed the activation of NT1 receptor gene by agents causing beta-catenin cytosolic accumulation, as well as a strong decline of endogenous receptor when wt-APC was restored. At the cellular level, the re-establishment of wt-APC phenotype resulted in the impaired functionality of NT1 receptor, like the breakdown in NT-induced intracellular calcium mobilization and the loss of NT pro-invasive effect. We corroborated the Wnt/APC signalling pathway on the NT1 receptor promoter activation with human colon carcinogenesis, and showed that NT1 receptor gene activation was perfectly correlated with nuclear or cytoplasmic beta-catenin localization while NT1 receptor was absent when beta-catenin was localized at the cell-cell junction in early adenomas of patients with familial adenomatous polyposis, hereditary non-polyposis colorectal cancer and loss of heterozygosity tumours. In this report we establish a novel link in vitro between the Tcf/beta-catenin pathway and NT1 receptor promoter activation.

  17. Characterization of early events involved in human dendritic cell maturation induced by sensitizers: Cross talk between MAPK signalling pathways

    International Nuclear Information System (INIS)

    Trompezinski, Sandra; Migdal, Camille; Tailhardat, Magalie; Le Varlet, Beatrice; Courtellemont, Pascal; Haftek, Marek; Serres, Mireille

    2008-01-01

    Dendritic cells (DCs), efficient-antigen presenting cells play an important role in initiating and regulating immune responses. DC maturation following exposure to nickel or DNCB induced an up-regulation of phenotypic markers and inflammatory cytokine secretion. Early intracellular mechanisms involved in DC maturation required to be precise. To address this purpose, DCs derived from human monocytes were treated with sensitizers (nickel, DNCB or thimerosal) in comparison with an irritant (SDS). Our data confirming the up-regulation of CD86, CD54 and cytokine secretion (IL-8 and TNFα) induced by sensitizers but not by SDS, signalling transduction involved in DC maturation was investigated using these chemicals. Kinase activity measurement was assessed using two new sensitive procedures (Face TM and CBA) requiring few cells. SDS did not induce changes in signalling pathways whereas NiSO 4 , DNCB and thimerosal markedly activated p38 MAPK and JNK, in contrast Erk1/2 phosphorylation was completely inhibited by DNCB or thimerosal and only activated by nickel. A pre-treatment with p38 MAPK inhibitor (SB203580) suppressed Erk1/2 inhibition induced by DNCB or thimerosal demonstrating a direct interaction between p38 MAPK and Erk1/2. A pre-treatment with an antioxidant, N-acetyl-L-cysteine (NAC) markedly reduced Erk1/2 inhibition and p38 MAPK phosphorylation induced by DNCB and thimerosal, suggesting a direct activation of p38 MAPK via an oxidative stress and a regulation of MAPK signalling pathways depending on chemicals. Because of a high sensitivity of kinase activity measurements, these procedures will be suitable for weak or moderate sensitizer screening

  18. Studies of identified hadrons in qq-bar events at LEPI, in W sup + W sup - and qq-bar events at LEPII and search for stable and long-lived heavy charged particles

    CERN Document Server

    Neufeld, N

    1999-01-01

    The use of RICH detectors allows the identification of charged pions, kaons and protons, covering the full momentum range 0.7qq-bar, Z sup 0->bb-bar and Z sup 0->uu-bar, dd-bar, ss-bar, selected from approx 1,400,000 Z sup 0 decays collected by DELPHI in 1994. This study has been extended to high-energy qq-bar events at LEPII. New heavy particles from 2 GeV/c sup 2 to the kinematic limit at LEPII have been searched using the RICH detectors.

  19. A genetic screen for modifiers of UFO meristem activity identifies three novel FUSED FLORAL ORGANS genes required for early flower development in Arabidopsis.

    Science.gov (United States)

    Levin, J Z; Fletcher, J C; Chen, X; Meyerowitz, E M

    1998-06-01

    In a screen to identify novel genes required for early Arabidopsis flower development, we isolated four independent mutations that enhance the Ufo phenotype toward the production of filamentous structures in place of flowers. The mutants fall into three complementation groups, which we have termed FUSED FLORAL ORGANS (FFO) loci. ffo mutants have specific defects in floral organ separation and/or positioning; thus, the FFO genes identify components of a boundary formation mechanism(s) acting between developing floral organ primordia. FFO1 and FFO3 have specific functions in cauline leaf/stem separation and in first- and third-whorl floral organ separation, with FFO3 likely acting to establish and FFO1 to maintain floral organ boundaries. FFO2 acts at early floral stages to regulate floral organ number and positioning and to control organ separation within and between whorls. Plants doubly mutant for two ffo alleles display additive phenotypes, indicating that the FFO genes may act in separate pathways. Plants doubly mutant for an ffo gene and for ufo, lfy, or clv3 reveal that the FFO genes play roles related to those of UFO and LFY in floral meristem initiation and that FFO2 and FFO3 may act to control cell proliferation late in inflorescence development.

  20. Events occurring during the previous lactation, the dry period, and peripartum as risk factors for early lactation mastitis in cows receiving 2 different intramammary dry cow therapies.

    Science.gov (United States)

    Pinedo, P J; Fleming, C; Risco, C A

    2012-12-01

    The objective of this study was to investigate the association between mastitis events occurring during the previous lactation, the dry period, and the peripartum period on the incidence of early lactation mastitis in cows receiving ceftiofur hydrochloride or penicillin dihydrostreptomycin as intramammary dry cow antibiotic therapy. Cows (n=402) from 2 large dairy farms in Central Florida were enrolled in the study at the time of dry-off processing and were randomly assigned to 1 of 2 dry cow therapies: ceftiofur hydrochloride or penicillin dihydrostreptomycin. Composite milk samples were collected at dry-off and after calving for bacteriological examination and somatic cell count. Peripartal health disorders were monitored during the first 30 d of lactation and included calving difficulty, metritis, ketosis, and left displaced abomasum. Milk production and individual somatic cell scores (SCS) were recorded monthly by the Dairy Herd Improvement Association. The main outcome variables were the risk of clinical mastitis during the first 30 and 60 d of lactation, and the risk of subclinical mastitis at the first 2 monthly Dairy Herd Improvement Association tests after calving (up to 70 d in milk). Additionally, the SCS and the presence of mastitis pathogens in milk at dry-off and at calving were analyzed. Explanatory variables consisted of events occurring during the previous lactation, at dry-off and during the dry period, at calving, and within the first 30 d after calving. Multiple events occurring during the previous lactation had a significant effect on the incidence of mastitis in the subsequent lactation. These events included low milk yield, intermediate lactation length, clinical mastitis, and lactation SCS average. Similarly, intramammary infections with environmental bacteria at dry-off increased the chances of clinical mastitis the first month after calving. Dry-off therapy had a significant effect on mastitis incidence; cows treated with ceftiofur

  1. Measurement of the Jet Vertex Charge algorithm performance for identified $b$-jets in $t\\bar{t}$ events in $pp$ collisions with the ATLAS detector

    CERN Document Server

    The ATLAS collaboration

    2018-01-01

    The Jet Vertex Charge algorithm, developed recently within the ATLAS collaboration, discriminates between jets resulting from the hadronisation of a bottom quark or bottom antiquark. This note describes a measurement of the performance of the algorithm and the extraction of data-to-simulation scale factors, made using $b$-tagged jets in candidate single lepton $t\\bar{t}$ events. The data sample was collected by the ATLAS detector at the LHC using $pp$ collisions at $\\sqrt{s}$ = 13 TeV in 2015 and 2016 and corresponds to a total integrated luminosity of 36.1 fb$^{-1}$ . Overall, good agreement is found between data and the simulation.

  2. Adverse events in diabetic foot infections: a case control study comparing early versus delayed medical treatment after home remedies

    Directory of Open Access Journals (Sweden)

    Cawich SO

    2014-11-01

    outcomes when patients delay conventional medical therapy in favour of home remedies to treat diabetic foot infections. These treatments need not be mutually exclusive. We encourage persons with diabetes who wish to try home remedies to seek medical advice in addition as a part of holistic care. Keywords: diabetic foot infections, adverse events, medical treatment, home remedies

  3. Exploring DNA methylation changes in promoter, intragenic, and intergenic regions as early and late events in breast cancer formation

    International Nuclear Information System (INIS)

    Rauscher, Garth H.; Kresovich, Jacob K.; Poulin, Matthew; Yan, Liying; Macias, Virgilia; Mahmoud, Abeer M.; Al-Alem, Umaima; Kajdacsy-Balla, Andre; Wiley, Elizabeth L.; Tonetti, Debra; Ehrlich, Melanie

    2015-01-01

    Breast cancer formation is associated with frequent changes in DNA methylation but the extent of very early alterations in DNA methylation and the biological significance of cancer-associated epigenetic changes need further elucidation. Pyrosequencing was done on bisulfite-treated DNA from formalin-fixed, paraffin-embedded sections containing invasive tumor and paired samples of histologically normal tissue adjacent to the cancers as well as control reduction mammoplasty samples from unaffected women. The DNA regions studied were promoters (BRCA1, CD44, ESR1, GSTM2, GSTP1, MAGEA1, MSI1, NFE2L3, RASSF1A, RUNX3, SIX3 and TFF1), far-upstream regions (EN1, PAX3, PITX2, and SGK1), introns (APC, EGFR, LHX2, RFX1 and SOX9) and the LINE-1 and satellite 2 DNA repeats. These choices were based upon previous literature or publicly available DNA methylome profiles. The percent methylation was averaged across neighboring CpG sites. Most of the assayed gene regions displayed hypermethylation in cancer vs. adjacent tissue but the TFF1 and MAGEA1 regions were significantly hypomethylated (p ≤0.001). Importantly, six of the 16 regions examined in a large collection of patients (105 – 129) and in 15-18 reduction mammoplasty samples were already aberrantly methylated in adjacent, histologically normal tissue vs. non-cancerous mammoplasty samples (p ≤0.01). In addition, examination of transcriptome and DNA methylation databases indicated that methylation at three non-promoter regions (far-upstream EN1 and PITX2 and intronic LHX2) was associated with higher gene expression, unlike the inverse associations between cancer DNA hypermethylation and cancer-altered gene expression usually reported. These three non-promoter regions also exhibited normal tissue-specific hypermethylation positively associated with differentiation-related gene expression (in muscle progenitor cells vs. many other types of normal cells). The importance of considering the exact DNA region analyzed and the

  4. Erroneous cardiac ECG-gated PET list-mode trigger events can be retrospectively identified and replaced by an offline reprocessing approach: first results in rodents

    International Nuclear Information System (INIS)

    Böning, Guido; Todica, Andrei; Vai, Alessandro; Lehner, Sebastian; Xiong, Guoming; Mille, Erik; Ilhan, Harun; Fougère, Christian la; Bartenstein, Peter; Hacker, Marcus

    2013-01-01

    The assessment of left ventricular function, wall motion and myocardial viability using electrocardiogram (ECG)-gated [ 18 F]-FDG positron emission tomography (PET) is widely accepted in human and in preclinical small animal studies. The nonterminal and noninvasive approach permits repeated in vivo evaluations of the same animal, facilitating the assessment of temporal changes in disease or therapy response. Although well established, gated small animal PET studies can contain erroneous gating information, which may yield to blurred images and false estimation of functional parameters. In this work, we present quantitative and visual quality control (QC) methods to evaluate the accuracy of trigger events in PET list-mode and physiological data. Left ventricular functional analysis is performed to quantify the effect of gating errors on the end-systolic and end-diastolic volumes, and on the ejection fraction (EF). We aim to recover the cardiac functional parameters by the application of the commonly established heart rate filter approach using fixed ranges based on a standardized population. In addition, we propose a fully reprocessing approach which retrospectively replaces the gating information of the PET list-mode file with appropriate list-mode decoding and encoding software. The signal of a simultaneously acquired ECG is processed using standard MATLAB vector functions, which can be individually adapted to reliably detect the R-peaks. Finally, the new trigger events are inserted into the PET list-mode file. A population of 30 mice with various health statuses was analyzed and standard cardiac parameters such as mean heart rate (119 ms ± 11.8 ms) and mean heart rate variability (1.7 ms ± 3.4 ms) derived. These standard parameter ranges were taken into account in the QC methods to select a group of nine optimal gated and a group of eight sub-optimal gated [ 18 F]-FDG PET scans of mice from our archive. From the list-mode files of the optimal gated group

  5. Social anxiety and negative early life events in university students Eventos negativos na infância e ansiedade social em estudantes universitários

    Directory of Open Access Journals (Sweden)

    Cynthia Binelli

    2012-06-01

    Full Text Available INTRODUCTION: There is substantial evidence regarding the impact of negative life events during childhood on the aetiology of psychiatric disorders. We examined the association between negative early life events and social anxiety in a sample of 571 Spanish University students. METHODS: In a cross-sectional survey conducted in 2007, we collected data through a semistructured questionnaire of sociodemographic variables, personal and family psychiatric history, and substance abuse. We assessed the five early negative life events: (i the loss of someone close, (ii emotional abuse, (iii physical abuse, (iv family violence, and (v sexual abuse. All participants completed the Liebowitz Social Anxiety Scale. RESULTS: Mean (SD age was 21 (4.5, 75% female, LSAS score was 40 (DP = 22, 14.2% had a psychiatric family history and 50.6% had negative life events during childhood. Linear regression analyses, after controlling for age, gender, and family psychiatric history, showed a positive association between family violence and social score (p = 0.03. None of the remaining stressors produced a significant increase in LSAS score (p > 0.05. CONCLUSION: University students with high levels of social anxiety presented higher prevalence of negative early life events. Thus, childhood family violence could be a risk factor for social anxiety in such a population.INTRODUÇÃO: Existem evidências substanciais sobre o impacto de eventos negativos da vida durante a infância na etiologia dos transtornos psiquiátricos. Examinamos a associação entre os eventos negativos ocorridos na infância e a ansiedade social em uma amostra de 571 estudantes universitários espanhóis. MÉTODOS: Em um estudo transversal realizado em 2007, foram coletados os dados de variáveis sociodemográficas, história psiquiátrica pessoal e familiar e abuso de substâncias por meio de um questionário semiestruturado e avaliamos cinco eventos negativos ocorridos na infância: (i a perda de

  6. An Event Reporting and Early-Warning Safety System Based on the Internet of Things for Underground Coal Mines: A Case Study

    Directory of Open Access Journals (Sweden)

    Byung Wan Jo

    2017-09-01

    Full Text Available Fatal accidents associated with underground coal mines require the implementation of high-level gas monitoring and miner’s localization approaches to promote underground safety and health. This study introduces a real-time monitoring, event-reporting and early-warning platform, based on cluster analysis for outlier detection, spatiotemporal statistical analysis, and an RSS range-based weighted centroid localization algorithm for improving safety management and preventing accidents in underground coal mines. The proposed platform seamlessly integrates monitoring, analyzing, and localization approaches using the Internet of Things (IoT, cloud computing, a real-time operational database, application gateways, and application program interfaces. The prototype has been validated and verified at the operating underground Hassan Kishore coal mine. Sensors for air quality parameters including temperature, humidity, CH4, CO2, and CO demonstrated an excellent performance, with regression constants always greater than 0.97 for each parameter when compared to their commercial equivalent. This framework enables real-time monitoring, identification of abnormal events (>90%, and verification of a miner’s localization (with <1.8 m of error in the harsh environment of underground mines. The main contribution of this study is the development of an open source, customizable, and cost-effective platform for effectively promoting underground coal mine safety. This system is helpful for solving the problems of accessibility, serviceability, interoperability, and flexibility associated with safety in coal mines.

  7. Early and late pathogenic events of newborn mice encephalitis experimentally induced by itacaiunas and curionópolis bracorhabdoviruses infection.

    Directory of Open Access Journals (Sweden)

    José Antonio Picanço Diniz

    Full Text Available In previous reports we proposed a new genus for Rhabdoviridae and described neurotropic preference and gross neuropathology in newborn albino Swiss mice after Curionopolis and Itacaiunas infections. In the present report a time-course study of experimental encephalitis induced by Itacaiunas and Curionopolis virus was conducted both in vivo and in vitro to investigate cellular targets and the sequence of neuroinvasion. We also investigate, after intranasal inoculation, clinical signs, histopathology and apoptosis in correlation with viral immunolabeling at different time points. Curionopolis and Itacaiunas viral antigens were first detected in the parenchyma of olfactory pathways at 2 and 3 days post-inoculation (dpi and the first clinical signs were observed at 4 and 8 dpi, respectively. After Curionopolis infection, the mortality rate was 100% between 5 and 6 dpi, and 35% between 8 and 15 dpi after Itacaiunas infection. We identified CNS mice cell types both in vivo and in vitro and the temporal sequence of neuroanatomical olfactory areas infected by Itacaiunas and Curionopolis virus. Distinct virulences were reflected in the neuropathological changes including TUNEL immunolabeling and cytopathic effects, more intense and precocious after intracerebral or in vitro inoculations of Curionopolis than after Itacaiunas virus. In vitro studies revealed neuronal but not astrocyte or microglial cytopathic effects at 2 dpi, with monolayer destruction occurring at 5 and 7 dpi with Curionopolis and Itacaiunas virus, respectively. Ultrastructural changes included virus budding associated with interstitial and perivascular edema, endothelial hypertrophy, a reduced and/or collapsed small vessel luminal area, thickening of the capillary basement membrane, and presence of phagocytosed apoptotic bodies. Glial cells with viral budding similar to oligodendrocytes were infected with Itacaiunas virus but not with Curionopolis virus. Thus, Curionopolis and

  8. Early and Late Pathogenic Events of Newborn Mice Encephalitis Experimentally Induced by Itacaiunas and Curionópolis Bracorhabdoviruses Infection

    Science.gov (United States)

    Diniz, José Antonio Picanço; dos Santos, Zaire Alves; Braga, Marcio Augusto Galvão; Dias, Ádila Liliane Barros; da Silva, Daisy Elaine Andrade; Medeiros, Daniele Barbosa de Almeida; Barros, Vera Lucia Reis de Souza; Chiang, Jannifer Oliveira; Zoghbi, Kendra Eyllen de Freitas; Quaresma, Juarez Antônio Simões; Takiya, Christina Maeda; Moura Neto, Vivaldo; de Souza, Wanderley; Vasconcelos, Pedro Fernando da Costa; Diniz, Cristovam Wanderley Picanço

    2008-01-01

    In previous reports we proposed a new genus for Rhabdoviridae and described neurotropic preference and gross neuropathology in newborn albino Swiss mice after Curionopolis and Itacaiunas infections. In the present report a time-course study of experimental encephalitis induced by Itacaiunas and Curionopolis virus was conducted both in vivo and in vitro to investigate cellular targets and the sequence of neuroinvasion. We also investigate, after intranasal inoculation, clinical signs, histopathology and apoptosis in correlation with viral immunolabeling at different time points. Curionopolis and Itacaiunas viral antigens were first detected in the parenchyma of olfactory pathways at 2 and 3 days post-inoculation (dpi) and the first clinical signs were observed at 4 and 8 dpi, respectively. After Curionopolis infection, the mortality rate was 100% between 5 and 6 dpi, and 35% between 8 and 15 dpi after Itacaiunas infection. We identified CNS mice cell types both in vivo and in vitro and the temporal sequence of neuroanatomical olfactory areas infected by Itacaiunas and Curionopolis virus. Distinct virulences were reflected in the neuropathological changes including TUNEL immunolabeling and cytopathic effects, more intense and precocious after intracerebral or in vitro inoculations of Curionopolis than after Itacaiunas virus. In vitro studies revealed neuronal but not astrocyte or microglial cytopathic effects at 2 dpi, with monolayer destruction occurring at 5 and 7 dpi with Curionopolis and Itacaiunas virus, respectively. Ultrastructural changes included virus budding associated with interstitial and perivascular edema, endothelial hypertrophy, a reduced and/or collapsed small vessel luminal area, thickening of the capillary basement membrane, and presence of phagocytosed apoptotic bodies. Glial cells with viral budding similar to oligodendrocytes were infected with Itacaiunas virus but not with Curionopolis virus. Thus, Curionopolis and Itacaiunas viruses share

  9. The preventing recurrent vascular events and neurological worsening through intensive organized case-management (PREVENTION trial protocol [clinicaltrials.gov identifier: NCT00931788

    Directory of Open Access Journals (Sweden)

    Tsuyuki Ross

    2010-04-01

    Full Text Available Abstract Background Survivors of transient ischemic attack (TIA or stroke are at high risk for recurrent vascular events and aggressive treatment of vascular risk factors can reduce this risk. However, vascular risk factors, especially hypertension and high cholesterol, are not managed optimally even in those patients seen in specialized clinics. This gap between the evidence for secondary prevention of stroke and the clinical reality leads to suboptimal patient outcomes. In this study, we will be testing a pharmacist case manager for delivery of stroke prevention services. We hypothesize this new structure will improve processes of care which in turn should lead to improved outcomes. Methods We will conduct a prospective, randomized, controlled open-label with blinded ascertainment of outcomes (PROBE trial. Treatment allocation will be concealed from the study personnel, and all outcomes will be collected in an independent and blinded manner by observers who have not been involved in the patient's clinical care or trial participation and who are masked to baseline measurements. Patients will be randomized to control or a pharmacist case manager treating vascular risk factors to guideline-recommended target levels. Eligible patients will include all adult patients seen at stroke prevention clinics in Edmonton, Alberta after an ischemic stroke or TIA who have uncontrolled hypertension (defined as systolic blood pressure (BP > 140 mm Hg or dyslipidemia (fasting LDL-cholesterol > 2.00 mmol/L and who are not cognitively impaired or institutionalized. The primary outcome will be the proportion of subjects who attain 'optimal BP and lipid control'(defined as systolic BP Conclusions Nearly one-quarter of those who survive a TIA or minor stroke suffer another vascular event within a year. If our intervention improves the provision of secondary prevention therapies in these patients, the clinical (and financial implications will be enormous.

  10. The Sky in Early Modern English Literature A Study of Allusions to Celestial Events in Elizabethan and Jacobean Writing, 1572-1620

    CERN Document Server

    Levy, David H

    2011-01-01

    When a dissertation gets completed, the normal rule is that it is never read. By anyone.  David H. Levy’s dissertation - The Sky in Early Modern English Literature:  A Study of Allusions to Celestial Events in Elizabethan and Jacobean Writing, 1572-1620 - is different.  It opens a whole new interdisciplinary field, which involves the beautiful relationship between the night sky and the works of the early modern period of English Literature.  Although the sky enters into much of literature through the ages, the period involving William Shakespeare and his colleagues is particularly rich.               When Shakespeare was about 8 years old, his father probably took him outside his Stratford home into their northward-facing back yard.  There, father and son gazed upon the first great new star visible in the past 500 years, shining forth as brightly as Venus, and even visible in daylight.  This new star, which we now know as a supernova, completely unhinged old ideas about the cosmos.  Com...

  11. Effects of twenty-minute 3G mobile phone irradiation on event related potential components and early gamma synchronization in auditory oddball paradigm.

    Science.gov (United States)

    Stefanics, G; Thuróczy, G; Kellényi, L; Hernádi, I

    2008-11-19

    We investigated the potential effects of 20 min irradiation from a new generation Universal Mobile Telecommunication System (UMTS) 3G mobile phone on human event related potentials (ERPs) in an auditory oddball paradigm. In a double-blind task design, subjects were exposed to either genuine or sham irradiation in two separate sessions. Before and after irradiation subjects were presented with a random series of 50 ms tone burst (frequent standards: 1 kHz, P=0.8, rare deviants: 1.5 kHz, P=0.2) at a mean repetition rate of 1500 ms while electroencephalogram (EEG) was recorded. The subjects' task was to silently count the appearance of targets. The amplitude and latency of the N100, N200, P200 and P300 components for targets and standards were analyzed in 29 subjects. We found no significant effects of electromagnetic field (EMF) irradiation on the amplitude and latency of the above ERP components. In order to study possible effects of EMF on attentional processes, we applied a wavelet-based time-frequency method to analyze the early gamma component of brain responses to auditory stimuli. We found that the early evoked gamma activity was insensitive to UMTS RF exposition. Our results support the notion, that a single 20 min irradiation from new generation 3G mobile phones does not induce measurable changes in latency or amplitude of ERP components or in oscillatory gamma-band activity in an auditory oddball paradigm.

  12. Early events of secretory granule formation in the rat parotid acinar cell under the influence of isoproterenol. An ultrastructural and lectin cytochemical study

    Directory of Open Access Journals (Sweden)

    F D’Amico

    2009-12-01

    Full Text Available The events involved in the maturation process of acinar secretory granules of rat parotid gland were investigated ultrastructurally and cytochemically by using a battery of four lectins [Triticum vulgaris agglutinin (WGA, Ulex europaeus agglutinin I (UEA-I, Glycine max agglutinin (SBA, Arachys hypogaea agglutinin (PNA]. In order to facilitate the study, parotid glands were chronically stimulated with isoproterenol to induce secretion. Specimens were embedded in the Lowicryl K4M resin. The trans-Golgi network (TGN derived secretory granules, which we refer to as immature secretory granules, were found to be intermediate structures in the biogenesis process of the secretory granules in the rat parotid acinar cell. These early structures do not seem to be the immediate precursor of the mature secretory granules: in fact, a subsequent interaction process between these early immature granule forms and TGN elements seems to occur, leading, finally, to the mature granules. These findings could explain the origin of the polymorphic subpopulations of the secretory granules in the normal acinar cells of the rat parotid gland. The lectin staining patterns were characteristic of each lectin. Immature and mature secretory gran- ules were labelled with WGA, SBA, PNA, and lightly with UEA-I. Cis and intermediate cisternae of the Golgi apparatus were labelled with WGA, and trans cisternae with WGA and SBA.

  13. Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci

    Directory of Open Access Journals (Sweden)

    Merok Marianne A

    2010-05-01

    Full Text Available Abstract Background Estimates suggest that up to 30% of colorectal cancers (CRC may develop due to an increased genetic risk. The mean age at diagnosis for CRC is about 70 years. Time of disease onset 20 years younger than the mean age is assumed to be indicative of genetic susceptibility. We have compared high resolution tumor genome copy number variation (CNV (Roche NimbleGen, 385 000 oligo CGH array in microsatellite stable (MSS tumors from two age groups, including 23 young at onset patients without known hereditary syndromes and with a median age of 44 years (range: 28-53 and 17 elderly patients with median age 79 years (range: 69-87. Our aim was to identify differences in the tumor genomes between these groups and pinpoint potential susceptibility loci. Integration analysis of CNV and genome wide mRNA expression data, available for the same tumors, was performed to identify a restricted candidate gene list. Results The total fraction of the genome with aberrant copy number, the overall genomic profile and the TP53 mutation spectrum were similar between the two age groups. However, both the number of chromosomal aberrations and the number of breakpoints differed significantly between the groups. Gains of 2q35, 10q21.3-22.1, 10q22.3 and 19q13.2-13.31 and losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT, RG9MTD2, and ZNF574, had significantly different mRNA expression comparing median expression levels across the transcriptome between the two groups. Conclusions Ten genomic loci, containing more than 500 protein coding genes, are identified as more often altered in tumors from early onset versus late

  14. Identifying Relationships between High-Risk Sexual Behaviors and Screening Positive for Chlamydia and Gonorrhea in School-Wide Screening Events

    Science.gov (United States)

    Salerno, Jennifer; Darling-Fisher, Cindy; Hawkins, Nicole M.; Fraker, Elizabeth

    2013-01-01

    Background: This article describes a school-wide sexually transmitted infection (STI) screening to identify adolescent high-risk sexual behaviors, STI history/incidence, and presence of chlamydia and gonorrhea, and examines relationships between high-risk behaviors and screening positive for chlamydia and gonorrhea in an alternative high school…

  15. High soluble CD30, CD25 and IL-6 may identify patients with worse survival in CD30+ cutaneous lymphomas and early mycosis fungoides

    Science.gov (United States)

    Kadin, Marshall E.; Pavlov, Igor; Delgado, Julio C.; Vonderheid, Eric C.

    2011-01-01

    Histopathology alone cannot predict outcome of patients with CD30+ primary cutaneous lymphoproliferative disorders (CD30CLPD) and early mycosis fungoides (MF). To test the hypothesis that serum cytokines/cytokine receptors provide prognostic information in these disorders, we measured soluble CD30 (sCD30), sCD25, and selected cytokines in cell cultures and sera of 116 patients with CD30CLPD and 96 patients with early MF followed up to 20 years. Significant positive correlation was found between sCD30 levels and sCD25, CD40L, IL-6, and IL-8, suggesting CD30+ neoplastic cells secrete these cytokines, but not Th2 cytokines. In vitro studies confirmed sCD30, sCD25, IL-6 and IL-8 are secreted by CD30CLPD-derived cell lines. CD30CLPD patients with above normal sCD30 and sCD25 had worse overall and disease-related survivals, but only sCD30 retained significance in Cox models that included advanced age. High sCD30 also identified patients with worse survival in early MF. Increased IL-6 and IL-8 correlated with poor disease-related survival in CD30CLPD patients, We conclude that: (1) neoplastic cells of some CD30CLPD patients do not resemble Th2 cells, (2) high serum sCD30, sCD25, IL-6, and perhaps IL-8 levels may provide prognostic information useful for patient management. PMID:22071475

  16. Early Glycemic Control and Magnitude of HbA1c Reduction Predict Cardiovascular Events and Mortality: Population-Based Cohort Study of 24,752 Metformin Initiators.

    Science.gov (United States)

    Svensson, Elisabeth; Baggesen, Lisbeth M; Johnsen, Søren P; Pedersen, Lars; Nørrelund, Helene; Buhl, Esben S; Haase, Christiane L; Thomsen, Reimar W

    2017-06-01

    We investigated the association of early achieved HbA 1c level and magnitude of HbA 1c reduction with subsequent risk of cardiovascular events or death in patients with type 2 diabetes who initiate metformin. This was a population-based cohort study including all metformin initiators with HbA 1c tests in Northern Denmark, 2000-2012. Six months after metformin initiation, we classified patients by HbA 1c achieved (<6.5% or higher) and by magnitude of HbA 1c change from the pretreatment baseline. We used Cox regression to examine subsequent rates of acute myocardial infarction, stroke, or death, controlling for baseline HbA 1c and other confounding factors. We included 24,752 metformin initiators (median age 62.5 years, 55% males) with a median follow-up of 2.6 years. The risk of a combined outcome event gradually increased with rising levels of HbA 1c achieved compared with a target HbA 1c of <6.5%: adjusted hazard ratio (HR) 1.18 (95% CI 1.07-1.30) for 6.5-6.99%, HR 1.23 (1.09-1.40) for 7.0-7.49%, HR 1.34 (1.14-1.57) for 7.5-7.99%, and HR 1.59 (1.37-1.84) for ≥8%. Results were consistent for individual outcome events and robust by age-group and other patient characteristics. A large absolute HbA 1c reduction from baseline also predicted outcome: adjusted HR 0.80 (0.65-0.97) for Δ = -4, HR 0.98 (0.80-1.20) for Δ = -3, HR 0.92 (0.78-1.08) for Δ = -2, and HR 0.99 (0.89-1.10) for Δ = -1 compared with no HbA 1c change (Δ = 0). A large initial HbA 1c reduction and achievement of low HbA 1c levels within 6 months after metformin initiation are associated with a lower risk of cardiovascular events and death in patients with type 2 diabetes. © 2017 by the American Diabetes Association.

  17. Identifying Barriers to Delivering the Awakening and Breathing Coordination, Delirium, and Early Exercise/Mobility Bundle to Minimize Adverse Outcomes for Mechanically Ventilated Patients: A Systematic Review.

    Science.gov (United States)

    Costa, Deena Kelly; White, Matthew R; Ginier, Emily; Manojlovich, Milisa; Govindan, Sushant; Iwashyna, Theodore J; Sales, Anne E

    2017-08-01

    Improved outcomes are associated with the Awakening and Breathing Coordination, Delirium, and Early exercise/mobility bundle (ABCDE); however, implementation issues are common. As yet, no study has integrated the barriers to ABCDE to provide an overview of reasons for less successful efforts. The purpose of this review was to identify and catalog the barriers to ABCDE delivery based on a widely used implementation framework, and to provide a resource to guide clinicians in overcoming barriers to implementation. We searched MEDLINE via PubMed, CINAHL, and Scopus for original research articles from January 1, 2007, to August 31, 2016, that identified barriers to ABCDE implementation for adult patients in the ICU. Two reviewers independently reviewed studies, extracted barriers, and conducted thematic content analysis of the barriers, guided by the Consolidated Framework for Implementation Research. Discrepancies were discussed, and consensus was achieved. Our electronic search yielded 1,908 articles. After applying our inclusion/exclusion criteria, we included 49 studies. We conducted thematic content analysis of the 107 barriers and identified four classes of ABCDE barriers: (1) patient-related (ie, patient instability and safety concerns); (2) clinician-related (ie, lack of knowledge, staff safety concerns); (3) protocol-related (ie, unclear protocol criteria, cumbersome protocols to use); and, not previously identified in past reviews, (4) ICU contextual barriers (ie, interprofessional team care coordination). We provide the first, to our knowledge, systematic differential diagnosis of barriers to ABCDE delivery, moving beyond the conventional focus on patient-level factors. Our analysis offers a differential diagnosis checklist for clinicians planning ABCDE implementation to improve patient care and outcomes. Copyright © 2017 American College of Chest Physicians. All rights reserved.

  18. A model-based assessment of the cost–utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients

    International Nuclear Information System (INIS)

    Snowsill, Tristan; Huxley, Nicola; Hoyle, Martin; Jones-Hughes, Tracey; Coelho, Helen; Cooper, Chris; Frayling, Ian; Hyde, Chris

    2015-01-01

    Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Individuals with Lynch syndrome have an increased risk of colorectal cancer, endometrial cancer, ovarian and other cancers. Lynch syndrome remains underdiagnosed in the UK. Reflex testing for Lynch syndrome in early-onset colorectal cancer patients is proposed as a method to identify more families affected by Lynch syndrome and offer surveillance to reduce cancer risks, although cost-effectiveness is viewed as a barrier to implementation. The objective of this project was to estimate the cost–utility of strategies to identify Lynch syndrome in individuals with early-onset colorectal cancer in the NHS. A decision analytic model was developed which simulated diagnostic and long-term outcomes over a lifetime horizon for colorectal cancer patients with and without Lynch syndrome and for relatives of those patients. Nine diagnostic strategies were modelled which included microsatellite instability (MSI) testing, immunohistochemistry (IHC), BRAF mutation testing (methylation testing in a scenario analysis), diagnostic mutation testing and Amsterdam II criteria. Biennial colonoscopic surveillance was included for individuals diagnosed with Lynch syndrome and accepting surveillance. Prophylactic hysterectomy with bilateral salpingo-oophorectomy (H-BSO) was similarly included for women diagnosed with Lynch syndrome. Costs from NHS and Personal Social Services perspective and quality-adjusted life years (QALYs) were estimated and discounted at 3.5% per annum. All strategies included for the identification of Lynch syndrome were cost-effective versus no testing. The strategy with the greatest net health benefit was MSI followed by BRAF followed by diagnostic genetic testing, costing £5,491 per QALY gained over no testing. The effect of prophylactic H-BSO on health-related quality of life (HRQoL) is uncertain and could

  19. A model-based assessment of the cost-utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients.

    Science.gov (United States)

    Snowsill, Tristan; Huxley, Nicola; Hoyle, Martin; Jones-Hughes, Tracey; Coelho, Helen; Cooper, Chris; Frayling, Ian; Hyde, Chris

    2015-04-25

    Lynch syndrome is an autosomal dominant cancer predisposition syndrome caused by mutations in the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2. Individuals with Lynch syndrome have an increased risk of colorectal cancer, endometrial cancer, ovarian and other cancers. Lynch syndrome remains underdiagnosed in the UK. Reflex testing for Lynch syndrome in early-onset colorectal cancer patients is proposed as a method to identify more families affected by Lynch syndrome and offer surveillance to reduce cancer risks, although cost-effectiveness is viewed as a barrier to implementation. The objective of this project was to estimate the cost-utility of strategies to identify Lynch syndrome in individuals with early-onset colorectal cancer in the NHS. A decision analytic model was developed which simulated diagnostic and long-term outcomes over a lifetime horizon for colorectal cancer patients with and without Lynch syndrome and for relatives of those patients. Nine diagnostic strategies were modelled which included microsatellite instability (MSI) testing, immunohistochemistry (IHC), BRAF mutation testing (methylation testing in a scenario analysis), diagnostic mutation testing and Amsterdam II criteria. Biennial colonoscopic surveillance was included for individuals diagnosed with Lynch syndrome and accepting surveillance. Prophylactic hysterectomy with bilateral salpingo-oophorectomy (H-BSO) was similarly included for women diagnosed with Lynch syndrome. Costs from NHS and Personal Social Services perspective and quality-adjusted life years (QALYs) were estimated and discounted at 3.5% per annum. All strategies included for the identification of Lynch syndrome were cost-effective versus no testing. The strategy with the greatest net health benefit was MSI followed by BRAF followed by diagnostic genetic testing, costing £5,491 per QALY gained over no testing. The effect of prophylactic H-BSO on health-related quality of life (HRQoL) is uncertain and could outweigh

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

    Directory of Open Access Journals (Sweden)

    Muslih Khamis D.

    2014-09-01

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

  1. Mobile phone sensors and supervised machine learning to identify alcohol use events in young adults: Implications for just-in-time adaptive interventions.

    Science.gov (United States)

    Bae, Sangwon; Chung, Tammy; Ferreira, Denzil; Dey, Anind K; Suffoletto, Brian

    2017-11-27

    Real-time detection of drinking could improve timely delivery of interventions aimed at reducing alcohol consumption and alcohol-related injury, but existing detection methods are burdensome or impractical. To evaluate whether phone sensor data and machine learning models are useful to detect alcohol use events, and to discuss implications of these results for just-in-time mobile interventions. 38 non-treatment seeking young adult heavy drinkers downloaded AWARE app (which continuously collected mobile phone sensor data), and reported alcohol consumption (number of drinks, start/end time of prior day's drinking) for 28days. We tested various machine learning models using the 20 most informative sensor features to classify time periods as non-drinking, low-risk (1 to 3/4 drinks per occasion for women/men), and high-risk drinking (>4/5 drinks per occasion for women/men). Among 30 participants in the analyses, 207 non-drinking, 41 low-risk, and 45 high-risk drinking episodes were reported. A Random Forest model using 30-min windows with 1day of historical data performed best for detecting high-risk drinking, correctly classifying high-risk drinking windows 90.9% of the time. The most informative sensor features were related to time (i.e., day of week, time of day), movement (e.g., change in activities), device usage (e.g., screen duration), and communication (e.g., call duration, typing speed). Preliminary evidence suggests that sensor data captured from mobile phones of young adults is useful in building accurate models to detect periods of high-risk drinking. Interventions using mobile phone sensor features could trigger delivery of a range of interventions to potentially improve effectiveness. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Early events in the pathogenesis of foot-and-mouth disease in pigs; identification of oropharyngeal tonsils as sites of primary and sustained viral replication.

    Directory of Open Access Journals (Sweden)

    Carolina Stenfeldt

    Full Text Available A time-course study was performed to elucidate the early events of foot-and-mouth disease virus (FMDV infection in pigs subsequent to simulated natural, intra-oropharyngeal, inoculation. The earliest detectable event was primary infection in the lingual and paraepiglottic tonsils at 6 hours post inoculation (hpi characterized by regional localization of viral RNA, viral antigen, and infectious virus. At this time FMDV antigen was localized in cytokeratin-positive epithelial cells and CD172a-expressing leukocytes of the crypt epithelium of the paraepiglottic tonsils. De novo replication of FMDV was first detected in oropharyngeal swab samples at 12 hpi and viremia occurred at 18-24 hpi, approximately 24 hours prior to the appearance of vesicular lesions. From 12 through 78 hpi, microscopic detection of FMDV was consistently localized to cytokeratin-positive cells within morphologically characteristic segments of oropharyngeal tonsil crypt epithelium. During this period, leukocyte populations expressing CD172a, SLA-DQ class II and/or CD8 were found in close proximity to infected epithelial cells, but with little or no co-localization with viral proteins. Similarly, M-cells expressing cytokeratin-18 did not co-localize with FMDV proteins. Intra-epithelial micro-vesicles composed of acantholytic epithelial cells expressing large amounts of structural and non-structural FMDV proteins were present within crypts of the tonsil of the soft palate during peak clinical infection. These findings inculpate the paraepiglottic tonsils as the primary site of FMDV infection in pigs exposed via the gastrointestinal tract. Furthermore, the continuing replication of FMDV in the oropharyngeal tonsils during viremia and peak clinical infection with no concurrent amplification of virus occurring in the lower respiratory tract indicates that these sites are the major source of shedding of FMDV from pigs.

  3. Monitoring and forecasting local landslide hazard in the area of Longyearbyen, Svalbard - early progress and experiences from the Autumn 2016 events

    Science.gov (United States)

    Wang, Thea; Krøgli, Ingeborg; Boje, Søren; Colleuille, Hervé

    2017-04-01

    Since 2013 the Norwegian Water Resources and Energy Directorate (NVE) has operated a landslide early warning system (LEWS) for mainland Norway. The Svalbard islands, situated 800 km north of the Norwegian mainland, and 1200 km from the North Pole, are not part of the conventional early warning service. However, following the fatal snow avalanche event 19 Dec. 2015 in the settlement of Longyearbyen (78° north latitude), local authorities and the NVE have initiated monitoring of the hydro-meteorological conditions for the area of Longyearbyen, as an extraordinary precaution. Two operational forecasting teams from the NVE; the snow avalanche and the landslide hazard forecasters, perform hazard assessment related to snow avalanches, slush flows, debris flows, shallow slides and local flooding. This abstract will focus on recent experiences made by the landslide hazard team during the autumn 2016 landslide events, caused by a record setting wet and warm summer and autumn of 2016. The general concept of the Norwegian LEWS is based on frequency intervals of extreme hydro-meteorological conditions. This general concept has been transposed to the Longyearbyen area. Although the climate is considerably colder and drier than mainland Norway, experiences so far are positive and seem useful to the local authorities. Initially, the landslide hazard evaluation was intended to consider only slush flow hazard during the snow covered season. However, due to the extraordinary warm and wet summer and autumn 2016, the landslide hazard forecasters unexpectedly had to issue warnings for the local authorities due to increased risk of shallow landslides and debris flows. This was done in close cooperation with the Norwegian Meteorological Institute, who provided weather forecasts from the recently developed weather prediction model, AROME-Arctic. Two examples, from 14-15 Oct and 8-9 Nov 2016, will be given to demonstrate how the landslide hazard assessment for the Longyearbyen area is

  4. Changes in the Phosphoproteome and Metabolome Link Early Signaling Events to Rearrangement of Photosynthesis and Central Metabolism in Salinity and Oxidative Stress Response in Arabidopsis.

    Science.gov (United States)

    Chen, Yanmei; Hoehenwarter, Wolfgang

    2015-12-01

    Salinity and oxidative stress are major factors affecting and limiting the productivity of agricultural crops. The molecular and biochemical processes governing the plant response to abiotic stress have often been researched in a reductionist manner. Here, we report a systemic approach combining metabolic labeling and phosphoproteomics to capture early signaling events with quantitative metabolome analysis and enzyme activity assays to determine the effects of salt and oxidative stress on plant physiology. K(+) and Na(+) transporters showed coordinated changes in their phosphorylation pattern, indicating the importance of dynamic ion homeostasis for adaptation to salt stress. Unique phosphorylation sites were found for Arabidopsis (Arabidopsis thaliana) SNF1 kinase homolog10 and 11, indicating their central roles in the stress-regulated responses. Seven Sucrose Non-fermenting1-Related Protein Kinase2 kinases showed varying levels of phosphorylation at multiple serine/threonine residues in their kinase domain upon stress, showing temporally distinct modulation of the various isoforms. Salinity and oxidative stress also lead to changes in protein phosphorylation of proteins central to photosynthesis, in particular the kinase State Transition Protein7 required for state transition and light-harvesting II complex proteins. Furthermore, stress-induced changes of the phosphorylation of enzymes of central metabolism were observed. The phosphorylation patterns of these proteins were concurrent with changes in enzyme activity. This was reflected by altered levels of metabolites, such as the sugars sucrose and fructose, glycolysis intermediates, and amino acids. Together, our study provides evidence for a link between early signaling in the salt and oxidative stress response that regulates the state transition of photosynthesis and the rearrangement of primary metabolism. © 2015 American Society of Plant Biologists. All Rights Reserved.

  5. Integrative analysis of deep sequencing data identifies estrogen receptor early response genes and links ATAD3B to poor survival in breast cancer.

    Directory of Open Access Journals (Sweden)

    Kristian Ovaska

    Full Text Available Identification of responsive genes to an extra-cellular cue enables characterization of pathophysiologically crucial biological processes. Deep sequencing technologies provide a powerful means to identify responsive genes, which creates a need for computational methods able to analyze dynamic and multi-level deep sequencing data. To answer this need we introduce here a data-driven algorithm, SPINLONG, which is designed to search for genes that match the user-defined hypotheses or models. SPINLONG is applicable to various experimental setups measuring several molecular markers in parallel. To demonstrate the SPINLONG approach, we analyzed ChIP-seq data reporting PolII, estrogen receptor α (ERα, H3K4me3 and H2A.Z occupancy at five time points in the MCF-7 breast cancer cell line after estradiol stimulus. We obtained 777 ERa early responsive genes and compared the biological functions of the genes having ERα binding within 20 kb of the transcription start site (TSS to genes without such binding site. Our results show that the non-genomic action of ERα via the MAPK pathway, instead of direct ERa binding, may be responsible for early cell responses to ERα activation. Our results also indicate that the ERα responsive genes triggered by the genomic pathway are transcribed faster than those without ERα binding sites. The survival analysis of the 777 ERα responsive genes with 150 primary breast cancer tumors and in two independent validation cohorts indicated the ATAD3B gene, which does not have ERα binding site within 20 kb of its TSS, to be significantly associated with poor patient survival.

  6. Integrated orbital time scale of the Valanginian-Hauterivian (Early Cretaceous): Chronological relationships between Paraná-Etendeka LIP, Weissert and Faraoni events

    Science.gov (United States)

    Martinez, Mathieu; Deconinck, Jean-François; Pellenard, Pierre; Riquier, Laurent; Company, Miguel; Moiroud, Mathieu; Reboulet, Stéphane

    2014-05-01

    During the Valanginian and the Hauterivian stages, the Weissert and Faraoni Events recorded global perturbations of the carbon cycle, marine organic matter deposits and rapid ecosystem changes. Both events were successively attributed to the activity of the Paraná-Etendeka Large Igneous Province (LIP). However, due to the scarcity of the radiometric ages available for this time interval, the chronological relationships between these events and the activity of the Paraná-Etendeka LIP remain unclear. Recently, the duration of the Valanginian Stage was calculated using a cyclostratigraphic approach on GSSP candidates and stratotypes (Martinez et al., 2013), but could not be anchored on a radiometric age. Here, we propose a duration assessment of the Hauterivian Stage using a similar cyclostratigraphic approach on the hemipelagic marl-limestone alternations from the La Charce section (Hauterivian GSSP candidate; SE France) and the Río Argos section (Barremian GSSP candidate; SE Spain). This duration could be anchored on an U/Pb age from a tuff level precisely dated using calcareous nannofossils and chemostratigraphy, to provide a refined geological time scale for the Valanginian and the Hauterivian stages. A total of 2000 spectral gamma-ray measurements were performed with a constant 0.20-m sample step. Spectral analyses were performed on the gamma-ray series to detect any sedimentary cycle. The precession, obliquity, 100-kyr and 405-kyr eccentricity cycles were identified by comparing sedimentary to orbital period ratios. The duration of the Hauterivian Stage could be assessed at 5.9 myr, using the 405-kyr eccentricity cycle as a reference. By anchoring the U/Pb age of Aguirre-Urreta et al. (2008) on the orbital time scale provided for the Valanginian-Hauterivian stages, the base of the Valanginian Stage could be dated at -140.2 ± 1.5 Ma, the base of the Hauterivian at -135.1 ± 1.5 Ma and the base of the Barremian at -129.2 ± 1.5 Ma. In addition, the Weissert

  7. Automatic Event Detection and Picking of P, S Seismic Phases for Earthquake Early Warning: A Case Study of the 2008 Wenchuan Earthquake

    Science.gov (United States)

    WANG, Z.; Zhao, B.

    2015-12-01

    We develop an automatic seismic phase arrival detection and picking algorithm for the impending earthquakes occurred with diverse focal mechanisms and depths. The polarization analysis of the three-component seismograms is utilized to distinguish between P and S waves through a sliding time window. When applying the short term average/long term average (STA/LTA) method to the polarized data, we also construct a new characteristics function that can sensitively reflect the changes of signals' amplitude and frequency, providing a better detection for the phase arrival. Then an improved combination method of the higher order statistics and the Akaike information criteria (AIC) picker is applied to the refined signal to lock on the arrival time with a higher degree of accuracy. We test our techniques to the aftershocks of the Ms8.0 Wenchuan earthquake, where hundreds of three-component acceleration records with magnitudes of 4.0 to 6.4 are treated. In comparison to the analyst picks, the results of the proposed detection algorithms are shown to perform well and can be applied from a single instrument within a network of stations for the large seismic events in the Earthquake Early Warning System (EEWS).

  8. Abnormal Mitochondrial Dynamics and Synaptic Degeneration as Early Events in Alzheimer’s Disease: Implications to Mitochondria-Targeted Antioxidant Therapeutics

    Science.gov (United States)

    Reddy, P. Hemachandra; Tripathy, Raghav; Troung, Quang; Thirumala, Karuna; Reddy, Tejaswini P.; Anekonda, Vishwanath; Shirendeb, Ulziibat P.; Calkins, Marcus J.; Reddy, Arubala P.; Mao, Peizhong; Manczak, Maria

    2011-01-01

    Synaptic pathology and mitochondrial oxidative damage are early events in Alzheimer’s disease (AD) progression. Loss of synapses and synaptic damage are the best correlate of cognitive deficits found in AD patients. Recent research on amyloid bet (Aβ) and mitochondria in AD revealed that Aβ accumulates in synapses and synaptic mitochondria, leading to abnormal mitochondrial dynamics and synaptic degeneration in AD neurons. Further, recent studies using live-cell imaging and primary neurons from amyloid beta precursor protein (AβPP) transgenic mice revealed that reduced mitochondrial mass, defective axonal transport of mitochondria and synaptic degeneration, indicating that Aβ is responsible for mitochondrial and synaptic deficiencies. Tremendous progress has been made in studying antioxidant approaches in mouse models of AD and clinical trials of AD patients. This article highlights the recent developments made in Aβ-induced abnormal mitochondrial dynamics, defective mitochondrial biogenesis, impaired axonal transport and synaptic deficiencies in AD. This article also focuses on mitochondrial approaches in treating AD, and also discusses latest research on mitochondria-targeted antioxidants in AD. PMID:22037588

  9. Extensive proteomic screening identifies the obesity-related NYGGF4 protein as a novel LRP1-interactor, showing reduced expression in early Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Taddei Kevin

    2010-01-01

    Full Text Available Abstract Background The low-density lipoprotein receptor related protein 1 (LRP1 has been implicated in Alzheimer's disease (AD but its signalling has not been fully evaluated. There is good evidence that the cytoplasmic domain of LRP1 is involved in protein-protein interactions, important in the cell biology of LRP1. Results We carried out three yeast two-hybrid screens to identify proteins that interact with the cytoplasmic domain of LRP1. The screens included both conventional screens as well as a novel, split-ubiquitin-based screen in which an LRP1 construct was expressed and screened as a transmembrane protein. The split-ubiquitin screen was validated in a screen using full-length amyloid protein precursor (APP, which successfully identified FE65 and FE65L2, as well as novel interactors (Rab3a, Napg, and ubiquitin b. Using both a conventional screen as well as the split-ubiquitin screen, we identified NYGGF4 as a novel LRP1 interactor. The interaction between LRP1 and NYGGF4 was validated using two-hybrid assays, coprecipitation and colocalization in mammalian cells. Mutation analysis demonstrated a specific interaction of NYGGF4 with an NPXY motif that required an intact tyrosine residue. Interestingly, while we confirmed that other LRP1 interactors we identified, including JIP1B and EB-1, were also able to bind to APP, NYGGF4 was unique in that it showed specific binding with LRP1. Expression of NYGGF4 decreased significantly in patients with AD as compared to age-matched controls, and showed decreasing expression with AD disease progression. Examination of Nyggf4 expression in mice with different alleles of the human APOE4 gene showed significant differences in Nyggf4 expression. Conclusions These results implicate NYGGF4 as a novel and specific interactor of LRP1. Decreased expression of LRP1 and NYGGF4 over disease, evident with the presence of even moderate numbers of neuritic plaques, suggests that LRP1-NYGGF4 is a system altered

  10. Proteomics mapping of cord blood identifies haptoglobin "switch-on" pattern as biomarker of early-onset neonatal sepsis in preterm newborns.

    Science.gov (United States)

    Buhimschi, Catalin S; Bhandari, Vineet; Dulay, Antonette T; Nayeri, Unzila A; Abdel-Razeq, Sonya S; Pettker, Christian M; Thung, Stephen; Zhao, Guomao; Han, Yiping W; Bizzarro, Matthew; Buhimschi, Irina A

    2011-01-01

    Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns. We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A proteomics discovery phase employing two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry identified 19 differentially-expressed proteins in cord blood of newborns with culture-confirmed EONS (n = 3) versus GA-matched controls (n = 3). Ontological classifications of the proteins included transfer/carrier, immunity/defense, protease/extracellular matrix. The 1(st)-level external validation conducted in the remaining 174 samples confirmed elevated haptoglobin and haptoglobin-related protein immunoreactivity (Hp&HpRP) in newborns with EONS (presumed and culture-confirmed) independent of GA at birth and birthweight (PLCA) was further used for unbiased classification of all 180 cases based on probability of "antenatal IAI exposure" as latent variable. This was then subjected to 2(nd)-level validation against indicators of adverse short-term neonatal outcome. The optimal LCA algorithm combined Hp&HpRP switch pattern (most input), interleukin-6 and neonatal hematological indices yielding two non-overlapping newborn clusters with low (≤20%) versus high (≥70%) probability of IAI exposure. This approach reclassified ∼30% of clinical EONS diagnoses lowering the number needed to harm and increasing the odds ratios for several adverse outcomes including intra-ventricular hemorrhage. Antenatal exposure to IAI results in precocious switch-on of Hp&HpRP expression. As EONS biomarker, cord blood Hp&HpRP has potential to improve the selection of newborns for prompt and targeted treatment at birth.

  11. Proteomics Mapping of Cord Blood Identifies Haptoglobin “Switch-On” Pattern as Biomarker of Early-Onset Neonatal Sepsis in Preterm Newborns

    Science.gov (United States)

    Buhimschi, Catalin S.; Bhandari, Vineet; Dulay, Antonette T.; Nayeri, Unzila A.; Abdel-Razeq, Sonya S.; Pettker, Christian M.; Thung, Stephen; Zhao, Guomao; Han, Yiping W.; Bizzarro, Matthew; Buhimschi, Irina A.

    2011-01-01

    Background Intra-amniotic infection and/or inflammation (IAI) are important causes of preterm birth and early-onset neonatal sepsis (EONS). A prompt and accurate diagnosis of EONS is critical for improved neonatal outcomes. We sought to explore the cord blood proteome and identify biomarkers and functional protein networks characterizing EONS in preterm newborns. Methodology/Principal Findings We studied a prospective cohort of 180 premature newborns delivered May 2004-September 2009. A proteomics discovery phase employing two-dimensional differential gel electrophoresis (2D-DIGE) and mass spectrometry identified 19 differentially-expressed proteins in cord blood of newborns with culture-confirmed EONS (n = 3) versus GA-matched controls (n = 3). Ontological classifications of the proteins included transfer/carrier, immunity/defense, protease/extracellular matrix. The 1st-level external validation conducted in the remaining 174 samples confirmed elevated haptoglobin and haptoglobin-related protein immunoreactivity (Hp&HpRP) in newborns with EONS (presumed and culture-confirmed) independent of GA at birth and birthweight (PLCA) was further used for unbiased classification of all 180 cases based on probability of “antenatal IAI exposure” as latent variable. This was then subjected to 2nd-level validation against indicators of adverse short-term neonatal outcome. The optimal LCA algorithm combined Hp&HpRP switch pattern (most input), interleukin-6 and neonatal hematological indices yielding two non-overlapping newborn clusters with low (≤20%) versus high (≥70%) probability of IAI exposure. This approach reclassified ∼30% of clinical EONS diagnoses lowering the number needed to harm and increasing the odds ratios for several adverse outcomes including intra-ventricular hemorrhage. Conclusions/Significance Antenatal exposure to IAI results in precocious switch-on of Hp&HpRP expression. As EONS biomarker, cord blood Hp&HpRP has potential to improve the

  12. The corpus-predominant gastritis index can be an early and reversible marker to identify the gastric cancer risk of Helicobacter pylori-infected nonulcer dyspepsia.

    Science.gov (United States)

    Cheng, Hsiu-Chi; Tsai, Yu-Ching; Yang, Hsiao-Bai; Yeh, Yi-Chun; Chang, Wei-Lun; Kuo, Hsin-Yu; Lu, Cheng-Chan; Sheu, Bor-Shyang

    2017-08-01

    Corpus-predominant gastritis index (CGI) is an early histological marker to identify Helicobacter pylori-infected gastric cancer relatives at risk of cancer. This study validated whether CGI is more prevalent in H. pylori-infected nonulcer dyspepsia (NUD) subjects than in duodenal ulcer (DU) controls and whether it is reversible after H. pylori eradication or is correlated with noninvasive biomarkers. In this longitudinal cohort study, 573 H. pylori-infected subjects were enrolled, including 349 NUD and 224 DU. Gastric specimens were provided to assess CGI, spasmolyic polypeptide-expressing metaplasia (SPEM), and Operative Link on Gastric Intestinal Metaplasia assessment (OLGIM). Serum pepsinogen I and II levels were assessed using enzyme-linked immunosorbent assay. CGI subjected were followed up at least 1 year after H. pylori eradication. NUD subjects had higher prevalence rates of CGI (47.0% vs 29.9%, Pgastritis and intestinal metaplasia. NUD subjects with CGI had higher risk of SPEM (OR 2.86, P<.001) and lower serum pepsinogen I/II ratios (P<.001) than those without CGI. Serum pepsinogen I/II ratios <9 could predict CGI modestly (AUROC 0.69, 95% CI: 0.63-0.74). CGI was regressed after eradication (P<.001). CGI was more prevalent in H. pylori-infected NUD subjects than in controls, was correlated with SPEM, and may serve as a marker earlier than OLGIM to indicate risk of gastric cancer. Moreover, CGI could be regressed after eradication. © 2017 John Wiley & Sons Ltd.

  13. Bridging the Faraoni and Selli oceanic anoxic events: short and repetitive dys- and anaerobic episodes during the late Hauterivian to early Aptian in the central Tethys

    Science.gov (United States)

    Föllmi, K. B.; Bôle, M.; Jammet, N.; Froidevaux, P.; Godet, A.; Bodin, S.; Adatte, T.; Matera, V.; Fleitmann, D.; Spangenberg, J. E.

    2011-06-01

    A detailed stratigraphical and geochemical analysis was performed on the upper part of the Maiolica Formation outcropping in the Breggia (southern Switzerland) and Capriolo sections (northern Italy). In these localities, the Maiolica Formation consists of well-bedded, partly siliceous, pelagic, micritic carbonate, which lodges numerous thin, dark and organic-rich layers. Stable-isotope, phosphorus, organic-carbon and a suite of redox-sensitive trace-metal contents (RSTE: Mo, U, Co, V and As) were measured. Higher densities of organic-rich layers were identified in the uppermost Hauterivian, lower Barremian and the Barremian-Aptian boundary intervals, whereas the upper Barremian interval and the interval immediately following the Barremian-Aptian boundary interval are characterized by lower densities of organic-rich layers. TOC contents, RSTE pattern and Corg:Ptot ratios indicate that most layers were deposited under dysaerobic rather than anaerobic conditions and that latter conditions were likely restricted to short intervals in the latest Hauterivian, the early Barremian and the pre-Selli early Aptian. Correlations are possible with organic-rich intervals in central Italy (the Gorgo a Cerbara section) and the Boreal northwest German Basin, and with the facies and drowning pattern in the evolution of the Helvetic segment of the northern Tethyan carbonate platform. Our data and correlations suggest that the latest Hauterivian witnessed the progressive installation of dysaerobic conditions in the Tethys, which went along with the onset in sediment condensation, phosphogenesis and platform drowning on the northern Tethyan margin, and which culminated in the Faraoni anoxic episode. This brief episode is followed by further episodes of dysaerobic conditions in the Tethys and the northwest German Basin, which became more frequent and progressively stronger in the late early Barremian. Platform drowning persisted and did not halt before the latest early Barremian. The

  14. Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Jiangan Xie

    Full Text Available M. bovis strain Bacillus Calmette-Guérin (BCG has been the only licensed live attenuated vaccine against tuberculosis (TB for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine. From 397 VAERS BCG AE case reports, we identified 64 AEs statistically significantly associated with the BCG TB vaccine and 14 AEs with the BCG cancer vaccine. Our meta-analysis of 41 peer-reviewed journal reports identified 48 AEs associated with the BCG TB vaccine and 43 AEs associated with the BCG cancer vaccine. Among all identified AEs from VAERS and literature reports, 25 AEs belong to serious AEs. The Ontology of Adverse Events (OAE-based ontological hierarchical analysis indicated that the AEs associated with the BCG TB vaccine were enriched in immune system (e.g., lymphadenopathy and lymphadenitis, skin (e.g., skin ulceration and cyanosis, and respiratory system (e.g., cough and pneumonia; in contrast, the AEs associated with the BCG cancer vaccine mainly occurred in the urinary system (e.g., dysuria, pollakiuria, and hematuria. With these distinct AE profiles detected, this study also discovered three AEs (i.e., chills, pneumonia, and C-reactive protein increased shared by the BCG TB vaccine and bladder cancer vaccine. Furthermore, our deep investigation of 24 BCG-associated death cases from VAERS identified the important effects of age, vaccine co-administration, and immunosuppressive status on the final BCG

  15. A review for identification of initiating events in event tree development process on nuclear power plants

    International Nuclear Information System (INIS)

    Riyadi, Eko H.

    2014-01-01

    Initiating event is defined as any event either internal or external to the nuclear power plants (NPPs) that perturbs the steady state operation of the plant, if operating, thereby initiating an abnormal event such as transient or loss of coolant accident (LOCA) within the NPPs. These initiating events trigger sequences of events that challenge plant control and safety systems whose failure could potentially lead to core damage or large early release. Selection for initiating events consists of two steps i.e. first step, definition of possible events, such as by evaluating a comprehensive engineering, and by constructing a top level logic model. Then the second step, grouping of identified initiating event's by the safety function to be performed or combinations of systems responses. Therefore, the purpose of this paper is to discuss initiating events identification in event tree development process and to reviews other probabilistic safety assessments (PSA). The identification of initiating events also involves the past operating experience, review of other PSA, failure mode and effect analysis (FMEA), feedback from system modeling, and master logic diagram (special type of fault tree). By using the method of study for the condition of the traditional US PSA categorization in detail, could be obtained the important initiating events that are categorized into LOCA, transients and external events

  16. A review for identification of initiating events in event tree development process on nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Riyadi, Eko H., E-mail: e.riyadi@bapeten.go.id [Center for Regulatory Assessment of Nuclear Installation and Materials, Nuclear Energy Regulatory Agency (BAPETEN), Jl. Gajah Mada 8 Jakarta 10120 (Indonesia)

    2014-09-30

    Initiating event is defined as any event either internal or external to the nuclear power plants (NPPs) that perturbs the steady state operation of the plant, if operating, thereby initiating an abnormal event such as transient or loss of coolant accident (LOCA) within the NPPs. These initiating events trigger sequences of events that challenge plant control and safety systems whose failure could potentially lead to core damage or large early release. Selection for initiating events consists of two steps i.e. first step, definition of possible events, such as by evaluating a comprehensive engineering, and by constructing a top level logic model. Then the second step, grouping of identified initiating event's by the safety function to be performed or combinations of systems responses. Therefore, the purpose of this paper is to discuss initiating events identification in event tree development process and to reviews other probabilistic safety assessments (PSA). The identification of initiating events also involves the past operating experience, review of other PSA, failure mode and effect analysis (FMEA), feedback from system modeling, and master logic diagram (special type of fault tree). By using the method of study for the condition of the traditional US PSA categorization in detail, could be obtained the important initiating events that are categorized into LOCA, transients and external events.

  17. Proteome analysis identifies the Dpr protein of Streptococcus mutans as an important factor in the presence of early streptococcal colonizers of tooth surfaces.

    Directory of Open Access Journals (Sweden)

    Akihiro Yoshida

    Full Text Available Oral streptococci are primary colonizers of tooth surfaces and Streptococcus mutans is the principal causative agent of dental caries in humans. A number of proteins are involved in the formation of monospecies biofilms by S. mutans. This study analyzed the protein expression profiles of S. mutans biofilms formed in the presence or absence of S. gordonii, a pioneer colonizer of the tooth surface, by two-dimensional gel electrophoresis (2-DE. After identifying S. mutans proteins by Mass spectrometric analysis, their expression in the presence of S. gordonii was analyzed. S. mutans was inoculated with or without S. gordonii DL1. The two species were compartmentalized using 0.2-μl Anopore membranes. The biofilms on polystyrene plates were harvested, and the solubilized proteins were separated by 2-DE. When S. mutans biofilms were formed in the presence of S. gordonii, the peroxide resistance protein Dpr of the former showed 4.3-fold increased expression compared to biofilms that developed in the absence of the pioneer colonizer. In addition, we performed a competition assay using S. mutans antioxidant protein mutants together with S. gordonii and other initial colonizers. Growth of the dpr-knockout S. mutans mutant was significantly inhibited by S. gordonii, as well as by S. sanguinis. Furthermore, a cell viability assay revealed that the viability of the dpr-defective mutant was significantly attenuated compared to the wild-type strain when co-cultured with S. gordonii. Therefore, these results suggest that Dpr might be one of the essential proteins for S. mutans survival on teeth in the presence of early colonizing oral streptococci.

  18. Proteome Analysis Identifies the Dpr Protein of Streptococcus mutans as an Important Factor in the Presence of Early Streptococcal Colonizers of Tooth Surfaces

    Science.gov (United States)

    Yoshida, Akihiro; Niki, Mamiko; Yamamoto, Yuji; Yasunaga, Ai; Ansai, Toshihiro

    2015-01-01

    Oral streptococci are primary colonizers of tooth surfaces and Streptococcus mutans is the principal causative agent of dental caries in humans. A number of proteins are involved in the formation of monospecies biofilms by S. mutans. This study analyzed the protein expression profiles of S. mutans biofilms formed in the presence or absence of S. gordonii, a pioneer colonizer of the tooth surface, by two-dimensional gel electrophoresis (2-DE). After identifying S. mutans proteins by Mass spectrometric analysis, their expression in the presence of S. gordonii was analyzed. S. mutans was inoculated with or without S. gordonii DL1. The two species were compartmentalized using 0.2-μl Anopore membranes. The biofilms on polystyrene plates were harvested, and the solubilized proteins were separated by 2-DE. When S. mutans biofilms were formed in the presence of S. gordonii, the peroxide resistance protein Dpr of the former showed 4.3-fold increased expression compared to biofilms that developed in the absence of the pioneer colonizer. In addition, we performed a competition assay using S. mutans antioxidant protein mutants together with S. gordonii and other initial colonizers. Growth of the dpr-knockout S. mutans mutant was significantly inhibited by S. gordonii, as well as by S. sanguinis. Furthermore, a cell viability assay revealed that the viability of the dpr-defective mutant was significantly attenuated compared to the wild-type strain when co-cultured with S. gordonii. Therefore, these results suggest that Dpr might be one of the essential proteins for S. mutans survival on teeth in the presence of early colonizing oral streptococci. PMID:25816242

  19. A working procedure for identifying emerging food safety issues at an early stage: Implications for European and international risk management practices

    NARCIS (Netherlands)

    Marvin, H.J.P.; Kleter, G.A.; Frewer, L.J.; Cope, S.F.; Wentholt, M.T.A.; Rowe, G.

    2009-01-01

    There is a need for early identification of emerging food safety issues in order to prevent them from developing into health risks. In this paper, various existing methods and procedures which can be used for early identification of safety issues are reviewed, including the monitoring of the

  20. Surveillance of vector populations and malaria transmission during the 2009/10 El Niño event in the western Kenya highlands: opportunities for early detection of malaria hyper-transmission

    Directory of Open Access Journals (Sweden)

    Wanjala Christine L

    2011-07-01

    Full Text Available Abstract Background Vector control in the highlands of western Kenya has resulted in a significant reduction of malaria transmission and a change in the vectorial system. Climate variability as a result of events such as El Niño increases the highlands suitability for malaria transmission. Surveillance and monitoring is an important component of early transmission risk identification and management. However, below certain disease transmission thresholds, traditional tools for surveillance such as entomological inoculation rates may become insensitive. A rapid diagnostic kit comprising Plasmodium falciparum circumsporozoite surface protein and merozoite surface protein antibodies in humans was tested for early detection of transmission surges in the western Kenya highlands during an El Niño event (October 2009-February 2010. Methods Indoor resting female adult malaria vectors were collected in western Kenya highlands in four selected villages categorized into two valley systems, the U-shaped (Iguhu and Emutete and the V-shaped valleys (Marani and Fort Ternan for eight months. Members of the Anopheles gambiae complex were identified by PCR. Blood samples were collected from children 6-15 years old and exposure to malaria was tested using a circum-sporozoite protein and merozoite surface protein immunchromatographic rapid diagnostic test kit. Sporozoite ELISA was conducted to detect circum-sporozoite protein, later used for estimation of entomological inoculation rates. Results Among the four villages studied, an upsurge in antibody levels was first observed in October 2009. Plasmodium falciparum sporozoites were then first observed in December 2009 at Iguhu village and February 2010 at Emutete. Despite the upsurge in Marani and Fort Ternan no sporozoites were detected throughout the eight month study period. The antibody-based assay had much earlier transmission detection ability than the sporozoite-based assay. The proportion of An. arabiensis

  1. Special Experts Meeting: Identifying and Overcoming Barriers to the Effective Consideration of Human and Organizational Factors in Event Analysis and Root Cause Analysis. Nuclear Energy Agency / Working Group on Human and Organizational Factors

    International Nuclear Information System (INIS)

    2011-01-01

    The main mission of the Nuclear Energy Agency (NEA) Working Group on Human and Organisational Factors (WGHOF) is to improve the understanding and treatment of human and organisational factors (HOF) within the nuclear industry in order to support the continued safety performance of nuclear installations and improve the effectiveness of regulatory practices in member countries. WGHOF developed a CSNI (Committee on the Safety of Nuclear Installations) Activity Proposal Sheet (CAPS) outlining the work and milestones necessary towards achieving the following objectives: - Identify barriers to analyzing and correctly identifying the Human and Organisational Factors (HOF) causes of events; - Identify barriers to implementing lessons learned from these analyses; and - Develop recommendations for overcoming these barriers to: improve the identification of HOF causes of events and support the successful implementation of appropriate corrective actions The CAPS can be found in Appendix A. The first activity under the plan was the development of a questionnaire. This was distributed to WGHOF members and their counterparts from the Working Group on Operating Experience (WGOE). The questionnaire was comprised of 20 questions based on the objectives of the CSNI Activity Proposed Sheet. The intended survey participants were licensees with previous experience conducting root cause analyses. Responses were received from 26 respondents from 11 different countries. The results of the questionnaire were analyzed to identify themes for further discussion during a specialist meeting planned for September 2009. The following themes were presented during the WGHOF meeting in March of 2009 and endorsed for further work: - Roles and Influence of Senior Management, - Skills and Knowledge of the Investigators, - Qualitative Nature of HOF, - Influence of the Regulator, - Systematic Approach to Investigation. A summary of the questionnaire responses is provided in Appendix B

  2. Florbetaben PET in the Early Diagnosis of Alzheimer's Disease: A Discrete Event Simulation to Explore Its Potential Value and Key Data Gaps

    Science.gov (United States)

    Guo, Shien; Getsios, Denis; Hernandez, Luis; Cho, Kelly; Lawler, Elizabeth; Altincatal, Arman; Lanes, Stephan; Blankenburg, Michael

    2012-01-01

    The growing understanding of the use of biomarkers in Alzheimer's disease (AD) may enable physicians to make more accurate and timely diagnoses. Florbetaben, a beta-amyloid tracer used with positron emission tomography (PET), is one of these diagnostic biomarkers. This analysis was undertaken to explore the potential value of florbetaben PET in the diagnosis of AD among patients with suspected dementia and to identify key data that are needed to further substantiate its value. A discrete event simulation was developed to conduct exploratory analyses from both US payer and societal perspectives. The model simulates the lifetime course of disease progression for individuals, evaluating the impact of their patient management from initial diagnostic work-up to final diagnosis. Model inputs were obtained from specific analyses of a large longitudinal dataset from the New England Veterans Healthcare System and supplemented with data from public data sources and assumptions. The analyses indicate that florbetaben PET has the potential to improve patient outcomes and reduce costs under certain scenarios. Key data on the use of florbetaben PET, such as its influence on time to confirmation of final diagnosis, treatment uptake, and treatment persistency, are unavailable and would be required to confirm its value. PMID:23326754

  3. Florbetaben PET in the Early Diagnosis of Alzheimer's Disease: A Discrete Event Simulation to Explore Its Potential Value and Key Data Gaps

    Directory of Open Access Journals (Sweden)

    Shien Guo

    2012-01-01

    Full Text Available The growing understanding of the use of biomarkers in Alzheimer's disease (AD may enable physicians to make more accurate and timely diagnoses. Florbetaben, a beta-amyloid tracer used with positron emission tomography (PET, is one of these diagnostic biomarkers. This analysis was undertaken to explore the potential value of florbetaben PET in the diagnosis of AD among patients with suspected dementia and to identify key data that are needed to further substantiate its value. A discrete event simulation was developed to conduct exploratory analyses from both US payer and societal perspectives. The model simulates the lifetime course of disease progression for individuals, evaluating the impact of their patient management from initial diagnostic work-up to final diagnosis. Model inputs were obtained from specific analyses of a large longitudinal dataset from the New England Veterans Healthcare System and supplemented with data from public data sources and assumptions. The analyses indicate that florbetaben PET has the potential to improve patient outcomes and reduce costs under certain scenarios. Key data on the use of florbetaben PET, such as its influence on time to confirmation of final diagnosis, treatment uptake, and treatment persistency, are unavailable and would be required to confirm its value.

  4. Extreme air pollution events in Hokkaido, Japan, traced back to early snowmelt and large-scale wildfires over East Eurasia: Case studies.

    Science.gov (United States)

    Yasunari, Teppei J; Kim, Kyu-Myong; da Silva, Arlindo M; Hayasaki, Masamitsu; Akiyama, Masayuki; Murao, Naoto

    2018-04-25

    To identify the unusual climate conditions and their connections to air pollutions in a remote area due to wildfires, we examine three anomalous large-scale wildfires in May 2003, April 2008, and July 2014 over East Eurasia, as well as how products of those wildfires reached an urban city, Sapporo, in the northern part of Japan (Hokkaido), significantly affecting the air quality. NASA's MERRA-2 (the Modern-Era Retrospective analysis for Research and Applications, Version 2) aerosol re-analysis data closely reproduced the PM 2.5 variations in Sapporo for the case of smoke arrival in July 2014. Results show that all three cases featured unusually early snowmelt in East Eurasia, accompanied by warmer and drier surface conditions in the months leading to the fires, inducing long-lasting soil dryness and producing climate and environmental conditions conducive to active wildfires. Due to prevailing anomalous synoptic-scale atmospheric motions, smoke from those fires eventually reached a remote area, Hokkaido, and worsened the air quality in Sapporo. In future studies, continuous monitoring of the timing of Eurasian snowmelt and the air quality from the source regions to remote regions, coupled with the analysis of atmospheric and surface conditions, may be essential in more accurately predicting the effects of wildfires on air quality.

  5. DNA methylation profiling of sorted cells from myelofibrosis patients reveals aberrant epigenetic regulation of immune pathways and identifies early MPN driver genes

    DEFF Research Database (Denmark)

    Nielsen, Helene Myrtue; Andersen, Christen Lykkegaard; Kristensen, Lasse Sommer

    2015-01-01

    Background: Primary myelofibrosis (PMF) belongs to the heterogeneous group of chronic myeloproliferative neoplasms (MPN) together with essential thrombocytosis (ET) and polycythemia vera (PV). It has been suggested that these neoplasms represent a biological continuum from early cancer stage (ET...

  6. Identifying functional network changing patterns in individuals at clinical high-risk for psychosis and patients with early illness schizophrenia: A group ICA study

    Directory of Open Access Journals (Sweden)

    Yuhui Du

    2018-01-01

    Full Text Available Although individuals at clinical high risk (CHR for psychosis exhibit a psychosis-risk syndrome involving attenuated forms of the positive symptoms typical of schizophrenia (SZ, it remains unclear whether their resting-state brain intrinsic functional networks (INs show attenuated or qualitatively distinct patterns of functional dysconnectivity relative to SZ patients. Based on resting-state functional magnetic imaging data from 70 healthy controls (HCs, 53 CHR individuals (among which 41 subjects were antipsychotic medication-naive, and 58 early illness SZ (ESZ patients (among which 53 patients took antipsychotic medication within five years of illness onset, we estimated subject-specific INs using a novel group information guided independent component analysis (GIG-ICA and investigated group differences in INs. We found that when compared to HCs, both CHR and ESZ groups showed significant differences, primarily in default mode, salience, auditory-related, visuospatial, sensory-motor, and parietal INs. Our findings suggest that widespread INs were diversely impacted. More than 25% of voxels in the identified significant discriminative regions (obtained using all 19 possible changing patterns excepting the no-difference pattern from six of the 15 interrogated INs exhibited monotonically decreasing Z-scores (in INs from the HC to CHR to ESZ, and the related regions included the left lingual gyrus of two vision-related networks, the right postcentral cortex of the visuospatial network, the left thalamus region of the salience network, the left calcarine region of the fronto-occipital network and fronto-parieto-occipital network. Compared to HCs and CHR individuals, ESZ patients showed both increasing and decreasing connectivity, mainly hypo-connectivity involving 15% of the altered voxels from four INs. The left supplementary motor area from the sensory-motor network and the right inferior occipital gyrus in the vision-related network showed a

  7. Transitional changes in microfossil assemblages in the Japan Sea from the Late Pliocene to Early Pleistocene related to global climatic and local tectonic events

    Science.gov (United States)

    Itaki, Takuya

    2016-12-01

    Many micropaleontological studies based on data from on-land sections, oil wells, and deep-sea drilling cores have provided important information about environmental changes in the Japan Sea that are related to the global climate and the local tectonics of the Japanese Islands. Here, major changes in the microfossil assemblages during the Late Pliocene to Early Pleistocene are reviewed. Late Pliocene (3.5-2.7 Ma) surface-water assemblages were characterized mainly by cold-temperate planktonic flora and fauna (nannofossils, diatoms, radiolarians, and planktonic foraminifera), suggesting that nutrient-rich North Pacific surface waters entered the Japan Sea via northern straits. The common occurrence of Pacific-type deep-water radiolarians during this period also suggests that deep water from the North Pacific entered the Japan Sea via the northern straits, indicating a sill depth >500 m. A weak warm-water influence is recognized along the Japanese coast, suggesting a small inflow of warm water via a southern strait. Nannofossil and sublittoral ostracod assemblages record an abrupt cooling event at 2.75 Ma that correlates with the onset of the Northern Hemisphere glaciation. Subsequ