Sample records for early phase protective

  1. Proactive Integration of Planetary Protection Needs Into Early Design Phases of Human Exploration Missions

    NASA Astrophysics Data System (ADS)

    Race, Margaret; Conley, Catharine

    discussed by the study participants to date have set the agenda for additional work that will continue for at least another year, culminating in a final report that should be useful to current and new nations and partnerships in planning human missions beyond LEO. In addition, over the past two years, NASA has made progress in integrating planetary protection considerations into mission designs along with other important human, environmental and science needs. Details about planetary protection have also been incorporated into the latest Addendum of the Design Reference Architecture (DRA) for human missions to Mars. Other ongoing studies of Mars human mission architecture, technologies and operations have likewise been integrating PP requirements and guidelines into cross-cutting measures of various types. An important objective of all these studies is to proactively gather and communicate PP information to the broad community of planners, engineers and assorted partners who are facing the challenges of future human exploration missions. By analyzing ways to integrate PP provisions effectively into early mission phases in synergism with other needs, these projects and studies will help ensure that all institutions and organizations avoid releasing harmful contamination on bodies with biological potential, thereby ensuring protection of the Earth and astronauts throughout their missions and safeguarding the integrity of science exploration—all in compliance with the 1967 Outer Space Treaty.

  2. Phase III of Early Restoration | NOAA Gulf Spill Restoration

    Science.gov Websites

    information about this phase of Early Restoration, including fact sheets on each project. The final Phase III 44 projects are documented in a final Record of Decision. Information about Phase III of Early Archive Home Phase III of Early Restoration Phase III of Early Restoration Beach habitat would be restored

  3. Phase III Early Restoration Public Meetings | NOAA Gulf Spill Restoration

    Science.gov Websites

    Archive Home Phase III Early Restoration Public Meetings Phase III Early Restoration Public Meetings share Posted on December 6, 2013 | Assessment and Early Restoration Restoration Area Title: Phase III Early on the draft plan for the third phase of Early Restoration, which proposes more than $625 million in

  4. Phase V of Early Restoration | NOAA Gulf Spill Restoration

    Science.gov Websites

    Phase V Early Restoration Plan and Environmental Assessment. The project will acquire land along Florida million. Phase V Early Restoration Plan and Environmental Assessment (pdf, 10 MB) Draft Phase V Early Restoration Plan and Environmental Assessment (Executive Summary) (2 MB) Phase V Fact Sheet (pdf, 2 MB) Gulf

  5. Phase IV of Early Restoration | NOAA Gulf Spill Restoration

    Science.gov Websites

    Trustees published the Final Phase IV Early Restoration Plan and Environmental Assessments. The plan habitats. Useful Links: Final Phase IV Early Restoration Plan and Environmental Assessments (pdf, 4.8 MB ) Final Phase IV Early Restoration Plan and Environmental Assessments Executive Summary (pdf, 729 KB

  6. Cytokine expression during early and late phase of acute Puumala hantavirus infection

    PubMed Central

    2011-01-01

    Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa . Conclusion High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection

  7. Gene expression profiles of Vibrio parahaemolyticus in the early stationary phase.

    PubMed

    Meng, L; Alter, T; Aho, T; Huehn, S

    2015-09-01

    Vibrio (V.) parahaemolyticus is an aquatic bacterium capable of causing foodborne gastroenteritis. In the environment or the food chain, V. parahaemolyticus cells are usually forced into the stationary phase, the common phase for bacterial survival in the environment. So far, little is known about whole genomic expression of V. parahaemolyticus in the early stationary phase compared with the exponential growth phase. We performed whole transcriptomic profiling of V. parahaemolyticus cells in both phases (exponential and early stationary phase). Our data showed in total that 172 genes were induced in early stationary phase, while 61 genes were repressed in early stationary phase compared with the exponential phase. Three functional categories showed stable gene expression in the early stationary phase. Eleven functional categories showed that up-regulation of genes was dominant over down-regulation in the early stationary phase. Although genes related to endogenous metabolism were repressed in the early stationary phase, massive regulation of gene expression occurred in the early stationary phase, indicating the expressed gene set of V. parahaemolyticus in the early stationary phase impacts environmental survival. Vibrio (V.) parahaemolyticus is one of the main bacterial causes of foodborne intestinal infections. This bacterium usually is forced into stationary phase in the environment, which includes, e.g. seafood. When bacteria are in stationary phase, physiological changes can lead to a resistance to many stresses, including physical and chemical challenges during food processing. To the best of our knowledge, highlighting the whole genome expression changes in the early stationary phase compared with exponential phase, as well as the investigation of physiological changes of V. parahaemolyticus such as the survival mechanism in the stationary phase has been the very first study in this field. © 2015 The Society for Applied Microbiology.

  8. Global Anomaly Detection in Two-Dimensional Symmetry-Protected Topological Phases

    NASA Astrophysics Data System (ADS)

    Bultinck, Nick; Vanhove, Robijn; Haegeman, Jutho; Verstraete, Frank

    2018-04-01

    Edge theories of symmetry-protected topological phases are well known to possess global symmetry anomalies. In this Letter we focus on two-dimensional bosonic phases protected by an on-site symmetry and analyze the corresponding edge anomalies in more detail. Physical interpretations of the anomaly in terms of an obstruction to orbifolding and constructing symmetry-preserving boundaries are connected to the cohomology classification of symmetry-protected phases in two dimensions. Using the tensor network and matrix product state formalism we numerically illustrate our arguments and discuss computational detection schemes to identify symmetry-protected order in a ground state wave function.

  9. Pharmacogenomics in early-phase clinical development

    PubMed Central

    Burt, Tal; Dhillon, Savita

    2015-01-01

    Pharmacogenomics (PGx) offers the promise of utilizing genetic fingerprints to predict individual responses to drugs in terms of safety, efficacy and pharmacokinetics. Early-phase clinical trial PGx applications can identify human genome variations that are meaningful to study design, selection of participants, allocation of resources and clinical research ethics. Results can inform later-phase study design and pipeline developmental decisions. Nevertheless, our review of the clinicaltrials.gov database demonstrates that PGx is rarely used by drug developers. Of the total 323 trials that included PGx as an outcome, 80% have been conducted by academic institutions after initial regulatory approval. Barriers for the application of PGx are discussed. We propose a framework for the role of PGx in early-phase drug development and recommend PGx be universally considered in study design, result interpretation and hypothesis generation for later-phase studies, but PGx results from underpowered studies should not be used by themselves to terminate drug-development programs. PMID:23837482

  10. Risk behaviours among early adolescents: risk and protective factors.

    PubMed

    Wang, Ruey-Hsia; Hsu, Hsiu-Yueh; Lin, Shu-Yuan; Cheng, Chung-Ping; Lee, Shu-Li

    2010-02-01

    This paper is a report of a study conducted to examine the influence of risk/protective factors on risk behaviours of early adolescents and whether protective factors moderate their impact. An understanding of how risk and protective factors operate to influence risk behaviours of early adolescents will better prepare nurses to perform interventions appropriately to reduce risk behaviours of early adolescents. A cross-sectional study was carried out, based on a sample of public junior high schools (from 7th to 9th grades) in one city and one county in Taiwan. An anonymous questionnaire designed to measure five risk factors, six protective factors and risk behaviours was administered from October 2006 to March 2007. Data from 878 students were used for the present analysis. Pearson's correlations, anova with random effect models, and generalized linear models were used to analyse the statistically significant explanatory variables for risk behaviours. Gender, perceived father's risk behaviour, perceived mother's risk behaviour, health self-efficacy, interaction of health self-efficacy and perceived peers' risk behaviour, and interaction of emotional regulation and perceived peers' risk behaviour were statistically significant explanatory variables of risk behaviours. Health self-efficacy and emotional regulation moderated the negative effects of peers' perceived risk behaviour on risk behaviours. All protective factors were negative statistically correlated with risk behaviours, and all risk factors positively statistically correlated with risk behaviours. Male adolescents should be considered an at-risk group for risk behaviour intervention. Nurses could provide early adolescents with training regarding health self-efficacy improvement, self-esteem enhancement, emotional regulation skills to reduce their risk behaviours.

  11. Computational Power of Symmetry-Protected Topological Phases.

    PubMed

    Stephen, David T; Wang, Dong-Sheng; Prakash, Abhishodh; Wei, Tzu-Chieh; Raussendorf, Robert

    2017-07-07

    We consider ground states of quantum spin chains with symmetry-protected topological (SPT) order as resources for measurement-based quantum computation (MBQC). We show that, for a wide range of SPT phases, the computational power of ground states is uniform throughout each phase. This computational power, defined as the Lie group of executable gates in MBQC, is determined by the same algebraic information that labels the SPT phase itself. We prove that these Lie groups always contain a full set of single-qubit gates, thereby affirming the long-standing conjecture that general SPT phases can serve as computationally useful phases of matter.

  12. Computational Power of Symmetry-Protected Topological Phases

    NASA Astrophysics Data System (ADS)

    Stephen, David T.; Wang, Dong-Sheng; Prakash, Abhishodh; Wei, Tzu-Chieh; Raussendorf, Robert

    2017-07-01

    We consider ground states of quantum spin chains with symmetry-protected topological (SPT) order as resources for measurement-based quantum computation (MBQC). We show that, for a wide range of SPT phases, the computational power of ground states is uniform throughout each phase. This computational power, defined as the Lie group of executable gates in MBQC, is determined by the same algebraic information that labels the SPT phase itself. We prove that these Lie groups always contain a full set of single-qubit gates, thereby affirming the long-standing conjecture that general SPT phases can serve as computationally useful phases of matter.

  13. Early Intervention Services for Early-Phase Psychosis - Centre for integrative psychiatry in Psychiatric Hospital "Sveti Ivan", Croatia.

    PubMed

    Matić, Katarina; Gereš, Natko; Gerlach, Josefina; Prskalo-Čule, Diana; Zadravec Vrbanc, Tihana; Lovretić, Vanja; Librenjak, Dina; Vuk Pisk, Sandra; Ivezić, Ena; Šimunović Filipčić, Ivona; Jeleč, Vjekoslav; Filipčić, Igor

    2018-06-01

    There is a growing body of evidence suggesting that early and effective management in the critical early years of schizophrenia can improve long-term outcomes. The objective of this study was to evaluate time to relapse of the patients with early-phase psychosis treated in the Centre for integrative psychiatry (CIP). We performed a retrospective cohort study on the sample of 373 early-phase psychosis patients admitted to Psychiatric Hospital "Sveti Ivan", Zagreb Croatia: from January 1, 2015 to December 31, 2017. The primary outcome was time to relapse. Patients who were admitted to group psychotherapeutic program after the end of acute treatment had 70% lower hazard for relapse (HR=0.30; 95% CI 0.16-0.58). Patients who were included first in the psychotherapeutic program and then treated and controlled in the daily hospital had 74% lower hazard for relapse (HR=0.26; 95% CI 0.10-0.67). In early-phase psychosis, integrative early intervention service has relevant beneficial effects compare to treatment as usual. These results justified the implementation of multimodal early intervention services in treatment of patients with early-phase psychosis.

  14. Quantum phase transition and protected ideal transport in a Kondo chain

    DOE PAGES

    Tsvelik, A. M.; Yevtushenko, O. M.

    2015-11-30

    We study the low energy physics of a Kondo chain where electrons from a one-dimensional band interact with magnetic moments via an anisotropic exchange interaction. It is demonstrated that the anisotropy gives rise to two different phases which are separated by a quantum phase transition. In the phase with easy plane anisotropy, Z2 symmetry between sectors with different helicity of the electrons is broken. As a result, localization effects are suppressed and the dc transport acquires (partial) symmetry protection. This effect is similar to the protection of the edge transport in time-reversal invariant topological insulators. The phase with easy axismore » anisotropy corresponds to the Tomonaga-Luttinger liquid with a pronounced spin-charge separation. The slow charge density wave modes have no protection against localizatioin.« less

  15. Sprayable Phase Change Coating Thermal Protection Material

    NASA Technical Reports Server (NTRS)

    Richardson, Rod W.; Hayes, Paul W.; Kaul, Raj

    2005-01-01

    NASA has expressed a need for reusable, environmentally friendly, phase change coating that is capable of withstanding the heat loads that have historically required an ablative thermal insulation. The Space Shuttle Program currently relies on ablative materials for thermal protection. The problem with an ablative insulation is that, by design, the material ablates away, in fulfilling its function of cooling the underlying substrate, thus preventing the insulation from being reused from flight to flight. The present generation of environmentally friendly, sprayable, ablative thermal insulation (MCC-l); currently use on the Space Shuttle SRBs, is very close to being a reusable insulation system. In actual flight conditions, as confirmed by the post-flight inspections of the SRBs, very little of the material ablates. Multi-flight thermal insulation use has not been qualified for the Space Shuttle. The gap that would have to be overcome in order to implement a reusable Phase Change Coating (PCC) is not unmanageable. PCC could be applied robotically with a spray process utilizing phase change material as filler to yield material of even higher strength and reliability as compared to MCC-1. The PCC filled coatings have also demonstrated potential as cryogenic thermal coatings. In experimental thermal tests, a thin application of PCC has provided the same thermal protection as a much thicker and heavier application of a traditional ablative thermal insulation. In addition, tests have shown that the structural integrity of the coating has been maintained and phase change performance after several aero-thermal cycles was not affected. Experimental tests have also shown that, unlike traditional ablative thermal insulations, PCC would not require an environmental seal coat, which has historically been required to prevent moisture absorption by the thermal insulation, prevent environmental degradation, and to improve the optical and aerodynamic properties. In order to reduce

  16. Porous protective solid phase micro-extractor sheath

    DOEpatents

    Andresen, Brian D.; Randich, Erik

    2005-03-29

    A porous protective sheath for active extraction media used in solid phase microextraction (SPME). The sheath permits exposure of the media to the environment without the necessity of extending a fragile coated fiber from a protective tube or needle. Subsequently, the sheath can pierce and seal with GC-MS septums, allowing direct injection of samples into inlet ports of analytical equipment. Use of the porous protective sheath, within which the active extraction media is contained, mitigates the problems of: 1) fiber breakage while the fiber is extended during sampling, 2) active media coating loss caused by physical contact of the bare fiber with the sampling environment; and 3) coating slough-off during fiber extension and retraction operations caused by rubbing action between the fiber and protective needle or tube.

  17. Phase III Early Restoration Meeting | NOAA Gulf Spill Restoration

    Science.gov Websites

    Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News Publications Press Releases Story programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

  18. Phase III Early Restoration Meeting - Pensacola, FL (rescheduled) | NOAA

    Science.gov Websites

    Restoration Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

  19. Guidelines for the use of protected/permissive left-turn phasing

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

    Agent, K.R.

    1987-07-01

    Turning left across opposing traffic at a signalized intersection could result in a traffic accident, as well as create motorist delay. A solution to the left-turn problem may be the addition of a left-turn phase when certain guidelines are met. After a decision has been made to add a left-turn phase, one of two basic alternative phasing methods is . In a previous research study, the results of replacing protected-only (exclusive) with protected/permissive (permissive) phasing at four trial intersections were studied. The permissive phasing provided a substantial reduction in delay and was popular with local drivers. However, several left-turn relatedmore » accidents occurred at those locations. Since those initial trial installations, permissive phasing has been used at several intersections across the state. This created a larger data base that could be used to determine when permissive phasing could be used without causing an accident problem. The objective of this study was to develop guidelines to aid traffic engineers in deciding whether permissive left-turn phasing is appropriate for use at a given location.« less

  20. Floquet Symmetry-Protected Topological Phases in Cold-Atom Systems

    NASA Astrophysics Data System (ADS)

    Potirniche, I.-D.; Potter, A. C.; Schleier-Smith, M.; Vishwanath, A.; Yao, N. Y.

    2017-09-01

    We propose and analyze two distinct routes toward realizing interacting symmetry-protected topological (SPT) phases via periodic driving. First, we demonstrate that a driven transverse-field Ising model can be used to engineer complex interactions which enable the emulation of an equilibrium SPT phase. This phase remains stable only within a parametric time scale controlled by the driving frequency, beyond which its topological features break down. To overcome this issue, we consider an alternate route based upon realizing an intrinsically Floquet SPT phase that does not have any equilibrium analog. In both cases, we show that disorder, leading to many-body localization, prevents runaway heating and enables the observation of coherent quantum dynamics at high energy densities. Furthermore, we clarify the distinction between the equilibrium and Floquet SPT phases by identifying a unique micromotion-based entanglement spectrum signature of the latter. Finally, we propose a unifying implementation in a one-dimensional chain of Rydberg-dressed atoms and show that protected edge modes are observable on realistic experimental time scales.

  1. Metacognition in Early Phase Psychosis: Toward Understanding Neural Substrates

    PubMed Central

    Vohs, Jenifer L.; Hummer, Tom A.; Yung, Matthew G.; Francis, Michael M.; Lysaker, Paul H.; Breier, Alan

    2015-01-01

    Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis. PMID:26132568

  2. Prethermal Phases of Matter Protected by Time-Translation Symmetry

    NASA Astrophysics Data System (ADS)

    Else, Dominic V.; Bauer, Bela; Nayak, Chetan

    2017-01-01

    In a periodically driven (Floquet) system, there is the possibility for new phases of matter, not present in stationary systems, protected by discrete time-translation symmetry. This includes topological phases protected in part by time-translation symmetry, as well as phases distinguished by the spontaneous breaking of this symmetry, dubbed "Floquet time crystals." We show that such phases of matter can exist in the prethermal regime of periodically driven systems, which exists generically for sufficiently large drive frequency, thereby eliminating the need for integrability or strong quenched disorder, which limited previous constructions. We prove a theorem that states that such a prethermal regime persists until times that are nearly exponentially long in the ratio of certain couplings to the drive frequency. By similar techniques, we can also construct stationary systems that spontaneously break continuous time-translation symmetry. Furthermore, we argue that for driven systems coupled to a cold bath, the prethermal regime could potentially persist to infinite time.

  3. Design Tools for Cost-Effective Implementation of Planetary Protection Requirements

    NASA Technical Reports Server (NTRS)

    Hamlin, Louise; Belz, Andrea; Evans, Michael; Kastner, Jason; Satter, Celeste; Spry, Andy

    2006-01-01

    Since the Viking missions to Mars in the 1970s, accounting for the costs associated with planetary protection implementation has not been done systematically during early project formulation phases, leading to unanticipated costs during subsequent implementation phases of flight projects. The simultaneous development of more stringent planetary protection requirements, resulting from new knowledge about the limits of life on Earth, together with current plans to conduct life-detection experiments on a number of different solar system target bodies motivates a systematic approach to integrating planetary protection requirements and mission design. A current development effort at NASA's Jet Propulsion Laboratory is aimed at integrating planetary protection requirements more fully into the early phases of mission architecture formulation and at developing tools to more rigorously predict associated cost and schedule impacts of architecture options chosen to meet planetary protection requirements.

  4. Minimalist approach to the classification of symmetry protected topological phases

    NASA Astrophysics Data System (ADS)

    Xiong, Zhaoxi

    A number of proposals with differing predictions (e.g. group cohomology, cobordisms, group supercohomology, spin cobordisms, etc.) have been made for the classification of symmetry protected topological (SPT) phases. Here we treat various proposals on equal footing and present rigorous, general results that are independent of which proposal is correct. We do so by formulating a minimalist Generalized Cohomology Hypothesis, which is satisfied by existing proposals and captures essential aspects of SPT classification. From this Hypothesis alone, formulas relating classifications in different dimensions and/or protected by different symmetry groups are derived. Our formalism is expected to work for fermionic as well as bosonic phases, Floquet as well as stationary phases, and spatial as well as on-site symmetries.

  5. Robust symmetry-protected metrology with the Haldane phase

    NASA Astrophysics Data System (ADS)

    Bartlett, Stephen D.; Brennen, Gavin K.; Miyake, Akimasa

    2018-01-01

    We propose a metrology scheme that is made robust to a wide range of noise processes by using the passive, error-preventing properties of symmetry-protected topological phases. The so-called fractionalized edge mode of an antiferromagnetic Heisenberg spin-1 chain in a rotationally- symmetric Haldane phase can be used to measure the direction of an unknown electric field, by exploiting the way in which the field direction reduces the symmetry of the chain. Specifically, the direction (and when supplementing with a known background field, also the strength) of the field is registered in the holonomy under an adiabatic sensing protocol, and the degenerate fractionalized edge mode is protected through this process by the remaining reduced symmetry. We illustrate the scheme with respect to a potential realization by Rydberg dressed atoms.

  6. Classification of symmetry-protected phases for interacting fermions in two dimensions

    NASA Astrophysics Data System (ADS)

    Cheng, Meng; Bi, Zhen; You, Yi-Zhuang; Gu, Zheng-Cheng

    2018-05-01

    Recently, it has been established that two-dimensional bosonic symmetry-protected topological (SPT) phases with on-site unitary symmetry G can be completely classified by the group cohomology H3( G ,U (1 ) ) . Later, group supercohomology was proposed as a partial classification for SPT phases of interacting fermions. In this work, we revisit this problem based on the algebraic theory of symmetry and defects in two-dimensional topological phases. We reproduce the partial classifications given by group supercohomology, and we also show that with an additional H1(G ,Z2) structure, a complete classification of SPT phases for two-dimensional interacting fermion systems with a total symmetry group G ×Z2f is obtained. We also discuss the classification of interacting fermionic SPT phases protected by time-reversal symmetry.

  7. Force Protection Basing: Fact Sheet

    DTIC Science & Technology

    2017-11-29

    experimentation and demonstrations during FY15. The FY16 demonstration assessed the capability to protect a contingency base within objective metrics for time and...protection technologies 2 had baseline capabilities assessed in early FY15; followed by integration experimentation and demonstrations during FY15...included DOTMLPF integration and the finalization of CONOPs and TTPs for basing protection using experimental data. CONOPs/TTPs for the phases of

  8. Effectiveness of Child Protection Training for Pre-Service Early Childhood Educators

    ERIC Educational Resources Information Center

    McKee, Bronagh E.; Dillenburger, Karola

    2012-01-01

    International evidence confirms that early childhood educators can enter professional practice unprepared for child protection due to inadequate pre-service preparation. This paper makes an original contribution by using the Child Protection Questionnaire for Educators (CPQE) to examine the pre- and post-intervention child maltreatment and…

  9. Fluctuation-driven electroweak phase transition. [in early universe

    NASA Technical Reports Server (NTRS)

    Gleiser, Marcelo; Kolb, Edward W.

    1992-01-01

    We examine the dynamics of the electroweak phase transition in the early Universe. For Higgs masses in the range 46 less than or = M sub H less than or = 150 GeV and top quark masses less than 200 GeV, regions of symmetric and asymmetric vacuum coexist to below the critical temperature, with thermal equilibrium between the two phases maintained by fluctuations of both phases. We propose that the transition to the asymmetric vacuum is completed by percolation of these subcritical fluctuations. Our results are relevant to scenarios of baryogenesis that invoke a weakly first-order phase transition at the electroweak scale.

  10. String order parameters for one-dimensional Floquet symmetry protected topological phases

    NASA Astrophysics Data System (ADS)

    Kumar, Ajesh; Dumitrescu, Philipp T.; Potter, Andrew C.

    2018-06-01

    Floquet symmetry protected topological (FSPT) phases are nonequilibrium topological phases enabled by time-periodic driving. FSPT phases of one-dimensional (1D) chains of bosons, spins, or qubits host dynamically protected edge states that can store quantum information without decoherence, making them promising for use as quantum memories. While FSPT order cannot be detected by any local measurement, here we construct nonlocal string order parameters that directly measure general 1D FSPT order. We propose a superconducting-qubit array based realization of the simplest Ising FSPT phase, which can be implemented with existing quantum computing hardware. We devise an interferometric scheme to directly measure the nonlocal string order using only simple one- and two-qubit operations and single-qubit measurements.

  11. Safety and Efficacy of the ACE-Inhibitor Ramipril in Alport Syndrome: The Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase III EARLY PRO-TECT Alport Trial in Pediatric Patients.

    PubMed

    Gross, Oliver; Friede, Tim; Hilgers, Reinhard; Görlitz, Anke; Gavénis, Karsten; Ahmed, Raees; Dürr, Ulrike

    2012-01-01

    Introduction. Retrospective observational data show that ACE-inhibitor therapy delays renal failure and improves life expectancy in Alport patients with proteinuria. The EARLY PRO-TECT Alport trial assesses the safety and efficacy of early therapy onset with ramipril in pediatric Alport patients. Methods and analysis. This double-blind, randomized, placebo-controlled, multicenter phase III trial (NCT01485978; EudraCT-number 2010-024300-10) includes 120 pediatric patients aged 24 months to 18 years with early stages of Alport syndrome (isolated hematuria or microalbuminuria). From March 2012, up to 80 patients will be randomized 1:1 to ramipril or placebo. In the event of disease progression during 3-year treatment, patients are unblinded and ramipril is initiated, if applicable. Approximately 40 patients receive open-label ramipril contributing to the safety database. Primary end-points are "time to progression to next disease level" and "incidence of adverse drug events before disease progression." Treatment effect estimates from the randomized comparison and Alport registry data will be combined in supportive analyses to maximize evidence. Conclusion. Without this trial, ACE inhibitors may become standard off-label treatment in Alport syndrome without satisfactory evidence base. The results are expected to be of relevance for therapy of all pediatric patients with kidney disease, and the trial protocol might serve as a model for other rare pediatric glomerulopathies.

  12. Possible realization of interacting symmetry-protected topological phases in topological crystalline insulators

    NASA Astrophysics Data System (ADS)

    Isobe, Hiroki; Fu, Liang

    2015-03-01

    The effects of electron-electron interaction in edge states of mirror-symmetry protected topological crystalline insulators (TCI's) are discussed. The analysis is performed by using bosonized Hamiltonian following the Tomonaga-Luttinger liquid theory. When two pairs of helical edge states exist, electron-electron interaction could gap out one edge mode, which is a possible realization of interacting symmetry-protected topological (SPT) phases. This type of SPT phase is closely related to a Luther-Emery liquid in spinful 1D system. We also propose a method of detecting the SPT phases by STM. The other focus of the study is the classification of SPT phases in mirror-symmetry protected TCI's. By adopting the Chern-Simons theory, we find that electron-electron interaction reduces the classification from Z to Z4. It means that the edge states can be gapped out when four pairs of edge states exist. In other cases, the edge modes cannot be fully gapped. Each of these states corresponds to a different SPT phase depending on the relevant interaction process.

  13. Predicting Reading Disability: Early Cognitive Risk and Protective Factors

    ERIC Educational Resources Information Center

    Eklund, Kenneth Mikael; Torppa, Minna; Lyytinen, Heikki

    2013-01-01

    This longitudinal study examined early cognitive risk and protective factors for Grade 2 reading disability (RD). We first examined the reading outcome of 198 children in four developmental cognitive subgroups that were identified in our previous analysis: dysfluent trajectory, declining trajectory, unexpected trajectory and typical trajectory. We…

  14. Immunization of pregnant women: Future of early infant protection

    PubMed Central

    Faucette, Azure N; Pawlitz, Michael D; Pei, Bo; Yao, Fayi; Chen, Kang

    2015-01-01

    Children in early infancy do not mount effective antibody responses to many vaccines against commons infectious pathogens, which results in a window of increased susceptibility or severity infections. In addition, vaccine-preventable infections are among the leading causes of morbidity in pregnant women. Immunization during pregnancy can generate maternal immune protection as well as elicit the production and transfer of antibodies cross the placenta and via breastfeeding to provide early infant protection. Several successful vaccines are now recommended to all pregnant women worldwide. However, significant gaps exist in our understanding of the efficacy and safety of other vaccines and in women with conditions associated with increased susceptible to high-risk pregnancies. Public acceptance of maternal immunization remained to be improved. Broader success of maternal immunization will rely on the integration of advances in basic science in vaccine design and evaluation and carefully planned clinical trials that are inclusive to pregnant women. PMID:26366844

  15. Volunteering for early phase gene transfer research in Parkinson disease.

    PubMed

    Kim, S Y H; Holloway, R G; Frank, S; Beck, C A; Zimmerman, C; Wilson, R; Kieburtz, K

    2006-04-11

    For early phase trials of novel interventions-such as gene transfer for Parkinson disease (PD)--whose focus is primarily on safety and tolerability, it is important that participants have a realistic understanding of the goals of such research. Recently, some have expressed concern that patients with PD may have unrealistic expectations. The authors examined why patients with PD might volunteer for invasive early phase research by interviewing 92 patients with PD and comparing those who would (n = 46) and those who would not (n = 46) participate in a hypothetical phase I gene-transfer study. The two groups' demographic, clinical, functional, and quality of life measures, as well as their understanding of the research protocol, were similar. The groups did not differ on their perception of potential for personal benefit nor on the level of likelihood of benefit they saw as a precondition for volunteering. However, those willing to participate tended to perceive lower probability of risk, were tolerant of greater probability of risk, and were more optimistic about the phase I study's potential benefits to society. They also appeared more decisive and action-oriented than the unwilling group. It is likely that the decision whether to participate in early phase PD gene transfer studies will depend mostly on patients' attitudes regarding risk, optimism about science, and an action orientation, rather than on their clinical, functional, or demographic characteristics.

  16. Implementing Effective Mission Systems Engineering Practices During Early Project Formulation Phases

    NASA Technical Reports Server (NTRS)

    Moton, Tryshanda

    2016-01-01

    Developing and implementing a plan for a NASA space mission can be a complicated process. The needs, goals, and objectives of any proposed mission or technology must be assessed early in the Project Life Cycle. The key to successful development of a space mission or flight project is the inclusion of systems engineering in early project formulation, namely during Pre-phase A, Phase A, and Phase B of the NASA Project Life Cycle. When a space mission or new technology is in pre-development, or "pre-Formulation", feasibility must be determined based on cost, schedule, and risk. Inclusion of system engineering during project formulation is key because in addition to assessing feasibility, design concepts are developed and alternatives to design concepts are evaluated. Lack of systems engineering involvement early in the project formulation can result in increased risks later in the implementation and operations phases of the project. One proven method for effective systems engineering practice during the pre-Formulation Phase is the use of a mission conceptual design or technology development laboratory, such as the Mission Design Lab (MDL) at NASA's Goddard Space Flight Center (GSFC). This paper will review the engineering process practiced routinely in the MDL for successful mission or project development during the pre-Formulation Phase.

  17. Topological phases protected by point group symmetry

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

    Song, Hao; Huang, Sheng -Jie; Fu, Liang

    We consider symmetry-protected topological (SPT) phases with crystalline point group symmetry, dubbed point group SPT (pgSPT) phases. We show that such phases can be understood in terms of lower-dimensional topological phases with on-site symmetry and that they can be constructed as stacks and arrays of these lower-dimensional states. This provides the basis for a general framework to classify and characterize bosonic and fermionic pgSPT phases, which can be applied for arbitrary crystalline point group symmetry and in arbitrary spatial dimensions. We develop and illustrate this framework by means of a few examples, focusing on three-dimensional states. We classify bosonic pgSPTmore » phases and fermionic topological crystalline superconductors with Z P 2 (reflection) symmetry, electronic topological crystalline insulators (TCIs) with U(1)×Z P 2 symmetry, and bosonic pgSPT phases with C 2v symmetry, which is generated by two perpendicular mirror reflections. We also study surface properties, with a focus on gapped, topologically ordered surface states. For electronic TCIs, we find a Z 8 × Z 2 classification, where the Z 8 corresponds to known states obtained from noninteracting electrons, and the Z 2 corresponds to a “strongly correlated” TCI that requires strong interactions in the bulk. Lastly, our approach may also point the way toward a general theory of symmetry-enriched topological phases with crystalline point group symmetry.« less

  18. The usage of phase change materials in fire fighter protective clothing: its effect on thermal protection

    NASA Astrophysics Data System (ADS)

    Zhao, Mengmeng

    2017-12-01

    The thermal protective performance of the fire fighter protective clothing is of vital importance for fire fighters. In the study fabrics treated by phase change materials (PCMs) were applied in the multi-layered fabrics of the fire fighter protective clothing ensemble. The PCM fabrics were placed at the different layers of the clothing and their thermal protective performance were measured by a TPP tester. Results show that with the application of the PCM fabrics the thermal protection of the multi-layered fabrics was greatly increased. The time to reach a second degree burn was largely reduced. The location of the PCM fabrics at the different layers did not affect much on the thermal protective performance. The higher amount of the PCM adds on, the higher thermal protection was brought. The fabrics with PCMs of a higher melting temperature could contribute to higher thermal protection.

  19. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

  20. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

  1. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

  2. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

  3. 40 CFR 76.8 - Early election for Group 1, Phase II boilers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

  4. Phase III Early Restoration Meeting - Corpus Christi, TX | NOAA Gulf Spill

    Science.gov Websites

    Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

  5. TRAVELLERS: a school-based early intervention programme helping young people manage and process change, loss and transition. Pilot phase findings.

    PubMed

    Dickinson, Pauline; Coggan, Carolyn; Bennett, Sara

    2003-06-01

    This paper outlines the conceptual background and findings from the pilot phase of TRAVELLERS--an early intervention programme designed to enhance protective factors for young people experiencing change, loss and transition events and early signs of emotional distress. The pilot study aimed to determine whether TRAVELLERS was a feasible, acceptable and promising intervention for young people within secondary schools in Aotearoa/New Zealand. The conceptual origins of the TRAVELLERS programme are described in terms of: adolescent mental health concerns; emerging mental health promotion theory and practice; and prevention and early intervention models. The key elements of the TRAVELLERS programme are described. The programme was piloted in two secondary schools, one rural and one urban with 34 participants (females n = 24, males n = 10). Evaluation methods included: review of programme materials; identification of potential selection tools appropriate to Year 9 students; analysis of selection questionnaire; and conduct of feedback from participants, facilitators and parents/caregivers. The TRAVELLERS programme provides a means of identifying and selecting young people who may benefit from participating in an early intervention programme. The programme has achieved a statistically significant reduction in participants' distress (p < 0.01). Young people were overwhelmingly enthusiastic about most aspects of TRAVELLERS. School personnel reported that TRAVELLERS was an appropriate and acceptable programme to the school. Targeted interventions provided within a supportive school environment can contribute to enhancing protective factors such as personal and interpersonal coping strategies, increased help-seeking behaviour, and young people feeling more positive about themselves and their lives. The pilot programme has been amended and prepared for a two year trial phase in 10 secondary schools during 2002-2003.

  6. Phase III Early Restoration Meeting - Lake Charles, LA | NOAA Gulf Spill

    Science.gov Websites

    Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News early restoration planning for Phase III and future early restoration plans. Open House: 5:30pm Public

  7. Left-turn phase: permissive, protected, or both? A quasi-experimental design in New York City.

    PubMed

    Chen, Li; Chen, Cynthia; Ewing, Reid

    2015-03-01

    The practice of left-turn phasing selection (permissive, protected-only, or both) varies from one locality to another. The literature evidence on this issue is equally mixed and insufficient. In this study, we evaluate the safety impacts of changing left-turn signal phasing from permissive to protected/permissive or protected-only at 68 intersections in New York City using a rigorous quasi-experimental design accompanied with regression modeling. Changes in police reported crashes including total crashes, multiple-vehicle crashes, left-turn crashes, pedestrian crashes and bicyclist crashes were compared between before period and after period for the treatment group and comparison group by means of negative binomial regression using a Generalized Estimating Equations (GEE) technique. Confounding factors such as the built environment characteristics that were not controlled in comparison group selection are accounted for by this approach. The results show that the change of permissive left-turn signal phasing to protected/permissive or protected-only signal phasing does not result in a significant reduction in intersection crashes. Though the protected-only signal phasing does reduce the left-turn crashes and pedestrian crashes, this reduction was offset by a possible increase in over-taking crashes. These results suggest that left-turn phasing should not be treated as a universal solution that is always better than the permissive control for left-turn vehicles. The selection and implementation of left-turn signal phasing needs to be done carefully, considering potential trade-offs between safety and delay, and many other factors such as geometry, traffic flows and operations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Early visual processing is enhanced in the midluteal phase of the menstrual cycle.

    PubMed

    Lusk, Bethany R; Carr, Andrea R; Ranson, Valerie A; Bryant, Richard A; Felmingham, Kim L

    2015-12-01

    Event-related potential (ERP) studies have revealed an early attentional bias in processing unpleasant emotional images in women. Recent neuroimaging data suggests there are significant differences in cortical emotional processing according to menstrual phase. This study examined the impact of menstrual phase on visual emotional processing in women compared to men. ERPs were recorded from 28 early follicular women, 29 midluteal women, and 27 men while they completed a passive viewing task of neutral and low- and high- arousing pleasant and unpleasant images. There was a significant effect of menstrual phase in early visual processing, as midluteal women displayed significantly greater P1 amplitude at occipital regions to all visual images compared to men. Both midluteal and early follicular women displayed larger N1 amplitudes than men (although this only reached significance for the midluteal group) to the visual images. No sex or menstrual phase differences were apparent in later N2, P3, or LPP. A condition effect demonstrated greater P3 and LPP amplitude to highly-arousing unpleasant images relative to all other stimuli conditions. These results indicate that women have greater early automatic visual processing compared to men, and suggests that this effect is particularly strong in women in the midluteal phase at the earliest stage of visual attention processing. Our findings highlight the importance of considering menstrual phase when examining sex differences in the cortical processing of visual stimuli. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Statistical controversies in clinical research: early-phase adaptive design for combination immunotherapies.

    PubMed

    Wages, N A; Slingluff, C L; Petroni, G R

    2017-04-01

    In recent years, investigators have asserted that the 3 + 3 design lacks flexibility, making its use in modern early-phase trial settings, such as combinations and/or biological agents, inefficient. More innovative approaches are required to address contemporary research questions, such as those posed in trials involving immunotherapies. We describe the implementation of an adaptive design for identifying an optimal treatment regimen, defined by low toxicity and high immune response, in an early-phase trial of a melanoma helper peptide vaccine plus novel adjuvant combinations. Operating characteristics demonstrate the ability of the method to effectively recommend optimal regimens in a high percentage of trials with reasonable sample sizes. The proposed design is a practical, early-phase, adaptive method for use with combined immunotherapy regimens. This design can be applied more broadly to early-phase combination studies, as it was used in an ongoing study of two small molecule inhibitors in relapsed/refractory mantle cell lymphoma. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. [Effect of immune modulation on immunogenic and protective activity of a live plague vaccine].

    PubMed

    Karal'nik, B V; Ponomareva, T S; Deriabin, P N; Denisova, T G; Mel'nikova, N N; Tugambaev, T I; Atshabar, B B; Zakarian, S B

    2014-01-01

    Comparative evaluation of the effect of polyoxidonium and betaleukin on immunogenic and protective activity of a live plague vaccine in model animal experiments. Plague vaccine EV, polyoxidonium, betaleukin, erythrocytic antigenic diagnosticum for determination of F1 antibodies and immune reagents for detection of lymphocytes with F1 receptors (LFR) in adhesive test developed by the authors were used. The experiments were carried out in 12 rabbits and 169 guinea pigs. Immune modulation accelerated the appearance and disappearance of LFR (early phase) and ensured a more rapid and intensive antibody formation (effector phase). Activation by betaleukin is more pronounced than by polyoxidonium. The more rapid and intensive was the development of early phase, the more effective was antibody response to the vaccine. Immune modulation in the experiment with guinea pigs significantly increased protective activity of the vaccine. The use of immune modulators increased immunogenic (in both early and effector phases of antigen-specific response) and protective activity of the EV vaccine. A connection between the acceleration of the first phase of antigen-specific response and general intensity of effector phase of immune response to the EV vaccine was detected. ,

  11. Determinants of Cancer Early Detection Behaviors:Application of Protection Motivation Theory.

    PubMed

    Rahaei, Zohreh; Ghofranipour, Fazlollah; Morowatisharifabad, Mohammad Ali; Mohammadi, Eesa

    2015-01-01

    Cancer is account for 13% of all deaths around the world and is the third cause of mortality in Iran. More than one third of these cases are pre-ventable and about 33% are curable with early detection. The aim of this study was to determine the predictors of cancer early detection (CED) behaviors applying Protection Motivation Theory (PMT). In this cross-sectional study, cluster sampling method was employed to recruit 260 individuals of above 20 years old in Yazd, Iran and a researcher designed questionnaire was completed through interviews for each of the respondents. PMT theoretical variables and CED behaviors were the basis of data collection procedure. Participants acquired 64.47% of the protection motivation, 30.97% of the passive and 45.64% of the active behaviors‟ possible scores. Theory constructs predicted 19.8%, 15.6% and 9.6% of the variations for protection motivation, passive and active behavior respectively. Protection motivation was responsible for 3.6% of passive and 8% of active behaviors‟ variations. Considering the scarceness of CED behaviors and the applicability of PMT in predicting these behaviors, utilization of the PMT‟s constructs in any interventional programs to accelerate CED behaviors could be an alternate methodological choice in the cancer control initiatives.

  12. The phase transitions between Z n × Z n bosonic topological phases in 1 + 1D, and a constraint on the central charge for the critical points between bosonic symmetry protected topological phases

    DOE PAGES

    Tsui, Lokman; Huang, Yen-Ta; Jiang, Hong-Chen; ...

    2017-03-27

    The study of continuous phase transitions triggered by spontaneous symmetry breaking has brought revolutionary ideas to physics. Recently, through the discovery of symmetry protected topological phases, it is realized that continuous quantum phase transition can also occur between states with the same symmetry but different topology. Here in this paper we study a specific class of such phase transitions in 1+1 dimensions – the phase transition between bosonic topological phases protected by Z n × Z n. We find in all cases the critical point possesses two gap opening relevant operators: one leads to a Landau-forbidden symmetry breaking phase transitionmore » and the other to the topological phase transition. We also obtained a constraint on the central charge for general phase transitions between symmetry protected bosonic topological phases in 1+1D.« less

  13. The phase transitions between Z n × Z n bosonic topological phases in 1 + 1D, and a constraint on the central charge for the critical points between bosonic symmetry protected topological phases

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

    Tsui, Lokman; Huang, Yen-Ta; Jiang, Hong-Chen

    The study of continuous phase transitions triggered by spontaneous symmetry breaking has brought revolutionary ideas to physics. Recently, through the discovery of symmetry protected topological phases, it is realized that continuous quantum phase transition can also occur between states with the same symmetry but different topology. Here in this paper we study a specific class of such phase transitions in 1+1 dimensions – the phase transition between bosonic topological phases protected by Z n × Z n. We find in all cases the critical point possesses two gap opening relevant operators: one leads to a Landau-forbidden symmetry breaking phase transitionmore » and the other to the topological phase transition. We also obtained a constraint on the central charge for general phase transitions between symmetry protected bosonic topological phases in 1+1D.« less

  14. Proteomic analysis of early phase of conidia germination in Aspergillus nidulans.

    PubMed

    Oh, Young Taek; Ahn, Chun-Seob; Kim, Jeong Geun; Ro, Hyeon-Su; Lee, Chang-Won; Kim, Jae Won

    2010-03-01

    In order to investigate proteins involved in early phase of conidia germination, proteomic analysis was performed using two-dimensional gel electrophoresis (2D-GE) in conjunction with MALDI-TOF mass spectrometry (MS). The expression levels of 241 proteins varied quantitatively with statistical significance (P<0.05) at the early phase of the germination stage. Out of these 57 were identified by MALDI-TOF MS. Through classification of physiological functions from Conserved Domain Database analysis, among the identified proteins, 21, 13, and 6 proteins were associated with energy metabolism, protein synthesis, and protein folding process, respectively. Interestingly, eight proteins, which are involved in detoxification of reactive oxygen species (ROS) including catalase A, thioredoxin reductase, and mitochondrial peroxiredoxin, were also identified. The expression levels of the genes were further confirmed using Northern blot and reverse transcriptase (RT)-PCR analyses. This study represents the first proteomic analysis of early phase of conidia germination and will contribute to a better understanding of the molecular events involved in conidia germination process. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  15. Baseline survey of sun-protection knowledge, practices and policy in early childhood settings in Queensland, Australia.

    PubMed

    Harrison, Simone L; Saunders, V; Nowak, M

    2007-04-01

    Excessive exposure to sunlight during early childhood increases the risk of developing skin cancer. Self-administered questionnaires exploring sun-protection knowledge, practices and policy were mailed to the directors/coordinators/senior teachers of all known early childhood services in Queensland, Australia, in 2002 (n = 1383; 56.5% response). Most (73.7%) services had a written sun-protection policy (SPP). However, 40.6% of pre-schools and kindergartens had not developed a written SPP. Most directors had moderate knowledge about sun-protection (median score: 7/12 [IQR 6, 8]), but few understood the UV index, the sun-protection factor rating for sunscreens or the association between childhood sun-exposure, mole development and melanoma. Pre-school teachers had lower knowledge scores than directors of long day care centers and other services (P = 0.0005). Staff members reportedly wore sun-protective hats, clothing and sunglasses more often than children. However, sunscreen use was higher among children than staff. Directors' knowledge scores predicted reported hat, clothing, sunscreen and shade utilization among children. Remoteness impacted negatively on director's knowledge (P = 0.043) and written SPP development (P = 0.0005). Higher composite sun-protection scores were reported for children and staff from services with written sun-protection policies. SPP development and increased sun-protection knowledge of directors may improve reported sun-protective behaviors of children and staff of early childhood services.

  16. Symmetry-protected topological phases with uniform computational power in one dimension

    NASA Astrophysics Data System (ADS)

    Raussendorf, Robert; Wang, Dong-Sheng; Prakash, Abhishodh; Wei, Tzu-Chieh; Stephen, David T.

    2017-07-01

    We investigate the usefulness of ground states of quantum spin chains with symmetry-protected topological order (SPTO) for measurement-based quantum computation. We show that, in spatial dimension 1, if an SPTO phase protects the identity gate, then, subject to an additional symmetry condition that is satisfied in all cases so far investigated, it can also be used for quantum computation.

  17. Selective Prevention Approaches to Build Protective Factors in Early Intervention

    ERIC Educational Resources Information Center

    Shapiro, Cheri J.

    2014-01-01

    Young children with disabilities may be at elevated risk for behavior problems as well as maltreatment. preventive approaches that can be infused into early intervention services are needed to support parents, build competencies among young children, and enhance protective factors that may temper risk. Two interventions--Stepping Stones Triple P,…

  18. Acute lipophilicity-dependent effect of intravascular simvastatin in the early phase of focal cerebral ischemia.

    PubMed

    Beretta, S; Pastori, C; Sala, G; Piazza, F; Ferrarese, C; Cattalini, A; de Curtis, M; Librizzi, L

    2011-05-01

    The acute effects of simvastatin lactone (lipophilic) and simvastatin acid (hydrophilic) on transient focal ischemia were assessed using the isolated guinea pig brain maintained in vitro by arterial perfusion. This new model of cerebral ischemia allows the assessment of the very early phase of the ischemic process, with the functional preservation of the vascular and neuronal compartments and the blood-brain barrier (bbb). The middle cerebral artery was transiently tied for 30 min followed by reperfusion for 60 min. Statins (nanomolar doses) were administered by intravascular continuous infusion starting 60 min before ischemia induction. Brain cortical activity and arterial vascular tone were continuously recorded. At the end of the experiment immunoreactivity for microtubule-associated protein 2 (MAP-2), expression of survival kinases (ERK and Akt) and total anti-oxidant capacity were assayed. Brains treated with simvastatin lactone showed i) reduced amplitude and delayed onset of ischemic depressions, ii) preservation of MAP-2 immunoreactivity, iii) activation of ERK signaling in the ischemic hemisphere and iv) increase in whole-brain anti-oxidant capacity. Treatment with the bbb-impermeable simvastatin acid was ineffective on the above-mentioned parameters. Vascular resistance recordings and Akt signaling were unchanged by any statin treatment. Our findings suggest that intravascular-delivered simvastatin exerts an acute lipophilicity-dependent protective effect in the early phase of cerebral ischemia. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Symmetry-protected topological phases of one-dimensional interacting fermions with spin-charge separation

    NASA Astrophysics Data System (ADS)

    Montorsi, Arianna; Dolcini, Fabrizio; Iotti, Rita C.; Rossi, Fausto

    2017-06-01

    The low energy behavior of a huge variety of one-dimensional interacting spinful fermionic systems exhibits spin-charge separation, described in the continuum limit by two sine-Gordon models decoupled in the charge and spin channels. Interaction is known to induce, besides the gapless Luttinger liquid phase, eight possible gapped phases, among which are the Mott, Haldane, charge-/spin-density, and bond-ordered wave insulators, and the Luther Emery liquid. Here we prove that some of these physically distinct phases have nontrivial topological properties, notably the presence of degenerate protected edge modes with fractionalized charge/spin. Moreover, we show that the eight gapped phases are in one-to-one correspondence with the symmetry-protected topological (SPT) phases classified by group cohomology theory in the presence of particle-hole symmetry P. The latter result is also exploited to characterize SPT phases by measurable nonlocal order parameters which follow the system evolution to the quantum phase transition. The implications on the appearance of exotic orders in the class of microscopic Hubbard Hamiltonians, possibly without P symmetry at higher energies, are discussed.

  20. Surface field theories of point group symmetry protected topological phases

    NASA Astrophysics Data System (ADS)

    Huang, Sheng-Jie; Hermele, Michael

    2018-02-01

    We identify field theories that describe the surfaces of three-dimensional bosonic point group symmetry protected topological (pgSPT) phases. The anomalous nature of the surface field theories is revealed via a dimensional reduction argument. Specifically, we study three different surface field theories. The first field theory is quantum electrodynamics in three space-time dimensions (QED3) with four flavors of fermions. We show this theory can describe the surfaces of a majority of bosonic pgSPT phases protected by a single mirror reflection, or by Cn v point group symmetry for n =2 ,3 ,4 ,6 . The second field theory is a variant of QED3 with charge-1 and charge-3 Dirac fermions. This field theory can describe the surface of a reflection symmetric pgSPT phase built by placing an E8 state on the mirror plane. The third field theory is an O (4 ) nonlinear sigma model with a topological theta term at θ =π , or, equivalently, a noncompact CP1 model. Using a coupled wire construction, we show this is a surface theory for bosonic pgSPT phases with U (1 ) ×Z2P symmetry. For the latter two field theories, we discuss the connection to gapped surfaces with topological order. Moreover, we conjecture that the latter two field theories can describe surfaces of more general bosonic pgSPT phases with Cn v point group symmetry.

  1. Performance analysis of microcomputer based differential protection of UHV lines under selective phase switching

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

    Bhatti, A.A.

    1990-04-01

    This paper examines the effects of primary and secondary fault quantities as well s of mutual couplings of neighboring circuits on the sensitivity of operation and threshold settings of a microcomputer based differential protection of UHV lines under selective phase switching. Microcomputer based selective phase switching allows the disconnection of minimum number of phases involved in a fault and requires the autoreclosing of these phases immediately after the extinction of secondary arc. During a primary fault a heavy current contribution to the healthy phases tends to cause an unwanted tripping. Faulty phases physically disconnected constitute an isolated fault which beingmore » coupled to the system affects the current and voltage levels of the healthy phases still retained in the system and may cause an unwanted tripping. The microcomputer based differential protection, appears to have poor performance when applied to uncompensated lines employing selective pole switching.« less

  2. A study of cannabinoid-1 receptors during the early phase of excitotoxic damage to rat spinal locomotor networks in vitro.

    PubMed

    Veeraraghavan, Priyadharishini; Dekanic, Ana; Nistri, Andrea

    2016-10-01

    Endocannabinoids acting on cannabinoid-1 receptors (CB1Rs) are proposed to protect brain and spinal neurons from excitotoxic damage. The ability to recover from spinal cord injury (SCI), in which excitotoxicity is a major player, is usually investigated at late times after modulation of CB1Rs whose role in the early phases of SCI remains unclear. Using the rat spinal cord in vitro as a model for studying SCI initial pathophysiology, we investigated if agonists or antagonists of CB1Rs might affect SCI induced by the excitotoxic agent kainate (KA) within 24h from a transient (1h) application of this glutamate agonist. The CB1 agonist anandamide (AEA or pharmacological block of its degradation) did not limit excitotoxic depolarization of spinal networks: cyclic adenosine monophosphate (cAMP) assay demonstrated that CB1Rs remained functional 24h later and similarly expressed among dead or survived cells. Locomotor-like network activity recorded from ventral roots could not recover with such treatments and was associated with persistent depression of synaptic transmission. Motoneurons, that are particularly vulnerable to KA, were not protected by AEA. Application of 2-arachidonoylglycerol also did not attenuate the electrophysiological and histological damage. The intensification of damage by the CB1 antagonist AM251 suggested that endocannabinoids were operative after excitotoxic stimulation, yet insufficient to contrast it efficiently. The present data indicate that the early phases of excitotoxic SCI could not be arrested by pharmacologically exploiting the endocannabinoid system, consistent with the notion that AEA and its derivatives are more useful to treat late SCI phases. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. An early warning and control system for urban, drinking water quality protection: China's experience.

    PubMed

    Hou, Dibo; Song, Xiaoxuan; Zhang, Guangxin; Zhang, Hongjian; Loaiciga, Hugo

    2013-07-01

    An event-driven, urban, drinking water quality early warning and control system (DEWS) is proposed to cope with China's urgent need for protecting its urban drinking water. The DEWS has a web service structure and provides users with water quality monitoring functions, water quality early warning functions, and water quality accident decision-making functions. The DEWS functionality is guided by the principles of control theory and risk assessment as applied to the feedback control of urban water supply systems. The DEWS has been deployed in several large Chinese cities and found to perform well insofar as water quality early warning and emergency decision-making is concerned. This paper describes a DEWS for urban water quality protection that has been developed in China.

  4. Challenges and perspective of drug repurposing strategies in early phase clinical trials.

    PubMed

    Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

    2015-01-01

    Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

  5. Renormalization group approach to symmetry protected topological phases

    NASA Astrophysics Data System (ADS)

    van Nieuwenburg, Evert P. L.; Schnyder, Andreas P.; Chen, Wei

    2018-04-01

    A defining feature of a symmetry protected topological phase (SPT) in one dimension is the degeneracy of the Schmidt values for any given bipartition. For the system to go through a topological phase transition separating two SPTs, the Schmidt values must either split or cross at the critical point in order to change their degeneracies. A renormalization group (RG) approach based on this splitting or crossing is proposed, through which we obtain an RG flow that identifies the topological phase transitions in the parameter space. Our approach can be implemented numerically in an efficient manner, for example, using the matrix product state formalism, since only the largest first few Schmidt values need to be calculated with sufficient accuracy. Using several concrete models, we demonstrate that the critical points and fixed points of the RG flow coincide with the maxima and minima of the entanglement entropy, respectively, and the method can serve as a numerically efficient tool to analyze interacting SPTs in the parameter space.

  6. Does Religious Involvement Protect against Early Drinking? A Behavior Genetic Approach

    ERIC Educational Resources Information Center

    Harden, K. Paige

    2010-01-01

    Background: Adolescent involvement in religious organizations has been hypothesized to protect against early age at first drink. However, the correlation between adolescent religiosity and later age at first drink may be confounded by environmental or genetic differences between families. This study tests whether, after controlling for shared…

  7. Fermionic Symmetry-Protected Topological Phase in a Two-Dimensional Hubbard Model

    DOE PAGES

    Chen, Cheng-Chien; Muechler, Lukas; Car, Roberto; ...

    2016-08-25

    We study the two-dimensional (2D) Hubbard model using exact diagonalization for spin-1/2 fermions on the triangular and honeycomb lattices decorated with a single hexagon per site. In certain parameter ranges, the Hubbard model maps to a quantum compass model on those lattices. On the triangular lattice, the compass model exhibits collinear stripe antiferromagnetism, implying d-density wave charge order in the original Hubbard model. On the honeycomb lattice, the compass model has a unique, quantum disordered ground state that transforms nontrivially under lattice reflection. The ground state of the Hubbard model on the decorated honeycomb lattice is thus a 2D fermionicmore » symmetry-protected topological phase. This state—protected by time-reversal and reflection symmetries—cannot be connected adiabatically to a free-fermion topological phase.« less

  8. Phase III Early Restoration Meeting - Galveston, TX | NOAA Gulf Spill

    Science.gov Websites

    Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

  9. Impact of incretin on early-phase insulin secretion and glucose excursion.

    PubMed

    Shen, Jie; Chen, Zhi; Chen, Chaofeng; Zhu, Xiao; Han, Yajuan

    2013-10-01

    This study investigated the impact of incretin on early-phase insulin secretion and glucose excursion. The normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) groups included 16, 8, and 19 subjects, respectively. Subjects underwent continuous glucose monitoring for 3 days, followed by an oral glucose tolerance test. Plasma glucose, insulin, glucagon, total glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-l (GLP-1) levels were measured at 30-min increments for 2 h after glucose intake. Differences with P < 0.05 were considered statistically significant. The area under the curve (AUC) of total GIP (120-min GIP-AUC) of the T2DM group was significantly lower than those of the NGT and IGT groups. The 120-min GLP-1-AUC of the NGT group was significantly larger than those of the T2DM and IGT groups. The early-phase insulin secretion index (ΔI30/ΔG30) of the T2DM group was significantly lower than those of the NGT and IGT groups. Mean amplitudes of glycemic excursions (MAGEs) went in the order of NGT < IGT < T2DM (P < 0.01, IGT vs. NGT; P < 0.001, T2DM vs. IGT). The 120-min GIP-AUC was negatively correlated with MAGE (r = -0.464), but uncorrelated with ΔI30/ΔG30. The 120-min GLP-1-AUC was positively correlated with ΔI30/ΔG30 (r = 0.580), but negatively correlated with MAGE (r = -0.606). Incretin may ameliorate glucose excursions, and GLP-1 may exert them by promoting early-phase insulin secretion. No correlation was observed between GIP secretion and early-phase insulin secretion.

  10. Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

    PubMed Central

    Aigbirhio, Franklin I.; Fryer, Tim D.; Menon, David K.; Warburton, Elizabeth A.; Baron, Jean-Claude

    2015-01-01

    Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1–6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD. PMID:26439113

  11. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Protection of low- and medium-voltage three... WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits § 77.901 Protection of low- and medium-voltage three-phase circuits. (a) Low- and medium-voltage circuits supplying...

  12. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Protection of low- and medium-voltage three... WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits § 77.901 Protection of low- and medium-voltage three-phase circuits. (a) Low- and medium-voltage circuits supplying...

  13. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Protection of low- and medium-voltage three... WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits § 77.901 Protection of low- and medium-voltage three-phase circuits. (a) Low- and medium-voltage circuits supplying...

  14. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Protection of low- and medium-voltage three... WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits § 77.901 Protection of low- and medium-voltage three-phase circuits. (a) Low- and medium-voltage circuits supplying...

  15. 30 CFR 77.901 - Protection of low- and medium-voltage three-phase circuits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Protection of low- and medium-voltage three... WORK AREAS OF UNDERGROUND COAL MINES Low- and Medium-Voltage Alternating Current Circuits § 77.901 Protection of low- and medium-voltage three-phase circuits. (a) Low- and medium-voltage circuits supplying...

  16. Strontium ranelate causes osteophytes overgrowth in a model of early phase osteoarthritis.

    PubMed

    Chu, Jian-Guo; Dai, Mu-Wei; Wang, Yu; Tian, Fa-Ming; Song, Hui-Ping; Xiao, Ya-Ping; Shao, Li-Tao; Zhang, Ying-Ze; Zhang, Liu

    2017-02-10

    Osteoarthritis (OA) involves cartilage changes as well as modifications of subchondral bone and synovial tissues. Strontium ranelate (SR), an anti-osteoporosis compound, which is currently in phase III clinical trial for treatment of OA. Evidences suggest that SR preferably deposited in osteophyte, other than in subchondral bone in early phase of OA. This phenomenon raises concern about its utility for OA treatment as a disease-modifying drug. To evaluate the effect of SR on cartilage, subchondral bone mass and subchondral trabecular bone structure in medial meniscectomized (MNX) guinea pigs. Thirty-six 3-month-old male Dunkin Hartley albino guinea pigs received either sham or medial meniscectomy operations. One week after the procedure, meniscectomized animals began 12 weeks of SR (625 mg/kg, daily) treatment by oral gavage for MNX + SR group, or normal saline for MNX + V group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro-architecture was analyzed. Both OARSI scores (P = 0.523 for marcoscopic scores, P = 0.297 for histological scores) and Cartilage thickness (P = 0.335) in MNX + SR group were comparable to MNX + V group. However, osteophyte sizes were larger in MNX + SR group (P = 0.014), and collapsed osteophytes in MNX + SR group (7 by 12) were significantly more than in MNX + V group (1 by 12) (P = 0.027), while immunohistochemistry indicates catabolic changes in osteophyte/plateau junction. Micro-CT analysis showed bone mineral density (BMD) (P = 0.001), bone volume fraction (BV/TV) (P = 0.008), trabecular spacing (Tb.Sp) (P = 0.020), trabecular thickness (Tb.Th) (P = 0.012) and structure model index (SMI) (P = 0.005) levels to be significantly higher in the MNX + SR group than in the MNX + V group. SR (625 mg/kg/day) did not protect cartilage from degeneration in MNX guinea pigs but subchondral bone was significantly enhanced. In early

  17. Early Risk Reduction Phase 1 FLIR/Laser Designator Window. Revision

    DTIC Science & Technology

    1991-12-31

    Sandwich-Type FLIR Windows," Air Force AFWAL-TR-83- 4122, Nov 1983. 4-1 Hughes Danbury Optical Systems Final Report, "ATA Window Technology Program," PRBll...Risk Reduction -- Phase I, Optical Properties Measurement Techniques of Three Wide Band Window Materials," 22 August 1991. xii I i 86PR0869 30... Optical Systems, Lexington, MA, 02173, 1 Feb 1991. 5-7 McDonnell Aircraft Company Technical Memorandum TM 256.91.0056.01, "Early Risk Reduction -- Phase

  18. Management of the second phase of labour: perineum protection techniques.

    PubMed

    Laganà, A S; Burgio, M A; Retto, G; Pizzo, A; Granese, R; Sturlese, E; Ciancimino, L; Chiofalo, B; Retto, A; Triolo, O

    2015-06-01

    The obstetric experience alongside scientific evidences in literature indicate several management techniques during the expulsive period of labour to minimize obstetric complications. Among the various methods that can be used for the protection of the perineum during the expulsive phase, some are performed prepartum (perineum massage), while most are used during childbirth. Among the second group, progressively increasing importance is assumed by the manual techniques to protect the perineum (using the "hands-on" and "hands-off") and by episiotomy. These techniques, when used in accordance to the guidelines, may favour the reduction of adverse outcomes for both the mother and the newborn, both immediately after birth and after a longer time. The midwife should be aware of the evidences in literature so that a critical analysis of the available techniques can be made and put in action during the expulsive phase in order to protect the mother and the foetus from any unfavourable outcomes. Currently, clinical evidence in literature is directing obstetric and medical staff towards a careful analysis of the maternal-foetal parameters, in order to achieve a precise assessment of the risks factors of intrapartum and postpartum outcomes. Increasingly, there is the need for close collaboration between the midwife and medical staff to ensure proper personalized assistance based on the peculiar characteristics of the woman and the fetus.

  19. Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT

    DTIC Science & Technology

    2016-08-01

    AWARD NUMBER: W81XWH-12-1-0138 TITLE: Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT PRINCIPAL INVESTIGATOR...NUMBER W81XWH-12-1-0138 Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...method for early detection of amyloid plaque in Alzheimer’s disease , with three Specific Aims: #1 Develop and optimize an x-ray PCCT to explore the

  20. Universal measurement-based quantum computation in two-dimensional symmetry-protected topological phases

    NASA Astrophysics Data System (ADS)

    Wei, Tzu-Chieh; Huang, Ching-Yu

    2017-09-01

    Recent progress in the characterization of gapped quantum phases has also triggered the search for a universal resource for quantum computation in symmetric gapped phases. Prior works in one dimension suggest that it is a feature more common than previously thought, in that nontrivial one-dimensional symmetry-protected topological (SPT) phases provide quantum computational power characterized by the algebraic structure defining these phases. Progress in two and higher dimensions so far has been limited to special fixed points. Here we provide two families of two-dimensional Z2 symmetric wave functions such that there exists a finite region of the parameter in the SPT phases that supports universal quantum computation. The quantum computational power appears to lose its universality at the boundary between the SPT and the symmetry-breaking phases.

  1. Wide-field phase imaging for the endoscopic detection of dysplasia and early-stage esophageal cancer

    NASA Astrophysics Data System (ADS)

    Fitzpatrick, C. R. M.; Gordon, G. S. D.; Sawyer, T. W.; Wilkinson, T. D.; Bohndiek, S. E.

    2018-02-01

    Esophageal cancer has a 5-year survival rate below 20%, but can be curatively resected if it is detected early. At present, poor contrast for early lesions in white light imaging leads to a high miss rate in standard-of- care endoscopic surveillance. Early lesions in the esophagus, referred to as dysplasia, are characterized by an abundance of abnormal cells with enlarged nuclei. This tissue has a different refractive index profile to healthy tissue, which results in different light scattering properties and provides a source of endogenous contrast that can be exploited for advanced endoscopic imaging. For example, point measurements of such contrast can be made with scattering spectroscopy, while optical coherence tomography generates volumetric data. However, both require specialist interpretation for diagnostic decision making. We propose combining wide-field phase imaging with existing white light endoscopy in order to provide enhanced contrast for dysplasia and early-stage cancer in an image format that is familiar to endoscopists. Wide-field phase imaging in endoscopy can be achieved using coherent illumination combined with phase retrieval algorithms. Here, we present the design and simulation of a benchtop phase imaging system that is compatible with capsule endoscopy. We have undertaken preliminary optical modelling of the phase imaging setup, including aberration correction simulations and an investigation into distinguishing between different tissue phantom scattering coefficients. As our approach is based on phase retrieval rather than interferometry, it is feasible to realize a device with low-cost components for future clinical implementation.

  2. Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective.

    PubMed

    Harder, Jeffrey M; Braine, Catherine E; Williams, Pete A; Zhu, Xianjun; MacNicoll, Katharine H; Sousa, Gregory L; Buchanan, Rebecca A; Smith, Richard S; Libby, Richard T; Howell, Gareth R; John, Simon W M

    2017-05-09

    Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wld s allele, which protects from axon dysfunction. We demonstrate that DBA/2J .Wld s mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J .Wld s mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J. Wld s mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma.

  3. Early immune responses are independent of RGC dysfunction in glaucoma with complement component C3 being protective

    PubMed Central

    Harder, Jeffrey M.; Braine, Catherine E.; Williams, Pete A.; Zhu, Xianjun; MacNicoll, Katharine H.; Sousa, Gregory L.; Buchanan, Rebecca A.; Smith, Richard S.; Howell, Gareth R.; John, Simon W. M.

    2017-01-01

    Various immune response pathways are altered during early, predegenerative stages of glaucoma; however, whether the early immune responses occur secondarily to or independently of neuronal dysfunction is unclear. To investigate this relationship, we used the Wlds allele, which protects from axon dysfunction. We demonstrate that DBA/2J.Wlds mice develop high intraocular pressure (IOP) but are protected from retinal ganglion cell (RGC) dysfunction and neuroglial changes that otherwise occur early in DBA/2J glaucoma. Despite this, immune pathways are still altered in DBA/2J.Wlds mice. This suggests that immune changes are not secondary to RGC dysfunction or altered neuroglial interactions, but may be directly induced by the increased strain imposed by high IOP. One early immune response following IOP elevation is up-regulation of complement C3 in astrocytes of DBA/2J and DBA/2J.Wlds mice. Unexpectedly, because the disruption of other complement components, such as C1Q, is protective in glaucoma, C3 deficiency significantly increased the number of DBA/2J eyes with nerve damage and RGC loss at an early time point after IOP elevation. Transcriptional profiling of C3-deficient cultured astrocytes implicated EGFR signaling as a hub in C3-dependent responses. Treatment with AG1478, an EGFR inhibitor, also significantly increased the number of DBA/2J eyes with glaucoma at the same early time point. These findings suggest that C3 protects from early glaucomatous damage, a process that may involve EGFR signaling and other immune responses in the optic nerve head. Therefore, therapies that target specific components of the complement cascade, rather than global inhibition, may be more applicable for treating human glaucoma. PMID:28446616

  4. Accumulation of unsaturated lipids in monocytes during early phase pyrogen tolerance.

    PubMed

    Szewczenko-Pawlikowski, M; Kozak, W

    2000-04-12

    This paper presents data that inspired a new explanation for the mechanism of early phase endotoxin tolerance. Rabbits injected intravenously with LPS from Salmonella abortus developed a two-phase fever (6 h) and monophasic hyperlipidemia of very low density lipoproteins (two consecutive days). If during these days rabbits were injected with the same dose of LPS at 24-h intervals, the second phase of fever disappeared, i.e. early phase pyrogenic tolerance was obtained. This was correlated with a decrease of lipoprotein hyperlipidemia (measured 1.5 h after LPS injection) and an accumulation of lipids rich in double bonds in monocytes (measured 3.5 h after LPS injection). Results showed that the degree of unsaturation of acyl chains (AC) in monocytes (AC/DB, DB=double bonds) is negatively correlated (r=-0.72) with fever response (fever index). The authors maintain that a gradual increase in monocyte membrane fluidity is an adaptation to repeated exposure of monocytes to lipid A and is responsible for the progressive desensitization of monocytes to endotoxin. It is suggested that disorders of this mechanism lead to an accumulation of abnormal quantities of saturated lipids and cholesterol within macrophages, which, as foam cells, are the starting point for atherosclerosis pathology.

  5. Phase III Early Restoration Meeting - Port Arthur, TX | NOAA Gulf Spill

    Science.gov Websites

    Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

  6. Phase III Early Restoration Meeting - Panama City, FL | NOAA Gulf Spill

    Science.gov Websites

    Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

  7. Beryllium and boron constraints on an early Galactic bright phase

    NASA Technical Reports Server (NTRS)

    Fields, Brian D.; Schramm, David N.; Truran, James W.

    1993-01-01

    The recent observations of Be and B in metal-deficient halo dwarfs are used to constrain a 'bright phase' of enhanced cosmic-ray flux in the early Galaxy. Assuming that this Be and B arises from cosmic-ray spallation in the early Galaxy, limits are placed on the intensity of the early (Population II) cosmic-ray flux relative to the present (Population I) flux. A simple estimate of bounds on the flux ratio is 1 - 40. This upper bound would restrict galaxies like our own from producing neutrino fluxes that would be detectable in any currently proposed detectors. It is found that the relative enhancement of the early flux varies inversely with the relative time of enhancement. It is noted that associated gamma-ray production via pp - pi sup 0 pp may be a significant contribution to the gamma-ray background above 100 MeV.

  8. Early Childhood Technology Integrated Instructional System (EC-TIIS) Phase 1: A Final Report

    ERIC Educational Resources Information Center

    Hutinger, Patricia; Robinson, Linda; Schneider, Carol

    2004-01-01

    The Early Childhood Technology Integrated Instructional System (EC-TIIS), a Steppingstones of Technology Innovation Phase 1--Development project, was developed by the Center for Best Practices in Early Childhood (the Center) at Western Illinois University as an online instructional system. EC-TIIS' ultimate goal was to improve technology services…

  9. Dispositional Optimism and Therapeutic Expectations in Early Phase Oncology Trials

    PubMed Central

    Jansen, Lynn A.; Mahadevan, Daruka; Appelbaum, Paul S.; Klein, William MP; Weinstein, Neil D.; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P.

    2016-01-01

    Purpose Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early phase oncology trials. Optimism, however, is not a unitary construct – it can also be defined as a general disposition, or what is called dispositional optimism. We assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. We also assessed how dispositional optimism related to unrealistic optimism. Methods Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Results Dispositional optimism was significantly associated with higher expectations for personal therapeutic benefit (Spearman r=0.333, p<0.0001), but was not associated with the therapeutic misconception. (Spearman r=−0.075, p=0.329). Dispositional optimism was weakly associated with unrealistic optimism (Spearman r=0.215, p=0.005). In multivariate analysis, both dispositional optimism (p=0.02) and unrealistic optimism (p<0.0001) were independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (p=.0001), but not dispositional optimism, was independently associated with the therapeutic misconception. Conclusion High expectations for therapeutic benefit among patient-subjects in early phase oncology trials should not be assumed to result from misunderstanding of specific information about the trials. Our data reveal that these expectations are associated with either a dispositionally positive outlook on life or biased expectations about specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early phase oncology research. PMID:26882017

  10. Symmetry protected topological Luttinger liquids and the phase transition between them

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

    None

    2018-01-01

    We show that a doped spin-1/2 ladder with antiferromagnetic intra-chain and ferromagnetic inter-chain coupling is a symmetry protected topologically non-trivial Luttinger liquid. Turning on a large easy-plane spin anisotropy drives the system to a topologically-trivial Luttinger liquid. Both phases have full spin gaps and exhibit power-law superconducting pair correlation. The Cooper pair symmetry is singletmore » $$d_{xy}$$ in the non-trivial phase and triplet $$S_z=0$$ in the trivial phase. The topologically non-trivial Luttinger liquid exhibits gapless spin excitations in the presence of a boundary, and it has no non-interacting or mean-field theory analog even when the fluctuating phase in the charge sector is pinned. As a function of the strength of spin anisotropy there is a topological phase transition upon which the spin gap closes. We speculate these Luttinger liquids are relevant to the superconductivity in metalized integer spin ladders or chains.« less

  11. 78 FR 39736 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ..., choosing a study population, using a control group and blinding, dose selection, treatment plans...] Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular... document entitled ``Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

  12. A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

    PubMed

    Devchand, Pallavi R; Schmidt, Birgitta A; Primo, Valeria C; Zhang, Qing-yin; Arnaout, M Amin; Serhan, Charles N; Nikolic, Boris

    2005-02-01

    Lipoxin A(4) (LXA(4)) and aspirin-triggered 15-epi-LXA(4) are potent endogenous lipid mediators thought to define the inflammatory set-point. We used single prophylactic administrations of a synthetic aspirin-triggered lipoxin A(4) signal mimetic, ATLa, to probe dynamics of early host-donor interactions in a mouse model for the inflammation-associated multifactorial disease of allogeneic bone marrow transplant (BMT) -induced graft-vs.-host disease (GvHD). We first demonstrated that both host and donor are responsive to the ATLa signals. The simple and restricted regimen of a single prophylactic administration of ATLa [100 ng/mL to donor cells or 1 microg (approximately 50 microg/kg) i.v. to host] was sufficient to delay death. Clinical indicators of weight, skin lesions, diarrhea and eye inflammation were monitored. Histological analyses on day 45 post-BMT showed that the degree of cellular trafficking, particularly neutrophil infiltrate, and protection of end-organ target pathology are different, depending on whether the host or donor was treated with ATLa. Taken together, these results chart some ATLa protective effects on GvHD cellular dynamics over time and identify a previously unrecognized effect of host neutrophils in the early phase post-BMT as important determinants in the dynamics of GvHD onset and progression.-Devchand, P. R., Schmidt, B. A., Primo, V. C., Zhang, Q.-y., Arnaout, M. A., Serhan, C. N., Nikolic, B. A synthetic eicosanoid LX-mimetic unravels host-donor interactions in allogeneic BMT-induced GvHD to reveal an early protective role for host neutrophils.

  13. Replacement of Ablators with Phase-Change Material for Thermal Protection of STS Elements

    NASA Technical Reports Server (NTRS)

    Kaul, Raj K.; Stuckey, Irvin; Munafo, Paul M. (Technical Monitor)

    2002-01-01

    As part of the research and development program to develop new Thermal Protection System (TPS) materials for aerospace applications at NASA's Marshall Space Flight Center (MSFC), an experimental study was conducted on a new concept for a non-ablative TPS material. Potential loss of TPS material and ablation by-products from the External Tank (ET) or Solid Rocket Booster (SRB) during Shuttle flight with the related Orbiter tile damage necessitates development of a non-ablative thermal protection system. The new Thermal Management Coating (TMC) consists of phase-change material encapsulated in micro spheres and a two-part resin system to adhere the coating to the structure material. The TMC uses a phase-change material to dissipate the heat produced during supersonic flight rather than an ablative material. This new material absorbs energy as it goes through a phase change during the heating portion of the flight profile and then the energy is slowly released as the phase-change material cools and returns to its solid state inside the micro spheres. The coating was subjected to different test conditions simulating design flight environments at the NASA/MSFC Improved Hot Gas Facility (IHGF) to study its performance.

  14. Numerical investigation of the early flight phase in ski-jumping.

    PubMed

    Gardan, N; Schneider, A; Polidori, G; Trenchard, H; Seigneur, J M; Beaumont, F; Fourchet, F; Taiar, R

    2017-07-05

    The purpose of this study is to develop a numerical methodology based on real data from wind tunnel experiments to investigate the effect of the ski jumper's posture and speed on aerodynamic forces in a wide range of angles of attack. To improve our knowledge of the aerodynamic behavior of the ski jumper and his equipment during the early flight phase of the ski jump, we applied CFD methodology to evaluate the influence of angle of attack (α=14°, 21.5°, 29°, 36.5° and 44°) and speed (u=23, 26 and 29m/s) on aerodynamic forces in the situation of stable attitude of the ski jumper's body and skis. The standard k-ω turbulence model was used to investigate both the influence of the ski jumper's posture and speed on aerodynamic performance during the early flight phase. Numerical results show that the ski jumper's speed has very little impact on the lift and drag coefficients. Conversely, the lift and drag forces acting on the ski jumper's body during the early flight phase of the jump are strongly influenced by the variations of the angle of attack. The present results suggest that the greater the ski jumper's angle of inclination, with respect to the relative flow, the greater the pressure difference between the lower and upper parts of the skier. Further studies will focus on the dependency of the parameters with both the angle of attack α and the body-ski angle β as control variables. It will be possible to test and optimize different ski jumping styles in different ski jumping hills and investigate different environmental conditions such as temperature, altitude or crosswinds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Dispositional optimism and therapeutic expectations in early-phase oncology trials.

    PubMed

    Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P

    2016-04-15

    Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism. Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Dispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; P<.0001), but was not associated with the therapeutic misconception (Spearman r, -0.075; P = .329). Dispositional optimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (P<.0001) were found to be independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception. High expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have

  16. Baseline Survey of Sun-Protection Knowledge, Practices and Policy in Early Childhood Settings in Queensland, Australia

    ERIC Educational Resources Information Center

    Harrison, Simone L.; Saunders, V.; Nowak, M.

    2007-01-01

    Excessive exposure to sunlight during early childhood increases the risk of developing skin cancer. Self-administered questionnaires exploring sun-protection knowledge, practices and policy were mailed to the directors/co-ordinators/senior teachers of all known early childhood services in Queensland, Australia, in 2002 (n = 1383; 56.5% response).…

  17. Development of Environmental Load Estimation Model for Road Drainage Systems in the Early Design Phase

    NASA Astrophysics Data System (ADS)

    Park, Jin-Young; Lee, Dong-Eun; Kim, Byung-Soo

    2017-10-01

    Due to the increasing concern about climate change, efforts to reduce environmental load are continuously being made in construction industry, and LCA (life cycle assessment) is being presented as an effective method to assess environmental load. Since LCA requires information on construction quantity used for environmental load estimation, however, it is not being utilized in the environmental review in the early design phase where it is difficult to obtain such information. In this study, computation system for construction quantity based on standard cross section of road drainage facilities was developed to compute construction quantity required for LCA using only information available in the early design phase to develop and verify the effectiveness of a model that can perform environmental load estimation. The result showed that it is an effective model that can be used in the early design phase as it revealed a 13.39% mean absolute error rate.

  18. Imaging of early acceleration phase of the 2013-2014 Boso slow slip event

    NASA Astrophysics Data System (ADS)

    Fukuda, J.; Kato, A.; Obara, K.; Miura, S.; Kato, T.

    2014-12-01

    Based on GPS and seismic data, we examine the spatiotemporal evolution of a slow slip event (SSE) and associated seismic activity that occurred off the Boso peninsula, central Japan, from December 2013 to January 2014. We use GPS data from 71 stations of the GEONET and 6 stations operated by Earthquake Research Institute of the University of Tokyo and Tohoku University around the Boso peninsula. We apply a modified version of the Network Inversion Filter to the GPS time series at the 77 stations to estimate the spatiotemporal evolution of daily cumulative slip and slip rate on the subducting Philippine Sea plate. In addition, we create an improved earthquake catalog by applying a matched filter technique to continuous seismograms and examine the spatiotemporal relations between slow slip and seismicity. We find that the SSE started in early December 2013. The spatiotemporal evolution of slow slip and seismicity is divided into two distinct phases, an earlier slow phase from early to 30 December 2013 (Phase I) and a subsequent faster phase from 30 December 2013 to 9 January 2014 (Phase II). During Phase I, slip accelerated slowly up to a maximum rate of 1.6 m/yr with potentially accelerating along-strike propagation at speeds on the order of 1 km/day or less and no accompanying seismicity. On the other hand, during Phase II, slip accelerated rapidly up to a maximum rate of 4.5 m/yr and then rapidly decelerated. The slip front propagated along strike at a constant speed of ~10 km/day. During the Phase II, slow slip was accompanied by seismic swarm activity that was highly correlated in space and time with slip rate, suggesting that the swarm activity was triggered by stress loading due to slow slip. Early slow acceleration of slip has not been identified in the past Boso SSEs in 1996, 2002, 2007, and 2011. It is not clear at this point whether the past Boso SSEs started with slow acceleration similarly to the 2013-2014 SSE. The transition from the slow to the

  19. Perspectives and Open Problems in the Early Phases of Left-Right Patterning

    PubMed Central

    Vandenberg, Laura N.; Levin, Michael

    2009-01-01

    Summary Embryonic left-right (LR) patterning is a fascinating aspect of embryogenesis. The field currently faces important questions about the origin of LR asymmetry, the mechanisms by which consistent asymmetry is imposed on the scale of the whole embryo, and the degree of conservation of early phases of LR patterning among model systems. Recent progress on planar cell polarity and cellular asymmetry in a variety of tissues and species provides a new perspective on the early phases of LR patterning. Despite the huge diversity in body-plans over which consistent LR asymmetry is imposed, and the apparent divergence in molecular pathways that underlie laterality, the data reveal conservation of physiological modules among phyla and a basic scheme of cellular chirality amplified by a planar cell polarity-like pathway over large cell fields. PMID:19084609

  20. Using a Strengths Approach to Early Childhood Teacher Preparation in Child Protection Using Work-Integrated Education

    ERIC Educational Resources Information Center

    Fenton, Angela

    2013-01-01

    This paper explores a collaborative strengths-based approach to investing in pre-service early childhood teacher education in the area of child protection. The doctoral research of the author, which evaluated a Strengths Approach as a cross-sector tool for implementing change in early-childhood education and in doing so researched a potential…

  1. Ultra-Early Phase pathologies of Alzheimer's disease and other neurodegenerative diseases.

    PubMed

    Okazawa, Hitoshi

    2017-01-01

    The concept of neurodegenerative diseases and the therapeutics targeting these intractable diseases are changing rapidly. Protein aggregation as the top of pathological cascade is now challenged, and many alternative ideas are proposed. Early molecular pathologies before microscopic detection of diseases protein aggregates, which I propose to call "Ultra-Early Phase pathologies or phase 0 pathologies", are the focus of research that might explain the failures of clinical trials with anti-Aβ antibodies against Alzheimer's disease. In this review article, I summarize the critical issues that should be successfully and consistently answered by a new concept of neurodegeneration. For reevaluating old concepts and reconstructing a new concept of neurodegeneration that will replace the old ones, non-biased comprehensive approaches including proteome combined with systems biology analyses will be a powerful tool. I introduce our recent efforts in this orientation that have reached to the stage of non-clinical proof of concept applicable to clinical trials.

  2. Feasibility of maternity protection in early pregnancy.

    PubMed

    Von Busch, Tammy A; Frazier, Linda M; Sigler, Samantha J; Molgaard, Craig A

    2002-01-01

    Many countries have maternity protection laws for women who need job modification or medical leave during pregnancy. This approach will prevent birth defects only if maternal job changes can be made before the critical period of organogenesis, which begins at three weeks' gestation. The authors studied the gestational ages at which pregnant women working with chemicals, radiation, and noise presented for occupational safety and health consultations. The work setting promoted early presentation because the consultation was free, convenient, mandatory, and would not result in job loss. Among the 213 pregnant women evaluated between 1996 and 2000, most (89.5%) had their occupational safety evaluations in the first trimester. Although this sounds ideal, the mean gestational age at presentation was 7.5 weeks, and only 3.3% of occupational health evaluations were initiated by three weeks' gestation. Environmental and biological monitoring showed that none of the women was exposed over occupational limits. These data suggest that a workplace free from reproductive hazards needs to be provided before conception.

  3. The early cellular signatures of protective immunity induced by live viral vaccination.

    PubMed

    Kohler, Siegfried; Bethke, Nicole; Böthe, Matthias; Sommerick, Sophie; Frentsch, Marco; Romagnani, Chiara; Niedrig, Matthias; Thiel, Andreas

    2012-09-01

    Here, we have used primary vaccination of healthy donors with attenuated live yellow fever virus 17D (YFV-17D) as a model to study the generation of protective immunity. In short intervals after vaccination, we analyzed the induction of YFV-17D specific T- and B-cell immunity, bystander activation, dendritic cell subsets, changes in serum cytokine levels, and YFV-17D-specific antibodies. We show activation of innate immunity and a concomitant decline of numbers of peripheral blood T and B cells. An early peak of antigen-specific T cells at day 2, followed by mobilization of innate immune cells, preceded the development of maximal adaptive immunity against YFV-17D at day 14 after vaccination. Interestingly, potent adaptive immunity as measured by high titers of neutralizing YFV-17D-specific antibodies, correlated with early activation and recruitment of YFV-17D-specific CD4(+) T cells and higher levels of sIL-6R. Thus our data might provide new insights into the interplay of innate and adaptive immunity for the induction of protective immunity. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Human Dose-Response Data for Francisella tularensis and a Dose- and Time-Dependent Mathematical Model of Early-Phase Fever Associated with Tularemia After Inhalation Exposure.

    PubMed

    McClellan, Gene; Coleman, Margaret; Crary, David; Thurman, Alec; Thran, Brandolyn

    2018-04-25

    Military health risk assessors, medical planners, operational planners, and defense system developers require knowledge of human responses to doses of biothreat agents to support force health protection and chemical, biological, radiological, nuclear (CBRN) defense missions. This article reviews extensive data from 118 human volunteers administered aerosols of the bacterial agent Francisella tularensis, strain Schu S4, which causes tularemia. The data set includes incidence of early-phase febrile illness following administration of well-characterized inhaled doses of F. tularensis. Supplemental data on human body temperature profiles over time available from de-identified case reports is also presented. A unified, logically consistent model of early-phase febrile illness is described as a lognormal dose-response function for febrile illness linked with a stochastic time profile of fever. Three parameters are estimated from the human data to describe the time profile: incubation period or onset time for fever; rise time of fever; and near-maximum body temperature. Inhaled dose-dependence and variability are characterized for each of the three parameters. These parameters enable a stochastic model for the response of an exposed population through incorporation of individual-by-individual variability by drawing random samples from the statistical distributions of these three parameters for each individual. This model provides risk assessors and medical decisionmakers reliable representations of the predicted health impacts of early-phase febrile illness for as long as one week after aerosol exposures of human populations to F. tularensis. © 2018 Society for Risk Analysis.

  5. Early follicular phase hormone levels in relation to patterns of alcohol, tobacco, and coffee use.

    PubMed

    Lucero, J; Harlow, B L; Barbieri, R L; Sluss, P; Cramer, D W

    2001-10-01

    To examine the effects of alcohol, caffeine, and tobacco use on early follicular phase FSH, LH, E2, and sex hormone-binding globulin (SHBG). Cross-sectional study. Academic medical center. Four hundred ninety-eight women selected from the general population, ages 36-45, who were not currently pregnant, breast feeding, or using exogenous hormones. A general questionnaire assessing demography, anthropometry, and smoking habits and a standardized dietary questionnaire assessing food and beverage frequencies, including sources of alcohol and caffeine. FSH, LH, E2, and SHBG levels measured during the early follicular phase of the menstrual cycle. Significant associations observed in a univariate analysis included age > or =40 and current smoking associated with higher FSH; higher body mass index (BMI) associated with lower SHBG levels; and daily alcohol use, cholesterol consumption greater than the median, and coffee use >1 cup/d associated with higher E2 levels. In a multivariate model, total caffeine use was significantly associated with E2 levels after adjustment for age, BMI, total calories, current smoking, alcohol, cholesterol consumption, and day of sampling. Early follicular phase E2 increased from 28.2 pg/mL for women consuming < or =100 mg of caffeine to 45.2 pg/mL for women consuming > or =500 mg of caffeine per day, about a 70% increase. Coffee consumption and total caffeine use may increase early follicular phase E2 levels independent of related habits of alcohol or tobacco use.

  6. Quantum phase transitions between a class of symmetry protected topological states

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

    Tsui, Lokman; Jiang, Hong-Chen; Lu, Yuan-Ming

    2015-07-01

    The subject of this paper is the phase transition between symmetry protected topological states (SPTs). We consider spatial dimension d and symmetry group G so that the cohomology group, Hd+1(G,U(1)), contains at least one Z2n or Z factor. We show that the phase transition between the trivial SPT and the root states that generate the Z2n or Z groups can be induced on the boundary of a (d+1)-dimensional View the MathML source-symmetric SPT by a View the MathML source symmetry breaking field. Moreover we show these boundary phase transitions can be “transplanted” to d dimensions and realized in lattice modelsmore » as a function of a tuning parameter. The price one pays is for the critical value of the tuning parameter there is an extra non-local (duality-like) symmetry. In the case where the phase transition is continuous, our theory predicts the presence of unusual (sometimes fractionalized) excitations corresponding to delocalized boundary excitations of the non-trivial SPT on one side of the transition. This theory also predicts other phase transition scenarios including first order transition and transition via an intermediate symmetry breaking phase.« less

  7. Quantum phase transitions between a class of symmetry protected topological states

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

    Tsui, Lokman; Jiang, Hong -Chen; Lu, Yuan -Ming

    2015-04-30

    The subject of this paper is the phase transition between symmetry protected topological states (SPTs). We consider spatial dimension d and symmetry group G so that the cohomology group, H d+1(G,U(1)), contains at least one Z 2n or Z factor. We show that the phase transition between the trivial SPT and the root states that generate the Z 2n or Z groups can be induced on the boundary of a (d+1)-dimensional G x Z T 2-symmetric SPT by a Z T 2 symmetry breaking field. Moreover we show these boundary phase transitions can be “transplanted” to d dimensions and realizedmore » in lattice models as a function of a tuning parameter. The price one pays is for the critical value of the tuning parameter there is an extra non-local (duality-like) symmetry. In the case where the phase transition is continuous, our theory predicts the presence of unusual (sometimes fractionalized) excitations corresponding to delocalized boundary excitations of the non-trivial SPT on one side of the transition. This theory also predicts other phase transition scenarios including first order transition and transition via an intermediate symmetry breaking phase.« less

  8. Functional neuroanatomical correlates of episodic memory impairment in early phase psychosis

    PubMed Central

    Hummer, Tom A.; Vohs, Jenifer L.; Yung, Matthew G.; Liffick, Emily; Mehdiyoun, Nicole F.; Radnovich, Alexander J.; McDonald, Brenna C.; Saykin, Andrew J.; Breier, Alan

    2015-01-01

    Studies have demonstrated that episodic memory (EM) is often preferentially disrupted in schizophrenia. The neural substrates that mediate EM impairment in this illness are not fully understood. Several functional magnetic resonance imaging (fMRI) studies have employed EM probe tasks to elucidate the neural underpinnings of impairment, though results have been inconsistent. The majority of EM imaging studies have been conducted in chronic forms of schizophrenia with relatively few studies in early phase patients. Early phase schizophrenia studies are important because they may provide information regarding when EM deficits occur and address potential confounds more frequently observed in chronic populations. In this study, we assessed brain activation during the performance of visual scene encoding and recognition fMRI tasks in patients with earlyphase psychosis (n=35) and age, sex, and race matched healthy control subjects (n = 20). Patients demonstrated significantly lower activation than controls in the right hippocampus and left fusiform gyrus during scene encoding and lower activation in the posterior cingulate, precuneus, and left middle temporal cortex during recognition of target scenes. Symptom levels were not related to the imaging findings, though better cognitive performance in patients was associated with greater right hippocampal activation during encoding. These results provide evidence of altered function in neuroanatomical circuitry subserving EM early in the course of psychotic illness, which may have implications for pathophysiological models of this illness. PMID:25749917

  9. 78 FR 5816 - Guidance for Industry on Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-28

    .... The guidance provides recommendations on when and how genomic principles should be considered and... recommendations on when and how genomic principles should be considered and applied in early-phase clinical... the larger, later adequate, and well-controlled trials (phase 3) that are needed to support marketing...

  10. Role of Occult and Post-acute Phase Replication in Protective Immunity Induced with a Novel Live Attenuated SIV Vaccine

    PubMed Central

    Ham, Claire; Ferguson, Deborah; Tudor, Hannah; Mattiuzzo, Giada; Klaver, Bep; Page, Mark; Stebbings, Richard; Das, Atze T.; Berkhout, Ben; Almond, Neil; Cranage, Martin P.

    2016-01-01

    In order to evaluate the role of persisting virus replication during occult phase immunisation in the live attenuated SIV vaccine model, a novel SIVmac239Δnef variant (SIVrtTA) genetically engineered to replicate in the presence of doxycycline was evaluated for its ability to protect against wild-type SIVmac239. Indian rhesus macaques were vaccinated either with SIVrtTA or with SIVmac239Δnef. Doxycycline was withdrawn from 4 of 8 SIVrtTA vaccinates before challenge with wild-type virus. Unvaccinated challenge controls exhibited ~107 peak plasma viral RNA copies/ml persisting beyond the acute phase. Six vaccinates, four SIVmac239Δnef and two SIVrtTA vaccinates exhibited complete protection, defined by lack of wild-type viraemia post-challenge and virus-specific PCR analysis of tissues recovered post-mortem, whereas six SIVrtTA vaccinates were protected from high levels of viraemia. Critically, the complete protection in two SIVrtTA vaccinates was associated with enhanced SIVrtTA replication in the immediate post-acute vaccination period but was independent of doxycycline status at the time of challenge. Mutations were identified in the LTR promoter region and rtTA gene that do not affect doxycycline-control but were associated with enhanced post-acute phase replication in protected vaccinates. High frequencies of total circulating CD8+T effector memory cells and a higher total frequency of SIV-specific CD8+ mono and polyfunctional T cells on the day of wild-type challenge were associated with complete protection but these parameters were not predictive of outcome when assessed 130 days after challenge. Moreover, challenge virus-specific Nef CD8+ polyfunctional T cell responses and antigen were detected in tissues post mortem in completely-protected macaques indicating post-challenge control of infection. Within the parameters of the study design, on-going occult-phase replication may not be absolutely required for protective immunity. PMID:28002473

  11. Geoeffectiveness during the early phase of Solar Cycle 24

    NASA Astrophysics Data System (ADS)

    Pande, Bimal

    Geoeffectiveness during the early phase of Solar Cycle 24 \\underline{} Abstract\\underline{} It is very important and interesting to understand the solar eruptions because it produces the geoeffectiveness in our Earth environment. In the rise phase of the solar cycle, geoeffective events are less frequent, thus this provide us better opportunity to study these events including the detection of their source regions. Keeping this in mind, we have analysed the data of rise phase of current solar cycle 24 ( 2009-2012). During above time period, we have selected 59 geoeffective events having Disturbance Storm Time (Dst) index < -50 nT. Based on the Dst index, we divided the events into two categories i.e. moderate (< -50 nT > -100 nT ) and intense ( <-100 nT). To locate the solar source regions of geoeffective and SEPs associated events, we have used available images, movies and Solar Geophysical data (SGD) list: for example movies from SOHO/EIT, images and movies from the Solar Dynamic Observatory (SDO). In this study, we will discuss and compare the different properties of associated CMEs, flares and their relation with geoeffectiveness.

  12. Lightning protection of wind turbines

    NASA Technical Reports Server (NTRS)

    Dodd, C. W.

    1982-01-01

    Possible damages to wind turbine components due to lightning strikes are discussed and means to prevent the damage are presented. A low resistance path to the ground is noted to be essential for any turbine system, including metal paths on nonmetal blades to conduct the strike. Surge arrestors are necessary to protect against overvoltages both from utility lines in normal operation and against lightning damage to control equipment and contactors in the generator. MOS structures are susceptible to static discharge injury, as are other semiconductor devices, and must be protected by the presence of static protection circuitry. It is recommended that the electronics be analyzed for the circuit transient response to a lightning waveform, to induced and dc current injection, that input/output leads be shielded, everything be grounded, and lightning-resistant components be chosen early in the design phase.

  13. Lightning protection of wind turbines

    NASA Astrophysics Data System (ADS)

    Dodd, C. W.

    1982-05-01

    Possible damages to wind turbine components due to lightning strikes are discussed and means to prevent the damage are presented. A low resistance path to the ground is noted to be essential for any turbine system, including metal paths on nonmetal blades to conduct the strike. Surge arrestors are necessary to protect against overvoltages both from utility lines in normal operation and against lightning damage to control equipment and contactors in the generator. MOS structures are susceptible to static discharge injury, as are other semiconductor devices, and must be protected by the presence of static protection circuitry. It is recommended that the electronics be analyzed for the circuit transient response to a lightning waveform, to induced and dc current injection, that input/output leads be shielded, everything be grounded, and lightning-resistant components be chosen early in the design phase.

  14. Marine collagen peptides protect against early alcoholic liver injury in rats.

    PubMed

    Lin, Bing; Zhang, Feng; Yu, Yongchao; Jiang, Qinghao; Zhang, Zhaofeng; Wang, Junbo; Li, Yong

    2012-04-01

    Marine collagen peptides (MCP) have been reported to exhibit antioxidative activity, which is the common property of numerous hepatoprotective agents. Previous studies have shown that MCP have biological functions including anti-hypertension, anti-ulcer, anti-skin ageing and extending the life span. However, its role in alcoholic liver injury remains unknown. The present study aimed to investigate the effects of MCP on early alcoholic liver injury in rats. Rats were administered with alcohol at a dose of 6 g/kg body weight intragastrically per d to induce early liver injury, which was then evaluated by serum markers and histopathological examination. Treatment with MCP could reverse the increased level of serum aminotransferase and reduce hepatic histological damage. In addition, MCP attenuated the alteration in serum superoxide dismutase and malondialdehyde levels. MCP also counteracted the increased levels of total cholesterol and TAG. However, no significant difference was observed in the contents of alcohol dehydrogenase both in liver and serum protein of rats. These findings suggest that MCP have a protective effect on early alcoholic liver injury in rats by their antioxidative activity and improving lipid metabolism.

  15. Organizing symmetry-protected topological phases by layering and symmetry reduction: A minimalist perspective

    NASA Astrophysics Data System (ADS)

    Xiong, Charles Zhaoxi; Alexandradinata, A.

    2018-03-01

    It is demonstrated that fermionic/bosonic symmetry-protected topological (SPT) phases across different dimensions and symmetry classes can be organized using geometric constructions that increase dimensions and symmetry-reduction maps that change symmetry groups. Specifically, it is shown that the interacting classifications of SPT phases with and without glide symmetry fit into a short exact sequence, so that the classification with glide is constrained to be a direct sum of cyclic groups of order 2 or 4. Applied to fermionic SPT phases in the Wigner-Dyson class AII, this implies that the complete interacting classification in the presence of glide is Z4⊕Z2⊕Z2 in three dimensions. In particular, the hourglass-fermion phase recently realized in the band insulator KHgSb must be robust to interactions. Generalizations to spatiotemporal glide symmetries are discussed.

  16. Family Risks and Protective Factors: Pathways to Early Head Start Toddlers' Social-Emotional Functioning

    ERIC Educational Resources Information Center

    Vick Whittaker, Jessica E.; Harden, Brenda Jones; See, Heather M.; Meisch, Allison D.; Westbrook, T'Pring R.

    2011-01-01

    Early Head Start children may be more likely to exhibit difficulties with social-emotional functioning due to the high-risk environments in which they live. However, positive parenting may serve as a protective factor against the influence of risk on children's outcomes. The current study examines the effects of contextual and proximal risks on…

  17. Application of Advanced Wide Area Early Warning Systems with Adaptive Protection

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

    Blumstein, Carl; Cibulka, Lloyd; Thorp, James

    2014-09-30

    Recent blackouts of power systems in North America and throughout the world have shown how critical a reliable power system is to modern societies, and the enormous economic and societal damage a blackout can cause. It has been noted that unanticipated operation of protection systems can contribute to cascading phenomena and, ultimately, blackouts. This project developed and field-tested two methods of Adaptive Protection systems utilizing synchrophasor data. One method detects conditions of system stress that can lead to unintended relay operation, and initiates a supervisory signal to modify relay response in real time to avoid false trips. The second methodmore » detects the possibility of false trips of impedance relays as stable system swings “encroach” on the relays’ impedance zones, and produces an early warning so that relay engineers can re-evaluate relay settings. In addition, real-time synchrophasor data produced by this project was used to develop advanced visualization techniques for display of synchrophasor data to utility operators and engineers.« less

  18. Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases.

    PubMed

    Tan, Shu-Yin; Hang, Fu; Purvarshi, Gowreesunkur; Li, Min-Qing; Meng, Da-Hua; Huang, Ling-Ling

    2015-10-01

    To evaluate the predictive value of three-dimensional (3D)-power Doppler sonography on recurrent miscarriage. The study patients were divided into a recurrent miscarriage group (30 cases) and a normal pregnancy group (21 cases). Measurement of endometrial thickness was performed using two-dimensional transvaginal ultrasound in the midluteal phase. The endometrial volume, vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in midluteal and placenta volume, as well as the VI, FI, and VFI of early pregnancy were measured using Virtual Organ Computer-aided Analysis of 3D-power Doppler ultrasound. Endometrial thickness, endometrial volume, endometrial vascular data, VI, FI, and VFI of the midluteal phase were lower in the recurrent miscarriage group compared with the normal pregnancy group (p < 0.05). Placental volume, VI, and VFI during early pregnancy were lower in the miscarriage group compared with the normal pregnancy group (p < 0.05). There was no significant change in FI between the recurrent miscarriage and control groups during early pregnancy (p > 0.05). The predictive accuracy of endometrial thickness, endometrial volume, VI, FI, and VFI in the midluteal phase, and placenta volume, VI, FI, and VFI in early pregnancy as measured by the receiver operating characteristic curve to predict miscarriage before 12 gestational weeks in participants was 0.681, 0.876, 0.770, 0.720, 0.879, 0.771, 0.907, 0.592, respectively. The 3D-power Doppler ultrasound is a more comprehensive and sensitive method for evaluating endometrial receptivity. Endometrial volume, VI, FI, and VFI in the midluteal phase, as well as VI in early pregnancy, can be considered as predictive factors for recurrent miscarriage. Copyright © 2015. Published by Elsevier B.V.

  19. Early warning of illegal development for protected areas by integrating cellular automata with neural networks.

    PubMed

    Li, Xia; Lao, Chunhua; Liu, Yilun; Liu, Xiaoping; Chen, Yimin; Li, Shaoying; Ai, Bing; He, Zijian

    2013-11-30

    Ecological security has become a major issue under fast urbanization in China. As the first two cities in this country, Shenzhen and Dongguan issued the ordinance of Eco-designated Line of Control (ELC) to "wire" ecologically important areas for strict protection in 2005 and 2009 respectively. Early warning systems (EWS) are a useful tool for assisting the implementation ELC. In this study, a multi-model approach is proposed for the early warning of illegal development by integrating cellular automata (CA) and artificial neural networks (ANN). The objective is to prevent the ecological risks or catastrophe caused by such development at an early stage. The integrated model is calibrated by using the empirical information from both remote sensing and handheld GPS (global positioning systems). The MAR indicator which is the ratio of missing alarms to all the warnings is proposed for better assessment of the model performance. It is found that the fast urban development has caused significant threats to natural-area protection in the study area. The integration of CA, ANN and GPS provides a powerful tool for describing and predicting illegal development which is in highly non-linear and fragmented forms. The comparison shows that this multi-model approach has much better performances than the single-model approach for the early warning. Compared with the single models of CA and ANN, this integrated multi-model can improve the value of MAR by 65.48% and 5.17% respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Effects of temperature on early-phase transmission of Yersina pestis by the flea, Xenopsylla cheopis.

    PubMed

    Schotthoefer, Anna M; Bearden, Scott W; Vetter, Sara M; Holmes, Jennifer; Montenieri, John A; Graham, Christine B; Woods, Michael E; Eisen, Rebecca J; Gage, Kenneth L

    2011-03-01

    Sharp declines in human and animal cases of plague, caused by the bacterium Yersinia pestis (Yersin), have been observed when outbreaks coincide with hot weather. Failure of biofilm production, or blockage, to occur in the flea, as temperatures reach 30 degrees C has been suggested as an explanation for these declines. Recent work demonstrating efficient flea transmission during the first few days after fleas have taken an infectious blood meal, in the absence of blockage (e.g., early-phase transmission), however, has called this hypothesis into question. To explore the potential effects of temperature on early-phase transmission, we infected colony-reared Xenopsylla cheopis (Rothchild) fleas with a wild-type strain of plague bacteria using an artificial feeding system, and held groups of fleas at 10, 23, 27, and 30 degrees C. Naive Swiss Webster mice were exposed to fleas from each of these temperatures on days 1-4 postinfection, and monitored for signs of infection for 21 d. Temperature did not significantly influence the rates of transmission observed for fleas held at 23, 27, and 30 degrees C. Estimated per flea transmission efficiencies for these higher temperatures ranged from 2.32 to 4.96% (95% confidence interval [CI]: 0.96-8.74). In contrast, no transmission was observed in mice challenged by fleas held at 10 degrees C (per flea transmission efficiency estimates, 0-1.68%). These results suggest that declines in human and animal cases during hot weather are not related to changes in the abilities of X. cheopis fleas to transmit Y. pestis infections during the early-phase period. By contrast, transmission may be delayed or inhibited at low temperatures, indicating that epizootic spread of Y. pestis by X. cheopis via early-phase transmission is unlikely during colder periods of the year.

  1. Development of the Updated Environmental Protection Agency Manual of Protective Action Guides (PAGS) and Protective Actions for Nuclear Incidents

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

    Carter, L.M.

    2008-07-01

    As a student intern with the United States Environmental Protection Agency (EPA) Headquarters, the author was trained in the National Response Plan (NRP) and assisted in the editing of the new (unpublished) EPA Protective Action Guides (PAGs) [1] which has been revised in light of the perceived post 9/11 potential for 'Dirty Bomb' and 'Improvised Nuclear Device' attacks on civilian areas. Technical aspects and the public policy aspects of developing the new guides are discussed. Early Phase initial responses discussed include: Notification of state and/or local authorities, immediate evacuation/sheltering prior to release information or measurements, monitoring of releases and exposuremore » rate measurements, estimation of dose consequences, implementation of protective actions in other areas. The new PAG clarifies the use of 1992 PAGs [2] for incidents other than nuclear power plant accidents, lowers projected thyroid dose for potassium iodine (KI), provides drinking water guidance, includes guidance for long-term site restoration, and updates dosimetry from ICRP 26 to ICRP 60. (authors)« less

  2. Resource quality of a symmetry-protected topologically ordered phase for quantum computation.

    PubMed

    Miller, Jacob; Miyake, Akimasa

    2015-03-27

    We investigate entanglement naturally present in the 1D topologically ordered phase protected with the on-site symmetry group of an octahedron as a potential resource for teleportation-based quantum computation. We show that, as long as certain characteristic lengths are finite, all its ground states have the capability to implement any unit-fidelity one-qubit gate operation asymptotically as a key computational building block. This feature is intrinsic to the entire phase, in that perfect gate fidelity coincides with perfect string order parameters under a state-insensitive renormalization procedure. Our approach may pave the way toward a novel program to classify quantum many-body systems based on their operational use for quantum information processing.

  3. Resource Quality of a Symmetry-Protected Topologically Ordered Phase for Quantum Computation

    NASA Astrophysics Data System (ADS)

    Miller, Jacob; Miyake, Akimasa

    2015-03-01

    We investigate entanglement naturally present in the 1D topologically ordered phase protected with the on-site symmetry group of an octahedron as a potential resource for teleportation-based quantum computation. We show that, as long as certain characteristic lengths are finite, all its ground states have the capability to implement any unit-fidelity one-qubit gate operation asymptotically as a key computational building block. This feature is intrinsic to the entire phase, in that perfect gate fidelity coincides with perfect string order parameters under a state-insensitive renormalization procedure. Our approach may pave the way toward a novel program to classify quantum many-body systems based on their operational use for quantum information processing.

  4. Formalin-Inactivated Coxiella burnetii Phase I Vaccine-Induced Protection Depends on B Cells To Produce Protective IgM and IgG

    PubMed Central

    Peng, Ying; Schoenlaub, Laura; Elliott, Alexandra; Mitchell, William; Zhang, Yan

    2013-01-01

    To further understand the mechanisms of formalin-inactivated Coxiella burnetii phase I (PI) vaccine (PIV)-induced protection, we examined if B cell, T cell, CD4+ T cell, or CD8+ T cell deficiency in mice significantly affects the ability of PIV to confer protection against a C. burnetii infection. Interestingly, compared to wild-type (WT) mice, PIV conferred comparable levels of protection in CD4+ T cell- or CD8+ T cell-deficient mice and partial protection in T cell-deficient mice but did not provide measurable protection in B cell-deficient mice. These results suggest that PIV-induced protection depends on B cells. In addition, anti-PI-specific IgM was the major detectable antibody (Ab) in immune sera from PIV-vaccinated CD4+ T cell-deficient mice, and passive transfer of immune sera from PIV-vaccinated CD4+ T cell-deficient mice conferred significant protection. These results suggest that T cell-independent anti-PI-specific IgM may contribute to PIV-induced protection. Our results also suggested that PIV-induced protection may not depend on complement activation and Fc receptor-mediated effector functions. Furthermore, our results demonstrated that both IgM and IgG from PIV-vaccinated WT mouse sera were able to inhibit C. burnetii infection in vivo, but only IgM from PIV-vaccinated CD4+ T cell-deficient mouse sera inhibited C. burnetii infection. Collectively, these findings suggest that PIV-induced protection depends on B cells to produce protective IgM and IgG and that T cell-independent anti-PI-specific IgM may play a critical role in PIV-induced protection against C. burnetii infection. PMID:23545296

  5. Early phase drugs and biologicals clinical trials on worldwide leading causes of death: a descriptive analysis.

    PubMed

    Dal-Ré, Rafael

    2011-06-01

    To describe the global effort targeting the major causes of mortality in terms of "open" early phase clinical trials with drugs and biologicals. Sixteen of the 20 leading causes of death were chosen; 9 of these were also amongst the top 10 causes of death in low-income countries. Studies were identified from the ClinicalTrials.gov database and included phase 1 and/or 2 "interventional" "open" trials, i.e. those recruiting or about to start recruitment. Trials were considered in terms of sponsorship [industry, universities and other organisations (UNO), and US federal agencies (NIH included)], genders and age groups included, and whether they were conducted with drugs and/or biologicals. The search was performed in March 2010. A total of 2,298 (824 phase 1; 1,474 phase 2) trials were retrieved. Of these, 67% were on trachea, bronchus, and lung cancers (25%); diabetes mellitus (15%); colon and rectum cancers (14%); and HIV/AIDS (12%). In contrast, only 4% were trials on diarrhoeal disease, nephrosis and nephritis, liver cirrhosis, and prematurity and low birth weight. UNO were the first source of funding. Fifty-two percent of phase 1 non-cancer trials were on healthy volunteers. Twenty-nine percent of all trials were co-funded. There were 4.6 times as many drug trials as those with biologicals. Only 7% were conducted with a combination of drugs and biologicals, the majority (78%) on cancers. Discrimination in terms of gender or age group was not observed. Four of the 16 diseases considered represented 2/3 of early phase trials. Cancers were a top priority for all sponsors. Increasing attention should be given to conditions with current and projected global high mortality rates that had few "open" early phase trials.

  6. The Relationship between Sun Protection Policy and Associated Practices in a National Sample of Early Childhood Services in Australia

    ERIC Educational Resources Information Center

    Ettridge, Kerry A.; Bowden, Jacqueline A.; Rayner, Joanne M.; Wilson, Carlene J.

    2011-01-01

    Limiting exposure to sunlight during childhood can significantly reduce the risk of skin cancer. This was the first national study to assess the sun protection policies and practices of early childhood services across Australia. It also examined the key predictors of services' sun protection practices. In 2007, 1017 respondents completed a…

  7. Worldwide isotope ratios of the Fukushima release and early-phase external dose reconstruction

    PubMed Central

    Chaisan, Kittisak; Smith, Jim T.; Bossew, Peter; Kirchner, Gerald; Laptev, Gennady V.

    2013-01-01

    Measurements of radionuclides (RNs) in air made worldwide following the Fukushima accident are quantitatively compared with air and soil measurements made in Japan. Isotopic ratios RN:137Cs of 131I, 132Te, 134,136Cs, are correlated with distance from release. It is shown, for the first time, that both within Japan and globally, ratios RN:137Cs in air were relatively constant for primarily particle associated radionuclides (134,136Cs; 132Te) but that 131I shows much lower local (<80 km) isotope ratios in soils relative to 137Cs. Derived isotope ratios are used to reconstruct external dose rate during the early phase post-accident. Model “blind” tests show more than 95% of predictions within a factor of two of measurements from 15 sites to the north, northwest and west of the power station. It is demonstrated that generic isotope ratios provide a sound basis for reconstruction of early-phase external dose rates in these most contaminated areas. PMID:24018776

  8. Phase Retrieval from Modulus Using Homeomorphic Signal Processing and the Complex Cepstrum: An Algorithm for Lightning Protection Systems

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

    Clark, G A

    2004-06-08

    In general, the Phase Retrieval from Modulus problem is very difficult. In this report, we solve the difficult, but somewhat more tractable case in which we constrain the solution to a minimum phase reconstruction. We exploit the real-and imaginary part sufficiency properties of the Fourier and Hilbert Transforms of causal sequences to develop an algorithm for reconstructing spectral phase given only spectral modulus. The algorithm uses homeomorphic signal processing methods with the complex cepstrum. The formal problem of interest is: Given measurements of only the modulus {vert_bar}H(k){vert_bar} (no phase) of the Discrete Fourier Transform (DFT) of a real, finite-length, stable,more » causal time domain signal h(n), compute a minimum phase reconstruction {cflx h}(n) of the signal. Then compute the phase of {cflx h}(n) using a DFT, and exploit the result as an estimate of the phase of h(n). The development of the algorithm is quite involved, but the final algorithm and its implementation are very simple. This work was motivated by a Phase Retrieval from Modulus Problem that arose in LLNL Defense Sciences Engineering Division (DSED) projects in lightning protection for buildings. The measurements are limited to modulus-only spectra from a spectrum analyzer. However, it is desired to perform system identification on the building to compute impulse responses and transfer functions that describe the amount of lightning energy that will be transferred from the outside of the building to the inside. This calculation requires knowledge of the entire signals (both modulus and phase). The algorithm and software described in this report are proposed as an approach to phase retrieval that can be used for programmatic needs. This report presents a brief tutorial description of the mathematical problem and the derivation of the phase retrieval algorithm. The efficacy of the theory is demonstrated using simulated signals that meet the assumptions of the algorithm. We see

  9. SunSmart: evaluation of a pilot school-based sun protection intervention in Hispanic early adolescents

    PubMed Central

    Miller, K. A.; Langholz, B. M.; Ly, T.; Harris, S. C.; Richardson, J. L.; Peng, D. H.; Cockburn, M. G.

    2015-01-01

    The incidence of melanoma is rising among Hispanic populations in the United States. The purpose of this study is to evaluate the impact of a pilot sun safety educational intervention conducted from 2006 to 2012 on Hispanic early adolescents in a high ultraviolet environment. Nineteen schools with high Hispanic enrollment were recruited from urban neighborhoods in Los Angeles. The analytic sample was restricted to students identifying as Hispanic or Latino (n = 777). A mixed effects linear model was used to test mean changes from pre- to posttest on students’ sun protection knowledge, attitudes and behaviors. Significant improvements were observed across several cognitive outcomes related to sun protection, including knowledge of and attitudes toward sun protection and self-efficacy to wear sunscreen. However, changes in sun protective behaviors were not achieved. Although some improvements were observed, future studies should identify the factors that motivate sun protection in this population and develop tailored prevention strategies, as improving the sun safe behaviors of Hispanic youths may aid in reducing the risk of melanoma in adulthood in this population. PMID:25801103

  10. Three steps to writing adaptive study protocols in the early phase clinical development of new medicines

    PubMed Central

    2014-01-01

    This article attempts to define terminology and to describe a process for writing adaptive, early phase study protocols which are transparent, self-intuitive and uniform. It provides a step by step guide, giving templates from projects which received regulatory authorisation and were successfully performed in the UK. During adaptive studies evolving data is used to modify the trial design and conduct within the protocol-defined remit. Adaptations within that remit are documented using non-substantial protocol amendments which do not require regulatory or ethical review. This concept is efficient in gathering relevant data in exploratory early phase studies, ethical and time- and cost-effective. PMID:24980283

  11. Cosmological QCD phase transition in steady non-equilibrium dissipative Hořava–Lifshitz early universe

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

    Khodadi, M., E-mail: M.Khodadi@sbu.ac.ir; Sepangi, H.R., E-mail: hr-sepangi@sbu.ac.ir

    We study the phase transition from quark–gluon plasma to hadrons in the early universe in the context of non-equilibrium thermodynamics. According to the standard model of cosmology, a phase transition associated with chiral symmetry breaking after the electro-weak transition has occurred when the universe was about 1–10 μs old. We focus attention on such a phase transition in the presence of a viscous relativistic cosmological background fluid in the framework of non-detailed balance Hořava–Lifshitz cosmology within an effective model of QCD. We consider a flat Friedmann–Robertson–Walker universe filled with a non-causal and a causal bulk viscous cosmological fluid respectively and investigatemore » the effects of the running coupling constants of Hořava–Lifshitz gravity, λ, on the evolution of the physical quantities relevant to a description of the early universe, namely, the temperature T, scale factor a, deceleration parameter q and dimensionless ratio of the bulk viscosity coefficient to entropy density (ξ)/s . We assume that the bulk viscosity cosmological background fluid obeys the evolution equation of the steady truncated (Eckart) and full version of the Israel–Stewart fluid, respectively. -- Highlights: •In this paper we have studied quark–hadron phase transition in the early universe in the context of the Hořava–Lifshitz model. •We use a flat FRW universe with the bulk viscosity cosmological background fluid obeying the evolution equation of the steady truncated (Eckart) and full version of the Israel–Stewart fluid, respectively.« less

  12. Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

    PubMed

    Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

    2017-02-01

    Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Endothelial gaps and adherent leukocytes in allergen-induced early- and late-phase plasma leakage in rat airways.

    PubMed Central

    Baluk, P.; Bolton, P.; Hirata, A.; Thurston, G.; McDonald, D. M.

    1998-01-01

    Exposure of sensitized individuals to antigen can induce allergic responses in the respiratory tract, manifested by early and late phases of vasodilatation, plasma leakage, leukocyte influx, and bronchoconstriction. Similar responses can occur in the skin, eye, and gastrointestinal tract. The early-phase response involves mast cell mediators and the late-phase response is leukocyte dependent, but the mechanism of leakage is not understood. We sought to identify the leaky blood vessels, to determine whether these vessels contained endothelial gaps, and to analyze the relationship of the gaps to adherent leukocytes, using biotinylated lectins or silver nitrate to stain the cells in situ and Monastral blue as a tracer to quantify plasma leakage. Most of the leakage occurred in postcapillary venules (< 40-microns diameter), whereas most of the leukocyte migration (predominantly neutrophils) occurred in collecting venules. Capillaries and arterioles did not leak. Endothelial gaps were found in the leaky venules, both by silver nitrate staining and by scanning electron microscopy, and 94% of the gaps were distinct from sites of leukocyte adhesion or migration. We conclude that endothelial gaps contribute to both early and late phases of plasma leakage induced by antigen, but most leakage occurs upstream to sites of leukocyte adhesion. Images Figure 3 Figure 5 Figure 6 Figure 7 PMID:9626051

  14. CP7_E2alf oral vaccination confers partial protection against early classical swine fever virus challenge and interferes with pathogeny-related cytokine responses

    PubMed Central

    2013-01-01

    The conventional C-strain vaccine induces early protection against classical swine fever (CSF), but infected animals cannot be distinguished from vaccinated animals. The CP7_E2alf marker vaccine, a pestivirus chimera, could be a suitable substitute for C-strain vaccine to control CSF outbreaks. In this study, single oral applications of CP7_E2alf and C-strain vaccines were compared for their efficacy to induce protection against a CSF virus (CSFV) challenge with the moderately virulent Bas-Rhin isolate, in pigs as early as two days post-immunization. This work emphasizes the powerful potential of CP7_E2alf vaccine administered orally by a rapid onset of partial protection similar to that induced by the C-strain vaccine. Furthermore, our results revealed that both vaccinations attenuated the effects induced by CSFV on production of the pig major acute phase protein (PigMAP), IFN-α, IL-12, IL-10, and TGF-β1 cytokines. By this interference, several cytokines that may play a role in the pathogeny induced by moderately virulent CSFV strains were revealed. New hypotheses concerning the role of each of these cytokines in CSFV pathogeny are discussed. Our results also show that oral vaccination with either vaccine (CP7_E2alf or C-strain) enhanced CSFV–specific IgG2 production, compared to infection alone. Interestingly, despite the similar antibody profiles displayed by both vaccines post-challenge, the production of CSFV-specific IgG1 and neutralizing antibodies without challenge was lower with CP7_E2alf vaccination than with C-strain vaccination, suggesting a slight difference in the balance of adaptive immune responses between these vaccines. PMID:23398967

  15. Early Potent Protection against Heterologous SIVsmE660 Challenge Following Live Attenuated SIV Vaccination in Mauritian Cynomolgus Macaques

    PubMed Central

    Berry, Neil; Ham, Claire; Mee, Edward T.; Rose, Nicola J.; Mattiuzzo, Giada; Jenkins, Adrian; Page, Mark; Elsley, William; Robinson, Mark; Smith, Deborah; Ferguson, Deborah; Towers, Greg; Almond, Neil; Stebbings, Richard

    2011-01-01

    Background Live attenuated simian immunodeficiency virus (SIV) vaccines represent the most effective means of vaccinating macaques against pathogenic SIV challenge. However, thus far, protection has been demonstrated to be more effective against homologous than heterologous strains. Immune correlates of vaccine-induced protection have also been difficult to identify, particularly those measurable in the peripheral circulation. Methodology/Principal Findings Here we describe potent protection in 6 out of 8 Mauritian-derived cynomolgus macaques (MCM) against heterologous virus challenge with the pathogenic, uncloned SIVsmE660 viral stock following vaccination with live attenuated SIVmac251/C8. MCM provided a characterised host genetic background with limited Major Histocompatibility Complex (MHC) and TRIM5α allelic diversity. Early protection, observed as soon as 3 weeks post-vaccination, was comparable to that of 20 weeks vaccination. Recrudescence of vaccine virus was most pronounced in breakthrough cases where simultaneous identification of vaccine and challenge viruses by virus-specific PCR was indicative of active co-infection. Persistence of the vaccine virus in a range of lymphoid tissues was typified by a consistent level of SIV RNA positive cells in protected vaccinates. However, no association between MHC class I /II haplotype or TRIM5α polymorphism and study outcome was identified. Conclusion/Significance This SIV vaccine study, conducted in MHC-characterised MCM, demonstrated potent protection against the pathogenic, heterologous SIVsmE660 challenge stock after only 3 weeks vaccination. This level of protection against this viral stock by intravenous challenge has not been hitherto observed. The mechanism(s) of protection by vaccination with live attenuated SIV must account for the heterologous and early protection data described in this study, including those which relate to the innate immune system. PMID:21853072

  16. Comparison of Short- and Long-Term Cardiac Mortality in Early Versus Late Stent Thrombosis (from Pooled PROTECT Trials).

    PubMed

    Secemsky, Eric A; Matteau, Alexis; Yeh, Robert W; Steg, Philippe Gabriel; Camenzind, Edoardo; Wijns, William; McFadden, Eugene; Mauri, Laura

    2015-06-15

    Studies have indicated varying mortality risks with timing of stent thrombosis (ST), but few have been adequately powered with prospective late follow-up. PROTECT randomized 8,709 subjects to either Endeavor zotarolimus-eluting or Cypher sirolimus-eluting stents. PROTECT Continued Access enrolled 1,018 patients treated with Endeavor zotarolimus-eluting stents. Subjects completed at least 4 and 3 years of follow-up, respectively. ARC-defined definite and probable ST events were stratified by time from index procedure: early (≤30 days), late (>30 and ≤360 days), and very late (>360 days). Rates of death and myocardial infarction were analyzed by ST timing. Median follow-up was 4.1 years. There were 184 ST events (1.9%): 61 early, 27 late, and 96 very late. Patient and procedural characteristics were similar between timing groups. There was no difference in dual-antiplatelet therapy use at discharge (97%) or 1 year (84%). Cardiac death in patients with ST at 4 years occurred in 32.1% compared with 2.5% in patients without ST (p <0.001). Combined rates of cardiac death and myocardial infarction did not differ according to ST timing, yet early ST was more commonly associated with cardiac death at 4 years than later ST (50.8% for early vs 18.5% for late vs 24.0% for very late; p <0.001). The relation between ST timing and outcomes did not differ between stent types. In conclusion, in prospective data, cardiac death was more common after early ST than later ST. Although ST remains infrequent, continued efforts to determine how to reduce ST, particularly within the first 30 days, are warranted. (The PROTECT trial is registered with ClinicalTrials.gov, number NCT00476957.). Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Contribution of economic evaluation to decision making in early phases of product development: a methodological and empirical review.

    PubMed

    Hartz, Susanne; John, Jürgen

    2008-01-01

    Economic evaluation as an integral part of health technology assessment is today mostly applied to established technologies. Evaluating healthcare innovations in their early states of development has recently attracted attention. Although it offers several benefits, it also holds methodological challenges. The aim of our study was to investigate the possible contributions of economic evaluation to industry's decision making early in product development and to confront the results with the actual use of early data in economic assessments. We conducted a literature research to detect methodological contributions as well as economic evaluations that used data from early phases of product development. Economic analysis can be beneficially used in early phases of product development for various purposes including early market assessment, R&D portfolio management, and first estimations of pricing and reimbursement scenarios. Analytical tools available for these purposes have been identified. Numerous empirical works were detected, but most do not disclose any concrete decision context and could not be directly matched with the suggested applications. Industry can benefit from starting economic evaluation early in product development in several ways. Empirical evidence suggests that there is still potential left unused.

  18. Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS

    PubMed Central

    Watanabe, Hama; Shitara, Yoshihiko; Aoki, Yoshinori; Inoue, Takanobu; Tsuchida, Shinya; Takahashi, Naoto; Taga, Gentaro

    2017-01-01

    A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an in-phase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants. PMID:28196885

  19. Inside information: Financial conflicts of interest for research subjects in early phase clinical trials.

    PubMed

    Helft, Paul R; Ratain, Mark J; Epstein, Richard A; Siegler, Mark

    2004-05-05

    In recent years, several research subjects have told us that they had bought or intended to buy stock in the companies sponsoring the clinical trials in which they were enrolled. This situation has led us to ask what, if any, are physician-investigators' scientific, ethical, and legal responsibilities concerning research subjects who choose to buy stock in the companies sponsoring the clinical trials in which they are participating. Although the scope of this problem is unknown and is likely to be small, this commentary examines the scientific, ethical, and legal concerns raised by such activities on the part of research subjects enrolled in early phase clinical trials. In addition, this commentary also outlines the basis for our opinion that research subjects involved in an early phase clinical trial should avoid the financial conflicts of interest created by trading stock in the company sponsoring the clinical trial.

  20. Integrating Crystallography into Early Metabolism Studies

    NASA Astrophysics Data System (ADS)

    Cruciani, Gabriele; Aristei, Yasmin; Goracci, Laura; Carosati, Emanuele

    Since bioavailability, activity, toxicity, distribution, and final elimination all depend on metabolic biotransformations, it would be extremely advantageous if this information to be produced early in the discovery phase. Once obtained, researchers can judge whether or not a potential candidate should be eliminated from the pipeline, or modified to improve chemical stability or safety. The use of in silico methods to predict the site of metabolism in Phase I cytochrome-mediated reactions is a starting point in any metabolic pathway prediction. This paper presents a new method, which provides the site of metabolism for any CYP-mediated reaction acting on unknown substrates. The methodology can be applied automatically to all the cytochromes whose Xray 3D structure is known, but can be also applied to homology model 3D structures. The fully automated procedure can be used to detect positions that should be protected in order to avoid metabolic degradation, or to check the suitability of a new scaffold or pro-drug. Therefore the procedure is also a valuable new tool in early ADME-Tox, where drug-safety and metabolic profile patterns must be evaluated as soon, and as early, as possible.

  1. Enabling Parametric Optimal Ascent Trajectory Modeling During Early Phases of Design

    NASA Technical Reports Server (NTRS)

    Holt, James B.; Dees, Patrick D.; Diaz, Manuel J.

    2015-01-01

    During the early phases of engineering design, the costs committed are high, costs incurred are low, and the design freedom is high. It is well documented that decisions made in these early design phases drive the entire design's life cycle. In a traditional paradigm, key design decisions are made when little is known about the design. As the design matures, design changes become more difficult -- in both cost and schedule -- to enact. Indeed, the current capability-based paradigm that has emerged because of the constrained economic environment calls for the infusion of knowledge acquired during later design phases into earlier design phases, i.e. bring knowledge acquired during preliminary and detailed design into pre-conceptual and conceptual design. An area of critical importance to launch vehicle design is the optimization of its ascent trajectory, as the optimal trajectory will be able to take full advantage of the launch vehicle's capability to deliver a maximum amount of payload into orbit. Hence, the optimal ascent trajectory plays an important role in the vehicle's affordability posture as the need for more economically viable access to space solutions are needed in today's constrained economic environment. The problem of ascent trajectory optimization is not a new one. There are several programs that are widely used in industry that allows trajectory analysts to, based on detailed vehicle and insertion orbit parameters, determine the optimal ascent trajectory. Yet, little information is known about the launch vehicle early in the design phase - information that is required of many different disciplines in order to successfully optimize the ascent trajectory. Thus, the current paradigm of optimizing ascent trajectories involves generating point solutions for every change in a vehicle's design parameters. This is often a very tedious, manual, and time-consuming task for the analysts. Moreover, the trajectory design space is highly non-linear and multi

  2. Divided attention can enhance early-phase memory encoding: the attentional boost effect and study trial duration.

    PubMed

    Mulligan, Neil W; Spataro, Pietro

    2015-07-01

    Divided attention during encoding typically produces marked reductions in later memory. The attentional boost effect (ABE) is a surprising variation on this phenomenon. In this paradigm, each study stimulus (e.g., a word) is presented along with a target or a distractor (e.g., different colored circles) in a detection task. Later memory is better for stimuli co-occurring with targets. The present experiments indicate that the ABE arises during an early phase of memory encoding that involves initial stimulus perception and comprehension rather than at a later phase entailing controlled, elaborative rehearsal. Experiment 1 demonstrated that the ABE was robust at a short study duration (700 ms) and did not increase with increasing study trial durations (1,500 ms and 4,000 ms). Furthermore, the target condition is boosted to the level of memory performance in a full-attention condition for the short duration but not the long duration. Both results followed from the early-phase account. This account also predicts that for very short study times (limiting the influence of late-phase controlled encoding and thus minimizing the usual negative effect of divided attention), the target condition will produce better memory than will the full-attention condition. Experiment 2 used a study time of 400 ms and found that words presented with targets lead to greater recognition accuracy than do either words presented with distractors or words in the full-attention condition. Consistent with the early-phase account, a divided attention condition actually produced superior memory than did the full-attention condition, a very unusual but theoretically predicted result. (c) 2015 APA, all rights reserved.

  3. Early Childhood Settings in 15 Countries: What Are Their Structural Characteristics? The IEA Preprimary Project, Phase 2.

    ERIC Educational Resources Information Center

    Olmsted, Patricia P., Ed.; Montie, Jeanne, Ed.

    This is the second of four monographs reporting the findings of Phase 2 of the International Association for the Evaluation of Educational Achievement (IEA) Preprimary Project, which presents data on the physical characteristics of children's early childhood settings. Early childhood settings were documented in the following 15 countries: (1)…

  4. Efficient runner safety assessment during early design phase and root cause analysis

    NASA Astrophysics Data System (ADS)

    Liang, Q. W.; Lais, S.; Gentner, C.; Braun, O.

    2012-11-01

    Fatigue related problems in Francis turbines, especially high head Francis turbines, have been published several times in the last years. During operation the runner is exposed to various steady and unsteady hydraulic loads. Therefore the analysis of forced response of the runner structure requires a combined approach of fluid dynamics and structural dynamics. Due to the high complexity of the phenomena and due to the limitation of computer power, the numerical prediction was in the past too expensive and not feasible for the use as standard design tool. However, due to continuous improvement of the knowledge and the simulation tools such complex analysis has become part of the design procedure in ANDRITZ HYDRO. This article describes the application of most advanced analysis techniques in runner safety check (RSC), including steady state CFD analysis, transient CFD analysis considering rotor stator interaction (RSI), static FE analysis and modal analysis in water considering the added mass effect, in the early design phase. This procedure allows a very efficient interaction between the hydraulic designer and the mechanical designer during the design phase, such that a risk of failure can be detected and avoided in an early design stage.The RSC procedure can also be applied to a root cause analysis (RCA) both to find out the cause of failure and to quickly define a technical solution to meet the safety criteria. An efficient application to a RCA of cracks in a Francis runner is quoted in this article as an example. The results of the RCA are presented together with an efficient and inexpensive solution whose effectiveness could be proven again by applying the described RSC technics. It is shown that, with the RSC procedure developed and applied as standard procedure in ANDRITZ HYDRO such a failure is excluded in an early design phase. Moreover, the RSC procedure is compatible with different commercial and open source codes and can be easily adapted to apply for

  5. Development of the self-learning machine for creating models of microprocessor of single-phase earth fault protection devices in networks with isolated neutral voltage above 1000 V

    NASA Astrophysics Data System (ADS)

    Utegulov, B. B.; Utegulov, A. B.; Meiramova, S.

    2018-02-01

    The paper proposes the development of a self-learning machine for creating models of microprocessor-based single-phase ground fault protection devices in networks with an isolated neutral voltage higher than 1000 V. Development of a self-learning machine for creating models of microprocessor-based single-phase earth fault protection devices in networks with an isolated neutral voltage higher than 1000 V. allows to effectively implement mathematical models of automatic change of protection settings. Single-phase earth fault protection devices.

  6. Characterization of Early-Phase Neutrophil Extracellular Traps in Urinary Tract Infections

    PubMed Central

    Yu, Yanbao; Kwon, Keehwan; Tsitrin, Tamara; Sikorski, Patricia; Nelson, Karen E.; Pieper, Rembert

    2017-01-01

    Neutrophils have an important role in the antimicrobial defense and resolution of urinary tract infections (UTIs). Our research suggests that a mechanism known as neutrophil extracellular trap (NET) formation is a defense strategy to combat pathogens that have invaded the urinary tract. A set of human urine specimens with very high neutrophil counts had microscopic evidence of cellular aggregation and lysis. Deoxyribonuclease I (DNase) treatment resulted in disaggregation of such structures, release of DNA fragments and a proteome enriched in histones and azurophilic granule effectors whose quantitative composition was similar to that of previously described in vitro-formed NETs. The effector proteins were further enriched in DNA-protein complexes isolated in native PAGE gels. Immunofluorescence microscopy revealed a flattened morphology of neutrophils associated with decondensed chromatin, remnants of granules in the cell periphery, and myeloperoxidase co-localized with extracellular DNA, features consistent with early-phase NETs. Nuclear staining revealed that a considerable fraction of bacterial cells in these structures were dead. The proteomes of two pathogens, Staphylococcus aureus and Escherichia coli, were indicative of adaptive responses to early-phase NETs, specifically the release of virulence factors and arrest of ribosomal protein synthesis. Finally, we discovered patterns of proteolysis consistent with widespread cleavage of proteins by neutrophil elastase, proteinase 3 and cathepsin G and evidence of citrullination in many nuclear proteins. PMID:28129394

  7. Sustained attention is favored by progesterone during early luteal phase and visuo-spatial memory by estrogens during ovulatory phase in young women.

    PubMed

    Solís-Ortiz, S; Corsi-Cabrera, M

    2008-08-01

    Studies examining the influence of the menstrual cycle on cognitive function have been highly contradictory. The maintenance of attention is key to successful information processing, however how it co-vary with other cognitive functions and mood in function of phases of the menstrual cycle is not well know. Therefore, neuropsychological performance of nine healthy women with regular menstrual cycles was assessed during ovulation (OVU), early luteal (EL), late luteal (LL) and menstrual (MEN) phases. Neuropsychological test scores of sustained attention, executive functions, manual coordination, visuo-spatial memory, verbal fluency, spatial ability, anxiety and depression were obtained and submitted to a principal components analysis (PCA). Five eigenvectors that accounted the 68.31% of the total variance were identified. Performance of the sustained attention was grouped in an independent eigenvector (component 1), and the scores on verbal fluency and visuo-spatial memory were grouped together in an eigenvector (component 5), which explained 17.69% and 12.03% of the total variance, respectively. The component 1 (p<0.034) and the component 5 (p<0.003) showed significant variations during the menstrual cycle. Sustained attention showed an increase in the EL phase, when the progesterone is high. Visuo-spatial memory was increased, while that verbal fluency was decreased during the OVU phase, when the estrogens levels are high. These results indicate that sustained attention is favored by early luteal phase progesterone and do not covaried with any other neuropsychological variables studied. The influence of the estrogens on visuo-spatial memory was corroborated, and covaried inversely with verbal fluency.

  8. Maintaining Traditions: A Qualitative Study of Early Childhood Caries Risk and Protective Factors in an Indigenous Community

    PubMed Central

    Levin, Ana; Sokal-Gutierrez, Karen; Hargrave, Anita; Funsch, Elizabeth; Hoeft, Kristin S.

    2017-01-01

    In lower middle-income economies (LMIE), the nutrition transition from traditional diets to sugary foods and beverages has contributed to widespread early childhood dental caries. This qualitative study explores perceived risk and protective factors, and overall experiences of early childhood nutrition and oral health in indigenous Ecuadorian families participating in a community-based oral health and nutrition intervention. Dental exams of 698 children age 6 months through 6 years determined each child’s caries burden. A convenience sample of 18 “outlier” families was identified: low-caries children with ≤2 carious teeth vs. high-caries children with ≥10 carious teeth. Semi-structured in-depth interviews with parents/caregivers explored the child’s diet, dental habits, and family factors related to nutrition and oral health. Interviews were transcribed and thematically analyzed using grounded theory. In the high-caries families, proximity to highway and stores, consumption of processed-food, and low parental monitoring of child behavior were identified as risk factors for ECC (early childhood caries). In the low-caries families, protective factors included harvesting and consuming food from the family farm, remote geography, and greater parental monitoring of child behavior. The study results suggest that maintaining traditional family farms and authoritative parenting to avoid processed foods/drinks and ensure tooth brushing could improve early childhood nutrition and oral health. PMID:28800116

  9. Maintaining Traditions: A Qualitative Study of Early Childhood Caries Risk and Protective Factors in an Indigenous Community.

    PubMed

    Levin, Ana; Sokal-Gutierrez, Karen; Hargrave, Anita; Funsch, Elizabeth; Hoeft, Kristin S

    2017-08-11

    In lower middle-income economies (LMIE), the nutrition transition from traditional diets to sugary foods and beverages has contributed to widespread early childhood dental caries. This qualitative study explores perceived risk and protective factors, and overall experiences of early childhood nutrition and oral health in indigenous Ecuadorian families participating in a community-based oral health and nutrition intervention. Dental exams of 698 children age 6 months through 6 years determined each child's caries burden. A convenience sample of 18 "outlier" families was identified: low-caries children with ≤2 carious teeth vs. high-caries children with ≥10 carious teeth. Semi-structured in-depth interviews with parents/caregivers explored the child's diet, dental habits, and family factors related to nutrition and oral health. Interviews were transcribed and thematically analyzed using grounded theory. In the high-caries families, proximity to highway and stores, consumption of processed-food, and low parental monitoring of child behavior were identified as risk factors for ECC (early childhood caries). In the low-caries families, protective factors included harvesting and consuming food from the family farm, remote geography, and greater parental monitoring of child behavior. The study results suggest that maintaining traditional family farms and authoritative parenting to avoid processed foods/drinks and ensure tooth brushing could improve early childhood nutrition and oral health.

  10. Association Between Vascular Density and Loss of Protective RAS During Early NPDR by Fractal Dimension

    NASA Technical Reports Server (NTRS)

    Radhakrishnan, Krisnan; Vyas, Ruchi J.; Murray, Matthew; Predovic, Marina; Lim, Shiyin; Bryant, Douglas; Yaqian, Duan; Grant, Maria B.; Chalam, K. V.; Parsons-Wingerter, Patricia

    2017-01-01

    compensation of protective RAS during early DR. Migratory dysfunction of CD34+ cells was further associated with DR. Conclusions: As assessed by the fractal dimension in our preliminary study, the space-filling capacity of veins, but not arteries, was greater in early NPDR than in control. Larger patient populations will be examined as we complete our ongoing longitudinal study. Results further suggest the protective RAS axis within diabetic CACs is lost early in DR and is associated with increased vascular remodeling as evidenced by VESGEN analysis.

  11. SunSmart: evaluation of a pilot school-based sun protection intervention in Hispanic early adolescents.

    PubMed

    Miller, K A; Langholz, B M; Ly, T; Harris, S C; Richardson, J L; Peng, D H; Cockburn, M G

    2015-06-01

    The incidence of melanoma is rising among Hispanic populations in the United States. The purpose of this study is to evaluate the impact of a pilot sun safety educational intervention conducted from 2006 to 2012 on Hispanic early adolescents in a high ultraviolet environment. Nineteen schools with high Hispanic enrollment were recruited from urban neighborhoods in Los Angeles. The analytic sample was restricted to students identifying as Hispanic or Latino (n = 777). A mixed effects linear model was used to test mean changes from pre- to posttest on students' sun protection knowledge, attitudes and behaviors. Significant improvements were observed across several cognitive outcomes related to sun protection, including knowledge of and attitudes toward sun protection and self-efficacy to wear sunscreen. However, changes in sun protective behaviors were not achieved. Although some improvements were observed, future studies should identify the factors that motivate sun protection in this population and develop tailored prevention strategies, as improving the sun safe behaviors of Hispanic youths may aid in reducing the risk of melanoma in adulthood in this population. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  12. Plasma sprayed manganese-cobalt spinel coatings: Process sensitivity on phase, electrical and protective performance

    NASA Astrophysics Data System (ADS)

    Han, Su Jung; Pala, Zdenek; Sampath, Sanjay

    2016-02-01

    Manganese cobalt spinel (Mn1.5Co1.5O4, MCO) coatings are prepared by the air plasma spray (APS) process to examine their efficacy in serving as protective coatings from Cr-poisoning of the cathode side in intermediate temperature-solid oxide fuel cells (IT-SOFCs). These complex oxides are susceptible to process induced stoichiometric and phase changes which affect their functional performance. To critically examine these effects, MCO coatings are produced with deliberate modifications to the spray process parameters to explore relationship among process conditions, microstructure and functional properties. The resultant interplay among particle thermal and kinetic energies are captured through process maps, which serve to characterize the parametric effects on properties. The results show significant changes to the chemistry and phase composition of the deposited material resulting from preferential evaporation of oxygen. Post deposition annealing recovers oxygen in the coatings and allows partial recovery of the spinel phase, which is confirmed through thermo-gravimetric analysis (TGA)/differential scanning calorimetry (DSC), X-ray Diffraction (XRD), and magnetic hysteresis measurements. In addition, coatings with high density after sintering show excellent electrical conductivity of 40 S cm-1 at 800 °C while simultaneously providing requisite protection characteristics against Cr-poisoning. This study provides a framework for optimal evaluation of MCO coatings in intermediate temperature SOFCs.

  13. Early Human Testing Initiative Phase 1 Regenerative Life Support Systems

    NASA Image and Video Library

    1995-08-08

    Early Human Testing (EHT) Initiative Phase 1 Regenerative Life Support Systems Laboratory (RLSSL). Nigel Packham activities in the Variable Pressure Growth Chamber which he lived inside for 15 days. A crowd of well-wishers outside the test chamber, at the console are John Lewis, Ed Mohr and Marybeth Edeen (15577). Packham exiting the chamber (15578-81). Packham is the focus of television cameras and reporters (15582-3). Don Henninger interviewed by reporters (15584). Packham is presented with a jacket after his stay in the chamber (15585). Packham inside the wheat growth chamber checking the condition of the plants (15586-7, 15597). Packham exercising on a recumbant bicycle (15588, 15592). Packham, through the window into the growth chamber, displays a handful of wheat plants to console monitor Dan Barta (15589-90). Group portrait of the team conducting the Early Human Testing Initiative Phase 1 Regenerative Life Support Systems test and include, front row, from left: Jeff Dominick and Don Overton and back row, from left, unidentified member, Marybeth Edeen, Nigel Packham, John Lewis, Ed Mohr, Dan Barta and Tim Monk (15591). Harry Halford prepares to send a package through the airlock to Packham (15593). Packham displays a handful of wheat plants (15594). Packham fixes himself a bowl of cereal (15595) and retrieves a carton of milk from the refrigerator (15596). Packham retrieves a package from the airlock (15598). Packham packs up trash in plastic bag (15599-600) and sends it back through the airlock (15601). Packham gets a cup of water (15602) and heats it in the microwave (15603).

  14. [The correlation between serum uric acid level and early-phase insulin secretion in subjects with normal glucose regulation].

    PubMed

    Lu, L; Zheng, F P; Li, H

    2016-05-01

    To investigate the correlation between serum uric acid (SUA) level and early-phase insulin secretion in subjects with normal glucose regulation (NGR). Totally 367 community NGR residents confirmed by a 75g oral glucose tolerance test were enrolled. The insulin resistance index (HOMA-IR) and the early-phase insulin secretion index after a glucose load (ΔI30/ΔG30) were used to estimate the insulin sensitivity and the early-phase insulin secretion, respectively. The subjects were divided into 4 groups according to the SUA level quartiles. Differences in early-phase insulin levels, ΔI30/ΔG30, and HOMA-IR were compared among the 4 groups. Age, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting insulin (FINS), 30 minutes postprandial insulin(30 minINS), 2 hours postprandial insulin(2hINS), HOMA-IR and TG levels increased across the rising categories of SUA levels, while the HDL-C was decreased across the SUA groups (P<0.01). The SUA level was positively correlated with age(r=0.157, P<0.01), BMI(r=0.262, P<0.01), waist circumference(r=0.372, P<0.01), systolic blood pressure(r=0.200, P<0.01), diastolic blood pressure(r=0.254, P<0.01), 30 minutes postprandial plasma glucose(r=0.118, P=0.023), FINS(r=0.249, P<0.01), 30minINS(r=0.189, P<0.01), 2hINS(r=0.206, P<0.01), glycosylated hemoglobin(HbA1c, r=0.106, P=0.042), HOMA-IR(r=0.244, P<0.01), TG(r=0.350, P<0.01), ΔI30/ΔG30(r=0.144, P<0.01), and negatively correlated with HDL-C level(r=-0.321, P<0.01). Multiple stepwise regression analysis showed that SUA(β=0.292, P<0.01) and HOMA-IR(β=29.821, P<0.01) were positively associated with ΔI30/ΔG30. SUA level is closely related with the early-phase insulin secretion in NGR subjects.

  15. 77 FR 36958 - Proposed Requirements-Race to the Top-Early Learning Challenge; Phase 2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-20

    ... DEPARTMENT OF EDUCATION 34 CFR Chapter II DEPARTMENT OF HEALTH AND HUMAN SERVICES 45 CFR Subtitle... Requirements--Race to the Top--Early Learning Challenge; Phase 2 AGENCY: Department of Education and Department of Health and Human Services. ACTION: Proposed requirements. SUMMARY: The Secretary of Education and...

  16. Antigravity treadmill training during the early rehabilitation phase following unicompartmental knee arthroplasty: A case series.

    PubMed

    Huang, Chun-Hao; Schroeder, E Todd; Powers, Christopher

    2018-02-26

    Patients who have undergone unicompartmental knee arthroplasty (UKA) have been reported to exhibit altered gait 19-25 months post-surgery. The most common gait impairment in this population is inadequate knee flexion and a corresponding decrease in the knee extensor moment during loading response (i.e., quadriceps avoidance). The purpose of this case series was to determine whether incorporation of antigravity treadmill training into a standard physical therapy program can eliminate quadriceps avoidance gait during the early rehabilitation phase following UKA. Four females who underwent UKA were recruited for this study. Participants completed antigravity treadmill training three times per week for 12 weeks in addition to their standard physical therapy program. Instrumented gait analysis was performed at baseline (pre-intervention), week 6 (mid-intervention), and week 12 (post-intervention). We found that peak knee flexion and the peak knee extensor moment during the weight acceptance phase of gait increased to normal values following the 12-week intervention period (14.1 ± 6.5° to 20.6 ± 1.5° and 0.4 ± 0.3 to 0.7 ± 0.2 Nm/kg respectively). The findings of this case series suggest that a standard physical therapy program that incorporates early gait training using an antigravity treadmill may be beneficial in eliminating "quadriceps avoidance" during the early rehabilitation phase following UKA.

  17. Early Leakage Protection System of LPG (Liquefied Petroleum Gas) Based on ATMega 16 Microcontroller

    NASA Astrophysics Data System (ADS)

    Sriwati; Ikhsan Ilahi, Nur; Musrawati; Baco, Syarifuddin; Suyuti'Andani Achmad, Ansar; Umrianah, Ejah

    2018-04-01

    LPG (Liquefied Petroleum Gas). LPG is a hydrocarbon gas production from refineries and gas refinery with the major components of propane gas (C3H8) and butane (C4H10). Limit flame (Flammable Range) or also called gas with air. Value Lower Explosive Limit (LEL) is the minimum limit of the concentration of fuel vapor in the air which if there is no source of fire, the gas will be burned. While the value of the Upper Explosive Limit (UEL), which limits the maximum concentration of fuel vapor in the air, which if no source of fire, the gas will be burned. Protection system is a defend mechanism of human, equipment, and buildings around the protected area. Goals to be achieved in this research are to design a protection system against the consequences caused by the leakage of LPG gas based on ATmega16 microcontroller. The method used in this research is to reduce the levels of leaked LPG and turned off the power source when the leakage of LPG is on the verge of explosive limit. The design of this protection system works accurately between 200 ppm up to 10000 ppm, which is still below the threshold of explosive. Thus protecting the early result of that will result in the leakage of LPG gas.

  18. Loop Braiding Statistics and Interacting Fermionic Symmetry-Protected Topological Phases in Three Dimensions

    NASA Astrophysics Data System (ADS)

    Cheng, Meng; Tantivasadakarn, Nathanan; Wang, Chenjie

    2018-01-01

    We study Abelian braiding statistics of loop excitations in three-dimensional gauge theories with fermionic particles and the closely related problem of classifying 3D fermionic symmetry-protected topological (FSPT) phases with unitary symmetries. It is known that the two problems are related by turning FSPT phases into gauge theories through gauging the global symmetry of the former. We show that there exist certain types of Abelian loop braiding statistics that are allowed only in the presence of fermionic particles, which correspond to 3D "intrinsic" FSPT phases, i.e., those that do not stem from bosonic SPT phases. While such intrinsic FSPT phases are ubiquitous in 2D systems and in 3D systems with antiunitary symmetries, their existence in 3D systems with unitary symmetries was not confirmed previously due to the fact that strong interaction is necessary to realize them. We show that the simplest unitary symmetry to support 3D intrinsic FSPT phases is Z2×Z4. To establish the results, we first derive a complete set of physical constraints on Abelian loop braiding statistics. Solving the constraints, we obtain all possible Abelian loop braiding statistics in 3D gauge theories, including those that correspond to intrinsic FSPT phases. Then, we construct exactly soluble state-sum models to realize the loop braiding statistics. These state-sum models generalize the well-known Crane-Yetter and Dijkgraaf-Witten models.

  19. The practical application of adaptive study design in early phase clinical trials: a retrospective analysis of time savings.

    PubMed

    Lorch, U; Berelowitz, K; Ozen, C; Naseem, A; Akuffo, E; Taubel, J

    2012-05-01

    The interest in adaptive study design is evident from the growing amount of clinical research employing this model in the mid to later stages of medicines development. Little has been published on the practical application and merits of adaptive study design in early phase clinical research. This paper describes a retrospective analysis performed on a sample of 29 industry lead adaptive early phase studies commencing between 1 January 2006 and 31 December 2010 in a clinical trials unit in London, England. All studies containing at least one adaptive feature in the original protocol were included in the analysis. The scope of the analysis was to assess whether the use of adaptive study designs provided tangible benefits over the use of conventional study designs using time savings as the main measure. We conclude that the use of adaptive study design saves time in early phase research programs. This is achieved by abolishing the need for substantial amendments or by mitigating their impact on timelines and by using adaptive scheduling efficiencies.

  20. White matter changes in early phase schizophrenia and cannabis use: an update and systematic review of diffusion tensor imaging studies.

    PubMed

    Cookey, Jacob; Bernier, Denise; Tibbo, Philip G

    2014-07-01

    The impact of cannabis use on the brain tissue is still unclear, both in the healthy developing brain and in people with schizophrenia. The focus of this review is on white matter, the primary connective infrastructure of the brain. We systematically reviewed diffusion tensor imaging (DTI) studies of early phase schizophrenia (illness effect), of cannabis use in otherwise healthy brains (drug effect), and of early phase schizophrenia with cannabis use (combined effects). Studies had to include a healthy, non-cannabis using, control group as well as report on fractional anisotropy as it is the most commonly used DTI index. We excluded cohorts with heavy alcohol or illicit drug use and studies with a sample size of less than 20 in the clinical group. We retained 17 studies of early phase schizophrenia, which together indicate deficits in white matter integrity observed in all fiber tract families, but most frequently in association, callosal and projection fibers. In otherwise healthy cannabis users (2 studies), deficits in white matter tracts were reported mainly in callosal fibers, but also in projection and limbic fibers. In cannabis users with early phase schizophrenia (1 study), deficits in white matter integrity were also observed in all fiber tract families, except for limbic fibers. The current literature points to several families of white matter tracts being differentially affected in early phase schizophrenia. Further work is required to reveal the impact of cannabis use in otherwise healthy people as well as those with schizophrenia. Paucity of available studies as well as restricting analysis to FA values represent the main limitations of this review. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Risk and protective factors in early child development: Results from the All Our Babies (AOB) pregnancy cohort.

    PubMed

    McDonald, Sheila; Kehler, Heather; Bayrampour, Hamideh; Fraser-Lee, Nonie; Tough, Suzanne

    2016-11-01

    Understanding factors that protect against early developmental delay among children who are experiencing adversity can inform prevention and early intervention strategies. To identify risk factors for development delay at one year and protective factors for developmental delay in 'at risk' environments (poor maternal mental health and socio-demographic risk). Data was analyzed from 3360 mother-child dyads who participated in the All Our Babies (AOB) pregnancy cohort. Participants completed four questionnaires spanning pregnancy to one year postpartum and provided access to medical records. Risk factors for developmental delay at age one were identified using bivariate methods and multivariable modeling. Protective factors for child development in 'at risk' family environments were identified using bivariate analyses. At one year, 17% of children were developmentally delayed, defined as scoring in the monitoring zone on at least 2 of the 5 developmental domains of the Ages and Stages Questionnaire. Prenatal depression, preterm birth, low community engagement, and non-daily parent-child interaction increased the risk of delay. Protective factors for children in 'at risk' environments included relationship happiness, parenting self-efficacy, community engagement, higher social support, and daily parent-child interaction. The study results suggest that maternal and infant outcomes would be improved, even for vulnerable women, through identification and intervention to address poor mental health and through normalizing engagement with low cost, accessible community resources that can also support parent-child interaction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. The Role of Early-Phase Transmission in the Spread of Yersinia pestis

    PubMed Central

    EISEN, REBECCA J.; DENNIS, DAVID T.; GAGE, KENNETH L.

    2015-01-01

    Early-phase transmission (EPT) of Yersinia pestis by unblocked fleas is a well-documented, replicable phenomenon with poorly defined mechanisms. We review evidence demonstrating EPT and current knowledge on its biological and biomechanical processes. We discuss the importance of EPT in the epizootic spread of Y. pestis and its role in the maintenance of plague bacteria in nature. We further address the role of EPT in the epidemiology of plague. PMID:26336267

  3. A model for early onset of protection against lethal challenge with highly pathogenic H5N1 influenza virus.

    PubMed

    Röhrs, Susanne; Kalthoff, Donata; Beer, Martin

    2014-05-07

    Highly pathogenic avian influenza viruses of subtype H5N1 sporadically cause severe disease in humans and involve the risk of inducing a pandemic by gaining the ability for human-to-human transmission. In naïve poultry, primarily gallinaceous birds, the virus induces fatal disease and the used inactivated vaccines occasionally are unable to provide efficient and early onset of protection. Therefore, optimized vaccines must be developed and evaluated in model systems. In our study, we tested a novel H5 neuraminidase-deleted influenza A virus variant to analyze the induction of a very early onset of immunity. Ferrets, mice and chickens were each immunized with a single vaccine dose seven, three and one day before lethal challenge infection, respectively. Sound protection was conferred in 100% of animals immunized seven days prior to challenge infection. In these animals, no clinical signs were observed, and no challenge virus RNA was detected by real-time RT-PCR analyses of swabs, nasal washings, and organ samples. Moreover, the attenuated modified-live virus variant protected all chickens, mice, and ferrets as early as three days after vaccination against severe clinical signs. Chickens and ferrets developed hemagglutinin-specific antibodies after seven days, but no neuraminidase-specific antibodies, making this kind of neuraminidase-negative strain suitable for the DIVA ("differentiating vaccinated from infected animals") strategy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. A Tetrazine-Labile Vinyl Ether Benzyloxycarbonyl Protecting Group (VeZ): An Orthogonal Tool for Solid-Phase Peptide Chemistry.

    PubMed

    Staderini, Matteo; Gambardella, Alessia; Lilienkampf, Annamaria; Bradley, Mark

    2018-06-01

    The vinyl ether benzyloxycarbonyl (VeZ) protecting group is selectively cleaved by treatment with tetrazines via an inverse electron-demand Diels-Alder reaction. This represents a new orthogonal protecting group for solid-phase peptide synthesis, with Fmoc-Lys(VeZ)-OH as a versatile alternative to Fmoc-Lys(Alloc)-OH and Fmoc-Lys(Dde)-OH, as demonstrated by the synthesis of two biologically relevant cyclic peptides.

  5. Exogenous Stimulation of Type I Interferon Protects Mice with Chronic Granulomatous Disease from Aspergillosis through Early Recruitment of Host-Protective Neutrophils into the Lung.

    PubMed

    Seyedmousavi, Seyedmojtaba; Davis, Michael J; Sugui, Janyce A; Pinkhasov, Tzvia; Moyer, Shannon; Salazar, Andres M; Chang, Yun C; Kwon-Chung, Kyung J

    2018-03-27

    Invasive aspergillosis (IA) remains the primary cause of morbidity and mortality in chronic granulomatous disease (CGD) patients, often due to infection by Aspergillus species refractory to antifungals. This motivates the search for alternative treatments, including immunotherapy. We investigated the effect of exogenous type I interferon (IFN) activation on the outcome of IA caused by three Aspergillus species, A. fumigatus , A. nidulans , and A. tanneri , in CGD mice. The animals were treated with poly(I):poly(C) carboxymethyl cellulose poly-l-lysine (PICLC), a mimetic of double-stranded RNA, 24 h preinfection and postinfection. The survival rates and lung fungal burdens were markedly improved by PICLC immunotherapy in animals infected with any one of the three Aspergillus species. While protection from IA was remarkable, PICLC induction of type I IFN in the lungs surged 24 h posttreatment and returned to baseline levels by 48 h, suggesting that PICLC altered early events in protection against IA. Immunophenotyping of recruited leukocytes and histopathological examination of tissue sections showed that PICLC induced similar cellular infiltrates as those in untreated-infected mice, in both cases dominated by monocytic cells and neutrophils. However, the PICLC immunotherapy resulted in a marked earlier recruitment of the leukocytes. Unlike with conidia, infection with A. nidulans germlings reduced the protective effect of PICLC immunotherapy. Additionally, antibody depletion of neutrophils totally reversed the protection, suggesting that neutrophils are crucial for PICLC-mediated protection. Together, these data show that prophylactic PICLC immunotherapy prerecruits these cells, enabling them to attack the conidia and thus resulting in a profound protection from IA. IMPORTANCE Patients with chronic granulomatous disease (CGD) are highly susceptible to invasive aspergillosis (IA). While Aspergillus fumigatus is the most-studied Aspergillus species, CGD patients

  6. Changes in the Milk Metabolome of the Giant Panda (Ailuropoda melanoleuca) with Time after Birth--Three Phases in Early Lactation and Progressive Individual Differences.

    PubMed

    Zhang, Tong; Zhang, Rong; Zhang, Liang; Zhang, Zhihe; Hou, Rong; Wang, Hairui; Loeffler, I Kati; Watson, David G; Kennedy, Malcolm W

    2015-01-01

    Ursids (bears) in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1-6 (Phase 1), days 7-20 (Phase 2), and beyond day 20 (Phase 3). While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth.

  7. Webcam Delivery of the Lidcombe Program for Early Stuttering: A Phase I Clinical Trial

    ERIC Educational Resources Information Center

    O'Brian, Sue; Smith, Kylie; Onslow, Mark

    2014-01-01

    Purpose: The Lidcombe Program is an operant treatment for early stuttering shown with meta-analysis to have a favorable odds ratio. However, many clients are unable to access the treatment because of distance and lifestyle factors. In this Phase I trial, we explored the potential efficacy, practicality, and viability of an Internet webcam Lidcombe…

  8. Diffusion-weighted MR imaging findings of kidneys in patients with early phase of obstruction.

    PubMed

    Bozgeyik, Zulkif; Kocakoc, Ercan; Sonmezgoz, Fitnet

    2009-04-01

    Diffusion-weighted (DW) magnetic resonance (MR) imaging is an MR technique used to show molecular diffusion. The apparent diffusion coefficient (ADC), as a quantitative parameter calculated from the DW MR images. The purpose of this study is to evaluate the ability of DW MR imaging in early phase of obstruction due to urolithiasis. Twenty-six patients with acute dilatation of the pelvicalyceal system detected by intravenous urography were included in this study. MR imaging was performed using a 1.5 T whole-body superconducting MR scanner. DW imaging can be performed using single-shot spin-echo, echo-planar imaging (EPI) sequences with the following diffusion gradient b values: 100, 600, 1000 s/mm(2). Circular region of interest (ROI) was placed in the renal parenchyma for the measurement of ADC values in the normal and obstructed kidney. For statistical analyses, Paired t test were used. In spite of obstructed kidneys had the lower ADC values compared to normal kidneys, these alterations were statistically insignificant. We did not observe significantly different ADC values of early phase of obstructed kidneys compared to normal kidneys.

  9. Protection relay of phase-shifting device with thyristor switch for high voltage power transmission lines

    NASA Astrophysics Data System (ADS)

    Lachugin, V. F.; Panfilov, D. I.; Akhmetov, I. M.; Astashev, M. G.; Shevelev, A. V.

    2014-12-01

    Problems of functioning of differential current protection systems of phase shifting devices (PSD) with mechanically changed coefficient of transformation of shunt transformer are analyzed. Requirements for devices of protection of PSD with thyristor switch are formulated. Based on use of nonlinear models of series-wound and shunt transformers of PSD modes of operation of major protection during PSD, switching to zero load operation and to operation under load and during short circuit operation were studied for testing PSD with failures. Use of the principle of duplicating by devices of differential current protection (with realization of functions of breaking) of failures of separate pares of PSD with thyristor switch was substantiated. To ensure protection sensitivity to the shunt transformer winding short circuit, in particular, to a short circuit that is not implemented in the current differential protection for PSD with mechanical switch, the differential current protection reacting to the amount of primary ampere-turns of high-voltage and low-voltage winding of this transformer was designed. Studies have shown that the use of differential current cutoff instead of overcurrent protection for the shunt transformer wndings allows one to provide the sensitivity during thyristor failure with the formation of a short circuit. The results of simulation mode for the PSD with switch thyristor designed to be installed as switching point of Voskhod-Tatarskaya-Barabinsk 220 kV transmission line point out the efficiency of the developed solutions that ensure reliable functioning of the PSD.

  10. Phase Transitions in the Early Universe: The Cosmology of Non-Minimal Scalar Sectors

    NASA Astrophysics Data System (ADS)

    Kost, Jeffrey D.

    Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically--such as during cosmological mass-generating phase transitions--the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this thesis, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the total late-time abundance of the system--often by many orders of magnitude--but also its distribution across the different fields. Second, we find that these effects can produce large parametric resonances which render the energy densities of the fields highly sensitive to the degree of mixing as well as the duration of the time interval over which the phase transition unfolds. Finally, we find that these effects can even give rise to a "re-overdamping" phenomenon which causes the total energy density of the system to behave in novel ways that differ from those exhibited by pure dark matter or vacuum energy. All of these features therefore give rise to new possibilities for early-universe phenomenology and cosmological evolution. They also highlight the importance of taking into account the time dependence associated with phase transitions in cosmological settings. In the second part of this thesis, we proceed to study the early-universe cosmology of a Kaluza-Klein (KK

  11. Cognitive function in early clinical phase huntington disease after rivastigmine treatment.

    PubMed

    Sešok, Sanja; Bolle, Nika; Kobal, Jan; Bucik, Valentin; Vodušek, David B

    2014-09-01

    In Huntington disease (HD) patients receiving rivastigmine treatment improvement of behavioral symptoms and of cognitive function (assessed with screening diagnostic instruments) has been reported. The aim of the present study was to verify such improvement in cognitive function by cognitive function assessment with a detailed neuropsychological battery covering all relevant cognitive systems expected to be impaired in early phase HD. Eighteen (18) HD patients entered the study and were randomly allocated to the rivastigmine and placebo group. All subjects underwent neuropsychological assessment at baseline. Follow-up neuropsychological assessment was applied after 6 months of rivastigmine or placebo treatment. Eighteen (18) healthy controls entered the study to control for practice effect and underwent neuropsychological assessment at baseline and after 6 months, without treatment. The neuropsychological battery consisted of assessment tools that are sensitive to cognitive impairment seen in early phase HD: CTMT, SDMT, Stroop (attention and information control), RFFT, TOL, Verbal fluency (executive functioning), CVLT-II, RCFT (learning and memory). Effect of rivastigmine and possible effect of practice was assessed using the mixed ANOVA model. No statistically significant effect of rivastigmine treatment on cognitive function in HD patients was detected. There was no evidence for practice or placebo effect. Detailed neuropsychological assessment did not confirm previously reported effect of rivastigmine treatment on cognitive function in HD patients. The limitations of our study are, in particular, small sample size and the lack of a single measure of relevant cognitive functioning in HD patients. Instead of focusing solely on statistical significance, a clinical relevance study is proposed to clarify the issue of rivastigmine effects in HD.

  12. Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual

    PubMed Central

    Massett, Holly A.; Mishkin, Grace; Rubinstein, Larry; Ivy, S. Percy; Denicoff, Andrea; Godwin, Elizabeth; DiPiazza, Kate; Bolognese, Jennifer; Zwiebel, James A.; Abrams, Jeffrey S.

    2016-01-01

    Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAPs) received for slow-accruing Phase 1 and 2 trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for Phase 1 trials and 66 for Phase 2 trials. Primary reasons cited for slow accrual were safety/toxicity (Phase 1: 48%), design/protocol concerns (Phase 1: 42%, Phase 2: 33%), and eligibility criteria (Phase 1: 41%, Phase 2: 35%). The most commonly proposed corrective actions were adding institutions (Phase 1: 43%, Phase 2: 85%) and amending the trial to change eligibility or design (Phase 1: 55%, Phase 2: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (Phase 1=48; Phase 2=46). Of these, 67% of Phase 1 and 70% of Phase 2 trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial lifecycles, but it may be more beneficial to invest in earlier accrual planning. PMID:27401246

  13. Precursors of Adolescent Substance Use from Early Childhood and Early Adolescence: Testing a Developmental Cascade Model

    PubMed Central

    Sitnick, Stephanie; Shaw, Daniel S.; Hyde, Luke

    2013-01-01

    This study examined developmentally-salient risk and protective factors of adolescent substance use assessed during early childhood and early adolescence using a sample of 310 low-income boys. Child problem behavior and proximal family risk and protective factors (i.e., parenting, maternal depression) during early childhood, as well as child and family factors and peer deviant behavior during adolescence were explored as potential precursors to later substance use during adolescence using structural equation modeling. Results revealed that early childhood risk and protective factors (i.e., child externalizing problems, mothers’ depressive symptomatology, and nurturant parenting) were indirectly related to substance use at the age of 17 via risk and protective factors during early and middle adolescence (i.e., parental knowledge and externalizing problems). The implications of these findings for early prevention and intervention are discussed. PMID:24029248

  14. Thermal buffering performance of composite phase change materials applied in low-temperature protective garments

    NASA Astrophysics Data System (ADS)

    Yang, Kai; Jiao, Mingli; Yu, Yuanyuan; Zhu, Xueying; Liu, Rangtong; Cao, Jian

    2017-07-01

    Phase change material (PCM) is increasingly being applied in the manufacturing of functional thermo-regulated textiles and garments. This paper investigated the thermal buffering performance of different composite PCMs which are suitable for the application in functional low-temperature protective garments. First, according to the criteria selecting PCM for functional textiles/garments, three kinds of pure PCM were selected as samples, which were n-hexadecane, n-octadecane and n-eicosane. To get the adjustable phase change temperature range and higher phase change enthalpy, three kinds of composite PCM were prepared using the above pure PCM. To evaluate the thermal buffering performance of different composite PCM samples, the simulated low-temperature experiments were performed in the climate chamber, and the skin temperature variation curves in three different low temperature conditions were obtained. Finally composite PCM samples’ thermal buffering time, thermal buffering capacity and thermal buffering efficiency were calculated. Results show that the comprehensive thermal buffering performance of n-octadecane and n-eicosane composite PCM is the best.

  15. Radiation protection program for early detection of breast cancer in a mammography facility

    NASA Astrophysics Data System (ADS)

    Villagomez Casimiro, Mariana; Ruiz Trejo, Cesar; Espejo Fonseca, Ruby

    2014-11-01

    Mammography is the best tool for early detection of Breast Cancer. In this diagnostic radiology modality it is necessary to establish the criteria to ensure the proper use and operation of the equipment used to obtain mammographic images in order to contribute to the safe use of ionizing radiation. The aim of the work was to implement at FUCAM-AC the radiation protection program which must be established for patients and radiation workers according to Mexican standards [1-4]. To achieve this goal, radiation protection and quality control manuals were elaborated [5]. Furthermore, a quality control program (QCP) in the mammography systems (analog/digital), darkroom included, has been implemented. Daily sensitometry, non-variability of the image quality, visualizing artifacts, revision of the equipment mechanical stability, compression force and analysis of repetition studies are some of the QCP routine tests that must be performed by radiological technicians of this institution as a set of actions to ensure the protection of patients. Image quality and patients dose assessment were performed on 4 analog equipment installed in 2 mobile units. In relation to dose assessment, all equipment passed the acceptance criteria (<3 mGy per projection). The image quality test showed that most images (70%)- presented artifacts. A brief summary of the results of quality control tests applied to the equipment and film processor are presented. To maintain an adequate level of quality and safety at FUCAM-AC is necessary that the proposed radiation protection program in this work is applied.

  16. Radiation protection program for early detection of breast cancer in a mammography facility

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

    Mariana, Villagomez Casimiro, E-mail: marjim10-66@ciencias.unam.mx, E-mail: cesar@fisica.unam.mx; Cesar, Ruiz Trejo, E-mail: marjim10-66@ciencias.unam.mx, E-mail: cesar@fisica.unam.mx; Ruby, Espejo Fonseca

    Mammography is the best tool for early detection of Breast Cancer. In this diagnostic radiology modality it is necessary to establish the criteria to ensure the proper use and operation of the equipment used to obtain mammographic images in order to contribute to the safe use of ionizing radiation. The aim of the work was to implement at FUCAM-AC the radiation protection program which must be established for patients and radiation workers according to Mexican standards [1–4]. To achieve this goal, radiation protection and quality control manuals were elaborated [5]. Furthermore, a quality control program (QCP) in the mammography systemsmore » (analog/digital), darkroom included, has been implemented. Daily sensitometry, non-variability of the image quality, visualizing artifacts, revision of the equipment mechanical stability, compression force and analysis of repetition studies are some of the QCP routine tests that must be performed by radiological technicians of this institution as a set of actions to ensure the protection of patients. Image quality and patients dose assessment were performed on 4 analog equipment installed in 2 mobile units. In relation to dose assessment, all equipment passed the acceptance criteria (<3 mGy per projection). The image quality test showed that most images (70%)– presented artifacts. A brief summary of the results of quality control tests applied to the equipment and film processor are presented. To maintain an adequate level of quality and safety at FUCAM-AC is necessary that the proposed radiation protection program in this work is applied.« less

  17. Occupant Protection Project

    NASA Technical Reports Server (NTRS)

    Bopp, Genie; Somers, Jeff; Granderson, Brad; Gernhardt, Mike; Currie, Nancy; Lawrence, Chuck

    2010-01-01

    Topics include occupant protection overview with a focus on crew protection during dynamic phases of flight; occupant protection collaboration; modeling occupant protection; occupant protection considerations; project approach encompassing analysis tools, injury criteria, and testing program development; injury criteria update methodology, unique effects of pressure suits and other factors; and a summary.

  18. Unknown loads affect force production capacity in early phases of bench press throws.

    PubMed

    Hernández Davó, J L; Sabido Solana, R; Sarabia Marínm, J M; Sánchez Martos, Á; Moya Ramón, M

    2015-10-01

    Explosive strength training aims to improve force generation in early phases of movement due to its importance in sport performance. The present study examined the influence of lack of knowledge about the load lifted in explosive parameters during bench press throws. Thirteen healthy young men (22.8±2.0 years) participated in the study. Participants performed bench press throws with three different loads (30, 50 and 70% of 1 repetition maximum) in two different conditions (known and unknown loads). In unknown condition, loads were changed within sets in each repetition and participants did not know the load, whereas in known condition the load did not change within sets and participants had knowledge about the load lifted. Results of repeated-measures ANOVA revealed that unknown conditions involves higher power in the first 30, 50, 100 and 150 ms with the three loads, higher values of ratio of force development in those first instants, and differences in time to reach maximal rate of force development with 50 and 70% of 1 repetition maximum. This study showed that unknown conditions elicit higher values of explosive parameters in early phases of bench press throws, thereby this kind of methodology could be considered in explosive strength training.

  19. Analysis of Loss-of-Coolant Accidents in the NIST Research Reactor - Early Phase

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

    Baek, Joo S.; Diamond, David

    A study of the fuel temperature during the early phase of a loss-of-coolant accident (LOCA) in the NIST research reactor (NBSR) was completed. Previous studies had been reported in the preliminary safety analysis report for the conversion of the NBSR from high-enriched uranium (HEU) fuel to low-enriched (LEU) fuel. Those studies had focused on the most vulnerable LOCA situation, namely, a double-ended guillotine break in the time period after reactor trip when water is drained from either the coolant channels inside the fuel elements or the region outside the fuel elements. The current study fills in a gap in themore » analysis which is the early phase of the event when there may still be water present but the reactor is at power or immediately after reactor trip and pumps have tripped. The calculations were done, for both the current HEU-fueled core and the proposed LEU core, with the TRACE thermal-hydraulic systems code. Several break locations and different break sizes were considered. In all cases the increase in the clad (or fuel meat) temperature was relatively small so that a large margin to the temperature threshold for blistering (the Safety Limit for the NBSR) remained.« less

  20. Changes in the Milk Metabolome of the Giant Panda (Ailuropoda melanoleuca) with Time after Birth – Three Phases in Early Lactation and Progressive Individual Differences

    PubMed Central

    Zhang, Tong; Zhang, Rong; Zhang, Liang; Zhang, Zhihe; Hou, Rong; Wang, Hairui; Loeffler, I. Kati; Watson, David G.; Kennedy, Malcolm W.

    2015-01-01

    Ursids (bears) in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1–6 (Phase 1), days 7–20 (Phase 2), and beyond day 20 (Phase 3). While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth. PMID:26630345

  1. Extinct radioactivities - A three-phase mixing model. [for early solar system abundances

    NASA Technical Reports Server (NTRS)

    Clayton, D. D.

    1983-01-01

    A new class of models is advanced for interpreting the relationship of radioactive abundances in the early solar system to their average concentration in the interstellar medium. The model assumes that fresh radioactivities are ejected from supernovae into the hot interstellar medium, and that the time scales for changes of phase into molecular clouds determine how much survives for formation therein of the solar system. A more realistic and physically motivated understanding of the low observed concentrations of I-129, Pu-244, and Pd-107 may result.

  2. Examination of a modified cell cycle synchronization method and bovine nuclear transfer using synchronized early G1 phase fibroblast cells.

    PubMed

    Urakawa, Manami; Ideta, Atsushi; Sawada, Tokihiko; Aoyagi, Yoshito

    2004-08-01

    Somatic cell nuclear transfer has a low success rate, due to a high incidence of fetal loss and increased perinatal morbidity/mortality. One factor that may affect the successful development of nuclear transfer embryos is the cell cycle stage of the donor cell. In order to establish a cell cycle synchronization method that can consistently produce cloned embryos and offspring, we examined the effects of different combinations of three cell treatments on the recovery rate of mitotic phase cells using bovine fetal fibroblasts. In the first experiment, we examined the recovery rate of mitotic phase cells by a combination of treatment with a metaphase arrestant (1 microM 2-methoxyestradiol), shaking the plate and selecting cells with a diameter of 20 microns. As a result, 99% of mitotic phase cells were recovered by repeating the combined treatment of metaphase arrestant and shaking, and collection of cells with a specific diameter. In the second experiment, nuclear transfer was carried out using early G1 phase cells by choosing pairs of bridged cells derived from mitotic phase cells recovered by the combined treatment of 1 microM 2-methoxyestradiol and shaking, and collection of cells with a diameter of 20 microns. The reconstructed embryos were transferred to recipient heifers to determine post-implantation development. Development of embryos reconstructed from early G1 phase cells from the >/=6 cells stage on Day 3 to the morula-blastocyst stage on Day 6 was 100%. Ten blastocysts constructed from two cell lines were transferred into 10 recipient heifers. Nine of the 10 recipients delivered single live calves. In conclusion, mitotic phase bovine fibroblast cells were easily recovered by the combined treatments of 1 microM 2-methoxyestradiol, shaking, and selecting cells of the appropriate diameter. Furthermore, nuclear transfer using cells in the early G1 phase as donor cells gave a high rate of offspring production.

  3. Auto-inhibitory regulation of angiotensin II functionality in hamster aorta during the early phases of dyslipidemia.

    PubMed

    Pereira, Priscila Cristina; Pernomian, Larissa; Côco, Hariane; Gomes, Mayara Santos; Franco, João José; Marchi, Kátia Colombo; Hipólito, Ulisses Vilela; Uyemura, Sergio Akira; Tirapelli, Carlos Renato; de Oliveira, Ana Maria

    2016-06-15

    Emerging data point the crosstalk between dyslipidemia and renin-angiotensin system (RAS). Advanced dyslipidemia is described to induce RAS activation in the vasculature. However, the interplay between early dyslipidemia and the RAS remains unexplored. Knowing that hamsters and humans have a similar lipid profile, we investigated the effects of early and advanced dyslipidemia on angiotensin II-induced contraction. Cumulative concentration-response curves for angiotensin II (1.0pmol/l to 1.0µmol/l) were obtained in the hamster thoracic aorta. We also investigated the modulatory action of NAD(P)H oxidase on angiotensin II-induced contraction using ML171 (Nox-1 inhibitor, 0.5µmol/l) and VAS2870 (Nox-4 inhibitor, 5µmol/l). Early dyslipidemia was detected in hamsters treated with a cholesterol-rich diet for 15 days. Early dyslipidemia decreased the contraction induced by angiotensin II and the concentration of Nox-4-derived hydrogen peroxide. Advanced dyslipidemia, observed in hamsters treated with cholesterol-rich diet for 30 days, restored the contractile response induced by angiotensin II by compensatory mechanism that involves Nox-4-mediated oxidative stress. The hyporresponsiveness to angiotensin II may be an auto-inhibitory regulation of the angiotensinergic function during early dyslipidemia in an attempt to reduce the effects of the upregulation of the vascular RAS during the advanced stages of atherogenesis. The recovery of vascular angiotensin II functionality during the advanced phases of dyslipidemia is the result of the upregulation of redox-pro-inflammatory pathway that might be most likely involved in atherogenesis progression rather than in the recovery of vascular function. Taken together, our findings show the early phase of dyslipidemia may be the most favorable moment for effective atheroprotective therapeutic interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis.

    PubMed

    Scalfari, Antonio; Romualdi, Chiara; Nicholas, Richard S; Mattoscio, Miriam; Magliozzi, Roberta; Morra, Aldo; Monaco, Salvatore; Muraro, Paolo A; Calabrese, Massimiliano

    2018-05-16

    To investigate the relationship among cortical radiologic changes, the number of early relapses (ERs), and the long-term course of multiple sclerosis (MS). In this cohort study, we assessed the number of cortical lesions (CLs) and white matter (WM) lesions and the cortical thickness (Cth) at clinical onset and after 7.9 mean years among 219 patients with relapsing remitting (RR) MS with 1 (Low-ER), 2 (Mid-ER), and ≥3 (High-ER) ERs during the first 2 years. Kaplan-Meier and Cox regression analyses investigated early factors influencing the risk of secondary progressive (SP) MS. Fifty-nine patients (27%) converted to SPMS in 6.1 mean years. A larger number of CLs at onset predicted a higher risk of SPMS (hazard ratio [HR] 2.16, 4.79, and 12.3 for 2, 5, and 7 CLs, respectively, p < 0.001) and shorter latency to progression. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset, accrued more CLs, experienced more severe cortical atrophy over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p < 0.001), a larger baseline CL (HR 2.21, p = 0.005) and WM lesion (HR 1.32, p = 0.03) volume, early changes of global Cth (HR 1.36, p = 0.03), and ≥3 ERs (HR 6.08, p < 0.001) independently predicted a higher probability of SP. Extensive cortical damage at onset is associated with florid inflammatory clinical activity and predisposes to a rapid occurrence of the progressive phase. Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy. © 2018 American Academy of Neurology.

  5. Feasibility study for early removal of HEU from CPP-651-Phase II

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

    Smith, C.V.; Henry, R.; Milligan, C.

    1997-09-01

    A two-phase feasibility study was initiated in late 1996 to identify a way to expedite the removal of SNM from the CPP-651 vault. The first phase of this study provided preliminary information that appeared promising, but needed additional detailed planning and evaluate to validate the concepts and conclusions. The focus of Phase 2 was to provide the validation via resource-loaded schedules and more detailed cost estimates. Section 1 describes the purpose and objectives of the Phase 2 tasks and the programmatic drivers that influence related CPP-651 high-enriched uranium (HEU) management issues. Section 2 identifies the evaluation criteria and methodology andmore » the transfer issues and barriers preventing shipment. Section 3 provides site-specific background information for the CPP-651 facility and the Idaho National Engineering and Environmental Laboratory (INEEL) and describes the development of the basic material removal schedule, the proposed base case plan for removal of SNM, and the proposed HEU material management/shipping issues and strategies. Section 4 identifies the proposed options for accelerated removal of SNM and how they were evaluated via detailed scheduling, resource histograms, and cost analysis. Section 5 summarizes principal tasks for implementing this plan and other related HEU CPP-651 management issues that require continued planning efforts to assure successful implementation of this proposed early removal strategy.« less

  6. Grandmother Involvement as a Protective Factor for Early Childhood Social Adjustment

    PubMed Central

    Barnett, Melissa A.; Scaramella, Laura V.; Neppl, Tricia K.; Ontai, Lenna L.; Conger, Rand D.

    2010-01-01

    Despite high rates of grandmother involvement with young grandchildren, very little research has examined the associations between non-residential grandmother involvement and grandchild social adjustment. The present study draws 127 families enrolled in the Family Transitions Project to consider the degree to which mother-reported maternal grandmother involvement buffers 3- and 4-year old grandchildren from economic, parenting, and child temperamental risks for reduced social competence and elevated externalizing behaviors. Findings indicate that higher levels of mother-reported grandmother involvement reduced the negative association between observed grandchild negative emotional reactivity and social competence. Further, high levels of mother-reported grandmother involvement protected grandchildren from the positive association between observed harsh mother parenting and grandchild externalizing behaviors. These findings underscore the relevance of moving beyond the nuclear family to understand factors linked to social adjustment during early childhood. PMID:20954774

  7. Tissue responses to low protracted doses of high let radiations or photons - Early and late damage relevant to radio-protective countermeasures

    NASA Technical Reports Server (NTRS)

    Ainsworth, E. J.; Afzal, S. M. J.; Crouse, D. A.; Hanson, W. R.; Fry, R. J. M.

    1989-01-01

    Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.

  8. Early-phase prandial insulin secretion: its role in the pathogenesis of type 2 diabetes mellitus and its modulation by repaglinide.

    PubMed

    Owens, D R; Cozma, L S; Luzio, S D

    2002-12-01

    The major contributory factor to increasing hyperglycaemia in established Type 2 diabetes mellitus (T2DM) appears to be the progressive delay and attenuation of the prandial insulin response. An important consequence of this derangement is that hepatic glucose production is no longer suppressed during times of prandial glucose intake. Together with a relative impairment in the rate of peripheral glucose disposal, this leads to supra-physiological plasma glucose excursions, which may damage the vasculature. An obvious therapeutic strategy, therefore, would be to increase insulin availability when most needed--in the early prandial phase. In experiments with exogenous insulin interventions, peak post-prandial blood glucose increments were curtailed without undue increases in total insulin exposure. However, available evidence suggests that the sulphonylurea glibenclamide does not effectively alter early-phase prandial insulin release but predominately increases late-phase and basal insulin output, thus incurring the risk of hypoglycaemia. The novel insulin secretagogue repaglinide, by contrast, augments early-phase prandial insulin secretion when taken before meals, as shown by studies in non-diabetic people and patients with newly diagnosed, previously untreated T2DM. Repaglinide exerts its greatest effect on the insulin secretion rate during the first 30 min after a meal is started, thereby going some way to restoring the early insulin secretion curve seen after a meal in non-diabetic people. No residual secretagogue activity is seen 4 hr after taking a single dose of up to 2 mg. Prandial glucose regulation with repaglinide could be associated with lower post-prandial glucose excursions and less risk of post-prandial hypoglycaemia than glibenclamide.

  9. Mechanisms of the early phases of plant gravitropism

    NASA Technical Reports Server (NTRS)

    Kiss, J. Z.

    2000-01-01

    Gravitropism is directed growth of a plant or plant organ in response to gravity and can be divided into the following temporal sequence: perception, transduction, and response. This article is a review of the research on the early events of gravitropism (i.e., phenomena associated with the perception and transduction phases). The two major hypotheses for graviperception are the protoplast-pressure and starch-statolith models. While most researchers support the concept of statoliths, there are suggestions that plants have multiple mechanisms of perception. Evidence supports the hypothesis that the actin cytoskeleton is involved in graviperception/transduction, but the details of these mechanisms remain elusive. A number of recent developments, such as increased use of the molecular genetic approach, magnetophoresis, and laser ablation, have facilitated research in graviperception and have allowed for refinement of the current models. In addition, the entire continuum of acceleration forces from hypo- to hyper-gravity have been useful in studying perception mechanisms. Future interdisciplinary molecular approaches and the availability of sophisticated laboratories on the International Space Station should help to develop new insights into mechanisms of gravitropism in plants.

  10. Early Restoration | NOAA Gulf Spill Restoration

    Science.gov Websites

    Early Restoration Plan. On April 20, 2011 we reached an agreement with BP to start restoration planning draft plan for the third phase of early restoration in December 2013. We are considering your comments : All Phase III information and documents Phase II Useful Links: Phase II Early Restoration Plan &

  11. Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual.

    PubMed

    Massett, Holly A; Mishkin, Grace; Rubinstein, Larry; Ivy, S Percy; Denicoff, Andrea; Godwin, Elizabeth; DiPiazza, Kate; Bolognese, Jennifer; Zwiebel, James A; Abrams, Jeffrey S

    2016-11-15

    Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408-16. ©2016 AACRSee related commentary by Mileham and Kim, p. 5397. ©2016 American Association for Cancer Research.

  12. Gram staining of protected pulmonary specimens in the early diagnosis of ventilator-associated pneumonia.

    PubMed

    Mimoz, O; Karim, A; Mazoit, J X; Edouard, A; Leprince, S; Nordmann, P

    2000-11-01

    We evaluated prospectively the use of Gram staining of protected pulmonary specimens to allow the early diagnosis of ventilator-associated pneumonia (VAP), compared with the use of 60 bronchoscopic protected specimen brushes (PSB) and 126 blinded plugged telescopic catheters (PTC) obtained from 134 patients. Gram stains were from Cytospin slides; they were studied for the presence of microorganisms in 10 and 50 fields by two independent observers and classified according to their Gram stain morphology. Quantitative cultures were performed after serial dilution and plating on appropriate culture medium. A final diagnosis of VAP, based on a culture of > or = 10(3) c.f.u. ml-1, was established after 81 (44%) samplings. When 10 fields were analysed, a strong relationship was found between the presence of bacteria on Gram staining and the final diagnosis of VAP (for PSB and PTC respectively: sensitivity 74 and 81%, specificity 94 and 100%, positive predictive value 91 and 100%, negative predictive value 82 and 88%). The correlation was less when we compared the morphology of microorganisms observed on Gram staining with those of bacteria obtained from quantitative cultures (for PSB and PTC respectively: sensitivity 54 and 69%, specificity 86 and 89%, positive predictive value 72 and 78%, negative predictive value 74 and 84%). Increasing the number of fields read to 50 was associated with a slight decrease in specificity and positive predictive value of Gram staining, but with a small increase in its sensitivity and negative predictive value. The results obtained by the two observers were similar to each other for both numbers of fields analysed. Gram staining of protected pulmonary specimens performed on 10 fields predicted the presence of VAP and partially identified (using Gram stain morphology) the microorganisms growing at significant concentrations, and could help in the early choice of the treatment of VAP. Increasing the number of fields read or having the Gram

  13. Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases.

    PubMed

    Kawakami, Kohsaku

    2009-09-01

    Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines.

  14. Men Managing, Not Teaching Foundation Phase: Teachers, Masculinity and the Early Years of Primary Schooling

    ERIC Educational Resources Information Center

    Moosa, Shaaista; Bhana, Deevia

    2017-01-01

    In this article we argue that eliminating the divisions of labour between men and women could work towards counteracting gender inequality within professions. Globally women are over-represented in the teaching of young children in the early years of primary school, or Foundation Phase (FP), as it is known in South Africa. We are concerned to go…

  15. The accelerating effect of chitosan-silica hybrid dressing materials on the early phase of wound healing.

    PubMed

    Park, Ji-Ung; Jung, Hyun-Do; Song, Eun-Ho; Choi, Tae-Hyun; Kim, Hyoun-Ee; Song, Juha; Kim, Sukwha

    2017-10-01

    Commercialized dressing materials with or without silver have played a passive role in early-phase wound healing, protecting the skin defects from infections, absorbing exudate, and preventing dehydration. Chitosan (CTS)-based sponges have been developed in pure or hybrid forms for accelerating wound healing, but their wound-healing capabilities have not been extensively compared with widely used commercial dressing materials, providing limited information in a practical aspect. In this study, we have developed CTS-silica (CTS-Si) hybrid sponges with water absorption, flexibility, and mechanical behavior similar to those of CTS sponges. In vitro and in vivo tests were performed to compare the CTS-Si sponges with three commercial dressing materials [gauze, polyurethane (PU), and silver-containing hydrofiber (HF-Ag)] in addition to CTS sponges. Both in vitro and in vivo tests showed that CTS-Si sponges promoted fibroblast proliferation, leading to accelerated collagen synthesis, whereas the CTS sponges did not exhibit significant differences in fibroblast proliferation and collagen synthesis from gauze, PU, and HF-Ag sponges. In case of CTS-Si, the inflammatory cells were actively recruited to the wound by the influence of the released silicon ions from CTS-Si sponges, which, in return, led to an enhanced secretion of growth factors, particularly TGF-β during the early stage. The higher level of TGF-β likely improved the proliferation of fibroblasts, and as a result, collagen synthesis by fibroblasts became remarkably productive, thereby increasing collagen density at the wound site. Therefore, the CTS-Si hybrid sponges have considerable potential as a wound-dressing material for accelerating wound healing. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1828-1839, 2017. © 2016 Wiley Periodicals, Inc.

  16. 77 FR 58359 - Applications for New Awards; Race to the Top-Early Learning Challenge; Phase 2

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-20

    ... amended by section 1832(b) of Division B of Pub. L. 112-10, the Department of Defense and Full-Year... DEPARTMENT OF EDUCATION DEPARTMENT OF HEALTH AND HUMAN SERVICES Applications for New Awards; Race to the Top--Early Learning Challenge; Phase 2 AGENCY: Department of Education and Department of...

  17. Reperfusion kinase phosphorylation is essential but not sufficient in the mediation of pharmacological preconditioning: Characterisation in the bi-phasic profile of early and late protection.

    PubMed

    Bell, Robert M; Clark, James E; Hearse, David J; Shattock, Michael J

    2007-01-01

    Pharmacological preconditioning (PPC) triggers early (ePPC) and delayed protection (dPPC), occurring within 1 h or after 24 h following the preconditioning stimulus, respectively, through recruitment of protein kinase signalling. Angiotensin II (ATII) is a recognised trigger of PPC, recruiting kinases and transcription factors known to be involved in both phases of protection. Our objectives were to determine whether ATII is capable of triggering dPPC and whether recruitment of pro-survival kinases, Akt and extracellular signal-regulated kinase (ERK), following the injurious ischaemic insult is essential for the mediation of PPC. In a mouse Langendorff model of ischaemia/reperfusion injury, we undertook to determine whether ATII triggers both ePPC and dPPC. Western blot analysis was used to determine kinase phosphorylation at reperfusion, and kinase inhibitors wortmannin and PD98059 were used to ascertain the significance of kinase regulation. We demonstrated that ATII triggered PPC with attenuation of infarction at 1 and 24 h (19+/-4% and 25+/-4% versus control, 35+/-4% of risk zone, p < 0.05), consistent with the ePPC and dPPC time-course. This bi-phasic protection was associated with significant post-ischaemic phosphorylation of both Akt and ERK within the first 5 min of reperfusion. Akt and ERK phosphorylation was increased following ePPC by 4.5+/-0.5 and 1.9+/-0.6 fold, respectively (p < 0.001), and dPPC by 24+/-2.0 and 2.1+/-0.1 fold, respectively (p < 0.001). Both wortmannin and PD98059 administered during reperfusion ameliorated the phosphorylation of Akt and ERK and abrogated the resistance to infarction resulting from both ePPC and dPPC (33+/-3% and 35+/-4%, respectively, versus controls 33+/-4% and 33+/-5%, p = NS). There was no evidence of augmented phosphorylation of either p38 kinase or JNK at either time point. We demonstrate that PPC results in a clearly delineated time-course of bi-phasic protection against injurious ischemic injury that is

  18. The Low-luminosity Type IIP Supernova 2016bkv with Early-phase Circumstellar Interaction

    NASA Astrophysics Data System (ADS)

    Nakaoka, Tatsuya; Kawabata, Koji S.; Maeda, Keiichi; Tanaka, Masaomi; Yamanaka, Masayuki; Moriya, Takashi J.; Tominaga, Nozomu; Morokuma, Tomoki; Takaki, Katsutoshi; Kawabata, Miho; Kawahara, Naoki; Itoh, Ryosuke; Shiki, Kensei; Mori, Hiroki; Hirochi, Jun; Abe, Taisei; Uemura, Makoto; Yoshida, Michitoshi; Akitaya, Hiroshi; Moritani, Yuki; Ueno, Issei; Urano, Takeshi; Isogai, Mizuki; Hanayama, Hidekazu; Nagayama, Takahiro

    2018-06-01

    We present optical and near-infrared observations of a low-luminosity (LL) Type IIP supernova (SN) 2016bkv from the initial rising phase to the plateau phase. Our observations show that the end of the plateau is extended to ≳140 days since the explosion, indicating that this SN takes one of the longest times to finish the plateau phase among Type IIP SNe (SNe IIP), including LL SNe IIP. The line velocities of various ions at the middle of the plateau phase are as low as 1000–1500 km s‑1, which is the lowest even among LL SNe IIP. These measurements imply that the ejecta mass in SN 2016bkv is larger than that of the well-studied LL IIP SN 2003Z. In the early phase, SN 2016bkv shows a strong bump in the light curve. In addition, the optical spectra in this bump phase exhibit a blue continuum accompanied by a narrow Hα emission line. These features indicate an interaction between the SN ejecta and the circumstellar matter (CSM) as in SNe IIn. Assuming the ejecta–CSM interaction scenario, the mass loss rate is estimated to be ∼ 1.7× {10}-2 {M}ȯ yr‑1 within a few years before the SN explosion. This is comparable to or even larger than the largest mass loss rate observed for the Galactic red supergiants (∼ {10}-3 {M}ȯ yr‑1 for VY CMa). We suggest that the progenitor star of SN 2016bkv experienced a violent mass loss just before the SN explosion.

  19. The progamic phase of an early-divergent angiosperm, Annona cherimola (Annonaceae)

    PubMed Central

    Lora, J.; Hormaza, J. I.; Herrero, M.

    2010-01-01

    Background and Aims Recent studies of reproductive biology in ancient angiosperm lineages are beginning to shed light on the early evolution of flowering plants, but comparative studies are restricted by fragmented and meagre species representation in these angiosperm clades. In the present study, the progamic phase, from pollination to fertilization, is characterized in Annona cherimola, which is a member of the Annonaceae, the largest extant family among early-divergent angiosperms. Beside interest due to its phylogenetic position, this species is also an ancient crop with a clear niche for expansion in subtropical climates. Methods The kinetics of the reproductive process was established following controlled pollinations and sequential fixation. Gynoecium anatomy, pollen tube pathway, embryo sac and early post-fertilization events were characterized histochemically. Key Results A plesiomorphic gynoecium with a semi-open carpel shows a continuous secretory papillar surface along the carpel margins, which run from the stigma down to the obturator in the ovary. The pollen grains germinate in the stigma and compete in the stigma-style interface to reach the narrow secretory area that lines the margins of the semi-open stylar canal and is able to host just one to three pollen tubes. The embryo sac has eight nuclei and is well provisioned with large starch grains that are used during early cellular endosperm development. Conclusions A plesiomorphic simple gynoecium hosts a simple pollen–pistil interaction, based on a support–control system of pollen tube growth. Support is provided through basipetal secretory activity in the cells that line the pollen tube pathway. Spatial constraints, favouring pollen tube competition, are mediated by a dramatic reduction in the secretory surface available for pollen tube growth at the stigma–style interface. This extramural pollen tube competition contrasts with the intrastylar competition predominant in more recently derived

  20. Hypoglycemic action of vitamin K1 protects against early-onset diabetic nephropathy in streptozotocin-induced rats.

    PubMed

    Sai Varsha, M K N; Raman, Thiagarajan; Manikandan, R; Dhanasekaran, G

    2015-10-01

    Vitamin K is a potent regulator of vascular dynamics and prevents vascular calcification. Vitamin K is increasingly being recognized for its antioxidant and antiinflammatory properties. Recently we demonstrated that vitamin K1 (5 mg/kg) protects against streptozotocin-induced type 1 diabetes and diabetic cataract. The aim of this study was to determine whether the hypoglycemic action of vitamin K1 could inhibit early-onset diabetic nephropathy in a streptozotocin-induced rat kidney. Male Wistar rats were administered with 35 mg/kg STZ and after 3 days were treated with vitamin K1 (5 mg/kg, twice a week) for 3 months. Blood glucose was monitored once a month. At the end of the study, animals were sacrificed and kidney was dissected out and analysed for free radicals, antioxidants, aldose reductase, membrane ATPases, histopathology evaluation and expression of pro- and anti-inflammatory cytokines. Urea, uric acid, creatinine, albumin and insulin levels were also estimated. Treatment of diabetic rats with vitamin K1 resulted in a decrease in blood glucose and prevented microalbuminuria. Vitamin K1 also reduced oxidative stress and protected renal physiology by modulating Ca(2+) and Na(+)/K(+)-ATPases. Vitamin K1 inhibited renal inflammation by reducing nuclear factor-κB and inducible nitric oxide synthase. Interleukin-10 levels were increased in renal tissues, suggesting the ability of vitamin K1 to trigger antiinflammatory state. The hypoglycemic action of vitamin K1 could have an indirect effect by inhibiting early-onset diabetic nephropathy triggered by high blood glucose. Vitamin K1 could be an important nutrient based interventional strategy for early onset diabetic nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. The early phase of /see symbol/ production development in adult Japanese learners of English.

    PubMed

    Saito, Kazuya; Munro, Murray J

    2014-12-01

    Although previous research indicates that Japanese speakers' second language (L2) perception and production of English /see symbol/ may improve with increased L2 experience, relatively little is known about the fine phonetic details of their /see symbol/ productions, especially during the early phase of L2 speech learning. This cross-sectional study examined acoustic properties of word-initial /see symbol/ from 60 Japanese learners with a length of residence of between one month and one year in Canada. Their performance was compared to that of 15 native speakers of English and 15 low-proficiency Japanese learners of English. Formant frequencies (F2 and F3) and F1 transition durations were evaluated under three task conditions--word reading, sentence reading, and timed picture description. Learners with as little as two to three months of residence demonstrated target-like F2 frequencies. In addition, increased LOR was predictive of more target-like transition durations. Although the learners showed some improvement in F3 as a function of LOR, they did so mainly at a controlled level of speech production. The findings suggest that during the early phase of L2 segmental development, production accuracy is task-dependent and is influenced by the availability of L1 phonetic cues for redeployment in L2.

  2. Invariant protection of high-voltage electric motors of technological complexes at industrial enterprises at partial single-phase ground faults

    NASA Astrophysics Data System (ADS)

    Abramovich, B. N.; Sychev, Yu A.; Pelenev, D. N.

    2018-03-01

    Development results of invariant protection of high-voltage motors at incomplete single-phase ground faults are observed in the article. It is established that current protections have low action selectivity because of an inadmissible decrease in entrance signals during the shirt circuit occurrence in the place of transient resistance. The structural functional scheme and an algorithm of protective actions where correction of automatic zero sequence currents signals of the protected accessions implemented according to the level of incompleteness of ground faults are developed. It is revealed that automatic correction of zero sequence currents allows one to provide the invariance of sensitivity factor for protection under the variation conditions of a transient resistance in the place of damage. Application of invariant protection allows one to minimize damages in 6-10 kV electrical installations of industrial enterprises for a cause of infringement of consumers’ power supply and their system breakdown due to timely localization of emergency of ground faults modes.

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

    PubMed

    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).

  4. Restoration of energy level in the early phase of acute pediatric pancreatitis.

    PubMed

    Mosztbacher, Dóra; Farkas, Nelli; Solymár, Margit; Pár, Gabriella; Bajor, Judit; Szűcs, Ákos; Czimmer, József; Márta, Katalin; Mikó, Alexandra; Rumbus, Zoltán; Varjú, Péter; Hegyi, Péter; Párniczky, Andrea

    2017-02-14

    Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better

  5. Restoration of energy level in the early phase of acute pediatric pancreatitis

    PubMed Central

    Mosztbacher, Dóra; Farkas, Nelli; Solymár, Margit; Pár, Gabriella; Bajor, Judit; Szűcs, Ákos; Czimmer, József; Márta, Katalin; Mikó, Alexandra; Rumbus, Zoltán; Varjú, Péter; Hegyi, Péter; Párniczky, Andrea

    2017-01-01

    Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better

  6. Welcome to the Twilight Zone: a forgotten early phase of human evolutionary studies.

    PubMed

    Delisle, Richard G

    2012-06-01

    The field of paleoanthropology arose out of a strange and unacknowledged early phase of development prior to about the 1930s. It is often assumed that a key pillar of the discipline, the unity of humankind--the notion that humans are clearly separated phylogenetically (genealogically) from other non-human primates--was widely accepted from the inception of paleoanthropology around 1860. However, a final consensus on this fundamental question only appeared later on in the 20th century. This paper will focus on two key areas of disagreement, which reveal the unsettled state of this question during this early period: the question of uncertainty with respect to the number, identity and boundary of primate species (including humans) which prevailed in the 18th, 19th and early 20th centuries; and the matter of uncertainty with respect to the nature of the phylogenetic relationships among the various human populations and the other primate species which prevailed between 1864 and 1931. Consideration of these matters reveals that the modern research structure that paleoanthropologists take for granted today is much more recent than believed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Early protection events in swine immunized with an experimental live attenuated classical swine fever marker vaccine, FlagT4G

    USDA-ARS?s Scientific Manuscript database

    Prophylactic vaccination using live attenuated classical swine fever (CSF) vaccines has been a very effective method to control disease in endemic regions and during outbreaks in previously disease-free areas. These vaccines confer effective protection against the disease at early times post-vaccina...

  8. Protection by and maintenance of CD4 effector memory and effector T cell subsets in persistent malaria infection.

    PubMed

    Opata, Michael M; Ibitokou, Samad A; Carpio, Victor H; Marshall, Karis M; Dillon, Brian E; Carl, Jordan C; Wilson, Kyle D; Arcari, Christine M; Stephens, Robin

    2018-04-01

    Protection at the peak of Plasmodium chabaudi blood-stage malaria infection is provided by CD4 T cells. We have shown that an increase in Th1 cells also correlates with protection during the persistent phase of malaria; however, it is unclear how these T cells are maintained. Persistent malaria infection promotes protection and generates both effector T cells (Teff), and effector memory T cells (Tem). We have previously defined new CD4 Teff (IL-7Rα-) subsets from Early (TeffEarly, CD62LhiCD27+) to Late (TeffLate, CD62LloCD27-) activation states. Here, we tested these effector and memory T cell subsets for their ability to survive and protect in vivo. We found that both polyclonal and P. chabaudi Merozoite Surface Protein-1 (MSP-1)-specific B5 TCR transgenic Tem survive better than Teff. Surprisingly, as Tem are associated with antigen persistence, Tem survive well even after clearance of infection. As previously shown during T cell contraction, TeffEarly, which can generate Tem, also survive better than other Teff subsets in uninfected recipients. Two other Tem survival mechanisms identified here are that low-level chronic infection promotes Tem both by driving their proliferation, and by programming production of Tem from Tcm. Protective CD4 T cell phenotypes have not been precisely determined in malaria, or other persistent infections. Therefore, we tested purified memory (Tmem) and Teff subsets in protection from peak pathology and parasitemia in immunocompromised recipient mice. Strikingly, among Tmem (IL-7Rαhi) subsets, only TemLate (CD62LloCD27-) reduced peak parasitemia (19%), though the dominant memory subset is TemEarly, which is not protective. In contrast, all Teff subsets reduced peak parasitemia by more than half, and mature Teff can generate Tem, though less. In summary, we have elucidated four mechanisms of Tem maintenance, and identified two long-lived T cell subsets (TemLate, TeffEarly) that may represent correlates of protection or a target for

  9. Muscle contributions to knee extension in the early stance phase in patients with knee osteoarthritis.

    PubMed

    Ogaya, Shinya; Kubota, Ryo; Chujo, Yuta; Hirooka, Eiko; Kwang-Ho, Kim; Hase, Kimitaka

    2017-10-01

    The aim of this study was to analyze individual muscle contributions to knee angular acceleration using a musculoskeletal simulation analysis and evaluate knee extension mechanics in the early stance phase in patients with knee osteoarthritis (OA). The subjects comprised 15 patients with medial knee OA and 14 healthy elderly individuals. All participants underwent gait performance test using 8 infrared cameras and two force plates to measure the kinetic and kinematic data. The simulation was driven by 92 Hill-type muscle-tendon units of the lower extremities and a trunk with 23° of freedom. We analyzed each muscle contribution to knee angular acceleration in the 5%-15% and 15%-25% periods of the stance phase (% SP) using an induced acceleration analysis. We compared accelerations by individual muscles between the two groups using an analysis of covariance for controlling gait speed. Patients with knee OA had a significantly lesser knee extension acceleration by the vasti muscles and higher knee acceleration by hip adductors than those in controls in 5-15% SP. In addition, knee OA resulted in significantly lesser knee extension acceleration by the vasti muscles in 15-25% SP. These results indicate that patients with knee OA have decreased dependency on the vasti muscles to control knee movements during early stance phase. Hip adductor muscles, which mainly control mediolateral motion, partly compensate for the weak knee extension by the vasti muscles in patients with knee OA. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. A Planetary Protection Strategy for the Mars Aerial Regional-Scale Environmental Survey (ARES) Mission Concept

    NASA Technical Reports Server (NTRS)

    Kuhl, Christopher A.

    2008-01-01

    The Aerial Regional-scale Environmental Survey (ARES) is a Mars exploration mission concept designed to send an airplane to fly through the lower atmosphere of Mars, with the goal of taking scientific measurements of the atmosphere, surface, and subsurface phenomenon. ARES was first proposed to the Mars Scout program in December 2002 for a 2007 launch opportunity and was selected to proceed with a Phase A study, step-2 proposal which was submitted in May 2003. ARES was not selected for the Scout mission, but efforts continued on risk reduction of the atmospheric flight system in preparation for the next Mars Scout opportunity in 2006. The ARES concept was again proposed in July 2006 to the Mars Scout program but was not selected to proceed into Phase A. This document describes the Planetary Protection strategy that was developed in ARES Pre Phase-A activities to help identify, early in the design process, certain hardware, assemblies, and/or subsystems that will require unique design considerations based on constraints imposed by Planetary Protection requirements. Had ARES been selected as an exploration project, information in this document would make up the ARES Project Planetary Protection Plan.

  11. 78 FR 69690 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ... and Gene Therapy Products; Extension of Comment Period AGENCY: Food and Drug Administration, HHS...: Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products'' that... sponsors of Investigational New Drug Applications for cellular therapy (CT) and gene therapy (GT) products...

  12. Ultrastructural Complexity of Nuclear Components During Early Apoptotic Phases in Breast Cancer Cells

    PubMed Central

    Castelli, Christian; Losa, Gabriele A.

    2001-01-01

    Fractal morphometry was used to investigate the ultrastructural features of the plasma membrane, perinuclear membrane and nuclear chromatin in SK‐BR‐3 human breast cancer cells undergoing apoptosis. Cells were incubated with 1 μM calcimycin (A23187) for 24 h. Cells in the early stage of apoptosis had fractal dimension (FD) values indicating that their plasma membranes were less rough (lower FD) than those of control cells, while their perinuclear membranes were unaffected. Changes of the chromatin texture within the entire nucleus and in selected nuclear domains were more pronounced in treated cells. This confirms that the morphological reorganization imputable to a loss of structural complexity (reduced FD) occurs in the early stage of apoptosis, is accompanied by the inhibition of distinct enzymatic events and precedes the onset of conventional cellular markers, which can only be detected during the active phases of the apoptotic process. PMID:11790854

  13. Advanced worker protection system. Topical report, Phase I

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

    Myers, J.

    1995-07-01

    The Department of Energy (DOE) is in the process of defining the magnitude and diversity of Decontamination and Decommissioning (D&D) obligations at its numerous sites. The DOE believes that existing technologies are inadequate to solve many challenging problems such as how to decontaminate structures and equipment cost effectively, what to do with materials and wastes generated, and how to adequately protect workers and the environment. Preliminary estimates show a tremendous need for effective use of resources over a relatively long period (over 30 years). Several technologies are being investigated which can potentially reduce D&D costs while providing appropriate protection tomore » DOE workers. The DOE recognizes that traditional methods used by the EPA in hazardous waste site clean up activities are insufficient to provide the needed protection and worker productivity demanded by DOE D&D programs. As a consequence, new clothing and equipment which can adequately protect workers while providing increases in worker productivity are being sought for implementation at DOE sites. This project will result in the development of an Advanced Worker Protection System (AWPS). The AWPS will be built around a life support backpack that uses liquid air to provide cooling as well as breathing gas to the worker. The backpack will be combined with advanced protective garments, advanced liquid cooling garment, respirator, communications, and support equipment to provide improved worker protection, simplified system, maintenance, and dramatically improve worker productivity through longer duration work cycles.« less

  14. The hepatocyte phase of Gd-EOB-DTPA-enhanced MRI in the evaluation of hepatic fibrosis and early liver cirrhosis in a rat model: an experimental study.

    PubMed

    Ma, Chunmei; Liu, Ailian; Wang, Yuanyuan; Geng, Xiaoling; Hao, Li; Song, Qingwei; Sun, Bo; Wang, Heqing; Zhao, Gang

    2014-07-17

    To evaluate the hepatocyte phase of Gd-EOB-DTPA-enhanced MRI in the early diagnosis of hepatic fibrosis and cirrhosis and assessment of liver function in a rat model. In 2 groups of SD rats, liver fibrosis was induced in experimental animals by repetitive carbon tetrachloride injections, while the control group received saline injections. Five experimental rats and 2 control rats were randomly selected at weeks 4, 8, 12. One week after carbon tetrachloride administration, MRI (FIRM T1WI) scan was performed. Gd-EOB-DTPA (0.08mL) was injected into the rat's tail vein and hepatocyte phase images were obtained after 20min. The pre-enhanced phase and hepatocyte phase signal intensities (SI) were measured, and the relative contrast enhancement index (RCEI) was calculated. ANOVA analysis (LSD) of RCEI values in controls (n=6), hepatic fibrosis (n=7), and histopathologically-determined early cirrhosis group (n=6) was performed. RECI values showed a decreasing trend in the control group, hepatic fibrosis and early cirrhosis groups (1.11±0.43, 0.96±0.22, and 0.57±0.33, respectively). While the difference between the control and early cirrhosis groups was statistically significant (p=0.013), there was no significant difference in the hepatic fibrosis group vs the control (p=0.416) and the hepatic fibrosis group vs the early cirrhosis group (p=0.054). Hepatocyte phase RCEI values obtained with Gd-EOB-DTPA-enhanced MRI scan indicate liver injury in hepatic fibrosis and early cirrhosis. RCEI values are helpful for early diagnosis of liver cirrhosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Maintenance phase in psoralen-ultraviolet A phototherapy of early-stage mycosis fungoides. A critically appraised topic.

    PubMed

    Grandi, V; Delfino, C; Pileri, A; Pimpinelli, N

    2017-08-01

    A 65-year-old patient affected by mycosis fungoides (MF) stage IB achieved complete remission (CR) after a cycle of PUVA phototherapy. The U.S. Cutaneous Lymphoma Consortium (USCLC) guidelines suggest that the patient should be kept in the maintenance phase, defined as a 'period of gradual decrease of frequency of UVL [ultraviolet light] while in clinical remission before discontinuation of phototherapy' by slowly tapering the number of psoralen-ultraviolet A (PUVA) applications over time up to clinical relapse. The USCLC guidelines also suggest a standardized schedule for the maintenance phase. Alternatively, the patient could end PUVA therapy and go straight to follow-up. The aim of this critically appraised topic (CAT) was to determine if a maintenance phase gives a significant benefit in terms of relapse rate (RR) and RFI in patients affected by early-stage MF who had achieved CR under PUVA phototherapy. Embase, PubMed and TRIP databases were searched for 'mycosis fungoides' AND [('photochemotherapy' OR 'puva') OR 'psoralen'] in June 2016. Three articles matched our inclusion criteria and are discussed in this CAT. In this field of research the literature is poor and the reported level of evidence is low. Only one of the studies was conducted prospectively, and none were randomized. No significant difference in terms of reduction in relapse rate or increase in RFI in patients who underwent a PUVA maintenance phase emerged when compared with those who went for simple follow-up. Further randomized clinical trials (RCTs) are required in order to evaluate maintenance phase vs. no treatment before it can be favoured as the standard protocol of treatment in early-stage MF. At the time of writing this paper, we report an ongoing Austrian multicentre RCT (Clinical Trial.gov identifier: NCT01686594) that will hopefully give useful results in this topic. © 2017 British Association of Dermatologists.

  16. Phytochrome-mediated germination and early development in spores of Dryopteris filix-mas L.: phase-specific and non phase-specific inhibition by staurosporine

    NASA Technical Reports Server (NTRS)

    Haas, C. J.; Scheuerlein, R.; Roux, S. J.

    1991-01-01

    The alkaloid staurosporine, currently known as the most potent inhibitor of protein kinase C, PKC, was tested for its ability to inhibit phytochrome-mediated spore germination in Dryopteris filix-mas L., evaluated by the induction of chlorophyll synthesis. Approximately half-maximal inhibition was obtained at a concentration of 10(-5) M. This effect of staurosporine was phase-specific and was found during the same period in which the presence of extracellular calcium is necessary for realization of the light signal. Furthermore, the ability of staurosporine to prevent progression of a germinated spore into early gametophyte development, evaluated by the accumulation of chlorophyll, was examined. Again, staurosporine (10(-5) M) significantly diminished chlorophyll accumulation, determined quantitatively in vivo by single-cell measurements, in a non-phase specific way. The fact that the phase-specific inhibitory effect of staurosporine in preventing germination was coincident with the phase-specific requirement of Ca2+ suggests that both Ca2+ and staurosporine affect the same step in the signal-transduction chain. A phosphorylation event catalysed by PKC or any Ca2+ -dependent protein kinase is proposed as the target of staurosporine and Ca2+.

  17. Methylene blue prevents surgery-induced peritoneal adhesions but impairs the early phase of anastomotic wound healing

    PubMed Central

    Dinc, Soykan; Ozaslan, Cihangir; Kuru, Bekir; Karaca, Sefa; Ustun, Huseyin; Alagol, Haluk; Renda, Nurten; Oz, Murat

    2006-01-01

    Objectives Adhesion formation continues to be an important problem in gastrointestinal surgery. In recent years, methylene blue (MB) has been reported to be an effective agent for preventing peritoneal adhesions. However, its effects on the wound healing process are unknown. In the present study, we investigated the effects of MB on the early and late phases of anastomotic wound healing and on adhesion formation. Methods We randomly categorized 92 rats into 2 groups in bursting pressure measurements and 50 rats into 3 groups in the adhesion model. We divided the animals into saline-treated (n = 46) or MB-treated (n = 46) groups. Bursting pressures of the anastomoses were measured on postoperative days 3 and 7. In biochemical studies, tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity were measured on postoperative days 3 and 7. In the adhesion model, we randomly categorized rats into sham (n = 10), saline-treated (n = 20) and MB-treated (n = 20) groups, and the formation of intraperitoneal adhesions was scored on postoperative day 14. We compared the measurement of bursting pressure and biochemical measurements of tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity. Histopathological findings of specimens were presented. Results During the early phase of wound healing (postoperative day 3), bursting pressures, tissue hydroxyproline, total nitrite/nitrate levels and nitric oxide synthase activity in the MB-treated group were significantly lower than those of the saline-treated group. On postoperative day 7, there was no significant difference in these parameters between MB and saline-treated groups. In the adhesion model, MB caused a significant reduction in the formation of peritoneal adhesions. Conclusion MB prevents peritoneal adhesions but causes a significant impairment of anastomotic bursting pressure during the early phase of the wound healing process by its transient

  18. Teachers' Beliefs on Foreign Language Teaching Practices in Early Phases of Primary Education: A Case Study

    ERIC Educational Resources Information Center

    Caner, Mustafa; Subasi, Gonca; Kara, Selma

    2010-01-01

    The purpose of the study was to examine whether teacher beliefs would play a role in their actual practices while teaching target language in early phases of primary education, principally, in kindergarten and first grades in a state school. As it is a very broad research area, the researchers exclusively analyzed teaching practices and teaching…

  19. A tale of two timescales: Mixing, mass generation, and phase transitions in the early universe

    NASA Astrophysics Data System (ADS)

    Dienes, Keith R.; Kost, Jeff; Thomas, Brooks

    2016-02-01

    Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically—such as during cosmological mass-generating phase transitions—the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this paper, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the total late-time abundance of the system—often by many orders of magnitude—but also its distribution across the different fields. Second, we find that these effects can produce large parametric resonances which render the energy densities of the fields highly sensitive to the degree of mixing as well as the duration of the time interval over which the phase transition unfolds. Finally, we find that these effects can even give rise to a "reoverdamping" phenomenon which causes the total energy density of the system to behave in novel ways that differ from those exhibited by pure dark matter or vacuum energy. All of these features therefore give rise to new possibilities for early-universe phenomenology and cosmological evolution. They also highlight the importance of taking into account the time dependence associated with phase transitions in cosmological settings.

  20. Development of wave and surge atlas for the design and protection of coastal bridges in South Louisiana - phase 2.

    DOT National Transportation Integrated Search

    2016-09-01

    This report summarizes the work performed by INTERA Incorporated (INTERA), for the Louisiana Department of Transportation and Development (DOTD) on Phase 2 of LTRC project No. 10-4ST, Development of Wave and Surge Atlas for the Design Protection o...

  1. Proteomics analysis identified peroxiredoxin 2 involved in early-phase left ventricular impairment in hamsters with cardiomyopathy.

    PubMed

    Kuzuya, Kentaro; Ichihara, Sahoko; Suzuki, Yuka; Inoue, Chisa; Ichihara, Gaku; Kurimoto, Syota; Oikawa, Shinji

    2018-01-01

    Given the hypothesis that inflammation plays a critical role in the progression of cardiovascular diseases, the aim of the present study was to identify new diagnostic and prognostic biomarkers of myocardial proteins involved in early-phase cardiac impairment, using proteomics analysis. Using the two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF tandem mass spectrometry, we compared differences in the expression of proteins in the whole left ventricles between control hamsters, dilated cardiomyopathic hamsters (TO-2), and hypertrophy cardiomyopathic hamsters (Bio14.6) at 6 weeks of age (n = 6, each group). Proteomic analysis identified 10 protein spots with significant alterations, with 7 up-regulated and 3 down-regulated proteins in the left ventricles of both TO-2 and Bio 14.6 hamsters, compared with control hamsters. Of the total alterations, peroxiredoxin 2 (PRDX2) showed significant upregulation in the left ventricles of TO-2 and Bio 14.6 hamsters. Our data suggest that PRDX2, a redox regulating molecule, is involved in early-phase left ventricular impairment in hamsters with cardiomyopathy.

  2. Extension of quality-by-design concept to the early development phase of pharmaceutical R&D processes.

    PubMed

    Csóka, Ildikó; Pallagi, Edina; Paál, Tamás L

    2018-03-27

    Here, we propose the extension of the quality-by-design (QbD) concept to also fit the early development phases of pharmaceuticals by adding elements that are currently widely applied, but not yet included in the QbD model in a structured way. These are the introduction of a 'zero' preformulation phase (i.e., selection of drug substance, possible dosage forms and administration routes based on the evaluated therapeutic need); building in stakeholders' (industry, patient, and regulatory) requirements into the quality target product profile (QTTP); and the use of modern quality management tools during the composition and process design phase [collecting critical quality attributes (CQAs) and selection of CPPs) for (still laboratory-scale) design space (DS) development. Moreover, during industrial scale-up, CQAs (as well as critical process parameters; CPPs) can be changed; however, we recommend that the existing QbD elements are reconsidered and updated after this phase. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever

    PubMed Central

    Thein, Tun Linn; Fang, Jinling; Pang, Junxiong; Ooi, Eng Eong; Leo, Yee Sin; Ong, Choon Nam; Tannenbaum, Steven R.

    2016-01-01

    Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (<96 h) was used to globally probe the serum metabolome to uncover early prognostic biomarkers of DHF. We identified 20 metabolites that are differentially enriched (p<0.05, fold change >1.5) in the serum, among which are two products of tryptophan metabolism–serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved

  4. Early risk and protective factors for problem gambling: A systematic review and meta-analysis of longitudinal studies.

    PubMed

    Dowling, N A; Merkouris, S S; Greenwood, C J; Oldenhof, E; Toumbourou, J W; Youssef, G J

    2017-02-01

    This systematic review aimed to identify early risk and protective factors (in childhood, adolescence or young adulthood) longitudinally associated with the subsequent development of gambling problems. A systematic search of peer-reviewed and grey literature from 1990 to 2015 identified 15 studies published in 23 articles. Meta-analyses quantified the effect size of 13 individual risk factors (alcohol use frequency, antisocial behaviours, depression, male gender, cannabis use, illicit drug use, impulsivity, number of gambling activities, problem gambling severity, sensation seeking, tobacco use, violence, undercontrolled temperament), one relationship risk factor (peer antisocial behaviours), one community risk factor (poor academic performance), one individual protective factor (socio-economic status) and two relationship protective factors (parent supervision, social problems). Effect sizes were on average small to medium and sensitivity analyses revealed that the results were generally robust to the quality of methodological approaches of the included articles. These findings highlight the need for global prevention efforts that reduce risk factors and screen young people with high-risk profiles. There is insufficient investigation of protective factors to adequately guide prevention initiatives. Future longitudinal research is required to identify additional risk and protective factors associated with problem gambling, particularly within the relationship, community, and societal levels of the socio-ecological model. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Cytomegalovirus infection in early childhood may be protective against glioblastoma multiforme, while later infection is a risk factor.

    PubMed

    Lehrer, Steven

    2012-05-01

    Glioblastoma multiforme is the most common and most aggressive type of primary brain tumor, accounting for 52% of all primary brain tumor cases and 20% of all intracranial tumors. Recently, evidence for a viral cause has been postulated, possibly cytomegalovirus (CMV). In one report, 80% of patients with newly diagnosed glioblastoma multiforme had detectable cytomegalovirus DNA in their peripheral blood, while sero-positive normal donors and other surgical patients did not exhibit detectable virus. However, another study reported that five glioblastoma patients showed no circulating CMV detected either with RT-PCR or blood culture. But CMV could still be a factor in the genesis of glioblastoma multiforme, if age at infection is taken into account, since the incidence of both glioblastoma multiforme and CMV infection are inversely related to socioeconomic status. CMV infection in early childhood, more common in lower socioeconomic groups, may be protective against glioblastoma multiforme, whereas CMV infection in later childhood or adulthood may be a risk factor for glioblastoma. If so, glioblastoma multiforme occurrence would resemble paralytic polio, where low socioeconomic status, poor hygiene and early infection are protective. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. The natural course of anxiety symptoms in early adolescence: factors related to persistence.

    PubMed

    Voltas, Núria; Hernández-Martínez, Carmen; Arija, Victoria; Canals, Josefa

    2017-11-01

    Anxiety disorders are the most common mental health problems during childhood and adolescence. This study examined the course of anxiety symptoms in early adolescents from the general population over three phases. Prospective cohort study. Two hundred and forty-two participants (mean-age of 13.52) from a baseline sample of 1514 (mean-age of 10.23) were followed up three times. Of the 1514 children, those with emotional risk and controls without risk constituted the second-phase sample (n = 562; mean-age of 11.25). The Screen for Child Anxiety Related Emotional Disorders-SCARED was administered in all three phases. Fifty-six percent and 32% of respondents showed total scores above the SCARED cutoff point at one and three years follow-up, respectively. Eight percent showed fluctuating symptoms. Fifty-five percent of respondents showed high scores for any subtype of anxiety over three years. Social phobia and generalized anxiety symptoms were the most prevalent and persistent. Participants with persistent separation anxiety showed the highest co-occurrence with symptoms of other psychopathological disorders. Participants with persistent anxiety showed lower academic performance. Being male was a protective factor against persistence. The data support anxiety maintenance during early adolescence. Early adolescence is a critical period which may involve other serious academic, social, and family problems.

  7. 77 FR 7174 - Correction Notice for Deepwater Horizon Oil Spill; Draft Phase I Early Restoration Plan and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ... DEPARTMENT OF THE INTERIOR Fish and Wildlife Service [FWS-R4-FHC-2012-N030; FVHC98130406900Y4-XXX-FF04G01000] Correction Notice for Deepwater Horizon Oil Spill; Draft Phase I Early Restoration Plan and Environmental Assessment AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice of availability and request...

  8. Evaluation of measles-rubella vaccination for mothers in early puerperal phase.

    PubMed

    Hisano, Michi; Kato, Tatsuo; Inoue, Eisuke; Sago, Haruhiko; Yamaguchi, Koushi

    2016-02-24

    The postpartum period is an ideal opportunity to vaccinate mothers with inadequate immunity to vaccine-preventable diseases including measles and rubella. A prospective study of measles-rubella (MR) vaccination in the early puerperal phase was conducted in 171 mothers, who had insufficient antibody titers when screened for immunity to measles (≤ 1:4 on the neutralization test [NT]) or rubella (≤ 1:16 on the hemagglutination inhibition [HI] test) during pregnancy. To evaluate the efficacy of MR vaccination in the postpartum period, we determined their post-vaccination antibody titers and immune responses to vaccination, and investigated the association between these and their prolactin (PRL) levels and Th1/Th2 ratios at the time of vaccination. We also examined the passage of viral RNA and antigen into breast milk. Of the 169 participants who completed the study schedule, 117 and 101 had low antibody titers against measles and rubella, respectively. In the measles-seronegative group, the antibody-positive rate was 87% on the NT assay, and the NT geometric mean antibody titer was 11.4 (95% confidence interval [CI], 10.0-13.0). In the rubella-seronegative group, the antibody-positive rate was 88% on the HI test assay, and the HI geometric mean antibody titer was 64.0 (95% CI, 53.9-76.0). There was no association between the post-vaccination antibody titers and the PRL levels or Th1/Th2 ratios at the time of vaccination. In the rubella-seronegative group, subjects with higher Th1/Th2 ratios showed higher rates of responsiveness than those with lower ratios (P=0.045). Although measles virus RNA was isolated from the breast milk of two vaccinated mothers, breastfeeding was not associated with clinical disease in any infants. MR vaccination in the early puerperal phase is considered an effective way to prevent the diseases, regardless of the mother's immunological status and hormonal milieu. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes

    PubMed Central

    Cullingford, Timothy E; Markou, Thomais; Fuller, Stephen J; Giraldo, Alejandro; Pikkarainen, Sampsa; Zoumpoulidou, Georgia; Alsafi, Ali; Ekere, Collins; Kemp, Timothy J; Dennis, Jayne L; Game, Laurence; Sugden, Peter H; Clerk, Angela

    2008-01-01

    Background Endothelin-1 stimulates Gq protein-coupled receptors to promote proliferation in dividing cells or hypertrophy in terminally differentiated cardiomyocytes. In cardiomyocytes, endothelin-1 rapidly (within minutes) stimulates protein kinase signaling, including extracellular-signal regulated kinases 1/2 (ERK1/2; though not ERK5), with phenotypic/physiological changes developing from approximately 12 h. Hypertrophy is associated with changes in mRNA/protein expression, presumably consequent to protein kinase signaling, but the connections between early, transient signaling events and developed hypertrophy are unknown. Results Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide. IEGs exhibited differential temporal and transient regulation, with expression of second phase RNAs within 1 h. Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited >50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%. Expression of only four transcripts was not inhibited. At 1 h, most RNAs (approximately 67%) were equally changed in total and polysomal RNA with approximately 17% of transcripts increased to a greater extent in polysomes. Thus, changes in expression of most protein-coding RNAs should be reflected in protein synthesis. However, approximately 16% of transcripts were essentially excluded from the polysomes, including some protein-coding mRNAs, presumably inefficiently translated. Conclusion The phasic, temporal regulation of early transcriptional responses induced by endothelin-1 in cardiomyocytes indicates that, even in terminally differentiated cells, signals are propagated beyond the primary signaling pathways through transcriptional networks leading to phenotypic changes (that is, hypertrophy). Furthermore, ERK1/2 signaling plays a major role in

  10. 40 CFR 63.74 - Demonstration of early reduction.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 10 2012-07-01 2012-07-01 false Demonstration of early reduction. 63.74 Section 63.74 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Governing Compliance Extensions for Early Reductions of Hazardous Air Pollutants § 63.74 Demonstration of...

  11. 40 CFR 63.74 - Demonstration of early reduction.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 10 2013-07-01 2013-07-01 false Demonstration of early reduction. 63.74 Section 63.74 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Governing Compliance Extensions for Early Reductions of Hazardous Air Pollutants § 63.74 Demonstration of...

  12. 40 CFR 63.74 - Demonstration of early reduction.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 10 2014-07-01 2014-07-01 false Demonstration of early reduction. 63.74 Section 63.74 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... Governing Compliance Extensions for Early Reductions of Hazardous Air Pollutants § 63.74 Demonstration of...

  13. PAR-2-mediated control of barrier function and motility differs between early and late phases of postinfectious gut dysfunction in the rat.

    PubMed

    Fernández-Blanco, Joan Antoni; Fernández-Blanco, Juan A; Hollenberg, Morley D; Martínez, Vicente; Vergara, Patri

    2013-02-15

    Proteinase-activated receptor-2 (PAR-2) and mast cell (MC) mediators contribute to inflammatory and functional gastrointestinal disorders. We aimed to characterize jejunal PAR-2-mediated responses and the potential MC involvement in the early and late phases of a rat model of postinfectious gut dysfunction. Jejunal tissues of control and Trichinella spiralis-infected (14 and 30 days postinfection) rats, treated or not with the MC stabilizer, ketotifen, were used. Histopathology and immunostaining were used to characterize inflammation, PAR-2 expression, and mucosal and connective tissue MCs. Epithelial barrier function (hydroelectrolytic transport and permeability) and motility were assessed in vitro in basal conditions and after PAR-2 activation. Intestinal inflammation on day 14 postinfection (early phase) was significantly resolved by day 30 (late phase) although MC counts and epithelial permeability remained increased. PAR-2-mediated ion transport (Ussing chambers, in vitro) and epithelial surface PAR-2 expression were reduced in the early phase, with a trend toward normalization during the late phase. In control conditions, PAR-2 activation (organ bath) induced biphasic motor responses (relaxation followed by excitation). At 14 days postinfection, spontaneous contractility and PAR-2-mediated relaxations were enhanced; motor responses were normalized on day 30. Postinfectious changes in PAR-2 functions were not affected by ketotifen treatment. We concluded that, in the rat model of Trichinella spiralis infection, alterations of intestinal PAR-2 function and expression depend on the inflammatory phase considered. A lack of a ketotifen effect suggests no interplay between MCs and PAR-2-mediated motility and ion transport alterations. These observations question the role of MC mediators in PAR-2-modulating postinfectious gut dysfunction.

  14. Cognitive effects of bilateral high frequency repetitive transcranial magnetic stimulation in early phase psychosis: a pilot study.

    PubMed

    Francis, Michael M; Hummer, Tom A; Vohs, Jenifer L; Yung, Matthew G; Visco, Andrew C; Mehdiyoun, Nikki F; Kulig, Teresa C; Um, Miji; Yang, Ziyi; Motamed, Mehrdad; Liffick, Emily; Zhang, Ying; Breier, Alan

    2018-05-31

    Cognitive dysfunction is a core facet of schizophrenia that is present early in the course of the illness and contributes to diminished functioning and outcomes. Repetitive transcranial magnetic stimulation (rTMS) is a relatively new neuropsychiatric intervention. Initially used in treatment resistant depression, investigators are now studying rTMS for other psychiatric diseases such as schizophrenia. In this study we examined the effect of high frequency rTMS on cognitive function in a group of individuals with early phase psychosis. Twenty subjects were randomized (1:1) in double-blind fashion to rTMS or sham condition. Over two weeks subjects underwent ten sessions of high frequency, bilateral, sequential rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Prior to beginning and following completion of study treatment, subjects completed a cognitive assessment and magnetic resonance imaging. Subjects receiving rTMS, compared to sham treatment, displayed improvement on a standardized cognitive battery both immediately following the course of study treatment and at follow-up two weeks later. Imaging results revealed that left frontal cortical thickness at baseline was correlated with treatment response. The study treatment was found to be safe and well tolerated. These results suggest that rTMS may hold promise for the treatment of cognitive dysfunction in the early phase of psychosis, and that MRI may provide biomarkers predicting response to the treatment.

  15. A German e-learning-training in the context of early preventive intervention and child protection: preliminary findings of a pre-post evaluation.

    PubMed

    Bressem, Kristina; Ziegenhain, Ute; Doelitzsch, Claudia; Hofer, Alexandra; Besier, Tanja; Fegert, Joerg M; Kuenster, Anne K

    2016-01-01

    In recent years, a number of government-sponsored initiatives have been implemented in Germany that are focused on early preventive intervention in child protection. In response to the need for interdisciplinary training in this area, the internet-based e-learning program "Early Preventive Intervention and Child Protection" was developed for professionals in the child welfare and health care systems working with families with infants and toddlers. The program is currently undergoing evaluation for effectiveness and user satisfaction. In a pre-post design, users are requested to complete questionnaires that assess three measures of expertise: theoretical knowledge of relevant fields, the ability to correctly identify subtle signals of infant communication, and the ability to assess maternal sensitivity. This article presents the contents of the program and the pre-training results (N = 1.294 participants). Descriptive analyses as well as Pearson correlations and Bonferroni corrections of error were conducted using the statistical program SPSS v. 21.0. The findings show that a wide range of professionals are making use of the program, and that their existing theoretical knowledge about early preventive intervention, as well as their ability to identify subtle signals of infant communication, is relatively good. However, their ability to assess maternal sensitivity, which is considered a crucial indicator for the risk of child abuse, was low. The outcome of the pre-training results indicates that professionals working in the area of child protection need to develop more capability in recognizing maternal sensitivity, in order to ensure early detection of families who are at risk and thus in need of support. Finally, the number of years of professional experience did not correlate with the scores on any of the three measures, which emphasizes the importance of providing interdisciplinary training in this area for all those working in child and family services

  16. Protection against early intestinal compromise by lipid-rich enteral nutrition through cholecystokinin receptors.

    PubMed

    de Haan, Jacco J; Thuijls, Geertje; Lubbers, Tim; Hadfoune, M'hamed; Reisinger, Kostan; Heineman, Erik; Greve, Jan-Willem M; Buurman, Wim A

    2010-07-01

    Early gut wall integrity loss and local intestinal inflammation are associated with the development of inflammatory complications in surgical and trauma patients. Prevention of these intestinal events is a potential target for therapies aimed to control systemic inflammation. Previously, we demonstrated in a rodent shock model that lipid-rich enteral nutrition attenuated systemic inflammation and prevented organ damage through a cholecystokinin receptor-dependent vagal pathway. The influence of lipid-rich nutrition on very early intestinal compromise as seen after shock is investigated. Next, the involvement of cholecystokinin receptors on the nutritional modulation of immediate gut integrity loss and intestinal inflammation is studied. Randomized controlled in vivo study. University research unit. Male Sprague-Dawley rats. Liquid lipid-rich nutrition or control low-lipid feeding was administered per gavage before hemorrhagic shock. Cholecystokinin receptor antagonists were used to investigate involvement of the vagal antiinflammatory pathway. Gut permeability to horseradish peroxidase increased as soon as 30 mins postshock and was prevented by lipid-rich nutrition compared with low-lipid (p<.01) and fasted controls (p<.001). Furthermore, lipid-rich nutrition reduced plasma levels of enterocyte damage marker ileal lipid binding protein at 60 mins (p<.05). Early gut barrier dysfunction correlated with rat mast cell protease plasma concentrations at 30 mins (rs=0.67; p<.001) and intestinal myeloperoxidase levels at 60 mins (rs=0.58; p<.05). Lipid-rich nutrition significantly reduced plasma rat mast cell protease (p<.01) and myeloperoxidase (p<.05) before systemic inflammation was detectable. Protective effects of lipid-rich nutrition were abrogated by cholecystokinin receptor antagonists (horseradish peroxidase; p<.05 and rat mast cell protease; p<.05). Lipid-rich enteral nutrition prevents early gut barrier loss, enterocyte damage, and local intestinal inflammation

  17. Decrease in early right alpha band phase synchronization and late gamma band oscillations in processing syntax in music.

    PubMed

    Ruiz, María Herrojo; Koelsch, Stefan; Bhattacharya, Joydeep

    2009-04-01

    The present study investigated the neural correlates associated with the processing of music-syntactical irregularities as compared with regular syntactic structures in music. Previous studies reported an early ( approximately 200 ms) right anterior negative component (ERAN) by traditional event-related-potential analysis during music-syntactical irregularities, yet little is known about the underlying oscillatory and synchronization properties of brain responses which are supposed to play a crucial role in general cognition including music perception. First we showed that the ERAN was primarily represented by low frequency (<8 Hz) brain oscillations. Further, we found that music-syntactical irregularities as compared with music-syntactical regularities, were associated with (i) an early decrease in the alpha band (9-10 Hz) phase synchronization between right fronto-central and left temporal brain regions, and (ii) a late ( approximately 500 ms) decrease in gamma band (38-50 Hz) oscillations over fronto-central brain regions. These results indicate a weaker degree of long-range integration when the musical expectancy is violated. In summary, our results reveal neural mechanisms of music-syntactic processing that operate at different levels of cortical integration, ranging from early decrease in long-range alpha phase synchronization to late local gamma oscillations. 2008 Wiley-Liss, Inc.

  18. Internal Dose from Food and Drink Ingestion in the Early Phase after the Accident

    NASA Astrophysics Data System (ADS)

    Kawai, Masaki; Yoshizawa, Nobuaki; Hirakawa, Sachiko; Murakami, Kana; Takizawa, Mari; Sato, Osamu; Takagi, Shunji; Miyatake, Hirokazu; Takahashi, Tomoyuki; Suzuki, Gen

    2017-09-01

    Activity concentrations in food and drink, represented by water and vegetables, have been monitored continuously since the Fukushima Daiichi Nuclear Power Plant accident, with a focus on radioactive cesium. On the other hand, iodine-131 was not measured systematically in the early phase after the accident. The activity concentrations of iodine-131 in food and drink are important to estimate internal exposure due to ingestion pathway. When the internal dose from ingestion in the evacuation areas is estimated, water is considered as the main ingestion pathway. In this study, we estimated the values of activity concentrations in water in the early phase after the accident, using a compartment model as an estimation method. The model uses measurement values of activity concentration and deposition rate of iodine-131 onto the ground, which is calculated from an atmospheric dispersion simulation. The model considers how drinking water would be affected by radionuclides deposited into water. We estimated the activity concentrations of water on Kawamata town and Minamisouma city during March of 2011 and the committed effective doses were 0.08 mSv and 0.06 mSv. We calculated the transfer parameters in the model for estimating the activity concentrations in the areas with a small amount of measurement data. In addition, we estimated the committed effective doses from vegetables using atmospheric dispersion simulation and FARMLAND model in case of eating certain vegetables as option information.

  19. Masks as Self-Study. Challenging and Sustaining Teachers' Personal and Professional Personae in Early-Mid Career Life Phases

    ERIC Educational Resources Information Center

    Leitch, Ruth

    2010-01-01

    Drawing on previous research identifying how teachers' capacities to sustain their effectiveness in different phases of their professional lives are affected positively and/or negatively by their sense of identity, this paper illuminates three early-mid career teachers' self-study inquiries, centring on mask work. The creative development of…

  20. HSP70.1 AND -70.3 ARE REQUIRED FOR LATE-PHASE PROTECTION INDUCED BY ISCHEMIC PRECONDITIONING OF MOUSE HEARTS

    EPA Science Inventory

    Heat-Shock Proteins 70.1 and 70.3 Are Required for Late-phase Protection
    Induced by Ischemic Preconditioning of the Mouse Heart
    Craig R. Hampton 1 , Akira Shimamoto 1 , Christine L. Rothnie 1 , Jeaneatte Griscavage-Ennis 1 ,
    Albert Chong 1 , David J. Dix 2 , Edward D. Ve...

  1. Differential role of afferent and efferent renal nerves in the maintenance of early- and late-phase Dahl S hypertension

    PubMed Central

    Foss, Jason D.; Fink, Gregory D.

    2015-01-01

    Clinical data suggest that renal denervation (RDNX) may be an effective treatment for human hypertension; however, it is unclear whether this therapeutic effect is due to ablation of afferent or efferent renal nerves. We have previously shown that RDNX lowers arterial pressure in hypertensive Dahl salt-sensitive (S) rats to a similar degree observed in clinical trials. In addition, we have recently developed a method for selective ablation of afferent renal nerves (renal-CAP). In the present study, we tested the hypothesis that the antihypertensive effect of RDNX in the Dahl S rat is due to ablation of afferent renal nerves by comparing the effect of complete RDNX to renal-CAP during two phases of hypertension in the Dahl S rat. In the early phase, rats underwent treatment after 3 wk of high-NaCl feeding when mean arterial pressure (MAP) was ∼140 mmHg. In the late phase, rats underwent treatment after 9 wk of high NaCl feeding, when MAP was ∼170 mmHg. RDNX reduced MAP ∼10 mmHg compared with sham surgery in both the early and late phase, whereas renal-CAP had no antihypertensive effect. These results suggest that, in the Dahl S rat, the antihypertensive effect of RDNX is not dependent on pretreatment arterial pressure, nor is it due to ablation of afferent renal nerves. PMID:26661098

  2. Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke.

    PubMed

    McCabe, Dominick J H; Murphy, Stephen J X; Starke, Richard; Harrison, Paul; Brown, Martin M; Sidhu, Paul S; Mackie, Ian J; Scully, Marie; Machin, Samuel J

    2015-01-15

    Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied. In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)). Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels. ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD. Copyright © 2014 Elsevier B.V. All rights

  3. The Impact of Early Design Phase Risk Identification Biases on Space System Project Performance

    NASA Technical Reports Server (NTRS)

    Reeves, John D., Jr.; Eveleigh, Tim; Holzer, Thomas; Sarkani, Shahryar

    2012-01-01

    Risk identification during the early design phases of complex systems is commonly implemented but often fails to result in the identification of events and circumstances that truly challenge project performance. Inefficiencies in cost and schedule estimation are usually held accountable for cost and schedule overruns, but the true root cause is often the realization of programmatic risks. A deeper understanding of frequent risk identification trends and biases pervasive during space system design and development is needed, for it would lead to improved execution of existing identification processes and methods.

  4. Conditioned Medium from Early-Outgrowth Bone Marrow Cells Is Retinal Protective in Experimental Model of Diabetes

    PubMed Central

    Duarte, Diego A.; Papadimitriou, Alexandros; Gilbert, Richard E.; Thai, Kerri; Zhang, Yanling; Rosales, Mariana A. B.; Lopes de Faria, José B.; Lopes de Faria, Jacqueline M.

    2016-01-01

    Bone marrow-derived cells were demonstrated to improve organ function, but the lack of cell retention within injured organs suggests that the protective effects are due to factors released by the cells. Herein, we tested cell therapy using early outgrowth cells (EOCs) or their conditioned media (CM) to protect the retina of diabetic animal models (type 1 and type 2) and assessed the mechanisms by in vitro study. Control and diabetic (db/db) mice (8 weeks of age) were randomized to receive a unique intravenous injection of 5×105EOCs or 0.25 ml thrice weekly tail-vein injections of 10x concentrated CM and Wystar Kyoto rats rendered diabetic were randomized to receive 0.50 ml thrice weekly tail-vein injections of 10x concentrated CM. Four weeks later, the animals were euthanized and the eyes were enucleated. Rat retinal Müller cells (rMCs) were exposed for 24 h to high glucose (HG), combined or not with EOC-conditioned medium (EOC-CM) from db/m EOC cultures. Diabetic animals showed increase in diabetic retinopathy (DR) and oxidative damage markers; the treatment with EOCs or CM infusions significantly reduced this damage and re-established the retinal function. In rMCs exposed to diabetic milieu conditions (HG), the presence of EOC-CM reduced reactive oxygen species production by modulating the NADPH-oxidase 4 system, thus upregulating SIRT1 activity and deacetylating Lys-310-p65-NFκB, decreasing GFAP and VEGF expressions. The antioxidant capacity of EOC-CM led to the prevention of carbonylation and nitrosylation posttranslational modifications on the SIRT1 molecule, preserving its activity. The pivotal role of SIRT1 on the mode of action of EOCs or their CM was also demonstrated on diabetic retina. These findings suggest that EOCs are effective as a form of systemic delivery for preventing the early molecular markers of DR and its conditioned medium is equally protective revealing a novel possibility for cell-free therapy for the treatment of DR. PMID:26836609

  5. [Spiral CT of the head-neck area: the advantages of the early arterial phase in the detection of squamous-cell carcinomas].

    PubMed

    Conrad, R; Pauleit, D; Layer, G; Kandyba, J; Kohlbecher, R; Hortling, N; Baselides, P; Schild, H

    1999-07-01

    To determine if scanning in the arterial phase improves detection of squamous cell carcinomas in the pharynx and larynx. In a prospective clinical study 20 patients with a pharyngeal or laryngeal carcinoma were examined with by spiral CT. 80 ml lopromid were intravenously injected as a bolus with a rate of 3 ml/sec. Two consecutive spiral CT scans were performed with start-delay times of 20 and 70 seconds respectively. Delineation and contrast enhancement of tumours, cervical lymph nodes and vessels were evaluated. The radiodensities (HU) of tumors, lymph nodes vessels, pharyngeal wall and muscle were measured. Comparing early and late start delay time scans tumor assessment in the early phase was better in 58%, less in 16% and equal in both scans in 26%. 82% of the pathologic lymph nodes had more peripheral enhancement than surrounding muscle tissue. During the arterial phase the measured radiodensities of the common carotid artery and jugular vein were significantly higher than in the second phase. Contrast-enhanced special CT permits accurate morphologic assessment (size, infiltration) of pharyngeal and supraglottic laryngeal squamous cell carcinoma, while pathologic lymph nodes already have a sufficient contrast enhancement for the detection.

  6. Α-Melanocyte-Stimulating Hormone Protects Early Diabetic Retina from Blood-Retinal Barrier Breakdown and Vascular Leakage via MC4R.

    PubMed

    Cai, Siwei; Yang, Qianhui; Hou, Mengzhu; Han, Qian; Zhang, Hanyu; Wang, Jiantao; Qi, Chen; Bo, Qiyu; Ru, Yusha; Yang, Wei; Gu, Zhongxiu; Wei, Ruihua; Cao, Yunshan; Li, Xiaorong; Zhang, Yan

    2018-01-01

    Blood-retinal barrier (BRB) breakdown and vascular leakage is the leading cause of blindness of diabetic retinopathy (DR). Hyperglycemia-induced oxidative stress and inflammation are primary pathogenic factors of this severe DR complication. An effective interventional modality against the pathogenic factors during early DR is needed to curb BRB breakdown and vascular leakage. This study sought to examine the protective effects of α-Melanocyte-stimulating hormone (α-MSH) on early diabetic retina against vascular hyperpermeability, electrophysiological dysfunction, and morphological deterioration in a rat model of diabetes and probe the mechanisms underlying the α-MSH's anti-hyperpermeability in both rodent retinas and simian retinal vascular endothelial cells (RF6A). Sprague Dawley rats were injected through tail vein with streptozotocin to induce diabetes. The rats were intravitreally injected with α-MSH or saline at Week 1 and 3 after hyperglycemia. In another 2 weeks, Evans blue assay, transmission electron microscopy, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to examine the protective effects of α-MSH in diabetic retinas. The expression of pro-inflammatory factors and tight junction at mRNA and protein levels in retinas was analyzed. Finally, the α-MSH's anti-hyperpermeability was confirmed in a high glucose (HG)-treated RF6A cell monolayer transwell culture by transendothelial electrical resistance (TEER) measurement and a fluorescein isothiocyanate-Dextran assay. Universal or specific melanocortin receptor (MCR) blockers were also employed to elucidate the MCR subtype mediating α-MSH's protection. Evans blue assay showed that BRB breakdown and vascular leakage was detected, and rescued by α-MSH both qualitatively and quantitatively in early diabetic retinas; electron microscopy revealed substantially improved retinal and choroidal vessel ultrastructures in α-MSH-treated diabetic retinas; scotopic ERG suggested

  7. Limited Human Factors Assessment of the QuadGard Limb Protection System: U.S. Marine Corps Systems Command Limb Protection Program Overview (QuadGard Phases 4 and 5 Production Designs)

    DTIC Science & Technology

    2011-09-01

    in calculating the ergonomics associated with ballistic protection. MARCORSYSCOM established three design requirements: (1) system compatibility...knob. The Velcro disengaged, as designed , to allow the wearer unimpeded leg movement. The control knob is used to adjust the driver’s seat height...QuadGard Phases IV and V Production Designs ) by Richard S. Bruno ARL-TR-5656 September 2011

  8. Media representations of early human development: protecting, feeding and loving the developing brain.

    PubMed

    O'Connor, Cliodhna; Joffe, Helene

    2013-11-01

    The public profile of neurodevelopmental research has expanded in recent years. This paper applies social representations theory to explore how early brain development was represented in the UK print media in the first decade of the 21st century. A thematic analysis was performed on 505 newspaper articles published between 2000 and 2010 that discussed early brain development. Media coverage centred around concern with 'protecting' the prenatal brain (identifying threats to foetal neurodevelopment), 'feeding' the infant brain (indicating the patterns of nutrition that enhance brain development) and 'loving' the young child's brain (elucidating the developmental significance of emotionally nurturing family environments). The media focused almost exclusively on the role of parental action in promoting optimal neurodevelopment, rarely acknowledging wider structural, cultural or political means of supporting child development. The significance of parental care was intensified by deterministic interpretations of critical periods, which implied that inappropriate parental input would produce profound and enduring neurobiological impairments. Neurodevelopmental research was also used to promulgate normative judgements concerning the acceptability of certain gender roles and family contexts. The paper argues that media representations of neurodevelopment stress parental responsibility for shaping a child's future while relegating the contributions of genetic or wider societal factors, and examines the consequences of these representations for society and family life. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Early cytokine modulation after the rapid induction phase of sublingual immunotherapy with mite monomeric allergoids.

    PubMed

    Di Gioacchino, M; Perrone, A; Petrarca, C; Di Claudio, F; Mistrello, G; Falagiani, P; Dadorante, V; Verna, N; Braga, M; Ballone, E; Cavallucci, E

    2008-01-01

    The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 microg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 microg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (p<0.0002) after treatment in group B patients, and this effect was higher (p=0.05) compared to group A patients. Furthermore, at the end of SLIT induction TNF-alpha, IL-4 and IFN-gamma production were reduced in group B patients (p<0.05, p=0.062 and p=0.060, respectively). The rapid induction scheme of sublingual immunotherapy induces an early immune suppression more effectively than the slower one. The rapid induction scheme should be the preferential way to start sublingual immunotherapy, particularly when monomeric allergoids are utilized.

  10. Helping Residents Protect Water Sources

    EPA Pesticide Factsheets

    Building on the successful early engagement of the Plain Sect agricultural community, the Eastern Lancaster County Source Water Protection Collaborative is expanding its efforts to involve local residents in the work of protecting drinking water sources.

  11. Inhibition of Late and Early Phases of Cancer Metastasis by the NF-κB Inhibitor DHMEQ Derived from Microbial Bioactive Metabolite Epoxyquinomicin: A Review.

    PubMed

    Lin, Yinzhi; Ukaji, Tamami; Koide, Naoki; Umezawa, Kazuo

    2018-03-03

    We previously designed and synthesized dehydroxyepoxyquinomicin (DHMEQ) as an inhibitor of NF-κB based on the structure of microbial secondary metabolite epoxyquinomicin C. DHMEQ showed anti-inflammatory and anticancer activity in various in vivo disease models without toxicity. On the other hand, the process of cancer metastasis consists of cell detachment from the primary tumor, invasion, transportation by blood or lymphatic vessels, invasion, attachment, and formation of secondary tumor. Cell detachment from the primary tumor and subsequent invasion are considered to be early phases of metastasis, while tumor cell attachment to the tissue and secondary tumor formation the late phases. The assay system for the latter phase was set up with intra-portal-vein injection of pancreatic cancer cells. Intraperitoneal administration of DHMEQ was found to inhibit liver metastasis possibly by decreasing the expression of MMP-9 and IL-8. Also, when the pancreatic cancer cells treated with DHMEQ were inoculated into the peritoneal cavity of mice, the metastatic foci formation was inhibited. These results indicate that DHMEQ is likely to inhibit the late phase of metastasis. Meanwhile, we have recently employed three-dimensional (3D) culture of breast cancer cells for the model of early phase metastasis, since the 3D invasion just includes cell detachment and invasion into the matrix. DHMEQ inhibited the 3D invasion of breast cancer cells at 3D-nontoxic concentrations. In this way, DHMEQ was shown to inhibit the late and early phases of metastasis. Thus, DHMEQ is likely to be useful for the suppression of cancer metastasis.

  12. Water-Soluble Phosphine-Protected Au₁₁ Clusters: Synthesis, Electronic Structure, and Chiral Phase Transfer in a Synergistic Fashion.

    PubMed

    Yao, Hiroshi; Iwatsu, Mana

    2016-04-05

    Synthesis of atomically precise, water-soluble phosphine-protected gold clusters is still currently limited probably due to a stability issue. We here present the synthesis, magic-number isolation, and exploration of the electronic structures as well as the asymmetric conversion of triphenylphosphine monosulfonate (TPPS)-protected gold clusters. Electrospray ionization mass spectrometry and elemental analysis result in the primary formation of Au11(TPPS)9Cl undecagold cluster compound. Magnetic circular dichroism (MCD) spectroscopy clarifies that extremely weak transitions are present in the low-energy region unresolved in the UV-vis absorption, which can be due to the Faraday B-terms based on the magnetically allowed transitions in the cluster. Asymmetric conversion without changing the nuclearity is remarkable by the chiral phase transfer in a synergistic fashion, which yields a rather small anisotropy factor (g-factor) of at most (2.5-7.0) × 10(-5). Quantum chemical calculations for model undecagold cluster compounds are then used to evaluate the optical and chiroptical responses induced by the chiral phase transfer. On this basis, we find that the Au core distortion is ignorable, and the chiral ion-pairing causes a slight increase in the CD response of the Au11 cluster.

  13. F247. INTERNALIZED STIGMA HAS A STRONGER RELATIONSHIP WITH INTRINSIC MOTIVATION COMPARED TO AMOTIVATION IN EARLY PHASE AND PROLONGED SCHIZOPHRENIA

    PubMed Central

    Firmin, Ruth; Luther, Lauren; Lysaker, Paul; Vohs, Jennifer

    2018-01-01

    Abstract Background Motivation deficits predict decreased functioning in schizophrenia. Recent work suggests deficits reflect challenges in separate domains: intrinsic motivation (one’s internal drive to engage in a behavior out of enjoyment or interest) and amotivation (one’s broader decrease in motivated behavior linked to avolition and anhedonia). Internalized stigma is another determinant of functioning for people with schizophrenia that may impact motivation. However, little is known about these relationships, including which aspects of motivation it may impact nor when these links emerge. Identifying the link between these constructs may help to identify whether internalized stigma may be a novel treatment target to facilitate improvements in motivation. Methods Forty adults with early phase schizophrenia and 66 adults with prolonged schizophrenia completed measures of internalized stigma, intrinsic motivation, and amotivation. Pearson’s correlations were examined followed by Fischer’s r-to-z transformations to compare differences in the magnitude of associations between internalized stigma and intrinsic motivation and internalized stigma and amotivation among the first episode and prolonged samples. Next, we conducted stepwise regressions to examine whether internalized stigma was associated with intrinsic motivation above and beyond associations with amotivation in each sample. Results In the early phase sample, the association between internalized stigma was greater with intrinsic motivation (r=-0.48, p=.00) compared to amotivation (r=0.27, p=0.10). Associations with internalized stigma in the prolonged sample were also greater with intrinsic motivation (r=-0.30, p=0.02) versus amotivation (r=0.19, p=0.12). The magnitude of the associations between internalized stigma and intrinsic motivation (z=1.03, p=0.15) and between internalized stigma and amotivation (z=0.41, p = 0.34) did not significantly differ when comparing phase of illness. Regression

  14. Studies of high temperature ternary phases in mixed-metal-rich early transition metal sulfide and phosphide systems

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

    Marking, Gregory Allen

    1994-01-04

    Investigations of ternary mixed early transition metal-rich sulfide and phosphide systems resulted in the discovery of new structures and new phases. A new series of Zr and Hf - group V transition metal - sulfur K-phases was synthesized and crystallographically characterized. When the group V transition metal was Nb or Ta, the unit cell volume was larger than any previously reported K-phase. The presence of adventitious oxygen was determined in two K-phases through a combination of neutron scattering and X-ray diffraction experiments. A compound Hf 10Ta 3S 3 was found to crystallize in a new-structure type similar to the knownmore » gamma brasses. This structure is unique in that it is the only reported "stuffed" gamma-brass type structure. The metal components, Hf and Ta, are larger in size and more electropositive than the metals found in normal gamma brasses (e.g. Cu and Zn) and because of the larger metallic radii, sulfur can be incorporated into the structure where it plays an integral role in stabilizing this phase relative to others. X-ray single-crystal, X-ray powder and neutron powder refinements were performed on this structure. A new structure was found in the ternary Nb-Zr-P system which has characteristics in common with many known early transition metal-rich sulfides, selenides, and phosphides. This structure has the simplest known interconnection of the basic building blocks known for this structural class. Anomalous scattering was a powerful tool for differentiating between Zr and Nb when using Mo Kα X-radiation. The compounds ZrNbP and HfNbP formed in the space group Prima with the simple Co 2Si structure which is among the most common structures found for crystalline solid materials. Solid solution compounds in the Ta-Nb-P, Ta-Zr-P, Nb-Zr-P, Hf-Nb-P, and Hf-Zr-S systems were crystallographically characterized. The structural information corroborated ideas about bonding in metal-rich compounds.« less

  15. 7T T₂*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease.

    PubMed

    van Rooden, Sanneke; Doan, Nhat Trung; Versluis, Maarten J; Goos, Jeroen D C; Webb, Andrew G; Oleksik, Ania M; van der Flier, Wiesje M; Scheltens, Philip; Barkhof, Frederik; Weverling-Rynsburger, Annelies W E; Blauw, Gerard Jan; Reiber, Johan H C; van Buchem, Mark A; Milles, Julien; van der Grond, Jeroen

    2015-01-01

    The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T2(∗)-weighted scans were acquired in 12 EOAD patients and 17 LOAD patients with mild to moderate disease and 27 healthy elderly control subjects. Lobar peak-to-peak phase shifts and regional mean phase contrasts were computed. An increased peak-to-peak phase shift was found for all lobar regions in EOAD patients compared with LOAD patients (p < 0.05). Regional mean phase contrast in EOAD patients was higher than in LOAD patients in the superior medial and middle frontal gyrus, anterior and middle cingulate gyrus, postcentral gyrus, superior and inferior parietal gyrus, and precuneus (p ≤ 0.042). These data suggest that EOAD patients have an increased iron accumulation, possibly related to an increased amyloid deposition, in specific cortical regions as compared with LOAD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Risk and Protective Factors Associated with Trajectories of Depressed Mood from Adolescence to Early Adulthood

    PubMed Central

    Costello, Darcé M.; Swendsen, Joel; Rose, Jennifer S.; Dierker, Lisa C.

    2009-01-01

    This study used semi-parametric group-based modeling to explore unconditional and conditional trajectories of self-reported depressed mood from age 12 to 25. Drawing on data from the National Longitudinal Study of Adolescent Health (N=11,559), four distinct trajectories were identified: no depressed mood, stable low depressed mood, early high declining depressed mood, and late escalating depressed mood. Baseline risk factors associated with greater likelihood of membership in depressed mood trajectory groups compared to the no depressed mood group included being female, Black/African American, Hispanic/Latino American, or Asian American, lower SES, using alcohol, tobacco, or other drugs on a weekly basis, and delinquent behavior. Baseline protective factors associated with greater likelihood of membership in the no depressed mood group compared to the depressed mood trajectory groups included two-parent family structure, feeling connected to parents, peers, or school, and self esteem. With the exception of delinquent behavior, risk and protective factors also distinguished the likelihood of membership among several of the three depressed mood groups. The results add to basic etiologic research regarding developmental pathways of depressed mood in adolescence and young adulthood. PMID:18377115

  17. Astaxanthin protects against early burn-wound progression in rats by attenuating oxidative stress-induced inflammation and mitochondria-related apoptosis

    PubMed Central

    Fang, Quan; Guo, Songxue; Zhou, Hanlei; Han, Rui; Wu, Pan; Han, Chunmao

    2017-01-01

    Burn-wound progression can occur in the initial or peri-burn area after a deep burn injury. The stasis zone has a higher risk of deterioration mediated by multiple factors but is also considered salvageable. Astaxanthin (ATX), which is extracted from some marine organisms, is a natural compound with a strong antioxidant effect that has been reported to attenuate organ injuries caused by traumatic injuries. Hence, we investigated the potential effects of ATX on preventing early burn-wound progression. A classic “comb” burn rat model was established in this study for histological and biological assessments, which revealed that ATX, particularly higher doses, alleviated histological deterioration in the stasis zone. Additionally, we observed dose-dependent improvements in oxidative stress and the release of inflammatory mediators after ATX treatment. Furthermore, ATX dose-dependently attenuated burn-induced apoptosis in the wound areas, and this effect was accompanied by increases in Akt and Bad phosphorylation and a downregulation of cytochrome C and caspase expression. In addition, the administration of Ly 294002 further verified the effect of ATX. In summary, we demonstrated that ATX protected against early burn-wound progression in a rat deep-burn model. This protection might be mediated by the attenuation of oxidative stress-induced inflammation and mitochondria-related apoptosis. PMID:28128352

  18. Archeological treasures protection based on early forest wildfire multi-band imaging detection system

    NASA Astrophysics Data System (ADS)

    Gouverneur, B.; Verstockt, S.; Pauwels, E.; Han, J.; de Zeeuw, P. M.; Vermeiren, J.

    2012-10-01

    Various visible and infrared cameras have been tested for the early detection of wildfires to protect archeological treasures. This analysis was possible thanks to the EU Firesense project (FP7-244088). Although visible cameras are low cost and give good results during daytime for smoke detection, they fall short under bad visibility conditions. In order to improve the fire detection probability and reduce the false alarms, several infrared bands are tested ranging from the NIR to the LWIR. The SWIR and the LWIR band are helpful to locate the fire through smoke if there is a direct Line Of Sight. The Emphasis is also put on the physical and the electro-optical system modeling for forest fire detection at short and longer ranges. The fusion in three bands (Visible, SWIR, LWIR) is discussed at the pixel level for image enhancement and for fire detection.

  19. Early stages of styrene-isoprene copolymerization in gas phase clusters probed by resonance enhanced multiphoton ionization.

    PubMed

    Mahmoud, Hatem; Germanenko, Igor N; El-Shall, M Samy

    2006-04-06

    We present direct evidence for the formation of the covalent bonded styrene (isoprene)(2) oligomer and the isoprene dimer ions following resonance ionization of the gas phase styrene-isoprene binary clusters. The application of resonance ionization to study polymerization reactions in clusters provides new information on the structure and mechanism of formation of the early stages of polymerization and holds considerable promise for the discovery of new initiation mechanisms and for the development of novel materials with unique properties.

  20. Early Origins of Child Obesity: Bridging Disciplines and Phases of Development - September 30–October 1, 2010

    PubMed Central

    Christoffel, Katherine Kaufer; Wang, Xiaobin; Binns, Helen J.

    2012-01-01

    This report summarizes a conference: “Early Origins of Child Obesity: Bridging Disciplines and Phases of Development”, held in Chicago on September 30–October 1, 2010. The conference was funded in part by the National Institutes of Health and the Williams Heart Foundation, to achieve the conference objective: forging a next-step research agenda related to the early origins of childhood obesity. This research agenda was to include working with an array of factors (from genetic determinants to societal ones) along a continuum from prenatal life to age 7, with an emphasis on how the developing child deals with the challenges presented by his/her environment (prenatal, parental, nutritional, etc.). The conference offered a unique opportunity to facilitate communication and planning of future work among a variety of researchers whose work separately addresses different periods in early life. Over the span of two days, speakers addressed existing, critical research topics within each of the most-studied age ranges. On the final day, workshops fostered the discussion needed to identify the highest priority research topics related to linking varied early factor domains. These are presented for use in planning future research and research funding. PMID:23443002

  1. Cognitive and Neuroplasticity Mechanisms by Which Congenital or Early Blindness May Confer a Protective Effect Against Schizophrenia

    PubMed Central

    Silverstein, Steven M.; Wang, Yushi; Keane, Brian P.

    2013-01-01

    Several authors have noted that there are no reported cases of people with schizophrenia who were born blind or who developed blindness shortly after birth, suggesting that congenital or early (C/E) blindness may serve as a protective factor against schizophrenia. By what mechanisms might this effect operate? Here, we hypothesize that C/E blindness offers protection by strengthening cognitive functions whose impairment characterizes schizophrenia, and by constraining cognitive processes that exhibit excessive flexibility in schizophrenia. After briefly summarizing evidence that schizophrenia is fundamentally a cognitive disorder, we review areas of perceptual and cognitive function that are both impaired in the illness and augmented in C/E blindness, as compared to healthy sighted individuals. We next discuss: (1) the role of neuroplasticity in driving these cognitive changes in C/E blindness; (2) evidence that C/E blindness does not confer protective effects against other mental disorders; and (3) evidence that other forms of C/E sensory loss (e.g., deafness) do not reduce the risk of schizophrenia. We conclude by discussing implications of these data for designing cognitive training interventions to reduce schizophrenia-related cognitive impairment, and perhaps to reduce the likelihood of the development of the disorder itself. PMID:23349646

  2. Historical time to disease progression and progression-free survival in patients with recurrent/refractory neuroblastoma treated in the modern era on Children's Oncology Group early-phase trials.

    PubMed

    London, Wendy B; Bagatell, Rochelle; Weigel, Brenda J; Fox, Elizabeth; Guo, Dongjing; Van Ryn, Collin; Naranjo, Arlene; Park, Julie R

    2017-12-15

    Early-phase trials in patients with recurrent neuroblastoma historically used an objective "response" of measureable disease (Response Evaluation Criteria In Solid Tumors [RECIST], without bone/bone marrow assessment) to select agents for further study. Historical cohorts may be small and potentially biased; to the authors' knowledge, disease recurrence studies from international registries are outdated. Using a large recent cohort of patients with recurrent/refractory neuroblastoma from Children's Oncology Group (COG) modern-era early-phase trials, the authors determined outcome and quantified parameters for designing future studies. The first early-phase COG trial enrollment (sequential) of 383 distinct patients with recurrent/refractory neuroblastoma on 23 phase 1, 3 phase 1/2, and 9 phase 2 trials (August 2002 to January 2014) was analyzed for progression-free survival (PFS), overall survival (OS), and time to disease progression (TTP). Planned frontline therapy for patients with high-risk neuroblastoma included hematopoietic stem cell transplantation (approximately two-thirds of patients underwent ≥1 hematopoietic stem cell transplantation); 13.2% of patients received dinutuximab. From the time of the patient's first early-phase trial enrollment (383 patients), the 1-year and 4-year PFS rates ( ± standard error) were 21% ± 2% and 6% ± 1%, respectively, whereas the 1-year and 4-year OS rates were 57% ± 3% and 20% ± 2%, respectively. The median TTP was 58 days (interquartile range, 31-183 days [350 patients]); the median follow-up was 25.3 months (33 patients were found to be without disease recurrence/progression). The median time from diagnosis to first disease recurrence/progression was 18.7 months (range, 1.4-64.8 months) (176 patients). MYCN amplification and 11q loss of heterozygosity were prognostic of worse PFS and OS (P = .003 and P<.0001, respectively, and P = .02 and P = .03, respectively) after early-phase trial

  3. Review of hardware cost estimation methods, models and tools applied to early phases of space mission planning

    NASA Astrophysics Data System (ADS)

    Trivailo, O.; Sippel, M.; Şekercioğlu, Y. A.

    2012-08-01

    The primary purpose of this paper is to review currently existing cost estimation methods, models, tools and resources applicable to the space sector. While key space sector methods are outlined, a specific focus is placed on hardware cost estimation on a system level, particularly for early mission phases during which specifications and requirements are not yet crystallised, and information is limited. For the space industry, cost engineering within the systems engineering framework is an integral discipline. The cost of any space program now constitutes a stringent design criterion, which must be considered and carefully controlled during the entire program life cycle. A first step to any program budget is a representative cost estimate which usually hinges on a particular estimation approach, or methodology. Therefore appropriate selection of specific cost models, methods and tools is paramount, a difficult task given the highly variable nature, scope as well as scientific and technical requirements applicable to each program. Numerous methods, models and tools exist. However new ways are needed to address very early, pre-Phase 0 cost estimation during the initial program research and establishment phase when system specifications are limited, but the available research budget needs to be established and defined. Due to their specificity, for vehicles such as reusable launchers with a manned capability, a lack of historical data implies that using either the classic heuristic approach such as parametric cost estimation based on underlying CERs, or the analogy approach, is therefore, by definition, limited. This review identifies prominent cost estimation models applied to the space sector, and their underlying cost driving parameters and factors. Strengths, weaknesses, and suitability to specific mission types and classes are also highlighted. Current approaches which strategically amalgamate various cost estimation strategies both for formulation and validation

  4. High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial

    PubMed Central

    Márta, Katalin; Szabó, Anikó N; Pécsi, Dániel; Varjú, Péter; Bajor, Judit; Gódi, Szilárd; Sarlós, Patrícia; Mikó, Alexandra; Szemes, Kata; Papp, Mária; Tornai, Tamás; Vincze, Áron; Márton, Zsolt; Vincze, Patrícia A; Lankó, Erzsébet; Szentesi, Andrea; Molnár, Tímea; Hágendorn, Roland; Faluhelyi, Nándor; Battyáni, István; Kelemen, Dezső; Papp, Róbert; Miseta, Attila; Verzár, Zsófia; Lerch, Markus M; Neoptolemos, John P; Sahin-Tóth, Miklós; Petersen, Ole H; Hegyi, Péter

    2017-01-01

    Introduction Acute pancreatitis (AP) is an inflammatory disease with no specific treatment. Mitochondrial injury followed by ATP depletion in both acinar and ductal cells is a recently discovered early event in its pathogenesis. Importantly, preclinical research has shown that intracellular ATP delivery restores the physiological function of the cells and protects from cell injury, suggesting that restoration of energy levels in the pancreas is therapeutically beneficial. Despite several high quality experimental observations in this area, no randomised trials have been conducted to date to address the requirements for energy intake in the early phase of AP. Methods/design This is a randomised controlled two-arm double-blind multicentre trial. Patients with AP will be randomly assigned to groups A (30 kcal/kg/day energy administration starting within 24 hours of hospital admission) or B (low energy administration during the first 72 hours of hospital admission). Energy will be delivered by nasoenteric tube feeding with additional intravenous glucose supplementation or total parenteral nutrition if necessary. A combination of multiorgan failure for more than 48 hours and mortality is defined as the primary endpoint, whereas several secondary endpoints such as length of hospitalisation or pain will be determined to elucidate more detailed differences between the groups. The general feasibility, safety and quality checks required for high quality evidence will be adhered to. Ethics and dissemination The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (55961-2/2016/EKU). This study will provide evidence as to whether early high energy nutritional support is beneficial in the clinical management of AP. The results of this trial will be published in an open access way and disseminated among medical doctors. Trial registration The trial has been registered at the ISRCTN

  5. No improvement of neuronal metabolism in the reperfusion phase with melatonin treatment after hypoxic-ischemic brain injury in the neonatal rat.

    PubMed

    Berger, Hester R; Morken, Tora Sund; Vettukattil, Riyas; Brubakk, Ann-Mari; Sonnewald, Ursula; Widerøe, Marius

    2016-01-01

    Mitochondrial impairment is a key feature underlying neonatal hypoxic-ischemic (HI) brain injury and melatonin is potentially neuroprotective through its effects on mitochondria. In this study, we have used (1) H and (13) C NMR spectroscopy after injection of [1-(13) C]glucose and [1,2-(13) C]acetate to examine neuronal and astrocytic metabolism in the early reperfusion phase after unilateral HI brain injury in 7-day-old rat pups, exploring the effects of HI on mitochondrial function and the potential protective effects of melatonin on brain metabolism. One hour after hypoxia-ischemia, astrocytic metabolism was recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was clearly impaired. Pyruvate carboxylation was also lower in both hemispheres after HI. The transfer of glutamate from neurons to astrocytes was higher whereas the transfer of glutamine from astrocytes to neurons was lower 1 h after HI in the contralateral hemisphere. Neuronal metabolism was equally affected in pups treated with melatonin (10 mg/kg) immediately after HI as in vehicle treated pups indicating that the given dose of melatonin was not capable of protecting the neuronal mitochondria in this early phase after HI brain injury. However, any beneficial effects of melatonin might have been masked by modulatory effects of the solvent dimethyl sulfoxide on cerebral metabolism. Neuronal and astrocytic metabolism was examined by (13) C and (1) H NMR spectroscopy in the early reperfusion phase after unilateral hypoxic-ischemic brain injury and melatonin treatment in neonatal rats. One hour after hypoxia-ischemia astrocytic mitochondrial metabolism had recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was impaired. Melatonin treatment did not show a protective effect on neuronal metabolism. © 2015 International Society for Neurochemistry.

  6. Hidden order and flux attachment in symmetry-protected topological phases: A Laughlin-like approach

    NASA Astrophysics Data System (ADS)

    Ringel, Zohar; Simon, Steven H.

    2015-05-01

    Topological phases of matter are distinct from conventional ones by their lack of a local order parameter. Still in the quantum Hall effect, hidden order parameters exist and constitute the basis for the celebrated composite-particle approach. Whether similar hidden orders exist in 2D and 3D symmetry protected topological phases (SPTs) is a largely open question. Here, we introduce a new approach for generating SPT ground states, based on a generalization of the Laughlin wave function. This approach gives a simple and unifying picture of some classes of SPTs in 1D and 2D, and reveals their hidden order and flux attachment structures. For the 1D case, we derive exact relations between the wave functions obtained in this manner and group cohomology wave functions, as well as matrix product state classification. For the 2D Ising SPT, strong analytical and numerical evidence is given to show that the wave function obtained indeed describes the desired SPT. The Ising SPT then appears as a state with quasi-long-range order in composite degrees of freedom consisting of Ising-symmetry charges attached to Ising-symmetry fluxes.

  7. Aural exostoses (surfer's ear) provide vital fossil evidence of an aquatic phase in Man's early evolution.

    PubMed

    Rhys Evans, P H; Cameron, M

    2017-11-01

    For over a century, otolaryngologists have recognised the condition of aural exostoses, but their significance and aetiology remains obscure, although they tend to be associated with frequent swimming and cold water immersion of the auditory canal. The fact that this condition is usually bilateral is predictable since both ears are immersed in water. However, why do exostoses only grow in swimmers and why do they grow in the deep bony meatus at two or three constant sites? Furthermore, from an evolutionary point of view, what is or was the purpose and function of these rather incongruous protrusions? In recent decades, paleoanthropological evidence has challenged ideas about early hominid evolution. In 1992 the senior author suggested that aural exostoses were evolved in early hominid Man for protection of the delicate tympanic membrane during swimming and diving by narrowing the ear canal in a similar fashion to other semiaquatic species. We now provide evidence for this theory and propose an aetiological explanation for the formation of exostoses.

  8. S-phase Synchronization Facilitates the Early Progression of Induced-Cardiomyocyte Reprogramming through Enhanced Cell-Cycle Exit.

    PubMed

    Bektik, Emre; Dennis, Adrienne; Pawlowski, Gary; Zhou, Chen; Maleski, Danielle; Takahashi, Satoru; Laurita, Kenneth R; Deschênes, Isabelle; Fu, Ji-Dong

    2018-05-04

    Direct reprogramming of fibroblasts into induced cardiomyocytes (iCMs) holds a great promise for regenerative medicine and has been studied in several major directions. However, cell-cycle regulation, a fundamental biological process, has not been investigated during iCM-reprogramming. Here, our time-lapse imaging on iCMs, reprogrammed by Gata4, Mef2c, and Tbx5 (GMT) monocistronic retroviruses, revealed that iCM-reprogramming was majorly initiated at late-G1- or S-phase and nearly half of GMT-reprogrammed iCMs divided soon after reprogramming. iCMs exited cell cycle along the process of reprogramming with decreased percentage of 5-ethynyl-20-deoxyuridine (EdU)⁺/α-myosin heavy chain (αMHC)-GFP⁺ cells. S-phase synchronization post-GMT-infection could enhance cell-cycle exit of reprogrammed iCMs and yield more GFP high iCMs, which achieved an advanced reprogramming with more expression of cardiac genes than GFP low cells. However, S-phase synchronization did not enhance the reprogramming with a polycistronic-viral vector, in which cell-cycle exit had been accelerated. In conclusion, post-infection synchronization of S-phase facilitated the early progression of GMT-reprogramming through a mechanism of enhanced cell-cycle exit.

  9. Carbachol improves secretion in the early phase after rabbit submandibular gland transplantation.

    PubMed

    Shi, L; Cong, X; Zhang, Y; Ding, C; Ding, Q W; Fu, F Y; Wu, L L; Yu, G Y

    2010-05-01

    To investigate the changes in the muscarinic receptor signaling pathway with submandibular gland (SMG) transplantation and whether carbachol improves secretion in transplanted SMGs. SMG autotransplantation was performed in a rabbit model. Carbachol (1 microM) was infused into the transplanted glands from postoperative day 1-7. The expression of the M1 and M3 muscarinic receptors, aquaporin-5 (AQP5), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was measured by RT-PCR, immunoblotting or immunofluorescence. The content of inositol 1, 4, 5-trisphosphate (IP(3)) was measured by radioimmunoassay. Salivary flow of the transplanted SMGs was decreased after transplantation. As well, the expressions of M1 and M3 receptors and their downstream signaling molecules, IP(3), p-ERK1/2 and AQP5, were all reduced. Atrophy of acinar cells was shown in transplanted glands. However, all these alterations were reversed after carbachol treatment for 7 days. Furthermore, carbachol directly increased the mRNA expression of AQP5 and phosphorylation of ERK1/2 in cultured neonatal rabbit SMG cells. A lack of acetylcholine and downregulation of the muscarinic receptor signaling pathway is involved in the early hypofunction of transplanted SMGs. Carbachol treatment could be a new therapeutic strategy to improve secretion and prevent the obstruction of Wharton's duct in the early phase after SMG transplantation.

  10. Differential involvement of IL-6 in the early and late phase of 1-methylnicotinamide (MNA) release in Concanavalin A-induced hepatitis.

    PubMed

    Sternak, Magdalena; Jakubowski, Andrzej; Czarnowska, Elzbieta; Slominska, Ewa M; Smolenski, Ryszard T; Szafarz, Malgorzata; Walczak, Maria; Sitek, Barbara; Wojcik, Tomasz; Jasztal, Agnieszka; Kaminski, Karol; Chlopicki, Stefan

    2015-09-01

    Exogenous 1-methylnicotinamide (MNA) displays anti-inflammatory activity. The aim of this work was to characterize the profile of release of endogenous MNA during the initiation and progression of murine hepatitis induced by Concanavalin A (ConA). In particular we aimed to clarify the role of interleukin-6 (IL-6) as well as the energy state of hepatocytes in MNA release in early and late phases of ConA-induced hepatitis in mice. Hepatitis was induced by ConA in IL-6(+/+) and IL-6(-/-) mice, and various parameters of liver inflammation and injury, as well as the energy state of hepatocytes, were analysed in relation to MNA release. The decrease in ATP/ADP and NADH/NAD ratios, cytokine release (IL-6, IFN-ɤ), acute phase response (e.g. haptoglobin) and liver injury (alanine aminotransaminase, ALT) were all blunted in ConA-induced hepatitis in IL-6(-/-) mice as compared to IL-6(+/+) mice. The release of MNA in response to Con A was also significantly blunted in IL-6(-/-) mice as compared to IL-6(+/+) mice in the early stage of ConA-induced hepatitis. In turn, nicotinamide N-methyltransferase (NNMT) and aldehyde oxidase (AO) activities were blunted in the liver and MNA plasma concentration was elevated to similar degree in the late stage after Concanavalin A in IL-6(+/+) and IL-6(-/-) mice. In conclusion, we demonstrated that in ConA-induced hepatitis, early, but not late MNA release was IL-6-dependent. Our results suggest that in the initiation and early hepatitis, MNA release is linked to the energy deficit/impaired redox status in hepatocytes, while in a later phase, MNA release is rather linked to the systemic inflammation. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

  12. Development and application of a biorelevant dissolution method using USP apparatus 4 in early phase formulation development.

    PubMed

    Fang, Jiang B; Robertson, Vivian K; Rawat, Archana; Flick, Tawnya; Tang, Zhe J; Cauchon, Nina S; McElvain, James S

    2010-10-04

    Dissolution testing is frequently used to determine the rate and extent at which a drug is released from a dosage form, and it plays many important roles throughout drug product development. However, the traditional dissolution approach often emphasizes its application in quality control testing and usually strives to obtain 100% drug release. As a result, dissolution methods are not necessarily biorelevant and meaningful application of traditional dissolution methods in the early phases of drug product development can be very limited. This article will describe the development of a biorelevant in vitro dissolution method using USP apparatus 4, biorelevant media, and real-time online UV analysis. Several case studies in the areas of formulation selection, lot-to-lot variability, and food effect will be presented to demonstrate the application of this method in early phase formulation development. This biorelevant dissolution method using USP apparatus 4 provides a valuable tool to predict certain aspects of the in vivo drug release. It can be used to facilitate the formulation development/selection for pharmacokinetic (PK) and clinical studies. It may also potentially be used to minimize the number of PK studies, and to aid in the design of more efficient PK and clinical studies.

  13. Early alpha-lipoic acid therapy protects from degeneration of the inner retinal layers and vision loss in an experimental autoimmune encephalomyelitis-optic neuritis model.

    PubMed

    Dietrich, Michael; Helling, Niklas; Hilla, Alexander; Heskamp, Annemarie; Issberner, Andrea; Hildebrandt, Thomas; Kohne, Zippora; Küry, Patrick; Berndt, Carsten; Aktas, Orhan; Fischer, Dietmar; Hartung, Hans-Peter; Albrecht, Philipp

    2018-03-07

    In multiple sclerosis (MS), neurodegeneration is the main reason for chronic disability. Alpha-lipoic acid (LA) is a naturally occurring antioxidant which has recently been demonstrated to reduce the rate of brain atrophy in progressive MS. However, it remains uncertain if it is also beneficial in the early, more inflammatory-driven phases. As clinical studies are costly and time consuming, optic neuritis (ON) is often used for investigating neuroprotective or regenerative therapeutics. We aimed to investigate the prospect for success of a clinical ON trial using an experimental autoimmune encephalomyelitis-optic neuritis (EAE-ON) model with visual system readouts adaptable to a clinical ON trial. Using an in vitro cell culture model for endogenous oxidative stress, we compared the neuroprotective capacity of racemic LA with the R/S-enantiomers and its reduced form. In vivo, we analyzed retinal neurodegeneration using optical coherence tomography (OCT) and the visual function by optokinetic response (OKR) in MOG 35-55 -induced EAE-ON in C57BL/6J mice. Ganglion cell counts, inflammation, and demyelination were assessed by immunohistological staining of retinae and optic nerves. All forms of LA provided equal neuroprotective capacities in vitro. In EAE-ON, prophylactic LA therapy attenuated the clinical EAE score and prevented the thinning of the inner retinal layer while therapeutic treatment was not protective on visual outcomes. A prophylactic LA treatment is necessary to protect from visual loss and retinal thinning in EAE-ON, suggesting that a clinical ON trial starting therapy after the onset of symptoms may not be successful.

  14. ADVANCED WORKER PROTECTION SYSTEM

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

    Judson Hedgehock

    2001-03-16

    From 1993 to 2000, OSS worked under a cost share contract from the Department of Energy (DOE) to develop an Advanced Worker Protection System (AWPS). The AWPS is a protective ensemble that provides the user with both breathing air and cooling for a NIOSH-rated duration of two hours. The ensemble consists of a liquid air based backpack, a Liquid Cooling Garment (LCG), and an outer protective garment. The AWPS project was divided into two phases. During Phase 1, OSS developed and tested a full-scale prototype AWPS. The testing showed that workers using the AWPS could work twice as long asmore » workers using a standard SCBA. The testing also provided performance data on the AWPS in different environments that was used during Phase 2 to optimize the design. During Phase 1, OSS also performed a life-cycle cost analysis on a representative clean up effort. The analysis indicated that the AWPS could save the DOE millions of dollars on D and D activities and improve the health and safety of their workers. During Phase 2, OSS worked to optimize the AWPS design to increase system reliability, to improve system performance and comfort, and to reduce the backpack weight and manufacturing costs. To support this design effort, OSS developed and tested several different generations of prototype units. Two separate successful evaluations of the ensemble were performed by the International Union of Operation Engineers (IUOE). The results of these evaluations were used to drive the design. During Phase 2, OSS also pursued certifying the AWPS with the applicable government agencies. The initial intent during Phase 2 was to finalize the design and then to certify the system. OSS and Scott Health and Safety Products teamed to optimize the AWPS design and then certify the system with the National Institute of Occupational Health and Safety (NIOSH). Unfortunately, technical and programmatic difficulties prevented us from obtaining NIOSH certification. Despite the inability of NIOSH to

  15. Water-soluble phosphine-protected Au9 clusters: Electronic structures and nuclearity conversion via phase transfer

    NASA Astrophysics Data System (ADS)

    Yao, Hiroshi; Tsubota, Shuhei

    2017-08-01

    In this article, isolation, exploration of electronic structures, and nuclearity conversion of water-soluble triphenylphosphine monosulfonate (TPPS)-protected nonagold (Au9) clusters are outlined. The Au9 clusters are obtained by the reduction of solutions containing TPPS and HAuCl4 and subsequent electrophoretic fractionation. Mass spectrometry and elemental analysis reveal the formation of [Au9(TPPS)8]5- nonagold cluster. UV-vis absorption and magnetic circular dichroism (MCD) spectra of aqueous [Au9(TPPS)8]5- are quite similar to those of [Au9(PPh3)8]3+ in organic solvent, so the solution-phase structures are likely similar for both systems. Simultaneous deconvolution analysis of absorption and MCD spectra demonstrates the presence of some weak electronic transitions that are essentially unresolved in the UV-vis absorption. Quantum chemical calculations for a model compound [Au9(pH3)8]3+ show that the possible (solution-phase) skeletal structure of the nonagold cluster has D2h core symmetry rather than C4-symmetrical centered crown conformation, which is known as the crystal form of the Au9 compound. Moreover, we find a new nuclearity conversion route from Au9 to Au8; that is, phase transfer of aqueous [Au9(TPPS)8]5- into chloroform using tetraoctylammonium bromide yields [Au8(TPPS)8]6- clusters in the absence of excess phosphine.

  16. Protective ventilation reduces Pseudomonas aeruginosa growth in lung tissue in a porcine pneumonia model.

    PubMed

    Sperber, Jesper; Nyberg, Axel; Lipcsey, Miklos; Melhus, Åsa; Larsson, Anders; Sjölin, Jan; Castegren, Markus

    2017-08-31

    Mechanical ventilation with positive end expiratory pressure and low tidal volume, i.e. protective ventilation, is recommended in patients with acute respiratory distress syndrome. However, the effect of protective ventilation on bacterial growth during early pneumonia in non-injured lungs is not extensively studied. The main objectives were to compare two different ventilator settings on Pseudomonas aeruginosa growth in lung tissue and the development of lung injury. A porcine model of severe pneumonia was used. The protective group (n = 10) had an end expiratory pressure of 10 cm H 2 O and a tidal volume of 6 ml x kg -1 . The control group (n = 10) had an end expiratory pressure of 5 cm H 2 O and a tidal volume of 10 ml x kg -1 . 10 11 colony forming units of Pseudomonas aeruginosa were inoculated intra-tracheally at baseline, after which the experiment continued for 6 h. Two animals from each group received only saline, and served as sham animals. Lung tissue samples from each animal were used for bacterial cultures and wet-to-dry weight ratio measurements. The protective group displayed lower numbers of Pseudomonas aeruginosa (p < 0.05) in the lung tissue, and a lower wet-to-dry ratio (p < 0.01) than the control group. The control group deteriorated in arterial oxygen tension/inspired oxygen fraction, whereas the protective group was unchanged (p < 0.01). In early phase pneumonia, protective ventilation with lower tidal volume and higher end expiratory pressure has the potential to reduce the pulmonary bacterial burden and the development of lung injury.

  17. Protections for Workers Who Must Enter Pesticide-Treated Areas Early

    EPA Pesticide Factsheets

    The Worker Protection Standard allows entry into a pesticide-treated area that remains under a restricted-entry interval only in a few narrow work situations. Learn about special protections that must be provided for workers in these situations.

  18. Absent 99mTc-MIBI Uptake in the Thyroid Gland during Early Phase of Parathyroid Scintigraphy in Patients with Primary and Secondary Hyperparathyroidism.

    PubMed

    Jovanovska, Anamarija; Stoilovska, Bojana; Mileva, Magdalena; Miladinova, Daniela; Majstorov, Venjamin; Ugrinska, Ana

    2018-05-20

    Thyroid uptake of technetium-99m methoxyisobutylisonitrile ( 99m Tc-MIBI) during parathyroid scintigraphy can be affected by various conditions. To evaluate the frequency of absent 99m Tc-MIBI uptake by the thyroid gland in the early phase of dual-phase parathyroid scintigraphy. The early planar images of dual phase Tc 99m MIBI parathyroid scintigraphy from 217 patients performed between 2014 and 2017 were retrospectively analysed. Patients were divided into two groups. The first group included 147 patients with primary hyperparathyroidism and the second group included 70 patients with chronic renal failure. Patient records, laboratory and ultrasonographic data were analysed in all patients. Descriptive statistic was used for data analysis. Out of all patients in the first group, 18 patients (12.24%) showed absent thyroid uptake. Thyroidectomy was performed in 44.4% of these patients, and the rest of them had some thyroid disease. Only one patient had no thyroid or another chronic disease. In the second group, 8 patients (11.42%) presented with absent thyroid uptake of MIBI. Among them, 5 patients had no history of thyroid disease and had been on hemodialysis programme, and 3 patients had hypothyroidism. Absent 99m Tc-MIBI uptake in the thyroid during the early phase of parathyroid scintigraphy is most frequently related to thyroid disease. A small proportion of patients with chronic renal failure can present with absent 99m Tc-MIBI uptake in the thyroid as well. The mechanism for this alteration is still unclear and needs further investigation.

  19. Vγ1+γδT, early cardiac infiltrated innate population dominantly producing IL-4, protect mice against CVB3 myocarditis by modulating IFNγ+ T response.

    PubMed

    Wan, Fangfang; Yan, Kepeng; Xu, Dan; Qian, Qian; Liu, Hui; Li, Min; Xu, Wei

    2017-01-01

    Viral myocarditis (VMC) is an inflammation of the myocardium closely associated with Coxsackievirus B3 (CVB3) infection. Vγ1 + γδT cells, one of early cardiac infiltrated innate population, were reported to protect CVB3 myocarditis while the precise mechanism not fully addressed. To explore cytokine profiles and kinetics of Vγ1 + γδT and mechanism of protection against VMC, flow cytometry was conducted on cardiac Vγ1 cells in C57BL/6 mice following CVB3 infection. The level of cardiac inflammation, transthoracic echocardiography and viral replication were evaluated after monoclonal antibody depletion of Vγ1γδT. We found that Vγ1 + γδT cells infiltration peaked in the heart at day3 post CVB3 infection and constituted a minor source of IFN-γ but major producers for early IL-4. Vγ1γδT cells were activated earlier holding a higher IL-4-producing efficiency than CD4 + Th cells in the heart. Depletion of Vγ1 + γδT resulted in a significantly exacerbated cardiac infiltration, increased T, macrophage and neutrophil population in heart homogenates and worse cardiomyopathy; which was accompanied by a significant expansion of peripheral IFNγ + CD4+ and CD8+T cells. Neutralization of IL-4 in mice resulted in an exacerbated acute myocarditis confirming the IL-4-mediated protective mechanism of Vγ1. Our findings identify a unique property of Vγ1 + γδT cells as one dominant early producers of IL-4 upon CVB3 acute infection which is a key mediator to protect mice against acute myocarditis by modulating IFNγ-secreting T response. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Early Intervention in Bipolar Disorder.

    PubMed

    Vieta, Eduard; Salagre, Estela; Grande, Iria; Carvalho, André F; Fernandes, Brisa S; Berk, Michael; Birmaher, Boris; Tohen, Mauricio; Suppes, Trisha

    2018-05-01

    Bipolar disorder is a recurrent disorder that affects more than 1% of the world population and usually has its onset during youth. Its chronic course is associated with high rates of morbidity and mortality, making bipolar disorder one of the main causes of disability among young and working-age people. The implementation of early intervention strategies may help to change the outcome of the illness and avert potentially irreversible harm to patients with bipolar disorder, as early phases may be more responsive to treatment and may need less aggressive therapies. Early intervention in bipolar disorder is gaining momentum. Current evidence emerging from longitudinal studies indicates that parental early-onset bipolar disorder is the most consistent risk factor for bipolar disorder. Longitudinal studies also indicate that a full-blown manic episode is often preceded by a variety of prodromal symptoms, particularly subsyndromal manic symptoms, therefore supporting the existence of an at-risk state in bipolar disorder that could be targeted through early intervention. There are also identifiable risk factors that influence the course of bipolar disorder, some of them potentially modifiable. Valid biomarkers or diagnosis tools to help clinicians identify individuals at high risk of conversion to bipolar disorder are still lacking, although there are some promising early results. Pending more solid evidence on the best treatment strategy in early phases of bipolar disorder, physicians should carefully weigh the risks and benefits of each intervention. Further studies will provide the evidence needed to finish shaping the concept of early intervention. AJP AT 175 Remembering Our Past As We Envision Our Future April 1925: Interpretations of Manic-Depressive Phases Earl Bond and G.E. Partridge reviewed a number of patients with manic-depressive illness in search of a unifying endo-psychic conflict. They concluded that understanding either phase of illness was "elusive" and

  1. The Interplay between Inflammation, Coagulation and Endothelial Injury in the Early Phase of Acute Pancreatitis: Clinical Implications

    PubMed Central

    Dumnicka, Paulina; Maduzia, Dawid; Ceranowicz, Piotr; Olszanecki, Rafał; Drożdż, Ryszard; Kuśnierz-Cabala, Beata

    2017-01-01

    Acute pancreatitis (AP) is an inflammatory disease with varied severity, ranging from mild local inflammation to severe systemic involvement resulting in substantial mortality. Early pathologic events in AP, both local and systemic, are associated with vascular derangements, including endothelial activation and injury, dysregulation of vasomotor tone, increased vascular permeability, increased leukocyte migration to tissues, and activation of coagulation. The purpose of the review was to summarize current evidence regarding the interplay between inflammation, coagulation and endothelial dysfunction in the early phase of AP. Practical aspects were emphasized: (1) we summarized available data on diagnostic usefulness of the markers of endothelial dysfunction and activated coagulation in early prediction of severe AP; (2) we reviewed in detail the results of experimental studies and clinical trials targeting coagulation-inflammation interactions in severe AP. Among laboratory tests, d-dimer and angiopoietin-2 measurements seem the most useful in early prediction of severe AP. Although most clinical trials evaluating anticoagulants in treatment of severe AP did not show benefits, they also did not show significantly increased bleeding risk. Promising results of human trials were published for low molecular weight heparin treatment. Several anticoagulants that proved beneficial in animal experiments are thus worth testing in patients. PMID:28208708

  2. Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation.

    PubMed

    Lo, Wai-Kit; Goldberg, Hilary J; Boukedes, Steve; Burakoff, Robert; Chan, Walter W

    2018-02-01

    Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain. To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation. This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use. A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications. Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.

  3. High performance protection circuit for power electronics applications

    NASA Astrophysics Data System (ADS)

    Tudoran, Cristian D.; Dǎdârlat, Dorin N.; Toşa, Nicoleta; Mişan, Ioan

    2015-12-01

    In this paper we present a high performance protection circuit designed for the power electronics applications where the load currents can increase rapidly and exceed the maximum allowed values, like in the case of high frequency induction heating inverters or high frequency plasma generators. The protection circuit is based on a microcontroller and can be adapted for use on single-phase or three-phase power systems. Its versatility comes from the fact that the circuit can communicate with the protected system, having the role of a "sensor" or it can interrupt the power supply for protection, in this case functioning as an external, independent protection circuit.

  4. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice.

    PubMed

    Jonscher, Karen R; Stewart, Michael S; Alfonso-Garcia, Alba; DeFelice, Brian C; Wang, Xiaoxin X; Luo, Yuhuan; Levi, Moshe; Heerwagen, Margaret J R; Janssen, Rachel C; de la Houssaye, Becky A; Wiitala, Ellen; Florey, Garrett; Jonscher, Raleigh L; Potma, Eric O; Fiehn, Oliver; Friedman, Jacob E

    2017-04-01

    Nonalcoholic fatty liver disease (NAFLD) is widespread in adults and children. Early exposure to maternal obesity or Western-style diet (WD) increases steatosis and oxidative stress in fetal liver and is associated with lifetime disease risk in the offspring. Pyrroloquinoline quinone (PQQ) is a natural antioxidant found in soil, enriched in human breast milk, and essential for development in mammals. We investigated whether a supplemental dose of PQQ, provided prenatally in a mouse model of diet-induced obesity during pregnancy, could protect obese offspring from progression of NAFLD. PQQ treatment given pre- and postnatally in WD-fed offspring had no effect on weight gain but increased metabolic flexibility while reducing body fat and liver lipids, compared with untreated obese offspring. Indices of NAFLD, including hepatic ceramide levels, oxidative stress, and expression of proinflammatory genes ( Nos2 , Nlrp3 , Il6 , and Ptgs2 ), were decreased in WD PQQ-fed mice, concomitant with increased expression of fatty acid oxidation genes and decreased Pparg expression. Notably, these changes persisted even after PQQ withdrawal at weaning. Our results suggest that supplementation with PQQ, particularly during pregnancy and lactation, protects offspring from WD-induced developmental programming of hepatic lipotoxicity and may help slow the advancing epidemic of NAFLD in the next generation.-Jonscher, K. R., Stewart, M. S., Alfonso-Garcia, A., DeFelice, B. C., Wang, X. X., Luo, Y., Levi, M., Heerwagen, M. J. R., Janssen, R. C., de la Houssaye, B. A., Wiitala, E., Florey, G., Jonscher, R. L., Potma, E. O., Fiehn, O. Friedman, J. E. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice. © FASEB.

  5. Novel therapy for renal protection.

    PubMed

    Zarbock, Alexander; Milles, Kindgen

    2015-08-01

    Acute kidney injury (AKI) is a common and serious complication that significantly increases morbidity, mortality, and cost of care after surgery. In this article, we review recent studies that deal with strategies for renal protection and the prevention of AKI after surgery. A prerequisite for any prophylactic intervention is the identification of patients at risk for AKI or those with acute kidney damage before kidney function deteriorates. In this context, new biomarkers can help to detect cellular injury early. This way, a window for interventions can be opened. Several studies demonstrated the tissue-protective effect of remote ischemic preconditioning in various organs. There is clear evidence that use of balanced crystalloid fluids and the avoidance of hyperchloremic solutions for infusion therapy can reduce the incidence of AKI. Preliminary data show a protective effect if dexmedetomidine is used as a sedative agent following cardiac surgery. The most important intervention with proven efficacy to protect from AKI is aggressive hemodynamic stabilization. Early identification of patients at risk for AKI is crucial to apply any protective intervention. An improved perioperative management is required to prevent AKI. Although pharmacological therapies aiming to protect AKI are under evaluation, hemodynamic optimization and avoidance of nephrotoxic drugs are critical for perioperative patient.

  6. Development of New Laser-Protective Dyes. Phase 1.

    DTIC Science & Technology

    1990-10-30

    technology to stabilize cyanine and squarylium dyes . This accomplishment will justify continued research on the synthesis and process development of...beyond. This is the subject of a proposed Phase II program. RESULTS AND DISCUSSION THERMAL STABILITY: In Phase I, dyes of the cyanine and squarylium ...Test in Appendix 1). Table 1 shows that the squarylium dyes are inherently more thermally stable than the cyanines. This observation supports

  7. Development of New Laser Protective Dyes. Phase 2.

    DTIC Science & Technology

    DYE LASERS, PROTECTION, LASERS, DYES , HAZARDS, SYNTHESIS, EYE SAFETY, OPTICAL MATERIALS, PLASTICS, LENSES, THERMAL STABILITY, CYANINE DYES , POLYCARBONATES, INJECTION MOLDING, NEAR INFRARED RADIATION, FLUORENES.

  8. Migration as a turning point in food habits: the early phase of dietary acculturation among women from South Asian, African, and Middle Eastern Countries living in Norway.

    PubMed

    Terragni, Laura; Garnweidner, Lisa M; Pettersen, Kjell Sverre; Mosdøl, Annhild

    2014-01-01

    This article explores the early phase of dietary acculturation after migration. South Asian, African and Middle Eastern women (N = 21) living in Norway were interviewed about their early experiences with food in a new context. The findings pointed to abrupt changes in food habits in the first period after migration. To various degrees, women reported unfamiliarity with foods in shops, uncertainty about meal formats and food preparation and fear of eating food prohibited by their religion. Their food consumption tended to be restricted to food items perceived as familiar or safe. Our findings indicate that the first period after migration represents a specific phase in the process of dietary acculturation. Early initiatives aimed at enhancing confidence in food and familiarity with the new food culture are recommended.

  9. The scaffold protein Nde1 safeguards the brain genome during S phase of early neural progenitor differentiation

    PubMed Central

    Houlihan, Shauna L; Feng, Yuanyi

    2014-01-01

    Successfully completing the S phase of each cell cycle ensures genome integrity. Impediment of DNA replication can lead to DNA damage and genomic disorders. In this study, we show a novel function for NDE1, whose mutations cause brain developmental disorders, in safeguarding the genome through S phase during early steps of neural progenitor fate restrictive differentiation. Nde1 mutant neural progenitors showed catastrophic DNA double strand breaks concurrent with the DNA replication. This evoked DNA damage responses, led to the activation of p53-dependent apoptosis, and resulted in the reduction of neurons in cortical layer II/III. We discovered a nuclear pool of Nde1, identified the interaction of Nde1 with cohesin and its associated chromatin remodeler, and showed that stalled DNA replication in Nde1 mutants specifically occurred in mid-late S phase at heterochromatin domains. These findings suggest that NDE1-mediated heterochromatin replication is indispensible for neuronal differentiation, and that the loss of NDE1 function may lead to genomic neurological disorders. DOI: http://dx.doi.org/10.7554/eLife.03297.001 PMID:25245017

  10. Cooperation between Epstein-Barr Virus Immune Evasion Proteins Spreads Protection from CD8+ T Cell Recognition across All Three Phases of the Lytic Cycle

    PubMed Central

    Quinn, Laura L.; Zuo, Jianmin; Abbott, Rachel J. M.; Shannon-Lowe, Claire; Tierney, Rosemary J.; Hislop, Andrew D.; Rowe, Martin

    2014-01-01

    CD8+ T cell responses to Epstein-Barr virus (EBV) lytic cycle expressed antigens display a hierarchy of immunodominance, in which responses to epitopes of immediate-early (IE) and some early (E) antigens are more frequently observed than responses to epitopes of late (L) expressed antigens. It has been proposed that this hierarchy, which correlates with the phase-specific efficiency of antigen presentation, may be due to the influence of viral immune-evasion genes. At least three EBV-encoded genes, BNLF2a, BGLF5 and BILF1, have the potential to inhibit processing and presentation of CD8+ T cell epitopes. Here we examined the relative contribution of these genes to modulation of CD8+ T cell recognition of EBV lytic antigens expressed at different phases of the replication cycle in EBV-transformed B-cells (LCLs) which spontaneously reactivate lytic cycle. Selective shRNA-mediated knockdown of BNLF2a expression led to more efficient recognition of immediate-early (IE)- and early (E)-derived epitopes by CD8+ T cells, while knock down of BILF1 increased recognition of epitopes from E and late (L)-expressed antigens. Contrary to what might have been predicted from previous ectopic expression studies in EBV-negative model cell lines, the shRNA-mediated inhibition of BGLF5 expression in LCLs showed only modest, if any, increase in recognition of epitopes expressed in any phase of lytic cycle. These data indicate that whilst BNLF2a interferes with antigen presentation with diminishing efficiency as lytic cycle progresses (IE>E>>L), interference by BILF1 increases with progression through lytic cycle (IEphase-specific effects that provide mechanistic insight

  11. High performance protection circuit for power electronics applications

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

    Tudoran, Cristian D., E-mail: cristian.tudoran@itim-cj.ro; Dădârlat, Dorin N.; Toşa, Nicoleta

    2015-12-23

    In this paper we present a high performance protection circuit designed for the power electronics applications where the load currents can increase rapidly and exceed the maximum allowed values, like in the case of high frequency induction heating inverters or high frequency plasma generators. The protection circuit is based on a microcontroller and can be adapted for use on single-phase or three-phase power systems. Its versatility comes from the fact that the circuit can communicate with the protected system, having the role of a “sensor” or it can interrupt the power supply for protection, in this case functioning as anmore » external, independent protection circuit.« less

  12. Project fires. Volume 2: Protective ensemble performance standards, phase 1B

    NASA Astrophysics Data System (ADS)

    Abeles, F. J.

    1980-05-01

    The design of the prototype protective ensemble was finalized. Prototype ensembles were fabricated and then subjected to a series of qualification tests which were based upon the protective ensemble performance standards PEPS requirements. Engineering drawings and purchase specifications were prepared for the new protective ensemble.

  13. 2,3-diphosphoglycerate, nucleotide phosophate, and organic and inorganic phosphate levels during the early phases of diabetic ketoacidosis.

    PubMed

    Kanter, Y; Gerson, J R; Bessman, A N

    1977-05-01

    The relation between serum and red blood cell (RBC) inorganic phosphate levels, RBC 2,3-diphosphoglycerate (2,3-DPG) levels, RBC nucleotide phosphate (Pn), and RBC total phosphate (Pt) levels were studied during the early phases of treatment and recovery from diabetic ketoacidosis (DKA). A steady drop in serum inorganic phosphate was found during the first 24 hours of insulin treatment and was most profound at 24 hours. No statistically significant changes (P less than 0.05) were found in red cell inorganic phosphate or nucleotide phosphate levels during the 24-hour study period. The levels of total red cell phosphate were lower in this group of patients than in nonacidotic diabetic subjects and decreased slightly after 24 hours of treatment. The red cell 2,3-DPG levels were low at the initiation of therapy and remained low during the 24-hour study period. Glucose, bicarbonate, lactate, and ketone levels fell in linear patterns with treatment. In view of the current evidence for the effects of low 2,3-DPG on oxygen delivery and the relation of low serum phosphate levels to RBC glycolysis and 2,3-DPG formation, this study reemphasizes the need for phosphate replacement during the early phases of treatment of DKA.

  14. Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

    PubMed Central

    Wahner-Roedler, Dietlind L.; Thompson, Jeffrey M.; Luedtke, Connie A.; King, Susan M.; Cha, Stephen S.; Elkin, Peter L.; Bruce, Barbara K.; Townsend, Cynthia O.; Bergeson, Jody R.; Eickhoff, Andrea L.; Loehrer, Laura L.; Sood, Amit; Bauer, Brent A.

    2011-01-01

    Most patients with fibromyalgia use complementary and alternative medicine (CAM). Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein) shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02) and by 18% in the placebo group (P < .001). The difference in change in scores between the groups was not significant (P = .16). With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004) and in the placebo group by 15% (P = .05). The change in scores was similar in the groups (P = .83). Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control) shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated. PMID:18990724

  15. 40 CFR 63.78 - Early reduction demonstration evaluation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Early reduction demonstration... Regulations Governing Compliance Extensions for Early Reductions of Hazardous Air Pollutants § 63.78 Early reduction demonstration evaluation. (a) The permitting authority will evaluate an early reduction...

  16. 40 CFR 63.78 - Early reduction demonstration evaluation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 9 2011-07-01 2011-07-01 false Early reduction demonstration... Regulations Governing Compliance Extensions for Early Reductions of Hazardous Air Pollutants § 63.78 Early reduction demonstration evaluation. (a) The permitting authority will evaluate an early reduction...

  17. 40 CFR 26.1123 - Early termination of research.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Early termination of research. 26.1123 Section 26.1123 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Basic Ethical Requirements for Third-Party Human Research for Pesticides Involving Intentional...

  18. 40 CFR 26.1123 - Early termination of research.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Early termination of research. 26.1123 Section 26.1123 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Basic Ethical Requirements for Third-Party Human Research for Pesticides Involving Intentional...

  19. 40 CFR 26.1123 - Early termination of research.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Early termination of research. 26.1123 Section 26.1123 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Basic Ethical Requirements for Third-Party Human Research for Pesticides Involving Intentional...

  20. 40 CFR 26.1123 - Early termination of research.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Early termination of research. 26.1123 Section 26.1123 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Basic Ethical Requirements for Third-Party Human Research for Pesticides Involving Intentional...

  1. 40 CFR 26.1123 - Early termination of research.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Early termination of research. 26.1123 Section 26.1123 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Basic Ethical Requirements for Third-Party Human Research for Pesticides Involving Intentional...

  2. Recombinant luteinizing hormone priming in early follicular phase for women undergoing in vitro fertilization: systematic review and meta-analysis.

    PubMed

    Hu, Linli; Bu, Zhiqin; Wang, Keyan; Sun, Yingpu

    2014-04-01

    To investigate the effect of recombinant human luteinizing hormone supplementation (rLH priming) during the early follicular phase on in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcomes. In order to evaluate available evidence regarding the efficacy of rLH priming in IVF/ICSI procedures, a systematic review and meta-analysis was preformed. Searches were conducted on MEDLINE®, EMBASE and the Cochrane Database of Clinical Trials without language limitation, but were restricted to randomized controlled trials (RCTs). Three RCTs including 346 patients were included in this meta-analysis, which demonstrated that rLH priming did not increase ongoing pregnancy rate. Although less recombinant follicle-stimulating hormone (rFSH) was required and the oestradiol level was higher on the day of human chorionic gonadotropin administration in the rLH priming group, the numbers of oocytes retrieved and embryos produced were comparable between patients treated with rLH priming and those treated with rFSH alone. This systematic review and meta-analysis has demonstrated that at present there is insufficient evidence that patients undergoing IVF/ICSI may benefit from rLH priming during the early follicular phase.

  3. Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis.

    PubMed

    Lin, Yan-Ren; Li, Chao-Jui; Syu, Shih-Han; Wen, Cheng-Hao; Buddhakosai, Waradee; Wu, Han-Ping; Hsu Chen, Cheng; Lu, Huai-En; Chen, Wen-Liang

    2016-01-01

    Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n = 20) and control (normal saline, n = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group ( p < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level.

  4. Early intervention for psychosis

    PubMed Central

    Marshall, Max; Rathbone, John

    2014-01-01

    Background Proponents of early intervention have argued that outcomes might be improved if more therapeutic efforts were focused on the early stages of schizophrenia or on people with prodromal symptoms. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection, and phase-specific treatment (phase-specific treatment is a psychological, social or physical treatment developed, or modified, specifically for use with people at an early stage of the illness). Early detection and phase-specific treatment may both be offered as supplements to standard care, or may be provided through a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia. Objectives To evaluate the effects of: (a) early detection; (b) phase-specific treatments; and (c) specialised early intervention teams in the treatment of people with prodromal symptoms or first-episode psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2009), inspected reference lists of all identified trials and reviews and contacted experts in the field. Selection criteria We included all randomised controlled trials (RCTs) designed to prevent progression to psychosis in people showing prodromal symptoms, or to improve outcome for people with first-episode psychosis. Eligible interventions, alone and in combination, included: early detection, phase-specific treatments, and care from specialised early intervention teams. We accepted cluster-randomised trials but excluded non-randomised trials. Data collection and analysis We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis (ITT). Main results Studies were diverse, mostly small

  5. A Mechanistic Model of Early FcεRI Signaling: Lipid Rafts and the Question of Protection from Dephosphorylation

    PubMed Central

    Barua, Dipak; Goldstein, Byron

    2012-01-01

    We present a model of the early events in mast cell signaling mediated by FcεRI where the plasma membrane is composed of many small ordered lipid domains (rafts), surrounded by a non-order region of lipids consisting of the remaining plasma membrane. The model treats the rafts as transient structures that constantly form and breakup, but that maintain a fixed average number per cell. The rafts have a high propensity for harboring Lyn kinase, aggregated, but not unaggregated receptors, and the linker for the activation of T cells (LAT). Phosphatase activity in the rafts is substantially reduced compared to the nonraft region. We use the model to analyze published experiments on the rat basophilic leukemia (RBL)-2H3 cell line that seem to contradict the notion that rafts offer protection. In these experiments IgE was cross-linked with a multivalent antigen and then excess monovalent hapten was added to break-up cross-links. The dephosphorylation of the unaggregated receptor (nonraft associated) and of LAT (raft associated) were then monitored in time and found to decay at similar rates, leading to the conclusion that rafts offer no protection from dephosphorylation. In the model, because the rafts are transient, a protein that is protected while in a raft will be subject to dephosphorylation when the raft breaks up and the protein finds itself in the nonraft region of the membrane. We show that the model is consistent with the receptor and LAT dephosphorylation experiments while still allowing rafts to enhance signaling by providing substantial protection from phosphatases. PMID:23284735

  6. Early functional outcome of two different orthotic concepts in ankle sprains: a randomized controlled trial.

    PubMed

    Best, Raymond; Böhle, Caroline; Schiffer, Thorsten; Petersen, Wolf; Ellermann, Andree; Brueggemann, Gert Peter; Liebau, Christian

    2015-07-01

    Purpose of the study was the evaluation of the early functional outcome of patients with an acute ankle sprain treated either with a semirigid, variable, phase-adapted modular ankle orthosis or an invariable orthotic reference device. Forty-seven patients with acute ankle sprain grade II or more were included. In addition, 77 healthy controls as a reference were investigated. The injured subjects were treated with one of the two devices by random for 6 weeks. Ankle scores (FAOS, AOFAS) were taken at baseline after injury, 1 and 3 months after injury. Functional performance tests (balance platform, zig zag run, shuttle run, vertical drop jump) were performed at 1 and 3 months after injury. No significant score differences could be found between the two intervention groups except for achieving a preinjury activity level after 3 months only in the modular orthosis group. Postural functional performances (balance test) also showed no significant differences whereas the results of the agility tests revealed small but significant better results in the modular orthosis group in comparison to the invariable orthosis group. Cohen's effect sizes were high. Differences between the two intervention groups were marginal and very small but significant and--regarding Cohen's effect sizes--effective. Especially relating to functional performance, this might be a careful indication that a more effective strategy for promoting a protected, rapid recovery to physical activity after ankle sprains might be achieved by applying a phase-adapted ankle orthosis. Especially in athletic patients, phase-adapted orthosis should be further investigated and considered to ensure fully protected ligament healing as well as to regain early functional recovery.

  7. Early-Time Solution of the Horizontal Unconfined Aquifer in the Buildup Phase

    NASA Astrophysics Data System (ADS)

    Gravanis, Elias; Akylas, Evangelos

    2017-10-01

    We derive the early-time solution of the Boussinesq equation for the horizontal unconfined aquifer in the buildup phase under constant recharge and zero inflow. The solution is expressed as a power series of a suitable similarity variable, which is constructed so that to satisfy the boundary conditions at both ends of the aquifer, that is, it is a polynomial approximation of the exact solution. The series turns out to be asymptotic and it is regularized by resummation techniques that are used to define divergent series. The outflow rate in this regime is linear in time, and the (dimensionless) coefficient is calculated to eight significant figures. The local error of the series is quantified by its deviation from satisfying the self-similar Boussinesq equation at every point. The local error turns out to be everywhere positive, hence, so is the integrated error, which in turn quantifies the degree of convergence of the series to the exact solution.

  8. Role of phase instabilities in the early response of bulk fused silica during laser-induced breakdown

    NASA Astrophysics Data System (ADS)

    Demange, P.; Negres, R. A.; Raman, R. N.; Colvin, J. D.; Demos, S. G.

    2011-08-01

    We report on the experimental and hydrocode modeling investigation of the early material response to localized energy deposition via nanosecond laser pulses in bulk fused silica. A time-resolved microscope system was used to acquire transient images with adequate spatial and temporal resolution to resolve the material behavior from the onset of the process. These images revealed a high-pressure shock front propagating at twice the speed of sound at ambient conditions and bounding a region of modified material at delays up to one nanosecond. Hydrocode simulations matching the experimental conditions were also performed and indicated initial pressures of ˜40 GPa and temperatures of ˜1 eV at the absorption region. Both the simulations and the image data show a clear boundary between distinct material phases, a hot plasma and solid silica, with a suggestion that growth of perturbations at the Rayleigh-Taylor unstable interface between the two phases is the seed mechanism for the growth of cracks into the stressed solid.

  9. [Semiquantitative measurement of progesterone receptors in luteal-phase-defect endometrial cells during secretory phase].

    PubMed

    Ma, Q; Han, Z; Huang, W

    1998-03-01

    To investigate the changes of endometrial progesterone receptor (PR) of luteal-phase-defect (LPD) patients during the secretory phase, thirteen patients with complaints of infertility or habitual abortion were studied. During the early-mid secretory phase, endometrial tissue was obtained by dilatation and curettage (D & C) for histological and receptor study: meanwhile serum E2, P, FSH, LH and PRL were measured. Based on histologic diagnosis, the patients were divided into two groups: the LPD group (n = 7) and the normal control group(n = 6). PR content was determined by immunohisto-chemical (IHC) assay. The results showed that during the early-mid luteal phase a significantly low PR content on endometrial glandular nucleus was observed in LPD group, compared with normal control(6.75 +/- 2.57 vs 9.50 +/- 1.64 P < 0.05), but no difference in serum progesterone was noted between the two groups. These findings suggest that during early-mid secretory phase, PR content on endometrial glandular nucleus decreases in LPD cases, which results in deficient response of endometrium to proper stimulus of progesterone. This change may cause endometrial secretory deficiency and blockade of embreyo implantation. That is why infertility or habitual abortion happened.

  10. Expectations of Benefit in Early-Phase Clinical Trials: Implications for Assessing the Adequacy of Informed Consent

    PubMed Central

    Weinfurt, Kevin P.; Seils, Damon M.; Tzeng, Janice P.; Compton, Kate L.; Sulmasy, Daniel P.; Astrow, Alan B.; Solarino, Nicholas A.; Schulman, Kevin A.; Meropol, Neal J.

    2009-01-01

    Background Participants in early-phase clinical trials have reported high expectations of benefit from their participation. There is concern that participants misunderstand the trials to which they have consented. Such concern is based on assumptions about what patients mean when they respond to questions about likelihood of benefit. Methods Participants were 27 women and 18 men in early-phase oncology trials at 2 academic medical centers in the United States. To determine whether expectations of benefit differ depending on how patients are queried, we randomly assigned participants to 1 of 3 interviews corresponding to 3 questions about likelihood of benefit: frequency-type, belief-type, and vague. In semistructured interviews, we queried participants about how they understood and answered the question. Participants then answered and discussed one of the other questions. Results Expectations of benefit in response to the belief-type question were significantly greater than expectations in response to the frequency-type and vague questions (P = .02). The most common justifications involved positive attitude (n = 27 [60%]) and references to physical health (n = 23 [51%]). References to positive attitude were most common among participants with higher (> 70%) expectations (n = 11 [85%]) and least common among those with lower (< 50%) expectations (n = 3 [27%]). Conclusions The wording of questions about likelihood of benefit shapes the expectations that patients express. Also, patients who express high expectations may not do so to communicate understanding, but rather to register optimism. Ongoing research will clarify the meaning of high expectations and examine methods for assessing understanding in this context. PMID:18378940

  11. A qualitative study evaluating causality attribution for serious adverse events during early phase oncology clinical trials.

    PubMed

    Mukherjee, Som D; Coombes, Megan E; Levine, Mitch; Cosby, Jarold; Kowaleski, Brenda; Arnold, Andrew

    2011-10-01

    In early phase oncology trials, novel targeted therapies are increasingly being tested in combination with traditional agents creating greater potential for enhanced and new toxicities. When a patient experiences a serious adverse event (SAE), investigators must determine whether the event is attributable to the investigational drug or not. This study seeks to understand the clinical reasoning, tools used and challenges faced by the researchers who assign causality to SAE's. Thirty-two semi-structured interviews were conducted with medical oncologists and trial coordinators at six Canadian academic cancer centres. Interviews were recorded and transcribed verbatim. Individual interview content analysis was followed by thematic analysis across the interview set. Our study found that causality assessment tends to be a rather complex process, often without complete clinical and investigational data at hand. Researchers described using a common processing strategy whereby they gather pertinent information, eliminate alternative explanations, and consider whether or not the study drug resulted in the SAE. Many of the interviewed participants voiced concern that causality assessments are often conducted quickly and tend to be highly subjective. Many participants were unable to identify any useful tools to help in assigning causality and welcomed more objectivity in the overall process. Attributing causality to SAE's is a complex process. Clinical trial researchers apply a logical system of reasoning, but feel that the current method of assigning causality could be improved. Based on these findings, future research involving the development of a new causality assessment tool specifically for use in early phase oncology clinical trials may be useful.

  12. Brain responses to food images during the early and late follicular phase of the menstrual cycle in healthy young women: relation to fasting and feeding1234

    PubMed Central

    Ziemke, Florencia; Magkos, Faidon; Barrios, Fernando A; Brinkoetter, Mary; Boyd, Ingrid; Rifkin-Graboi, Anne; Yannakoulia, Mary; Rojas, Rafael; Pascual-Leone, Alvaro; Mantzoros, Christos S

    2011-01-01

    Background: Food intake fluctuates throughout the menstrual cycle; it is greater during the early follicular and luteal phases than in the late follicular (periovulatory) phase. Ovarian steroids can influence brain areas that process food-related information, but the specific contribution of individual hormones and the importance of the prandial state remain unknown. Objective: The objective was to examine whether brain activation during food visualization is affected by changes in estradiol concentration in the fasted and fed conditions. Design: Nine eumenorrheic, lean young women [mean (±SD) age: 26.2 ± 3.2 y; body mass index (in kg/m2): 22.4 ± 1.2] completed 2 visits, one in the early (low estradiol) and one in the late (high estradiol) follicular phase of their menstrual cycle. At each visit, subjects underwent functional magnetic resonance imaging while they viewed food and nonfood images, before and after a standardized meal. Region-of-interest analysis was used to examine the effect of follicular phase and prandial state on brain activation (food > nonfood contrast) and its association with estradiol concentration. Results: Differences were identified in the inferior frontal and fusiform gyri. In these areas, visualization of food elicited greater activation in the fed state than during fasting but only in the late follicular phase, when estradiol concentration was high. The change in estradiol concentration across the follicular phase (late minus early) was inversely correlated with the change in fusiform gyrus activation in the fasted state but not in the fed state. Conclusion: Our findings suggest that estradiol may reduce food intake by decreasing sensitivity to food cues in the ventral visual pathway under conditions of energy deprivation. This trial was registered at clinicaltrials.gov as NCT00130117. PMID:21593494

  13. Rapamycin ameliorates inflammation and fibrosis in the early phase of cirrhotic portal hypertension in rats through inhibition of mTORC1 but not mTORC2.

    PubMed

    Wang, Weijie; Yan, Jiqi; Wang, Huakai; Shi, Minmin; Zhang, Mingjun; Yang, Weiping; Peng, Chenghong; Li, Hongwei

    2014-01-01

    Hepatic stellate cells (HSCs) transdifferentiation and subsequent inflammation are important pathological processes involved in the formation of cirrhotic portal hypertension. This study characterizes the pathogenetic mechanisms leading to cholestatic liver fibrosis and portal hypertension, and focuses on mammalian target of rapamycin (mTOR) pathway as a potential modulator in the early phase of cirrhotic portal hypertension. Early cirrhotic portal hypertension was induced by bile duct ligation (BDL) for three weeks. One week after operation, sham-operated (SHAM) and BDL rats received rapamycin (2 mg/kg/day) by intraperitoneal injection for fourteen days. Vehicle-treated SHAM and BDL rats served as controls. Fibrosis, inflammation, and portal pressure were evaluated by histology, morphometry, and hemodynamics. Expressions of pro-fibrogenic and pro-inflammatory genes in liver were measured by RT-PCR; alpha smooth muscle actin (α-SMA) and antigen Ki67 were detected by immunohistochemistry; expressions of AKT/mTOR signaling molecules, extracellular-signal-regulated kinase 1/2 (ERK1/2), p-ERK1/2, and interleukin-1 beta (IL-1β) were assessed by western blot. The AKT/mTOR signaling pathway was markedly activated in the early phase of cirrhotic portal hypertension induced by BDL in rats. mTOR blockade by rapamycin profoundly improved liver function by limiting inflammation, fibrosis and portal pressure. Rapamycin significantly inhibited the expressions of phosphorylated 70KD ribosomal protein S6 kinase (p-P70S6K) and phosphorylated ribosomal protein S6 (p-S6) but not p-AKT Ser473 relative to their total proteins in BDL-Ra rats. Those results suggested that mTOR Complex 1 (mTORC1) rather than mTORC2 was inhibited by rapamycin. Interestingly, we also found that the level of p-ERK1/2 to ERK1/2 was significantly increased in BDL rats, which was little affected by rapamycin. The AKT/mTOR signaling pathway played an important role in the early phase of cirrhotic portal

  14. High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial.

    PubMed

    Márta, Katalin; Szabó, Anikó N; Pécsi, Dániel; Varjú, Péter; Bajor, Judit; Gódi, Szilárd; Sarlós, Patrícia; Mikó, Alexandra; Szemes, Kata; Papp, Mária; Tornai, Tamás; Vincze, Áron; Márton, Zsolt; Vincze, Patrícia A; Lankó, Erzsébet; Szentesi, Andrea; Molnár, Tímea; Hágendorn, Roland; Faluhelyi, Nándor; Battyáni, István; Kelemen, Dezső; Papp, Róbert; Miseta, Attila; Verzár, Zsófia; Lerch, Markus M; Neoptolemos, John P; Sahin-Tóth, Miklós; Petersen, Ole H; Hegyi, Péter

    2017-09-14

    Acute pancreatitis (AP) is an inflammatory disease with no specific treatment. Mitochondrial injury followed by ATP depletion in both acinar and ductal cells is a recently discovered early event in its pathogenesis. Importantly, preclinical research has shown that intracellular ATP delivery restores the physiological function of the cells and protects from cell injury, suggesting that restoration of energy levels in the pancreas is therapeutically beneficial. Despite several high quality experimental observations in this area, no randomised trials have been conducted to date to address the requirements for energy intake in the early phase of AP. This is a randomised controlled two-arm double-blind multicentre trial. Patients with AP will be randomly assigned to groups A (30 kcal/kg/day energy administration starting within 24 hours of hospital admission) or B (low energy administration during the first 72 hours of hospital admission). Energy will be delivered by nasoenteric tube feeding with additional intravenous glucose supplementation or total parenteral nutrition if necessary. A combination of multiorgan failure for more than 48 hours and mortality is defined as the primary endpoint, whereas several secondary endpoints such as length of hospitalisation or pain will be determined to elucidate more detailed differences between the groups. The general feasibility, safety and quality checks required for high quality evidence will be adhered to. The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (55961-2/2016/EKU). This study will provide evidence as to whether early high energy nutritional support is beneficial in the clinical management of AP. The results of this trial will be published in an open access way and disseminated among medical doctors. The trial has been registered at the ISRCTN (ISRTCN 63827758). © Article author(s) (or their employer(s) unless

  15. High-level physical activity in childhood seems to protect against low back pain in early adolescence.

    PubMed

    Wedderkopp, N; Kjaer, P; Hestbaek, L; Korsholm, L; Leboeuf-Yde, C

    2009-02-01

    The evidence on the impact of physical activity on back pain in children and adolescents has been contradicting. It has also been shown that the physical activity cannot accurately be estimated in children using questionnaires. The aim of this study was to establish if physical activity in childhood had any impact on back pain reporting in early adolescence (3 years later), using an objective instrumental measurement of physical activity. Prospective cohort study. Representative random sample of Danish children from the city of Odense sampled at age 9 years and followed-up at age 12 years. The 1-month period prevalence of back pain (neck pain, mid back pain, and low back pain) was established using a structured interview. Physical activity was assessed with the MTI-accelerometer. The accelerometer provides a minute-by-minute measure of the physical activity performed. An overall measure of physical activity and time spent in high activity were studied in relation to back pain using logistic regression. The analyses were performed on the total sample and then stratified on back pain (yes/no) at baseline. High physical activity (HPA) levels seem to protect against future low back pain and appear to actually "treat" and reduce the odds of future mid back pain. When comparing the least active children to the most active children, the least active had a multivariate odds ratio of 3.3 of getting low back pain and 2.7 of getting mid back pain 3 years later. When stratified on back pain at baseline, this effect on mid back pain was especially noticeable in children who had had mid back pain already at baseline, with an odds ratio of 7.2. HPA in childhood seems to protect against low back pain and mid back pain in early adolescence. Larger prospective studies with repetitive follow-ups and preferably intervention studies should be performed, to see if these findings can be reproduced.

  16. Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia.

    PubMed

    Liu, Yu-Cheng; Lee, Yu-Da; Wang, Hwai-Lee; Liao, Kate Hsiurong; Chen, Kuen-Bao; Poon, Kin-Shing; Pan, Yu-Ling; Lai, Ted Weita

    2017-01-01

    Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8-24 h, whereas the late phase of BBB disruption begins 48-58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison

  17. Early-phase transmission of Yersinia pestis by unblocked fleas as a mechanism explaining rapidly spreading plague epizootics.

    PubMed

    Eisen, Rebecca J; Bearden, Scott W; Wilder, Aryn P; Montenieri, John A; Antolin, Michael F; Gage, Kenneth L

    2006-10-17

    Plague is a highly virulent disease believed to have killed millions during three historic human pandemics. Worldwide, it remains a threat to humans and is a potential agent of bioterrorism. Dissemination of Yersinia pestis, the etiological agent of plague, by blocked fleas has been the accepted paradigm for flea-borne transmission. However, this mechanism, which requires a lengthy extrinsic incubation period before a short infectious window often followed by death of the flea, cannot sufficiently explain the rapid rate of spread that typifies plague epidemics and epizootics. Inconsistencies between the expected rate of spread by blocked rat fleas and that observed during the Black Death has even caused speculation that plague was not the cause of this medieval pandemic. We used the primary vector to humans in North America, Oropsylla montana, which rarely becomes blocked, as a model for studying alternative flea-borne transmission mechanisms. Our data revealed that, in contrast to the classical blocked flea model, O. montana is immediately infectious, transmits efficiently for at least 4 d postinfection (early phase) and may remain infectious for a long time because the fleas do not suffer block-induced mortality. These factors match the criteria required to drive plague epizootics as defined by recently published mathematical models. The scenario of efficient early-phase transmission by unblocked fleas described in our study calls for a paradigm shift in concepts of how Y. pestis is transmitted during rapidly spreading epizootics and epidemics, including, perhaps, the Black Death.

  18. Skin manifestations in sulfur mustard exposed victims with ophthalmologic complications: Association between early and late phase.

    PubMed

    Hejazi, Somayeh; Soroush, Mohammadreza; Moradi, Ahmad; Khalilazar, Sara; Mousavi, Batool; Firooz, Alireza; Younespour, Shima

    2016-01-01

    Sulfur mustard (SM) was used during the Iraq-Iran war (1980-1988). Exposed veterans continue to suffer from its ocular, skin, and respiratory complications. We aimed to evaluate associations between early (at the time of acute exposure) and decades later skin manifestations in individuals with severe ophthalmologic complications secondary to sulfur mustard exposure. One hundred forty-nine veterans with severe ocular injuries were evaluated for acute and chronic skin complications. Logistic regression models were used to examine the associations between early and late skin manifestations. Late skin complaints were observed in nearly all survivors who had early skin lesions (131 out of 137; 95.62%). Seven out of 12 patients (58.33%) who did not have early skin lesions ultimately developed late skin complications. There was a significant relationship between the presence of lesions at the time of exposure and developing late skin complaints (two-sided Fisher's exact test, OR = 15.59, p < 0.001). There was an association between having at least one early skin lesion and occurrence of late skin complications. Survivors with blisters at the time of chemical exposure were more likely to complain of itching (95% CI: 3.63-25.97, p < 0.001), burning (OR = 11.16; 95% CI: 2.97-41.89, p < 0.001), pigmentation changes (OR = 10.17; 95% CI: 2.54-40.75, p = 0.001), dryness (OR = 6.71, 95% CI: 1.22-37.01, p = 0.03) or cherry angioma (OR = 2.59; 95% CI:1.21-5.55, p = 0.01) during the late phase. Using multivariate logistic models, early blisters remained significantly associated with latent skin complaints. Of note, the genitalia and great flexure areas were the most involved anatomical sites for both early and late skin lesions in SM exposed survivors. According to this study, the presence of blisters at the time of exposure to SM is the most important predictor of developing dermatologic complications decades later in patients with severe ophthalmologic

  19. Postpartum Circulating Markers of Inflammation and the Systemic Acute-Phase Response After Early-Onset Preeclampsia.

    PubMed

    van Rijn, Bas B; Bruinse, Hein W; Veerbeek, Jan H; Post Uiterweer, Emiel D; Koenen, Steven V; van der Bom, Johanna G; Rijkers, Ger T; Roest, Mark; Franx, Arie

    2016-02-01

    Preeclampsia is an inflammatory-mediated hypertensive disorder of pregnancy and seems to be an early indicator of increased cardiovascular risk, but mechanisms underlying this association are unclear. In this study, we identified levels of circulating inflammatory markers and dynamic changes in the systemic acute-phase response in 44 women with a history of severe early-onset preeclampsia, compared with 29 controls with only uneventful pregnancies at 1.5 to 3.5 years postpartum. Models used were in vivo seasonal influenza vaccination and in vitro whole-blood culture with T-cell stimulants and the toll-like receptor-4 ligand lipopolysaccharide. Outcome measures were C-reactive protein, interleukin-6 (IL-6), IL-18, fibrinogen, myeloperoxidase, and a panel of 13 cytokines representative of the innate and adaptive inflammatory response, in addition to established cardiovascular markers. The in vivo acute-phase response was higher for women with previous preeclampsia than that for controls without such a history, although only significant for C-reactive protein (P=0.04). Preeclampsia was associated with higher IL-1β (P<0.05) and IL-8 (P<0.01) responses to T-cell activation. Hierarchical clustering revealed 2 distinct inflammatory clusters associated with previous preeclampsia: an adaptive response cluster associated with increased C-reactive protein and IL-6 before and after vaccination, increased weight, and low high-density lipoprotein cholesterol; and a toll-like receptor-4 mediated the cluster associated with increased IL-18 before and after vaccination but not associated with other cardiovascular markers. Furthermore, we found interactions between previous preeclampsia, common TLR4 gene variants, and the IL-18 response to vaccination. In conclusion, preeclampsia is associated with alterations in the inflammatory response postpartum mostly independent of other established cardiovascular risk markers. © 2015 American Heart Association, Inc.

  20. Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION)

    PubMed Central

    Jabbour, Elias; Saglio, Giuseppe; Steegmann, Juan Luis; Shah, Neil P.; Boqué, Concepción; Chuah, Charles; Pavlovsky, Carolina; Mayer, Jiří; Cortes, Jorge; Baccarani, Michele; Kim, Dong-Wook; Bradley-Garelik, M. Brigid; Mohamed, Hesham; Wildgust, Mark; Hochhaus, Andreas

    2014-01-01

    This analysis explores the impact of early cytogenetic and molecular responses on the outcomes of patients with chronic myeloid leukemia in chronic phase (CML-CP) in the phase 3 DASatinib versus Imatinib Study In treatment-Naive CML patients trial with a minimum follow-up of 3 years. Patients with newly diagnosed CML-CP were randomized to receive 100 mg dasatinib (n = 259) or 400 mg imatinib (n = 260) once daily. The retrospective landmark analysis included patients evaluable at the relevant time point (3, 6, or 12 months). Median time to complete cytogenetic response was 3 vs 6 months with dasatinib vs imatinib. At 3 and 6 months, the proportion of patients with BCR-ABL transcript levels ≤10% was higher in the dasatinib arm. Deeper responses at 3, 6, and 12 months were observed in a higher proportion of patients on dasatinib therapy and were associated with better 3-year progression-free survival and overall survival in both arms. First-line dasatinib resulted in faster and deeper responses compared with imatinib. The achievement of an early molecular response was predictive of improved progression-free survival and overall survival, supporting new milestones for optimal response in patients with early CML-CP treated with tyrosine kinase inhibitors. This study was registered at www.clinicaltrials.gov as NCT00481247. PMID:24311723

  1. Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase.

    PubMed

    van Overbeek, Megan; de Lange, Titia

    2006-07-11

    Human chromosome ends are protected by shelterin, an abundant six-subunit protein complex that binds specifically to the telomeric-repeat sequences, regulates telomere length, and ensures that chromosome ends do not elicit a DNA-damage response (reviewed in). Using mass spectrometry of proteins associated with the shelterin component Rap1, we identified an SMN1/PSO2 nuclease family member that is closely related to Artemis. We refer to this protein as Apollo and report that Apollo has the ability to localize to telomeres through an interaction with the shelterin component TRF2. Although its low abundance at telomeres indicates that Apollo is not a core component of shelterin, Apollo knockdown with RNAi resulted in senescence and the activation of a DNA-damage signal at telomeres as evidenced by telomere-dysfunction-induced foci (TIFs). The TIFs occurred primarily in S phase, suggesting that Apollo contributes to a processing step associated with the replication of chromosome ends. Furthermore, some of the metaphase chromosomes showed two telomeric signals at single-chromatid ends, suggesting an aberrant telomere structure. We propose that the Artemis-like nuclease Apollo is a shelterin accessory factor required for the protection of telomeres during or after their replication.

  2. 78 FR 44475 - Protection System Maintenance Reliability Standard

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-24

    ... Protection System Maintenance--Phase 2 (Reclosing Relays)). 12. NERC states that the proposed Reliability... of the relay inputs and outputs that are essential to proper functioning of the protection system...] Protection System Maintenance Reliability Standard AGENCY: Federal Energy Regulatory Commission, Energy...

  3. Prognostic Performance Evaluation of the International Society on Thrombosis and Hemostasis and the Korean Society on Thrombosis and Hemostasis Scores in the Early Phase of Trauma.

    PubMed

    Kim, Hong Sug; Lee, Dong Hun; Lee, Byung Kook; Cho, Yong Soo

    2018-01-15

    Disseminated intravascular coagulation (DIC) contributes to poor outcome in the early phase of trauma. We aimed to analyze and compare the prognostic performances of the International Society on Thrombosis and Hemostasis (ISTH) and the Korean Society on Thrombosis and Hemostasis (KSTH) scores in the early phase of trauma. Receiver operating characteristics analysis was used to examine the prognostic performance of both scores, and multivariate analysis was used to estimate the prognostic impact of the ISTH and KSTH scores in the early phase of trauma. The primary outcome was 24-hour mortality and the secondary outcome was massive transfusion. Of 1,229 patients included in the study, the 24-hour mortality rate was 7.6% (n = 93), and 8.1% (n = 99) of patients who received massive transfusions. The area under the curves (AUCs) of the KSTH and ISTH scores for 24-hour mortality were 0.784 (95% confidence interval [CI], 0.760-0.807) and 0.744 (95% CI, 0.718-0.768), respectively. The AUC of KSTH and ISTH scores for massive transfusion were 0.758 (95% CI, 0.734-0.782) and 0.646 (95% CI, 0.619-0.673), respectively. The AUCs of the KSTH score was significantly different from those of the ISTH score. Overt DIC according to KSTH criteria only, was independently associated with 24-hour mortality (odds ratio [OR], 2.630; 95% CI, 1.456-4.752). Only the KSTH score was independently associated with massive transfusion (OR, 1.563; 95% CI, 1.182-2.068). The KSTH score demonstrates a better prognostic performance for outcomes than the ISTH score in the early phase of trauma. © 2018 The Korean Academy of Medical Sciences.

  4. 2015 Guidance on cancer immunotherapy development in early-phase clinical studies.

    PubMed

    2015-12-01

    The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of "cancer vaccines", which are based on the idea of vaccination, "effector cell therapy", classified as passive immunotherapy, and "inhibition of immunosuppression", which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune checkpoint inhibitors and adoptive immunotherapies with tumor-infiltrating lymphocytes and tumor-specific receptor gene-modified T cells indicate the beginning of a new era for cancer immunotherapy. This guidance summarizes ideas that will be helpful to those who plan to develop cancer immunotherapy. The aims of this guidance are to discuss and offer important points in early phase clinical studies of innovative cancer immunotherapy, with future progress in this field, and to contribute to the effective development of cancer immunotherapy aligned with the scope of regulatory science. This guidance covers cancer vaccines, effector cell therapy, and inhibition of immunosuppression, including immune checkpoint inhibitors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  5. Protection of Reinforcement with Corrosion Inhibitors, Phase II

    DOT National Transportation Integrated Search

    2000-12-01

    Costs due to corrosion of reinforcement in concrete caused by deicing salts have been estimated at up to $1 billion per year in the U.S. alone. For most situations, corrosion-inhibiting admixtures offer significant advantages over other protection me...

  6. Psychotropic and Anticonvulsant Drug Usage in Early Childhood Special Education Programs I. Phase One: A Preliminary Report: Prevalence, Attitude, Training, and Problems.

    ERIC Educational Resources Information Center

    Gadow, Kenneth D.

    As part of a three phase study designed to survey the teachers and parents of children receiving psychotropic and anticonvulsant drugs, 208 teachers of preschool special education children on medication were mailed questionnaires. The Early Childhood Medication Questionnaire used in the survey included items relating to teacher, program, and…

  7. Early Intervention for Alcohol Use Prevention and Vehicle Safety Skills: Evaluating the "Protecting You/Protecting Me" Curriculum

    ERIC Educational Resources Information Center

    Bohman, Thomas M.; Barker, Edward D.; Bell, Mary Lou; Lewis, Carol M.; Holleran, Lori; Pomeroy, Elizabeth

    2004-01-01

    The present study reports the evaluation results of the "Protecting You/Protecting Me" (PY/PM) alcohol use prevention and safety curriculum for third, fourth, and fifth graders when taught by high school peer leaders. The primary goal of the PY/PM prevention program, developed by Mothers Against Drunk Driving (MADD), is to prevent injury…

  8. The Diagnostic Usefulness of Serum Total Bile Acid Concentrations in the Early Phase of Acute Pancreatitis of Varied Etiologies.

    PubMed

    Maleszka, Aleksandra; Dumnicka, Paulina; Matuszyk, Aleksandra; Pędziwiatr, Michał; Mazur-Laskowska, Małgorzata; Sporek, Mateusz; Ceranowicz, Piotr; Olszanecki, Rafał; Kuźniewski, Marek; Kuśnierz-Cabala, Beata

    2017-01-06

    The most common causes of acute pancreatitis (AP) are biliary tract diseases with cholestasis and alcohol consumption. In 10%-15% of patients, etiology determination is difficult. Identification of the etiology allows for the implementation of adequate treatment. The aim of this study was to assess the utility of the serum concentrations of total bile acids (TBA) to diagnose AP etiology in the early phase of the disease. We included 66 patients with AP, admitted within the first 24 h from the onset of symptoms. TBA were measured in serum at 24, 48, and 72 h from the onset of AP, using an automated fifth generation assay. The bilirubin-to-TBA ratio (B/TBA) was calculated. TBA was highest on the first day of AP and decreased subsequently. In patients with biliary etiology, serum TBA was significantly higher compared to those with alcoholic and other etiologies. B/TBA was significantly higher in patients with alcoholic etiology. At admission, the cut-off values of 4.7 µmol/L for TBA and 4.22 for the B/TBA ratio allowed for a differentiation between biliary and other etiologies of AP with a diagnostic accuracy of 85 and 83%. Both TBA and B/TBA may help in the diagnosis of AP etiology in the early phase of AP.

  9. The protective effect of parental expectations against early adolescent smoking initiation.

    PubMed

    Simons-Morton, Bruce G

    2004-10-01

    Substantial research and theory suggests that smoking initiation is socially mediated, with both peers and parents playing important roles. To learn more about how parenting behaviors influence smoking initiation, students (n=1002) from four middle schools were surveyed at the beginning of the sixth grade (T1), and the end of the sixth (T2) and seventh (T3) grades. T1 and T2-T1 predictors were regressed on smoking initiation at the end of seventh grade. In bivariate logistic regression analyses, association with friends who smoke, attitudes toward deviance, outcome expectations for smoking, perceived school climate, parental expectations, parental involvement at T1 and increases in these variables (T2-T1) were associated with smoking initiation at T3, but only the T1 measures of social competence, academic engagement, school adjustment, perceived prevalence, parental monitoring and parental involvement were associated with smoking initiation at T3. In multivariate logistic regression analyses, parental expectations were negatively associated, and increases in attitudes accepting of deviance and affiliation with friends who smoke were positively associated with smoking initiation. Analysis of interactions indicated that parental expectations and monitoring did not mediate the effect on smoking initiation of attitudes toward deviance or the number of friends who smoke. These findings provide evidence that parental expectations may protect early adolescents against smoking even in the context of increases in favorable attitudes and friends who smoking.

  10. Innovative strategies for early clinical R&D.

    PubMed

    Butz, Robert F; Morelli, Gaetano

    2008-01-01

    Developments in translational medicine and regulatory initiatives associated with the FDA's Critical Path Initiative are creating new opportunities for innovation in early clinical R&D. The introduction of the exploratory IND process allows small, 'phase 0' clinical trials to be conducted prior to traditional phase I trials - sometimes requiring considerably less chemistry, manufacturing and controls, or preclinical support. Phase 0 clinical trials involving subtherapeutic, yet pharmacologically active, dose levels can provide an early demonstration of clinical proof of concept; such demonstration is of particular importance to small pharmaceutical and early-stage biotechnology companies. However, these opportunities for rapid entry into the clinic must be balanced by a consideration of the unique risks associated with first-in-human clinical trials, and by accounting for public concerns regarding drug safety in general. This feature review discusses how innovative clinical strategies can be used effectively in early drug development.

  11. Leu72Met408 Polymorphism of the Ghrelin Gene Is Associated With Early Phase of Gastric Emptying in the Patients With Functional Dyspepsia in Japan

    PubMed Central

    Yamawaki, Hiroshi; Futagami, Seiji; Shimpuku, Mayumi; Shindo, Tomotaka; Maruki, Yuuta; Nagoya, Hiroyuki; Kodaka, Yasuhiro; Sato, Hitomi; Gudis, Katya; Kawagoe, Tetsuro; Sakamoto, Choitsu

    2015-01-01

    Background/Aims There are no available data about the relationship between ghrelin gene genotypes and early phase of gastric emptying in functional dyspepsia (FD) as defined by Rome III classification. Methods We enrolled 74 patients presenting with typical symptoms of FD and 64 healthy volunteers. Gastric motility was evaluated using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and self-rating questionnaires for depression (SRQ-D) scores to determine status of depression. The Arg51Gln (346G>A), preproghrelin (3056T>C), Leu72Met (408C>A), Gln90Leu (3412T>A) and G-protein β3 (825C>T) polymorphisms were analyzed in the DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction. Results There was a significant relationship between the Gln90Leu3412 genotype and SRQ-D score in FD patients (P = 0.009). Area under the curve at 15 minutes (AUC15) value was significantly associated with the Leu72Met408 genotype (P = 0.015) but not with entire gastric emptying. Conclusions The Leu72Met (408C>A) single nucleotide polymorphism was significantly associated with early phase of gastric emptying in FD patients. Further studies will be necessary to clarify the association between ghrelin gene single nucleotide polymorphisms and early phase of gastric emptying in FD patients. PMID:25540946

  12. Leu72Met408 Polymorphism of the Ghrelin Gene Is Associated With Early Phase of Gastric Emptying in the Patients With Functional Dyspepsia in Japan.

    PubMed

    Yamawaki, Hiroshi; Futagami, Seiji; Shimpuku, Mayumi; Shindo, Tomotaka; Maruki, Yuuta; Nagoya, Hiroyuki; Kodaka, Yasuhiro; Sato, Hitomi; Gudis, Katya; Kawagoe, Tetsuro; Sakamoto, Choitsu

    2015-01-01

    There are no available data about the relationship between ghrelin gene genotypes and early phase of gastric emptying in functional dyspepsia (FD) as defined by Rome III classification. We enrolled 74 patients presenting with typical symptoms of FD and 64 healthy volunteers. Gastric motility was evaluated using the 13C-acetate breath test. We used Rome III criteria to evaluate upper abdominal symptoms and self-rating questionnaires for depression (SRQ-D) scores to determine status of depression. The Arg51Gln (346G->A), preproghrelin (3056T->C), Leu72Met (408C->A), Gln90Leu (3412T->A) and G-protein 3 (825C->T) polymorphisms were analyzed in the DNA from blood samples of enrolled subjects. Genotyping was performed by polymerase chain reaction. There was a significant relationship between the Gln90Leu3412 genotype and SRQ-D score in FD patients (P = 0.009). Area under the curve at 15 minutes (AUC15) value was significantly associated with the Leu72Met408 genotype (P = 0.015) but not with entire gastric emptying. The Leu72Met (408C->A) single nucleotide polymorphism was significantly associated with early phase of gastric emptying in FD patients. Further studies will be necessary to clarify the association between ghrelin gene single nucleotide polymorphisms and early phase of gastric emptying in FD patients.

  13. Nurturing care: promoting early childhood development.

    PubMed

    Britto, Pia R; Lye, Stephen J; Proulx, Kerrie; Yousafzai, Aisha K; Matthews, Stephen G; Vaivada, Tyler; Perez-Escamilla, Rafael; Rao, Nirmala; Ip, Patrick; Fernald, Lia C H; MacMillan, Harriet; Hanson, Mark; Wachs, Theodore D; Yao, Haogen; Yoshikawa, Hirokazu; Cerezo, Adrian; Leckman, James F; Bhutta, Zulfiqar A

    2017-01-07

    The UN Sustainable Development Goals provide a historic opportunity to implement interventions, at scale, to promote early childhood development. Although the evidence base for the importance of early childhood development has grown, the research is distributed across sectors, populations, and settings, with diversity noted in both scope and focus. We provide a comprehensive updated analysis of early childhood development interventions across the five sectors of health, nutrition, education, child protection, and social protection. Our review concludes that to make interventions successful, smart, and sustainable, they need to be implemented as multi-sectoral intervention packages anchored in nurturing care. The recommendations emphasise that intervention packages should be applied at developmentally appropriate times during the life course, target multiple risks, and build on existing delivery platforms for feasibility of scale-up. While interventions will continue to improve with the growth of developmental science, the evidence now strongly suggests that parents, caregivers, and families need to be supported in providing nurturing care and protection in order for young children to achieve their developmental potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Comparison of the solid-phase fragment condensation and phase-change approaches in the synthesis of salmon I calcitonin.

    PubMed

    Gatos, D; Tzavara, C

    2001-02-01

    Salmon I calcitonin was synthesized using both phase-change and conventional solid-phase fragment condensation (SPFC) approaches, utilizing the Rink amide linker (Fmoc-amido-2,4-dimethoxybenzyl-4-phenoxyacetic acid) combined with 2-chlorotrityl resin and the Fmoc/tBu(Trt)-based protection scheme. Phase-change synthesis, performed by the selective detachment of the fully protected C-terminal 22-mer peptide-linker from the resin and subsequent condensation in solution with the N-terminal 1-10 fragment, gave a product of slightly less purity (85 vs. 92%) than the corresponding synthesis on the solid-phase. In both cases salmon I calcitonin was easily obtained in high purity.

  15. Flow Test to Predict Early Hypotony and Hypertensive Phase After Ahmed Glaucoma Valve (AGV) Surgical Implantation.

    PubMed

    Cheng, Jason; Beltran-Agullo, Laura; Buys, Yvonne M; Moss, Edward B; Gonzalez, Johanna; Trope, Graham E

    2016-06-01

    To assess the validity of a preimplantation flow test to predict early hypotony [intraocular pressure (IOP)≤5 mm Hg on 2 consecutive visits and hypertensive phase (HP) (IOP>21 mm Hg) after Ahmed Glaucoma Valve (AGV) implantation. Prospective interventional study on patients receiving an AGV. A preimplantation flow test using a gravity-driven reservoir and an open manometer was performed on all AGVs. Opening pressure (OP) and closing pressure (CP) were defined as the pressure at which fluid was seen to flow or stop flowing through the AGV, respectively. OP and CP were measured twice per AGV. Patients were followed for 12 weeks. In total, 20 eyes from 19 patients were enrolled. At 12 weeks the mean IOP decreased from 29.2±9.1 to 16.8±5.2 mm Hg (P<0.01). The mean AGV OP was 17.5±5.4 mm Hg and the mean CP was 6.7±2.3 mm Hg. Early (within 2 wk postoperative) HP occurred in 37% and hypotony in 16% of cases. An 18 mm Hg cutoff for the OP gave a sensitivity of 0.71, specificity of 0.83, positive predictive value of 0.71, and negative predictive value of 0.83 for predicting an early HP. A 7 mm Hg cutoff for the CP yielded a sensitivity of 1.0, specificity of 0.38, positive predictive value of 0.23, and negative predictive value of 1.0 for predicting hypotony. Preoperative OP and CP may predict early hypotony or HP and may be used as a guide as to which AGV valves to discard before implantation surgery.

  16. Protective Vaccination against Blood-Stage Malaria of Plasmodium chabaudi: Differential Gene Expression in the Liver of Balb/c Mice toward the End of Crisis Phase

    PubMed Central

    Al-Quraishy, Saleh A.; Dkhil, Mohamed A.; Abdel-Baki, Abdel-Azeem A.; Delic, Denis; Wunderlich, Frank

    2016-01-01

    Protective vaccination induces self-healing of otherwise fatal blood-stage malaria of Plasmodium chabaudi in female Balb/c mice. To trace processes critically involved in self-healing, the liver, an effector against blood-stage malaria, is analyzed for possible changes of its transcriptome in vaccination-protected in comparison to non-protected mice toward the end of the crisis phase. Gene expression microarray analyses reveal that vaccination does not affect constitutive expression of mRNA and lincRNA. However, malaria induces significant (p < 0.01) differences in hepatic gene and lincRNA expression in vaccination-protected vs. non-vaccinated mice toward the end of crisis phase. In vaccination-protected mice, infections induce up-regulations of 276 genes and 40 lincRNAs and down-regulations of 200 genes and 43 lincRNAs, respectively, by >3-fold as compared to the corresponding constitutive expressions. Massive up-regulations, partly by >100-fold, are found for genes as RhD, Add2, Ank1, Ermap, and Slc4a, which encode proteins of erythrocytic surface membranes, and as Gata1 and Gfi1b, which encode transcription factors involved in erythrocytic development. Also, Cldn13 previously predicted to be expressed on erythroblast surfaces is up-regulated by >200-fold, though claudins are known as main constituents of tight junctions acting as paracellular barriers between epithelial cells. Other genes are up-regulated by <100- and >10-fold, which can be subgrouped in genes encoding proteins known to be involved in mitosis, in cell cycle regulation, and in DNA repair. Our data suggest that protective vaccination enables the liver to respond to P. chabaudi infections with accelerated regeneration and extramedullary erythropoiesis during crisis, which contributes to survival of otherwise lethal blood-stage malaria. PMID:27471498

  17. Formation mechanism of the protective layer in a blast furnace hearth

    NASA Astrophysics Data System (ADS)

    Jiao, Ke-xin; Zhang, Jian-liang; Liu, Zheng-jian; Xu, Meng; Liu, Feng

    2015-10-01

    A variety of techniques, such as chemical analysis, scanning electron microscopy-energy dispersive spectroscopy, and X-ray diffraction, were applied to characterize the adhesion protective layer formed below the blast furnace taphole level when a certain amount of titanium- bearing burden was used. Samples of the protective layer were extracted to identify the chemical composition, phase assemblage, and distribution. Furthermore, the formation mechanism of the protective layer was determined after clarifying the source of each component. Finally, a technical strategy was proposed for achieving a stable protective layer in the hearth. The results show that the protective layer mainly exists in a bilayer form in the sidewall, namely, a titanium-bearing layer and a graphite layer. Both the layers contain the slag phase whose major crystalline phase is magnesium melilite (Ca2MgSi2O7) and the main source of the slag phase is coke ash. It is clearly determined that solid particles such as graphite, Ti(C,N) and MgAl2O4 play an important role in the formation of the protective layer, and the key factor for promoting the formation of a stable protective layer is reasonable control of the evolution behavior of coke.

  18. Sport and early osteoarthritis: the role of sport in aetiology, progression and treatment of knee osteoarthritis.

    PubMed

    Vannini, F; Spalding, T; Andriolo, L; Berruto, M; Denti, M; Espregueira-Mendes, J; Menetrey, J; Peretti, G M; Seil, R; Filardo, G

    2016-06-01

    Sports activities are considered favourable for general health; nevertheless, a possible influence of sports practice on the development of early osteoarthritis (OA) is a cause for concern. A higher incidence of OA in knees and ankles of former high-impact sports players than in those of the normal population has been shown and it is still debatable whether the cause is either to be recognized generically in the higher number of injuries or in a joint overload. The possibility to address knee OA in its early phases may be strictly connected to the modification of specific extrinsic or intrinsic factors, related to the patient in order to save the joint from further disease progression; these include sport practice, equipment and load. Non-surgical therapies such as continuative muscles reinforce and training play a strong role in the care of athletes with early OA, particularly if professional. There is an overall agreement on the need of an early restoring of a proper meniscal, ligament and cartilage integrity in order to protect the knee and resume sports safely, whereas alignment is a point still strongly debatable especially for professional athletes. Remaining questions still to be answered are the risks of different sports in relation to one another, although an actual protective effect of low-impact sports, such as walking, swimming or cycling, has been recognized on the appearance or worsening of OA, the effect of continuing or ceasing to practice a sport on the natural history of early OA, and even following appropriate treatment is still unknown.

  19. Optimizing the early phase development of new analgesics by human pain biomarkers.

    PubMed

    Arendt-Nielsen, Lars; Hoeck, Hans Christian

    2011-11-01

    Human pain biomarkers are based on standardized acute activation of pain pathways/mechanisms and quantitative assessment of the evoked responses. This approach can be applied to healthy volunteers, to pain patients, and before and after pharmacological interventions to help understanding and profile the mode of action (proof-of-concept) of new and existing analgesic compounds. Standardized stimuli of different modalities can be applied to different tissues (multimodal and multi-tissue) for profiling analgesic compounds with respect to modulation of pain transduction, transmission, specific mechanisms and processing. This approach substantiates which specific compounds may work in particular clinical pain conditions. Human pain biomarkers can be translational and may bridge animal findings in clinical pain conditions, which in turn can provide new possibilities for designing more successful clinical trials. Biomarker based proof-of-concept drug studies in either volunteers or selected patient populations provide inexpensive, fast and reliable mechanism-based information about dose-efficacy relationships. This is important information in the early drug development phase and for designing large expensive clinical trials.

  20. Symmetric Topological Phases and Tensor Network States

    NASA Astrophysics Data System (ADS)

    Jiang, Shenghan

    Classification and simulation of quantum phases are one of main themes in condensed matter physics. Quantum phases can be distinguished by their symmetrical and topological properties. The interplay between symmetry and topology in condensed matter physics often leads to exotic quantum phases and rich phase diagrams. Famous examples include quantum Hall phases, spin liquids and topological insulators. In this thesis, I present our works toward a more systematically understanding of symmetric topological quantum phases in bosonic systems. In the absence of global symmetries, gapped quantum phases are characterized by topological orders. Topological orders in 2+1D are well studied, while a systematically understanding of topological orders in 3+1D is still lacking. By studying a family of exact solvable models, we find at least some topological orders in 3+1D can be distinguished by braiding phases of loop excitations. In the presence of both global symmetries and topological orders, the interplay between them leads to new phases termed as symmetry enriched topological (SET) phases. We develop a framework to classify a large class of SET phases using tensor networks. For each tensor class, we can write down generic variational wavefunctions. We apply our method to study gapped spin liquids on the kagome lattice, which can be viewed as SET phases of on-site symmetries as well as lattice symmetries. In the absence of topological order, symmetry could protect different topological phases, which are often referred to as symmetry protected topological (SPT) phases. We present systematic constructions of tensor network wavefunctions for bosonic symmetry protected topological (SPT) phases respecting both onsite and spatial symmetries.

  1. 40 CFR Appendix B to Part 63 - Sources Defined for Early Reduction Provisions

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 14 2011-07-01 2011-07-01 false Sources Defined for Early Reduction Provisions B Appendix B to Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... (CONTINUED) Pt. 63, App. B Appendix B to Part 63—Sources Defined for Early Reduction Provisions Source...

  2. Mechanism of Properties of Noble ZnS-SiO2 Protection Layer for Phase Change Optical Disk Media

    NASA Astrophysics Data System (ADS)

    Tsu, David V.; Ohta, Takeo

    2006-08-01

    A ZnS-SiO2 composite dielectric is widely used in the optical stack designs of rewritable optical recording media as an index-matching medium and as a protection layer for the high-index chalcogenide (compound with sixth group element of S, Se, Te) phase change material used in these media. The addition of Si and O to ZnS is primarily intended to stabilize against crystalline grain growth of ZnS with high numbers of direct overwriting cycles. In this study, we carry out infrared (IR) spectroscopy to clarify the role of Si in this stabilization process. IR spectroscopy is performed on sputter as-deposited and annealed ZnS-SiO2 dielectric protection layers. We find that Si exists not in the SiO2 oxide phase but as [SiS4-nOn] tetrahedrons. Moreover, zinc and sulfur do not exist as ZnS, but in highly chemically disordered ZnS:O crystallites. The highly directional and rigid covalent bonds in the [SiS4-nOn] tetrahedrons are key to establishing thermal stability against the coalescence of ZnS. The importance of the Si-S bond also extends into a more thorough understanding of the low thermal conductivity of the ZnS-SiO2 material. The consideration of elastic implications allows us to predict an average phonon velocity less than 50% compared to that in SiO2. With this, we predict a thermal conductivity of 0.0067 W cm-1 K-1 for this material, which is in complete agreement with measured values.

  3. Buffering boys and boosting girls: The protective and promotive effects of Early Head Start for children’s expressive language in the context of parenting stress

    PubMed Central

    Vallotton, C. D.; Harewood, T.; Ayoub, C. A.; Pan, B.; Mastergeorge, A. M.; Brophy-Herb, H.

    2011-01-01

    Children’s characteristics, including gender, influence their development by eliciting differential responses from their environments, and by influencing differential responses to their environments. Parenting-related stress, associated with poverty environments, negatively influences children’s language, likely through its impact on parent-child interactions, but may impact boys’ and girls’ development differently. Early intervention represents one tool for supporting development in at-risk toddlers, but gender-differences in effects of intervention are rarely described. The current studies assessed the effects of Early Head Start (EHS) on children’s productive vocabulary in the context of parenting stress and examined gender differences in program effects on vocbulary. Data were from the national EHS Research and Evaluation (EHSRE) study (Study 1, N = 3,001), and from a dataset associated with one EHSRE site (Study 2, N = 146) where additional data on productive vocabulary were collected. Study 1 found that at 24 months of age, the EHS program protected girls’ productive vocabulary from the negative effects of parenting stress, but had little impact on boys’ vocabulary. In Study 2, the local EHS site promoted girls’ vocabulary development over time from 14 to 36 months despite the negative effects of parenting stress, and protected boys’ vocabulary from the negative parenting stress effects. These results suggest differential ways in which at-risk toddlers are affected by early intervention. PMID:23166405

  4. Couple Therapy with Veterans: Early Improvements and Predictors of Early Dropout.

    PubMed

    Fischer, Melanie S; Bhatia, Vickie; Baddeley, Jenna L; Al-Jabari, Rawya; Libet, Julian

    2017-07-28

    Family services within Veterans Affairs Medical Centers fulfill an important role in addressing relationship distress among Veterans, which is highly prevalent and comorbid with psychopathology. However, even for evidence-based couple therapies, effectiveness is weaker compared to controlled studies, maybe because many Veteran couples drop out early and do not reach the "active" treatment stage after the 3-4 session assessment. In order to improve outcomes, it is critical to identify couples at high risk for early dropout, and understand whether couples may benefit from the assessment as an intervention. The current study examined (a) demographics, treatment delivery mode, relationship satisfaction, and psychological symptoms as predictors of dropout during and immediately following the assessment phase, and (b) changes in relationship satisfaction during assessment. 174 couples completed questionnaires during routine intake procedures. The main analyses focused on 140 male Veterans and their female civilian partners; 36.43% dropped out during the assessment phase and 24.74% of the remaining couples immediately following the first treatment session. More severe depressive symptoms in non-Veteran partners were associated with dropout during assessment. Relationship satisfaction improved significantly during the assessment phase for couples who did not drop out, with larger gains for non-Veteran partners. No demographics or treatment delivery mode were associated with dropout. Although more research is needed on engaging couples at risk for early dropout and maximizing early benefits, the findings suggest that clinicians should attend to the civilian partner's and Veteran's depressive symptoms at intake and consider the assessment part of active treatment. © 2017 Family Process Institute.

  5. 40 CFR 63.74 - Demonstration of early reduction.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 9 2011-07-01 2011-07-01 false Demonstration of early reduction. 63.74... Governing Compliance Extensions for Early Reductions of Hazardous Air Pollutants § 63.74 Demonstration of early reduction. (a) An owner or operator applying for an alternative emission limitation shall...

  6. Early phase clinical trials with human immunodeficiency virus-1 and malaria vectored vaccines in The Gambia: frontline challenges in study design and implementation.

    PubMed

    Afolabi, Muhammed O; Adetifa, Jane U; Imoukhuede, Egeruan B; Viebig, Nicola K; Kampmann, Beate; Bojang, Kalifa

    2014-05-01

    Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and malaria are among the most important infectious diseases in developing countries. Existing control strategies are unlikely to curtail these diseases in the absence of efficacious vaccines. Testing of HIV and malaria vaccines candidates start with early phase trials that are increasingly being conducted in developing countries where the burden of the diseases is high. Unique challenges, which affect planning and implementation of vaccine trials according to internationally accepted standards have thus been identified. In this review, we highlight specific challenges encountered during two early phase trials of novel HIV-1 and malaria vectored vaccine candidates conducted in The Gambia and how some of these issues were pragmatically addressed. We hope our experience will be useful for key study personnel involved in day-to-day running of similar clinical trials. It may also guide future design and implementation of vaccine trials in resource-constrained settings.

  7. [Contrast-enhanced Ultrasound in Diagnostic Imaging of Muscle Injuries: Perfusion Imaging in the Early Arterial Phase].

    PubMed

    Hotfiel, T; Carl, H D; Swoboda, B; Engelhardt, M; Heinrich, M; Strobel, D; Wildner, D

    2016-03-01

    Ultrasound is a standard procedure widely used in the diagnostic investigation of muscle injuries and widely described in the literature. Its advantages include rapid availability, cost effectiveness and the possibility to perform a real-time dynamic examination with the highest possible spatial resolution. In the diagnostic work-up of minor lesions (muscle stiffness, muscle strain), plain ultrasound has so far been inferior to MRI. The case presented by us is an example of the possibilities offered by contrast-enhanced ultrasound (CEUS) in the imaging of muscle injuries compared with plain B-mode image ultrasound and MRI imaging of the affected region. This case report is about a high-performance football player who sustained a muscle injury. He underwent an ultrasound examination (S 2000, 9L4 Probe, Siemens, Germany), which was performed simultaneously in the conventional and contrast-enhanced mode at the level of the lesion. An intravenous bolus injection of 4.8 ml of intravascular contrast agent (SonoVue(®), Bracco, Italy) was given via a cubital intravenous line. After that, the distribution of contrast agent was visualised in the early arterial phase. In addition, a plain magnetic resonance imaging scan of both thighs was performed for reference. On conventional ultrasound, the lesion was not clearly distinguishable from neighbouring tissue, whereas contrast-enhanced ultrasound demonstrated a well delineated, circumscribed area of impaired perfusion with hypoenhancement compared with the surrounding muscles at the clinical level of the lesion in the arterial wash-in phase (0-30 sec, after intravenous administration). The MRI scan revealed an edema signal with perifascial fluid accumulation in the corresponding site. The use of intravascular contrast agent enabled the sensitive detection of a minor injury by ultrasound for the first time. An intramuscular edema seen in the MRI scan showed a functional arterial perfusion impairment on ultrasound, which was

  8. HISPASAT launch and early operations phases: Computation and monitoring of geostationary satellite positioning

    NASA Technical Reports Server (NTRS)

    Brousse, Pascal; Desprairies, Arnaud

    1993-01-01

    Since 1974, CNES, the French National Space Agency, has been involved in the geostationary launch and early operations phases (LEOP) of moving satellites from a transfer orbit delivered by a launcher to a geostationary point. During the operations and their preparation, the Flight Dynamics Center (FDC), part of CNES LEOP facilities, is in charge of the space mechanics aspects. What is noteworthy about the Spanish HISPASAT satellite positioning is that all the operations were performed on the customer's premises, and consequently the FDC was duplicated in Madrid, Spain. The first part of this paper is the FDC presentation: its role, its hardware configuration, and its space dynamics ground control system called MERCATOR. The second part of this paper details the preparation used by the FDC for the HISPASAT mission: hardware and software installation in Madrid, integration with the other entities, and technical and operational qualifications. The third part gives results concerning flight dynamics aspects and operational activities.

  9. Rapamycin Ameliorates Inflammation and Fibrosis in the Early Phase of Cirrhotic Portal Hypertension in Rats through Inhibition of mTORC1 but Not mTORC2

    PubMed Central

    Wang, Weijie; Yan, Jiqi; Wang, Huakai; Shi, Minmin; Zhang, Mingjun; Yang, Weiping; Peng, Chenghong; Li, Hongwei

    2014-01-01

    Objective Hepatic stellate cells (HSCs) transdifferentiation and subsequent inflammation are important pathological processes involved in the formation of cirrhotic portal hypertension. This study characterizes the pathogenetic mechanisms leading to cholestatic liver fibrosis and portal hypertension, and focuses on mammalian target of rapamycin (mTOR) pathway as a potential modulator in the early phase of cirrhotic portal hypertension. Methods Early cirrhotic portal hypertension was induced by bile duct ligation (BDL) for three weeks. One week after operation, sham-operated (SHAM) and BDL rats received rapamycin (2 mg/kg/day) by intraperitoneal injection for fourteen days. Vehicle-treated SHAM and BDL rats served as controls. Fibrosis, inflammation, and portal pressure were evaluated by histology, morphometry, and hemodynamics. Expressions of pro-fibrogenic and pro-inflammatory genes in liver were measured by RT-PCR; alpha smooth muscle actin (α-SMA) and antigen Ki67 were detected by immunohistochemistry; expressions of AKT/mTOR signaling molecules, extracellular-signal-regulated kinase 1/2 (ERK1/2), p-ERK1/2, and interleukin-1 beta (IL-1β) were assessed by western blot. Results The AKT/mTOR signaling pathway was markedly activated in the early phase of cirrhotic portal hypertension induced by BDL in rats. mTOR blockade by rapamycin profoundly improved liver function by limiting inflammation, fibrosis and portal pressure. Rapamycin significantly inhibited the expressions of phosphorylated 70KD ribosomal protein S6 kinase (p-P70S6K) and phosphorylated ribosomal protein S6 (p-S6) but not p-AKT Ser473 relative to their total proteins in BDL-Ra rats. Those results suggested that mTOR Complex 1 (mTORC1) rather than mTORC2 was inhibited by rapamycin. Interestingly, we also found that the level of p-ERK1/2 to ERK1/2 was significantly increased in BDL rats, which was little affected by rapamycin. Conclusions The AKT/mTOR signaling pathway played an important role in the

  10. Topological crystalline magnets: Symmetry-protected topological phases of fermions

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

    Watanabe, Haruki; Fu, Liang

    Here, we introduce a novel class of interaction-enabled topological crystalline insulators in two- and three-dimensional electronic systems, which we call “topological crystalline magnet.” It is protected by the product of the time-reversal symmetry T and a mirror symmetry or a rotation symmetry R. A topological crystalline magnet exhibits two intriguing features: (i) it cannot be adiabatically connected to any Slater insulator and (ii) the edge state is robust against coupling electrons to the edge. These features are protected by the anomalous symmetry transformation property ( RT) 2 = -1 of the edge state. Finally, an anisotropic response to the externalmore » magnetic field can be an experimental signature.« less

  11. Topological crystalline magnets: Symmetry-protected topological phases of fermions

    DOE PAGES

    Watanabe, Haruki; Fu, Liang

    2017-02-27

    Here, we introduce a novel class of interaction-enabled topological crystalline insulators in two- and three-dimensional electronic systems, which we call “topological crystalline magnet.” It is protected by the product of the time-reversal symmetry T and a mirror symmetry or a rotation symmetry R. A topological crystalline magnet exhibits two intriguing features: (i) it cannot be adiabatically connected to any Slater insulator and (ii) the edge state is robust against coupling electrons to the edge. These features are protected by the anomalous symmetry transformation property ( RT) 2 = -1 of the edge state. Finally, an anisotropic response to the externalmore » magnetic field can be an experimental signature.« less

  12. Enriched classification of parafermionic gapped phases with time-reversal symmetry

    NASA Astrophysics Data System (ADS)

    Xu, Wen-Tao; Zhang, Guang-Ming

    2018-03-01

    Based on the recently established parafermionic matrix product states, we study the classification of one-dimensional gapped phases of parafermions with time-reversal (TR) symmetry satisfying T2=1 . Without extra symmetry, it has been found that Zp parafermionic gapped phases can be classified as topological phases, spontaneous symmetry breaking (SSB) phases, and a trivial phase, which are uniquely labeled by the divisors n of p . In the presence of TR symmetry, however, the enriched classification is characterized by three indices n , κ , and μ , where κ ∈Z2 denotes the linear or projective TR actions on the edges, and μ ∈Z2 indicates the commutation relations between the TR and (fractionalized) charge operator. For the Zr-symmetric parafermionic ground states, where r =p for trivial or topological phases, and r =p /n for SSB phases, each original gapped phase with odd r is divided into two phases, while each phase with even r is further separated into four phases. The gapped parafermionic phases with the TR symmetry include the symmetry protected topological phases, symmetry enriched topological phases, and the SSB coexisting symmetry protected topological phases. From analyzing the structures and symmetries of their reduced density matrices of these resulting topological phases, we can obtain the topologically protected degeneracies of their entanglement spectra.

  13. Ocular Protection from Laser Hazards. Phase 2

    DTIC Science & Technology

    1993-10-31

    including optics,electronics and surface protection. Physical vapor deposition ( PVD ) is the commonly used method to produce thin film coatings . Standard...control computer. In this part of the program, we intended to investigate various binary combinations of the following coating materials: SiC 2, Ta2O5 ...80 [ o Ta2O5 60 40 U 20 0 i I I Thickness [nm] 0 50 100 150 200 250 Figure 2. Dependence of the temperature in the coating chamber as a function of

  14. Failsafe automation of Phase II clinical trial interim monitoring for stopping rules.

    PubMed

    Day, Roger S

    2010-02-01

    In Phase II clinical trials in cancer, preventing the treatment of patients on a study when current data demonstrate that the treatment is insufficiently active or too toxic has obvious benefits, both in protecting patients and in reducing sponsor costs. Considerable efforts have gone into experimental designs for Phase II clinical trials with flexible sample size, usually implemented by early stopping rules. The intended benefits will not ensue, however, if the design is not followed. Despite the best intentions, failures can occur for many reasons. The main goal is to develop an automated system for interim monitoring, as a backup system supplementing the protocol team, to ensure that patients are protected. A secondary goal is to stimulate timely recording of patient assessments. We developed key concepts and performance needs, then designed, implemented, and deployed a software solution embedded in the clinical trials database system. The system has been in place since October 2007. One clinical trial tripped the automated monitor, resulting in e-mails that initiated statistician/investigator review in timely fashion. Several essential contributing activities still require human intervention, institutional policy decisions, and institutional commitment of resources. We believe that implementing the concepts presented here will provide greater assurance that interim monitoring plans are followed and that patients are protected from inadequate response or excessive toxicity. This approach may also facilitate wider acceptance and quicker implementation of new interim monitoring algorithms.

  15. Phase II Validation of a New Panel of Biomarkers for Early Detection of Ovarian Cancer — EDRN Public Portal

    Cancer.gov

    While all cancer patients could potentially benefit from earlier detection and prevention, the development of new screening technologies and chemoprevention for epithelial ovarian cancer (EOC) is unique in this regard. EOC is characterized by few early symptoms, presentation at an advanced stage, and poor survival. Presently there is no commercially available test that is diagnostic for either early or advanced stage epithelial ovarian cancer. The most commonly used marker, CA125, identifies a group of cell surface glycoproteins, which have uncertain biological behavior and very limited clinical utility for the detection of early stage disease. In recent years, several approaches have been used in order to develop a test for early detection, including the analysis of serum samples by SELDI-TOF and MALDI-TOF to find proteins or protein fragments of unknown identity that detect the presence/absence of cancer. Unfortunately, at the present time, none of these techniques have been shown to be adequate. Therefore, the development of a test that can detect early stages of the disease could dramatically improve treatment success and long-term survival. We have developed a new blood test based on a different approach: 1) we used known proteins related to cancer biology, 2) we characterized these proteins with several different screening steps using samples obtained from both healthy and cancer patient populations, and 3) validated the results with different techniques. Using split point analysis with four markers, 96 out of 100 EOC patients (96%) were correctly diagnosed with ovarian cancer (including 23 of 24 patients with Stage I/II EOC). In the healthy group, 6 out of 106 individuals were diagnosed incorrectly (5.6%). Working in collaboration with the Early Detection Network (EDRN/NCI/NIH), we performed Phase I discovery study confirming the potential application of this test for early detection of ovarian cancer (Preliminary results). The main objective of this pr

  16. [Advances in the pathophysiology and management of infections in the acute phase of stroke].

    PubMed

    Salat, David; Campos, Mireia; Montaner, Joan

    2012-12-15

    Infection in the acute phase of stroke has been identified as an independent predictor of poor outcome, both in the short and intermediate term. Various factors raising the risk of developing an infection (exposure to multiple pathogens, disruption of the protective function of the mucous membranes and a state of relative immunosuppression) coexist during the acute phase of stroke. Several risk factors have been identified for their development (especially increasing age and stroke severity). It has been proposed that infection contributes to a worse prognosis through different mechanisms, notably the development of an inflammatory response to brain tissue (with a potential to add secondary damage to that caused by the ischemic insult). Clinical trials evaluating the prophylactic and early administration of antibiotics to reduce the incidence of infection in the acute phase of stroke have yielded inconsistent results. Immunomodulating strategies, which may provide therapeutic alternatives in the future, are currently being evaluated. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  17. Topological Phase Transitions in Line-nodal Superconductors

    NASA Astrophysics Data System (ADS)

    Cho, Gil Young; Han, Sangeun; Moon, Eun-Gook

    Fathoming interplay between symmetry and topology of many-electron wave-functions deepens our understanding in quantum nature of many particle systems. Topology often protects zero-energy excitation, and in a certain class, symmetry is intrinsically tied to the topological protection. Namely, unless symmetry is broken, topological nature is intact. We study one specific case of such class, symmetry-protected line-nodal superconductors in three spatial dimensions (3d). Mismatch between phase spaces of order parameter fluctuation and line-nodal fermion excitation induces an exotic universality class in a drastic contrast to one of the conventional ϕ4 theory in 3d. Hyper-scaling violation and relativistic dynamic scaling with unusually large quantum critical region are main characteristics, and their implication in experiments is discussed. For example, continuous phase transition out of line-nodal superconductors has a linear phase boundary in a temperature-tuning parameter phase-diagram. This work was supported by the Brain Korea 21 PLUS Project of Korea Government and KAIST start-up funding.

  18. The Validation of Vapor Phase Hydrogen Peroxide Microbial Reduction for Planetary Protection and a Proposed Vacuum Process Specification

    NASA Technical Reports Server (NTRS)

    Chung, Shirley; Barengoltz, Jack; Kern, Roger; Koukol, Robert; Cash, Howard

    2006-01-01

    The Jet Propulsion Laboratory, in conjunction with the NASA Planetary Protection Officer, has selected the vapor phase hydrogen peroxide sterilization process for continued development as a NASA approved sterilization technique for spacecraft subsystems and systems. The goal is to include this technique, with an appropriate specification, in NPR 8020.12C as a low temperature complementary technique to the dry heat sterilization process.To meet microbial reduction requirements for all Mars in-situ life detection and sample return missions, various planetary spacecraft subsystems will have to be exposed to a qualified sterilization process. This process could be the elevated temperature dry heat sterilization process (115 C for 40 hours) which was used to sterilize the Viking lander spacecraft. However, with utilization of such elements as highly sophisticated electronics and sensors in modern spacecraft, this process presents significant materials challenges and is thus an undesirable bioburden reduction method to design engineers. The objective of this work is to introduce vapor hydrogen peroxide (VHP) as an alternative to dry heat microbial reduction to meet planetary protection requirements.The VHP process is widely used by the medical industry to sterilize surgical instruments and biomedical devices, but high doses of VHP may degrade the performance of flight hardware, or compromise material properties. Our goal for this study was to determine the minimum VHP process conditions to achieve microbial reduction levels acceptable for planetary protection.

  19. PROTECTIVE CLOTHING BASED ON PERMSELECTIVE MEMBRANE AND CARBON ADSORPTION

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

    J.G. Wijmans; J.O. Stull

    2001-11-07

    The goal of this project was to develop chemical protective clothing for use by DOE decontamination and decommissioning workers that is sufficiently water vapor permeable to keep the workers cool, thereby enhancing their productivity. This report describes the results of Phase II of a two-phase project to complete development of the novel permselective material and to test protective clothing made from the fabric. In Phase I a novel material incorporating a nonporous hydrophilic polyvinylacohol (PVA) layer, which is water vapor permeable but relatively impermeable to organic vapors, was developed. The results of the Phase I tests showed that the chemicalmore » resistance of the MTR material is comparable to that of Saranex/Tyvek materials, and that the comfort properties are closer to those of Tyvek (as measured in terms of CLO and permeability). Chemical resistance was measured using permeation tests against liquid dichloromethane. Comfort properties were ascertained by measuring the water vapor transmission of the material and by sweating manikin tests on whole protective suits. In addition, a cost/benefit analysis demonstrated that use of MTR's material technology could result in significant improvements in work productivity and cost savings if protective clothing items made from the new material were used more than once. In Phase II, MTR undertook a program to optimize the performance and production engineering for the new material technology. A partnership was formed with Kimberly-Clark Corporation to assist with a detailed evaluation of the MTR technology, and MTR used the services of Mr. Jeff Stull, President of the consulting firm International Personnel Protection, Inc., who conducted a detailed economic and application analysis for the developed fabric. The protective fabric manufacturing steps were simplified significantly, resulting in a 30% reduction in manufacturing costs and eliminating the necessity for capital investment in production equipment

  20. A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.

    PubMed

    Vormoor, B; Veal, G J; Griffin, M J; Boddy, A V; Irving, J; Minto, L; Case, M; Banerji, U; Swales, K E; Tall, J R; Moore, A S; Toguchi, M; Acton, G; Dyer, K; Schwab, C; Harrison, C J; Grainger, J D; Lancaster, D; Kearns, P; Hargrave, D; Vormoor, J

    2017-06-01

    Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies. © 2016 Wiley Periodicals, Inc.

  1. Premenstrual symptoms are associated with psychological and physical symptoms in early pregnancy.

    PubMed

    Winkel, Susanne; Einsle, Franziska; Wittchen, Hans-Ulrich; Martini, Julia

    2013-04-01

    The reproductive life of women is characterised by a number of distinct reproductive events and phases (e.g. premenstrual phase, peripartum, perimenopause). The hormonal transitions during these phases are often associated with both psychological and physical symptoms. Associations between these reproductive phases have been shown by numerous studies. However, the relationship between symptoms during the premenstrual phase and during early pregnancy has received little attention thus far, although early pregnancy is a time of dramatic hormonal as well as physical adaptation. Findings are based on a prospective longitudinal study with N = 306 pregnant women (MARI study). Three hundred five women that had menstrual bleeding in the year before pregnancy rated the severity of psychological and physical symptoms during premenstrual phases in the year preceding pregnancy. Besides this, they rated the severity of the same symptoms during early pregnancy (weeks 10 to 12 of gestation). The overall severity of premenstrual symptoms was significantly associated with the overall severity of early pregnancy symptoms (b = 0.4, 95% CI = 0.3-0.5; p < 0.001). The overall severity of early pregnancy symptoms was best predicted by the severity of premenstrual irritability. The best predictor for a particular symptom in early pregnancy mostly was the corresponding premenstrual symptom. The associations between premenstrual and early pregnancy symptoms support the reproductive hormone sensitivity hypothesis that some women are prone to repeatedly experience specific psychological and physical symptoms during different reproductive phases. The findings further imply that the nature of symptoms might be rather consistent between different reproductive phases.

  2. The Diagnostic Usefulness of Serum Total Bile Acid Concentrations in the Early Phase of Acute Pancreatitis of Varied Etiologies

    PubMed Central

    Maleszka, Aleksandra; Dumnicka, Paulina; Matuszyk, Aleksandra; Pędziwiatr, Michał; Mazur-Laskowska, Małgorzata; Sporek, Mateusz; Ceranowicz, Piotr; Olszanecki, Rafał; Kuźniewski, Marek; Kuśnierz-Cabala, Beata

    2017-01-01

    The most common causes of acute pancreatitis (AP) are biliary tract diseases with cholestasis and alcohol consumption. In 10%–15% of patients, etiology determination is difficult. Identification of the etiology allows for the implementation of adequate treatment. The aim of this study was to assess the utility of the serum concentrations of total bile acids (TBA) to diagnose AP etiology in the early phase of the disease. We included 66 patients with AP, admitted within the first 24 h from the onset of symptoms. TBA were measured in serum at 24, 48, and 72 h from the onset of AP, using an automated fifth generation assay. The bilirubin-to-TBA ratio (B/TBA) was calculated. TBA was highest on the first day of AP and decreased subsequently. In patients with biliary etiology, serum TBA was significantly higher compared to those with alcoholic and other etiologies. B/TBA was significantly higher in patients with alcoholic etiology. At admission, the cut-off values of 4.7 µmol/L for TBA and 4.22 for the B/TBA ratio allowed for a differentiation between biliary and other etiologies of AP with a diagnostic accuracy of 85 and 83%. Both TBA and B/TBA may help in the diagnosis of AP etiology in the early phase of AP. PMID:28067818

  3. Early protection of puppies against canine parvovirus: a comparison of two vaccines.

    PubMed

    McCaw, D L; Tate, D; Dubovi, E J; Johnson, J C

    1997-01-01

    Client-owned puppies randomly were assigned to receive one of two commercially available polyvalent vaccines. The response to the parvovirus portion of each vaccine was evaluated by determining antibody titers by hemagglutination inhibition. Significant differences were found between titers produced by the vaccines. Puppies vaccinated with one of the products had a more desirable result as demonstrated by a protective antibody titer after the first vaccination (p of 0.005), a protective antibody titer at a younger age (p of 0.02), a protective antibody titer by 12 weeks of age (p of 0.001), and a protective antibody titer by 16 weeks of age (p of 0.05). Puppies vaccinated with this product also had significantly higher titers at each sampling after vaccination.

  4. Free Trehalose Accumulation in Dormant Mycobacterium smegmatis Cells and Its Breakdown in Early Resuscitation Phase

    PubMed Central

    Shleeva, Margarita O.; Trutneva, Kseniya A.; Demina, Galina R.; Zinin, Alexander I.; Sorokoumova, Galina M.; Laptinskaya, Polina K.; Shumkova, Ekaterina S.; Kaprelyants, Arseny S.

    2017-01-01

    Under gradual acidification of growth medium resulting in the formation of dormant Mycobacterium smegmatis, a significant accumulation of free trehalose in dormant cells was observed. According to 1H- and 13C-NMR spectroscopy up to 64% of total organic substances in the dormant cell extract was represented by trehalose whilst the trehalose content in an extract of active cells taken from early stationary phase was not more than 15%. Trehalose biosynthesis during transition to the dormant state is provided by activation of genes involved in the OtsA-OtsB and TreY-TreZ pathways (according to RT-PCR). Varying the concentration of free trehalose in dormant cells by expression of MSMEG_4535 coding for trehalase we found that cell viability depends on trehalose level: cells with a high amount of trehalose survive much better than cells with a low amount. Upon resuscitation of dormant M. smegmatis, a decrease of free trehalose and an increase in glucose concentration occurred in the early period of resuscitation (after 2 h). Evidently, breakdown of trehalose by trehalase takes place at this time as a transient increase in trehalase activity was observed between 1 and 3 h of resuscitation. Activation of trehalase was not due to de novo biosynthesis but because of self-activation of the enzyme from the inactive state in dormant cells. Because, even a low concentration of ATP (2 mM) prevents self-activation of trehalase in vitro and after activation the enzyme is still sensitive to ATP we suggest that the transient character of trehalase activation in cells is due to variation in intracellular ATP concentration found in the early resuscitation period. The negative influence of the trehalase inhibitor validamycin A on the resuscitation of dormant cells proves the importance of trehalase for resuscitation. These experiments demonstrate the significance of free trehalose accumulation for the maintenance of dormant mycobacterial viability and the involvement of trehalose

  5. 29 CFR 553.225 - Early relief.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 3 2013-07-01 2013-07-01 false Early relief. 553.225 Section 553.225 Labor Regulations... FAIR LABOR STANDARDS ACT TO EMPLOYEES OF STATE AND LOCAL GOVERNMENTS Fire Protection and Law Enforcement Employees of Public Agencies Tour of Duty and Compensable Hours of Work Rules § 553.225 Early...

  6. 29 CFR 553.225 - Early relief.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Early relief. 553.225 Section 553.225 Labor Regulations... FAIR LABOR STANDARDS ACT TO EMPLOYEES OF STATE AND LOCAL GOVERNMENTS Fire Protection and Law Enforcement Employees of Public Agencies Tour of Duty and Compensable Hours of Work Rules § 553.225 Early...

  7. 29 CFR 553.225 - Early relief.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Early relief. 553.225 Section 553.225 Labor Regulations... FAIR LABOR STANDARDS ACT TO EMPLOYEES OF STATE AND LOCAL GOVERNMENTS Fire Protection and Law Enforcement Employees of Public Agencies Tour of Duty and Compensable Hours of Work Rules § 553.225 Early...

  8. Overdischarge protection in high-temperature cells and batteries

    DOEpatents

    Redey, Laszlo

    1990-01-01

    Overdischarge indication and protection is provided in a lithium alloy - metal sulfide, secondary electrochemical cell and batteries of such cells through use of a low lithium activity phase that ordinarily is not matched with positive electrode material. Low lithium activity phases such as Li.sub.0.1 Al.sub.0.9 and LiAlSi in correspondence with positive electrode material cause a downward gradient in cell voltage as an indication of overdischarge prior to damage to the cell. Moreover, the low lithium activity phase contributes lithium into the electrolyte and provides a lithium shuttling current as overdischarge protection after all of the positive electrode material is discharged.

  9. Overdischarge protection in high-temperature cells and batteries

    DOEpatents

    Redey, L.

    1990-06-19

    Overdischarge indication and protection is provided in a lithium alloy metal sulfide, secondary electrochemical cell and batteries of such cells through use of a low lithium activity phase that ordinarily is not matched with positive electrode material. Low lithium activity phases such as Li[sub 0.1]Al[sub 0.9] and LiAlSi in correspondence with positive electrode material cause a downward gradient in cell voltage as an indication of overdischarge prior to damage to the cell. Moreover, the low lithium activity phase contributes lithium into the electrolyte and provides a lithium shuttling current as overdischarge protection after all of the positive electrode material is discharged. 8 figs.

  10. A phase II trial for the efficacy of physiotherapy intervention for early-onset hip osteoarthritis: study protocol for a randomised controlled trial.

    PubMed

    Kemp, Joanne L; Moore, Kate; Fransen, Marlene; Russell, Trevor G; Crossley, Kay M

    2015-01-27

    Early-onset hip osteoarthritis is commonly seen in people undergoing hip arthroscopy and is associated with increased pain, reduced ability to participate in physical activity, reduced quality of life and reduced range of motion and muscle strength. Despite this, the efficacy of non-surgical interventions such as exercise therapies remains unknown. The primary aim is to establish the feasibility of a phase III randomised controlled trial investigating a targeted physiotherapy intervention for people with early-onset hip osteoarthritis. The secondary aims are to determine the size of treatment effects of a physiotherapy intervention, targeted to improve hip joint range and hip-related symptoms in early-onset hip osteoarthritis following hip arthroscopy, compared to a health-education control. This protocol describes a randomised, assessor- and participant-blind, controlled clinical trial. We will include 20 participants who are (i) aged between 18 and 50 years; (ii) have undergone hip arthroscopy during the past six to 12 months; (iii) have early-onset hip osteoarthritis (defined as chondrolabral pathology) at the time of hip arthroscopy; and (iv) experience hip-related pain during activities. Primary outcome will be the feasibility of a phase III clinical trial. Secondary outcomes will be (i) perceived global change score; (ii) hip-related symptoms (measured using the Hip disability and Osteoarthritis Outcome Score (HOOS) pain subscale, activity subscale, and sport and recreation subscale); (iii) hip quality of life (measured using the HOOS quality of life subscale and International Hip Outcome tool; (iv) hip muscle strength and (v) hip range of motion. The physiotherapy intervention is semi-standardised, including joint and soft tissue mobilisation and stretching, hip and trunk muscle retraining and functional and activity-specific retraining and education. The control intervention encompasses individualised health education, with the same frequency and duration

  11. Proline accumulation protects Saccharomyces cerevisiae cells in stationary phase from ethanol stress by reducing reactive oxygen species levels.

    PubMed

    Takagi, Hiroshi; Taguchi, Junpei; Kaino, Tomohiro

    2016-08-01

    During fermentation processes, Saccharomyces cerevisiae cells are exposed to multiple stresses, including a high concentration of ethanol that represents toxicity through intracellular reactive oxygen species (ROS) generation. We previously reported that proline protected yeast cells from damage caused by various stresses, such as freezing and ethanol. As an anti-oxidant, proline is suggested to scavenge intracellular ROS. In this study, we examined the role of intracellular proline during ethanol treatment in S. cerevisiae strains that accumulate different concentrations of proline. When cultured in YPD medium, there was a significant accumulation of proline in the put1 mutant strain, which is deficient in proline oxidase, in the stationary phase. Expression of the mutant PRO1 gene, which encodes the γ-glutamyl kinase variant (Asp154Asn or Ile150Thr) with desensitization to feedback inhibition by proline in the put1 mutant strain, showed a prominent increase in proline content as compared with that of the wild-type strain. The oxidation level was clearly increased in wild-type cells after exposure to ethanol, indicating that the generation of ROS occurred. Interestingly, proline accumulation significantly reduces the ROS level and increases the survival rate of yeast cells in the stationary phase under ethanol stress conditions. However, there was not a clear correlation between proline content and survival rate in yeast cells. An appropriate level of intracellular proline in yeast might be important for its stress-protective effect. Hence, the engineering of proline metabolism could be promising for breeding stress-tolerant industrial yeast strains. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Intravitreal injection of exendin-4 analogue protects retinal cells in early diabetic rats.

    PubMed

    Zhang, Yu; Zhang, Jingfa; Wang, Qingping; Lei, Xia; Chu, Qing; Xu, Guo-Tong; Ye, Wen

    2011-01-05

    To evaluate the protective effect of intravitreal injection of exendin-4 analogue (E4a) in early diabetic retinopathy (DR) and to explore its possible mechanism. Forty Sprague-Dawley rats were divided into three groups: normal (N), diabetic (D), and E4a-treated diabetic rats (E4a). Diabetes was induced by streptozotocin. Rats in the E4a group were treated with E4a (0.1 μg/2μL/eye), whereas the N and D groups were treated with the equivalent volume of normal saline. Electroretinography was performed at 1 month and 3 months after diabetes onset. Thicknesses and cell counts in each layer of the retina were evaluated. The concentration of glutamate was measured by high-performance liquid chromatography (HPLC). Expressions of glucagon-like peptide-1 receptor (GLP-1R) and GLAST (excitatory amino acid transporter) were detected at mRNA and protein levels and verified by immunohistochemistry in vitro and in vivo. The rMc-1 cells were cultured under high-glucose medium (25 mM), which mimicked diabetic conditions. Effects of E4a (10 μg/mL) were also tested in the rMc-1 culture system. E4a prevented the reduction in b-wave amplitude and oscillatory potential amplitude caused by diabetes. It also prevented the cell loss of outer nuclear layer and inner nuclear layer; the thickness and cell count in the outer nuclear layer were decreased in 1-month diabetic rats. The concentration of glutamate in the retina was higher in diabetic rats and was significantly reduced in the E4a-treated group. Consistent with such changes, retinal GLP-1R and GLAST expression were reduced in the diabetic retina but upregulated in E4a-treated rats. No improvement was found in the retina in both functional and morphologic parameters 3 months after treatment. Intravitreal administration of E4a can prevent the retina, functionally and morphologically, from the insults of diabetes in rats. GLP-1R and GLAST were proved to exist in the rat retina, and their lowered expressions in the diabetic retina

  13. Gauging Spatial Symmetries and the Classification of Topological Crystalline Phases

    NASA Astrophysics Data System (ADS)

    Thorngren, Ryan; Else, Dominic V.

    2018-01-01

    We put the theory of interacting topological crystalline phases on a systematic footing. These are topological phases protected by space-group symmetries. Our central tool is an elucidation of what it means to "gauge" such symmetries. We introduce the notion of a crystalline topological liquid and argue that most (and perhaps all) phases of interest are likely to satisfy this criterion. We prove a crystalline equivalence principle, which states that in Euclidean space, crystalline topological liquids with symmetry group G are in one-to-one correspondence with topological phases protected by the same symmetry G , but acting internally, where if an element of G is orientation reversing, it is realized as an antiunitary symmetry in the internal symmetry group. As an example, we explicitly compute, using group cohomology, a partial classification of bosonic symmetry-protected topological phases protected by crystalline symmetries in (3 +1 ) dimensions for 227 of the 230 space groups. For the 65 space groups not containing orientation-reversing elements (Sohncke groups), there are no cobordism invariants that may contribute phases beyond group cohomology, so we conjecture that our classification is complete.

  14. Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations.

    PubMed

    Marchandeau, Stéphane; Pontier, Dominique; Guitton, Jean-Sébastien; Letty, Jérôme; Fouchet, David; Aubineau, Jacky; Berger, Francis; Léonard, Yves; Roobrouck, Alain; Gelfi, Jacqueline; Peralta, Brigitte; Bertagnoli, Stéphane

    2014-03-04

    The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen.

  15. Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations

    PubMed Central

    2014-01-01

    The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen. PMID:24589193

  16. MER surface fault protection system

    NASA Technical Reports Server (NTRS)

    Neilson, Tracy

    2005-01-01

    The Mars Exploration Rovers surface fault protection design was influenced by the fact that the solar-powered rovers must recharge their batteries during the day to survive the night. the rovers needed to autonomously maintain thermal stability, initiate safe and reliable communication with orbiting assets or directly to Earth, while maintaining energy balance. This paper will describe the system fault protection design for the surface phase of the mission.

  17. Safety and effectiveness of stem cell therapies in early-phase clinical trials in stroke: a systematic review and meta-analysis.

    PubMed

    Nagpal, Anjali; Choy, Fong Chan; Howell, Stuart; Hillier, Susan; Chan, Fiona; Hamilton-Bruce, Monica A; Koblar, Simon A

    2017-08-30

    Stem cells have demonstrated encouraging potential as reparative therapy for patients suffering from post-stroke disability. Reperfusion interventions in the acute phase of stroke have shown significant benefit but are limited by a narrow window of opportunity in which they are beneficial. Thereafter, rehabilitation is the only intervention available. The current review summarises the current evidence for use of stem cell therapies in stroke from early-phase clinical trials. The safety and feasibility of administering different types of stem cell therapies in stroke seem to be reasonably proven. However, the effectiveness needs still to be established through bigger clinical trials with more pragmatic clinical trial designs that address the challenges raised by the heterogeneous nature of stroke per se, as well those due to unique characteristics of stem cells as therapeutic agents.

  18. Achievements in Stratospheric Ozone Protection

    EPA Pesticide Factsheets

    This report describes achievements in protecting the ozone layer, the benefits of these achievements, and strategies involved (e.g., using alternatives to ozone-depleting substances, phasing out harmful substances, and creating partnerships).

  19. Article having an improved platinum-aluminum-hafnium protective coating

    NASA Technical Reports Server (NTRS)

    Nagaraj, Bangalore Aswatha (Inventor); Williams, Jeffrey Lawrence (Inventor)

    2005-01-01

    An article protected by a protective coating has a substrate and a protective coating having an outer layer deposited upon the substrate surface and a diffusion zone formed by interdiffusion of the outer layer and the substrate. The protective coating includes platinum, aluminum, no more than about 2 weight percent hafnium, and substantially no silicon. The outer layer is substantially a single phase.

  20. Transcription factor Nrf2 hyperactivation in early-phase renal ischemia-reperfusion injury prevents tubular damage progression.

    PubMed

    Nezu, Masahiro; Souma, Tomokazu; Yu, Lei; Suzuki, Takafumi; Saigusa, Daisuke; Ito, Sadayoshi; Suzuki, Norio; Yamamoto, Masayuki

    2017-02-01

    Acute kidney injury is a devastating disease with high morbidity in hospitalized patients and contributes to the pathogenesis of chronic kidney disease. An underlying mechanism of acute kidney injury involves ischemia-reperfusion injury which, in turn, induces oxidative stress and provokes organ damage. Nrf2 is a master transcription factor that regulates the cellular response to oxidative stress. Here, we examined the role of Nrf2 in the progression of ischemia-reperfusion injury-induced kidney damage in mice using genetic and pharmacological approaches. Both global and tubular-specific Nrf2 activation enhanced gene expression of antioxidant and NADPH synthesis enzymes, including glucose-6-phosphate dehydrogenase, and ameliorated both the initiation of injury in the outer medulla and the progression of tubular damage in the cortex. Myeloid-specific Nrf2 activation was ineffective. Short-term administration of the Nrf2 inducer CDDO during the initial phase of injury ameliorated the late phase of tubular damage. This inducer effectively protected the human proximal tubular cell line HK-2 from oxidative stress-mediated cell death while glucose-6-phosphate dehydrogenase knockdown increased intracellular reactive oxygen species. These findings demonstrate that tubular hyperactivation of Nrf2 in the initial phase of injury prevents the progression of reactive oxygen species-mediated tubular damage by inducing antioxidant enzymes and NADPH synthesis. Thus, Nrf2 may be a promising therapeutic target for preventing acute kidney injury to chronic kidney disease transition. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  1. A phased approach to clinical testing: criteria for progressing from Phase I to Phase II to Phase III studies.

    PubMed

    André, F E; Foulkes, M A

    1998-01-01

    The overall intent of clinical testing is to establish, in a series of phased studies, the clinical tolerance and acceptable "safety" of the candidate vaccine, as well as the type, level and persistence of the immune response after its inoculation, to a representative target population, according to a convenient administration schedule. The final stages involve the direct or indirect demonstration of protective efficacy, if possible in the population(s) for which the vaccine is intended. In addition, consistency of production must be demonstrated. At all these stages, the amount of prior information from preclinical and other studies affects and informs the objectives and design of subsequent studies. Progression from one testing phase to the next is dependent upon attaining the pre-set objectives of each series of studies. The precise objectives to be met will be decided on a case-by-case basis. The earliest assessments in humans (Phase I) involve evaluation of short-term clinical tolerance as measured by local and general reactogenicity, and gross assessments of immunogenicity, in a small number of highly selected individuals in an idealised situation. The selection of "optimal" dose and schedule are the result of further dose-ranging investigations (Phase II), involving more volunteers, with longer, more detailed follow-up assessments. It is at this stage that the accumulated evidence on its immunogenicity profile should be sufficient to assess whether or not the vaccine is worthy of further development. The next level of investigation (Phase III) aims to measure with greater precision the vaccine protective efficacy in the intended target population(s) by comparison of infection and/or disease attack rates in vaccine and placebo recipients. In consistency studies different production lots, manufactured at commercial scale, are tested to demonstrate consistency of manufacture. Additional bridging studies to establish similarity of lots at different production

  2. Curcumin's Neuroprotective Efficacy in Drosophila Model of Idiopathic Parkinson's Disease Is Phase Specific: Implication of its Therapeutic Effectiveness

    PubMed Central

    Phom, Limamanen; Achumi, Bovito; Alone, Debasmita P.; Muralidhara

    2014-01-01

    Abstract Selective degeneration of dopaminergic neurons in the substantia nigra underlies the basic motor impairments of Parkinson's disease (PD). Curcumin has been used for centuries in traditional medicines in India. Our aim is to understand the efficacy of genotropic drug curcumin as a neuroprotective agent in PD. Analysis of different developmental stages in model organisms revealed that they are characterized by different patterns of gene expression which is similar to that of developmental stages of human. Genotropic drugs would be effective only during those life cycle stages for which their target molecules are available. Hence there exists a possibility that targets of genotropic compounds such as curcumin may not be present in all life stages. However, no reports are available in PD models illustrating the efficacy of curcumin in later phases of adult life. This is important because this is the period during which late-onset disorders such as idiopathic PD set in. To understand this paradigm, we tested the protective efficacy of curcumin in different growth stages (early, late health stage, and transition phase) in adult Drosophila flies. Results showed that it can rescue the motor defects during early stages of life but is ineffective at later phases. This observation was substantiated with the finding that curcumin treatment could replenish depleted brain dopamine levels in the PD model only during early stages of life cycle, clearly suggesting its limitation as a therapeutic agent in late-onset neurodegenerative disorders such as PD. PMID:25238331

  3. Unimpaired endogenous pain inhibition in the early phase of complex regional pain syndrome.

    PubMed

    Kumowski, N; Hegelmaier, T; Kolbenschlag, J; Maier, C; Mainka, T; Vollert, J; Enax-Krumova, E

    2017-05-01

    The complex regional pain syndrome (CRPS) is characterized by distal generalisation of pain beyond the initial trauma. This might be the result of impaired endogenous pain inhibition. We compared Conditioned Pain Modulation (CPM) between patients with CRPS (n = 24; pain: 4.5 ± 2.2, NRS 0-10; disease duration <1 year), neuralgia (n = 17; pain: 5.5 ± 1.1) and healthy subjects (n = 23) and its correlation with loss and gain of function as assessed by Quantitative Sensory Testing (QST). CPM was assessed with heat as test stimulus (TS) and cold water as conditioning stimulus (CS). The early CPM-effect was calculated as difference between heat pain during and before conditioning, the late CPM-effect, 5 minutes after and before conditioning, respectively. Heat pain decreased comparably after CS in all groups, resulting in a significant CPM-effect (healthy: -12.5 ± 12.4, NRS 0-100; CRPS: -14.7 ± 15.7; neuralgia: -7.9 ± 9.8; p < 0.001). When compared to healthy subjects, heat pain declined significantly steeper in CRPS patients (healthy: -2.0 ± 5.5, NRS 0-100/10 s; CRPS: -6.3 ± 8.1; p < 0.05). Only CRPS patients demonstrated a late CPM effect (-6.0 ± 9.0, p < 0.005). Neither spontaneous pain nor any QST parameter correlated with CPM, with the exception of a decreased cold pain threshold, which correlated with an enhanced CPM in CRPS patients only (r = -0.456, p < 0.05). An impairment of endogenous pain inhibition does not explain the extent of pain in the early stage of CRPS or in neuralgia. The unexpectedly high CPM in CRPS patients might result from activation of the intact descending pathways in response to central sensitization, as cold hyperalgesia correlated with the CPM-effect. Conditioned pain modulation (CPM) is not impaired in the early phase of complex regional pain syndrome (CRPS) and neuralgia. Only in CRPS higher CPM was associated with lower cold pain thresholds. © 2017 European Pain Federation - EFIC®.

  4. Early Childhood Risk and Protective Factors for Substance Use during Early Adolescence: Gender Differences.

    ERIC Educational Resources Information Center

    Friedman, Alfred S.; And Others

    1995-01-01

    Gathered substance use histories from African American male (n=318) and female (n=322) adolescents to determine whether gender differences affected early life risk factors for drug use or abuse. Family variables and subject behavior predicted degree of substance use and frequency of intoxication, but no risk factor applied to both genders. (SNR)

  5. Phase distribution of spliceosomal introns: implications for intron origin

    PubMed Central

    Nguyen, Hung D; Yoshihama, Maki; Kenmochi, Naoya

    2006-01-01

    Background The origin of spliceosomal introns is the central subject of the introns-early versus introns-late debate. The distribution of intron phases is non-uniform, with an excess of phase-0 introns. Introns-early explains this by speculating that a fraction of present-day introns were present between minigenes in the progenote and therefore must lie in phase-0. In contrast, introns-late predicts that the nonuniformity of intron phase distribution reflects the nonrandomness of intron insertions. Results In this paper, we tested the two theories using analyses of intron phase distribution. We inferred the evolution of intron phase distribution from a dataset of 684 gene orthologs from seven eukaryotes using a maximum likelihood method. We also tested whether the observed intron phase distributions from 10 eukaryotes can be explained by intron insertions on a genome-wide scale. In contrast to the prediction of introns-early, the inferred evolution of intron phase distribution showed that the proportion of phase-0 introns increased over evolution. Consistent with introns-late, the observed intron phase distributions matched those predicted by an intron insertion model quite well. Conclusion Our results strongly support the introns-late hypothesis of the origin of spliceosomal introns. PMID:16959043

  6. Beam-induced pressure gradients in the early phase of proton-heated solar flares

    NASA Technical Reports Server (NTRS)

    Tamres, David H.; Canfield, Richard C.; Mcclymont, A. N.

    1986-01-01

    The pressure gradient induced in a coronal loop by proton beam momentum deposition is calculated and compared with the thermal pressure gradient arising from nonuniform deposition of beam energy; it is assumed that the transfer of momentum and energy from beam to target occurs via the Coulomb interaciton. Results are presented for both a low mean energy and a high mean energy proton beam injected at the loop apex and characterized by a power-law energy spectrum. The present treatment takes account of the breakdown of the cold target approximation for the low-energy proton beam in the corona, where the thermal speed of target electrons exceeds the beam speed. It is found that proton beam momentum deposition plays a potentially significant role in flare dynamics only in the low mean energy case and only in the corona, where it may dominate the acceleration of target material for as long as several tens of seconds. This conclusion suggest that the presence of low-energy nonthermal protons may be inferred from velocity-sensitive coronal observations in the early impulsive phase.

  7. Protective Role of Intracellular Melatonin Against Oxidative Stress and UV Radiation in Saccharomyces cerevisiae.

    PubMed

    Bisquert, Ricardo; Muñiz-Calvo, Sara; Guillamón, José M

    2018-01-01

    Melatonin (Mel) is considered a potent natural antioxidant molecule given its free-radical scavenging ability. Its origin is traced back to the origin of aerobic life as early defense against oxidative stress and radiation. More complex signaling functions have been attributed to Mel as a result of evolution in different biological kingdoms, which comprise gene expression modulation, enzyme activity, and mitochondrial homeostasis regulation processes, among others. Since Mel production has been recently reported in wine yeast, we tested the protective effect of Mel on Saccharomyces cerevisiae against oxidative stress and UV light. As the optimal conditions for S. cerevisiae to synthesize Mel are still unknown, we developed an intracellular Mel-charging method to test its effect against stresses. To assess Mel's ability to protect S. cerevisiae from both stresses, we ran growth tests in liquid media and viability assays by colony count after Mel treatment, followed by stress. We also analyzed gene expression by qPCR on a selection of genes involved in stress protection in response to Mel treatment under oxidative stress and UV radiation. The viability in the Mel-treated cells after H 2 O 2 stress was up to 35% greater than for the untreated controls, while stress amelioration reached 40% for UVC light (254 nm). Mel-treated cells showed a significant shortened lag phase compared to the control cells under the stress and normal growth conditions. The gene expression analysis showed that Mel significantly modulated gene expression in the unstressed cells in the exponential growth phase, and also during various stress treatments.

  8. Optimization of Primary Drying in Lyophilization during Early Phase Drug Development using a Definitive Screening Design with Formulation and Process Factors.

    PubMed

    Goldman, Johnathan M; More, Haresh T; Yee, Olga; Borgeson, Elizabeth; Remy, Brenda; Rowe, Jasmine; Sadineni, Vikram

    2018-06-08

    Development of optimal drug product lyophilization cycles is typically accomplished via multiple engineering runs to determine appropriate process parameters. These runs require significant time and product investments, which are especially costly during early phase development when the drug product formulation and lyophilization process are often defined simultaneously. Even small changes in the formulation may require a new set of engineering runs to define lyophilization process parameters. In order to overcome these development difficulties, an eight factor definitive screening design (DSD), including both formulation and process parameters, was executed on a fully human monoclonal antibody (mAb) drug product. The DSD enables evaluation of several interdependent factors to define critical parameters that affect primary drying time and product temperature. From these parameters, a lyophilization development model is defined where near optimal process parameters can be derived for many different drug product formulations. This concept is demonstrated on a mAb drug product where statistically predicted cycle responses agree well with those measured experimentally. This design of experiments (DoE) approach for early phase lyophilization cycle development offers a workflow that significantly decreases the development time of clinically and potentially commercially viable lyophilization cycles for a platform formulation that still has variable range of compositions. Copyright © 2018. Published by Elsevier Inc.

  9. Overview of Early Transfer Guidance

    EPA Pesticide Factsheets

    To implement Congressionally mandated action, the U.S. Environmental Protection Agency (EPA) has issued guidance on the transfer of federal property contaminated with hazardous wastes, before cleanup completion. This eplains the early transfer process

  10. Planetary protection principles used for Phobos-Grunt mission

    NASA Astrophysics Data System (ADS)

    Martynov, M. B.; Alexashkin, S. N.; Khamidullina, N. M.; Orlov, O. I.; Novikova, N. D.; Deshevaya, E. A.; Trofimov, V. I.

    2011-12-01

    The article presents an analysis of the Phobos-Grunt mission, a classification of its phases in terms of planetary protection, and the main principles of activities management and definition of actions for fulfilling the planetary-protection requirements developed by Committee on Space Research.

  11. An attenuated quadruple gene mutant of Mycobacterium tuberculosis imparts protection against tuberculosis in guinea pigs

    PubMed Central

    Chauhan, Priyanka

    2018-01-01

    ABSTRACT Previously we had developed a triple gene mutant of Mycobacterium tuberculosis (MtbΔmms) harboring disruption in three genes, namely mptpA, mptpB and sapM. Though vaccination with MtbΔmms strain induced protection in the lungs of guinea pigs, the mutant strain failed to control the hematogenous spread of the challenge strain to the spleen. Additionally, inoculation with MtbΔmms resulted in some pathological damage to the spleens in the early phase of infection. In order to generate a strain that overcomes the pathology caused by MtbΔmms in spleen of guinea pigs and controls dissemination of the challenge strain, MtbΔmms was genetically modified by disrupting bioA gene to generate MtbΔmmsb strain. Further, in vivo attenuation of MtbΔmmsb was evaluated and its protective efficacy was assessed against virulent M. tuberculosis challenge in guinea pigs. MtbΔmmsb mutant strain was highly attenuated for growth and virulence in guinea pigs. Vaccination with MtbΔmmsb mutant generated significant protection in comparison to sham-immunized animals at 4 and 12 weeks post-infection in lungs and spleen of infected animals. However, the protection imparted by MtbΔmmsb was significantly less in comparison to BCG immunized animals. This study indicates the importance of attenuated multiple gene deletion mutants of M. tuberculosis for generating protection against tuberculosis. PMID:29242198

  12. Alpha phase precipitation from phase-separated beta phase in a model Ti-Mo-Al alloy studied by direct coupling of transmission electron microscopy and atom probe tomography

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

    Devaraj, Arun; Nag, Soumya; Banerjee, Rajarshi

    2013-10-19

    The benefit of direct coupling of APT with TEM dark field imaging to investigate early stages of phase transformation in multicomponent alloys is demonstrated by analyzing alpha phase precipitated in a model Ti-10 at% Mo-10 at% Al alloy during annealing at 400oC. Through such a direct coupling approach a thermodynamically unexpected solute partitioning trend between beta matrix and alpha precipitate is observed in the early stages of precipitation, which is explained based on possible nucleation of alpha phase in the Ti rich (Mo and Al depleted regions) created as a result of phase separation in beta matrix. On further highermore » temperature annealing at 600oC for 1 hour, the alpha precipitates were shown to grow and get enriched in Al and further depleted in Mo reaching the thermodynamic equilibrium.« less

  13. Career Planning and Development for Early-Career Scientists

    EPA Science Inventory

    Early career development can be looked at as being of two major phases. The first phase is the formal educational process leading to an awarded degree, postdoctoral training, and potentially formal certification in a scientific discipline. The second phase is the informal educa...

  14. Serum Uromodulin Levels in Prediction of Acute Kidney Injury in the Early Phase of Acute Pancreatitis.

    PubMed

    Kuśnierz-Cabala, Beata; Gala-Błądzińska, Agnieszka; Mazur-Laskowska, Małgorzata; Dumnicka, Paulina; Sporek, Mateusz; Matuszyk, Aleksandra; Gil, Krzysztof; Ceranowicz, Piotr; Walocha, Jerzy; Kucharz, Jakub; Pędziwiatr, Michał; Bartuś, Krzysztof; Trąbka, Rafał; Kuźniewski, Marek

    2017-06-14

    In health, uromodulin is the main protein of urine. Serum uromodulin concentrations (sUMOD) have been shown to correlate with kidney function. Acute kidney injury (AKI) is among the main complications of severe acute pancreatitis (AP). No reports exist on sUMOD in patients with AP, including the diagnostic usefulness for early prediction of AP severity. We measured sUMOD during first 72 h of AP. Sixty-six adult patients with AP were recruited at the surgical ward of the District Hospital in Sucha Beskidzka, Poland. AP was diagnosed according to the Revised Atlanta Classification. Blood samples were collected at 24, 48 and 72 h of AP, and sUMOD concentrations were measured with enzyme-linked immunosorbent test. sUMOD decreased non-significantly during the study. Patients with severe AP had non-significantly lower sUMOD concentrations than those with mild disease. Significant positive correlation was observed between sUMOD and estimated glomerular filtration rate on each day of the study and negative correlations were shown between sUMOD and age, serum creatinine, cystatin C and urea. Patients with AKI tended to have lower sUMOD. Although sUMOD correlated significantly with kidney function in the early phase of AP, measuring sUMOD did not allow to reliably predict AP severity or development of AKI.

  15. Consumer Protection for Educators.

    ERIC Educational Resources Information Center

    Wallace, James M.

    Educational changes are examined from the perspective of consumer protection--the direct consumers are the teachers being prepared; the indirect consumers are the students and the society that supports the schools. During the colonial and early national periods of American history, there was an absence of formal and separate teacher education.…

  16. Early Childhood Trauma

    ERIC Educational Resources Information Center

    National Child Traumatic Stress Network, 2010

    2010-01-01

    Early childhood trauma generally refers to the traumatic experiences that occur to children aged 0-6. Because infants' and young children's reactions may be different from older children's, and because they may not be able to verbalize their reactions to threatening or dangerous events, many people assume that young age protects children from the…

  17. Efficient natural defense mechanisms against Listeria monocytogenes in T and B cell-deficient allogeneic bone marrow radiation chimeras. Preactivated macrophages are the main effector cells in an early phase after bone marrow transfer

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

    Roesler, J.; Groettrup, E.B.; Baccarini, M.

    1989-09-01

    Radiation chimeras in the early phase after bone marrow transplantation are a good model to study the efficiency of the body's nonspecific defense system represented by macrophages (M phi), polymorphonuclear cells (PMN), and NK cells. These cell types are present in large numbers in spleen and liver at that time, whereas the specific immune system represented by T and B cells is functionally deficient. We previously reported enhanced activities in vitro of M phi (and PMN) from recipient animals in an early phase after allogeneic bone marrow transfer. We here demonstrate that these activities result in enhanced spontaneous resistance againstmore » Listeria monocytogenes in vivo: CFU of L. monocytogenes in spleen and liver 48 h after infection were about 1 or 2 to 4 log steps less than in untreated control mice of donor or host haplotype. This enhanced resistance decreased over the 4-mo period after marrow transfer. Preactivated M phi were identified as the most important effector cells. Isolated from spleen and peritoneal cavity, they performed enhanced killing of phagocytosed Listeria. Such preactivated M phi occurred in recipient animals after transfer of allogeneic but not of syngeneic bone marrow. The precise mechanism of M phi activation in the allogeneic radiation chimera in the complete absence of any detectable T cell function is not clear at present. However, these preactivated M phi display an important protective effect against L. monocytogenes: chimeras could eliminate Listeria without acquisition of positive delayed-type sensitivity when infected with 10(3) bacteria. An inoculum of 5 . 10(3) L. monocytogenes resulted either in prolonged survival compared with normal mice of the recipient haplotype or in definitive survival accompanied by a positive delayed-type sensitivity.« less

  18. Integration of planetary protection activities

    NASA Technical Reports Server (NTRS)

    Race, Margaret S.

    1995-01-01

    For decades, NASA has been concerned about the protection of planets and other solar system bodies from biological contamination. Its policies regarding biological contamination control for outbound and inbound planetary spacecraft have evolved to focus on three important areas: (1) the preservation of celestial objects and the space environment; (2) protection of Earth from extraterrestrial hazards; and (3) ensuring the integrity of its scientific investigations. Over the years as new information has been obtained from planetary exploration and research, planetary protection parameters and policies have been modified accordingly. The overall focus of research under this cooperative agreement has been to provide information about non-scientific and societal factors related to planetary protection and use it in the planning and implementation phases of future Mars sample return missions.

  19. 40 CFR 227.32 - Liquid, suspended particulate, and solid phases of a material.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... solid phases of a material. 227.32 Section 227.32 Protection of Environment ENVIRONMENTAL PROTECTION... MATERIALS Definitions § 227.32 Liquid, suspended particulate, and solid phases of a material. (a) For the... obtained above prior to centrifugation and filtration. The solid phase includes all material settling to...

  20. 40 CFR 227.32 - Liquid, suspended particulate, and solid phases of a material.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... solid phases of a material. 227.32 Section 227.32 Protection of Environment ENVIRONMENTAL PROTECTION... MATERIALS Definitions § 227.32 Liquid, suspended particulate, and solid phases of a material. (a) For the... obtained above prior to centrifugation and filtration. The solid phase includes all material settling to...

  1. KPU-300, a Novel Benzophenone–Diketopiperazine–Type Anti-Microtubule Agent with a 2-Pyridyl Structure, Is a Potent Radiosensitizer That Synchronizes the Cell Cycle in Early M Phase

    PubMed Central

    Okuyama, Kohei; Kaida, Atsushi; Hayashi, Yoshiki; Hayashi, Yoshio; Harada, Kiyoshi; Miura, Masahiko

    2015-01-01

    KPU-300 is a novel colchicine-type anti-microtubule agent derived from plinabulin (NPI-2358). We characterized the effects of KPU-300 on cell cycle kinetics and radiosensitization using HeLa cells expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci). Cells treated with 30 nM KPU-300 for 24 h were efficiently synchronized in M phase and contained clearly detectable abnormal Fucci fluorescence. Two-dimensional flow-cytometric analysis revealed a fraction of cells distinct from the normal Fucci fluorescence pattern. Most of these cells were positive for an M phase marker, the phosphorylated form of histone H3. Cells growing in spheroids responded similarly to the drug, and the inner quiescent fraction also responded after recruitment to the growth fraction. When such drug-treated cells were irradiated in monolayer, a remarkable radiosensitization was observed. To determine whether this radiosensitization was truly due to the synchronization in M phase, we compared the radiosensitivity of cells synchronized by KPU-300 treatment and cells in early M phase isolated by a combined method that took advantage of shake-off and the properties of the Fucci system. Following normalization against the surviving fraction of cells treated with KPU-300 alone, the surviving fractions of cells irradiated in early M phase coincided. Taken together with potential vascular disrupting function in vivo, we propose a novel radiosensitizing strategy using KPU-300. PMID:26716455

  2. KPU-300, a Novel Benzophenone-Diketopiperazine-Type Anti-Microtubule Agent with a 2-Pyridyl Structure, Is a Potent Radiosensitizer That Synchronizes the Cell Cycle in Early M Phase.

    PubMed

    Okuyama, Kohei; Kaida, Atsushi; Hayashi, Yoshiki; Hayashi, Yoshio; Harada, Kiyoshi; Miura, Masahiko

    2015-01-01

    KPU-300 is a novel colchicine-type anti-microtubule agent derived from plinabulin (NPI-2358). We characterized the effects of KPU-300 on cell cycle kinetics and radiosensitization using HeLa cells expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci). Cells treated with 30 nM KPU-300 for 24 h were efficiently synchronized in M phase and contained clearly detectable abnormal Fucci fluorescence. Two-dimensional flow-cytometric analysis revealed a fraction of cells distinct from the normal Fucci fluorescence pattern. Most of these cells were positive for an M phase marker, the phosphorylated form of histone H3. Cells growing in spheroids responded similarly to the drug, and the inner quiescent fraction also responded after recruitment to the growth fraction. When such drug-treated cells were irradiated in monolayer, a remarkable radiosensitization was observed. To determine whether this radiosensitization was truly due to the synchronization in M phase, we compared the radiosensitivity of cells synchronized by KPU-300 treatment and cells in early M phase isolated by a combined method that took advantage of shake-off and the properties of the Fucci system. Following normalization against the surviving fraction of cells treated with KPU-300 alone, the surviving fractions of cells irradiated in early M phase coincided. Taken together with potential vascular disrupting function in vivo, we propose a novel radiosensitizing strategy using KPU-300.

  3. Advanced Extravehicular Protective System (AEPS) study

    NASA Technical Reports Server (NTRS)

    Williams, J. L.; Webbon, B. W.; Copeland, R. J.

    1972-01-01

    A summary is presented of Advanced Extravehicular Protective Systems (AEPS) for the future missions beyond Skylab in earth orbit, on the lunar surface, and on the Martian surface. The study concentrated on the origination of regenerable life support concepts for use in portable extravehicular protective systems, and included evaluation and comparison with expendable systems, and selection of life support subsystems. The study was conducted in two phases. In the first phase, subsystem concepts for performing life support functions in AEPS which are regenerable or partially regenerable were originated, and in addition, expendable subsystems were considered. Parametric data for each subsystem concept were evolved including subsystem weight and volume, power requirement, thermal control requirement; base regeneration equipment weight and volume, requirement. The second phase involved an evaluation of the impact of safety considerations involving redundant and/or backup systems on the selection of the regenerable life support subsystems. In addition, the impact of the space shuttle program on regenerable life support subsystem development was investigated.

  4. Early Childhood Program: Summary of Context Analysis Phase.

    ERIC Educational Resources Information Center

    Southwest Educational Development Lab., Austin, TX.

    Progress made in the field of early childhood development during the past decade is examined to provide the background and rationale for tree programs funded by the National Institute of Education (NIE) in 1974: a parenting information center, a multimedia child care training package, and television spots related to child rearing principles. The…

  5. Alkaline Phosphatase Protects Lipopolysaccharide-Induced Early Pregnancy Defects in Mice

    PubMed Central

    Lei, Wei; Ni, Hua; Herington, Jennifer; Reese, Jeff; Paria, Bibhash C.

    2015-01-01

    Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women. PMID:25910276

  6. Alkaline phosphatase protects lipopolysaccharide-induced early pregnancy defects in mice.

    PubMed

    Lei, Wei; Ni, Hua; Herington, Jennifer; Reese, Jeff; Paria, Bibhash C

    2015-01-01

    Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women.

  7. Advanced microprocessor based power protection system using artificial neural network techniques

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

    Chen, Z.; Kalam, A.; Zayegh, A.

    This paper describes an intelligent embedded microprocessor based system for fault classification in power system protection system using advanced 32-bit microprocessor technology. The paper demonstrates the development of protective relay to provide overcurrent protection schemes for fault detection. It also describes a method for power fault classification in three-phase system based on the use of neural network technology. The proposed design is implemented and tested on a single line three phase power system in power laboratory. Both the hardware and software development are described in detail.

  8. Lentiviral haemopoietic stem-cell gene therapy in early-onset metachromatic leukodystrophy: an ad-hoc analysis of a non-randomised, open-label, phase 1/2 trial.

    PubMed

    Sessa, Maria; Lorioli, Laura; Fumagalli, Francesca; Acquati, Serena; Redaelli, Daniela; Baldoli, Cristina; Canale, Sabrina; Lopez, Ignazio D; Morena, Francesco; Calabria, Andrea; Fiori, Rossana; Silvani, Paolo; Rancoita, Paola M V; Gabaldo, Michela; Benedicenti, Fabrizio; Antonioli, Gigliola; Assanelli, Andrea; Cicalese, Maria Pia; Del Carro, Ubaldo; Sora, Maria Grazia Natali; Martino, Sabata; Quattrini, Angelo; Montini, Eugenio; Di Serio, Clelia; Ciceri, Fabio; Roncarolo, Maria Grazia; Aiuti, Alessandro; Naldini, Luigi; Biffi, Alessandra

    2016-07-30

    Metachromatic leukodystrophy (a deficiency of arylsulfatase A [ARSA]) is a fatal demyelinating lysosomal disease with no approved treatment. We aimed to assess the long-term outcomes in a cohort of patients with early-onset metachromatic leukodystrophy who underwent haemopoietic stem-cell gene therapy (HSC-GT). This is an ad-hoc analysis of data from an ongoing, non-randomised, open-label, single-arm phase 1/2 trial, in which we enrolled patients with a molecular and biochemical diagnosis of metachromatic leukodystrophy (presymptomatic late-infantile or early-juvenile disease or early-symptomatic early-juvenile disease) at the Paediatric Clinical Research Unit, Ospedale San Raffaele, in Milan. Trial participants received HSC-GT, which consisted of the infusion of autologous HSCs transduced with a lentiviral vector encoding ARSA cDNA, after exposure-targeted busulfan conditioning. The primary endpoints of the trial are safety (toxicity, absence of engraftment failure or delayed haematological reconstitution, and safety of lentiviral vector-tranduced cell infusion) and efficacy (improvement in Gross Motor Function Measure [GMFM] score relative to untreated historical controls, and ARSA activity, 24 months post-treatment) of HSC-GT. For this ad-hoc analysis, we assessed safety and efficacy outcomes in all patients who had received treatment and been followed up for at least 18 months post-treatment on June 1, 2015. This trial is registered with ClinicalTrials.gov, number NCT01560182. Between April, 2010, and February, 2013, we had enrolled nine children with a diagnosis of early-onset disease (six had late-infantile disease, two had early-juvenile disease, and one had early-onset disease that could not be definitively classified). At the time of analysis all children had survived, with a median follow-up of 36 months (range 18-54). The most commonly reported adverse events were cytopenia (reported in all patients) and mucositis of different grades of severity (in five

  9. Early childhood risk and resilience factors for behavioural and emotional problems in middle childhood.

    PubMed

    Cabaj, Jason L; McDonald, Sheila W; Tough, Suzanne C

    2014-07-01

    Mental disorders in childhood have a considerable health and societal impact but the associated negative consequences may be ameliorated through early identification of risk and protective factors that can guide health promoting and preventive interventions. The objective of this study was to inform health policy and practice through identification of demographic, familial and environmental factors associated with emotional or behavioural problems in middle childhood, and the predictors of resilience in the presence of identified risk factors. A cohort of 706 mothers followed from early pregnancy was surveyed at six to eight years post-partum by a mail-out questionnaire, which included questions on demographics, children's health, development, activities, media and technology, family, friends, community, school life, and mother's health. Although most children do well in middle childhood, of 450 respondents (64% response rate), 29.5% and 25.6% of children were found to have internalising and externalising behaviour problem scores in the lowest quintile on the NSCLY Child Behaviour Scales. Independent predictors for problem behaviours identified through multivariable logistic regression modelling included being male, demographic risk, maternal mental health risk, poor parenting interactions, and low parenting morale. Among children at high risk for behaviour problems, protective factors included high maternal and child self-esteem, good maternal emotional health, adequate social support, good academic performance, and adequate quality parenting time. These findings demonstrate that several individual and social resilience factors can counter the influence of early adversities on the likelihood of developing problem behaviours in middle childhood, thus informing enhanced public health interventions for this understudied life course phase.

  10. Resting Heart Rate Predicts Depression and Cognition Early after Ischemic Stroke: A Pilot Study.

    PubMed

    Tessier, Arnaud; Sibon, Igor; Poli, Mathilde; Audiffren, Michel; Allard, Michèle; Pfeuty, Micha

    2017-10-01

    Early detection of poststroke depression (PSD) and cognitive impairment (PSCI) remains challenging. It is well documented that the function of autonomic nervous system is associated with depression and cognition. However, their relationship has never been investigated in the early poststroke phase. This pilot study aimed at determining whether resting heart rate (HR) parameters measured in early poststroke phase (1) are associated with early-phase measures of depression and cognition and (2) could be used as new tools for early objective prediction of PSD or PSCI, which could be applicable to patients unable to answer usual questionnaires. Fifty-four patients with first-ever ischemic stroke, without cardiac arrhythmia, were assessed for resting HR and heart rate variability (HRV) within the first week after stroke and for depression and cognition during the first week and at 3 months after stroke. Multiple regression analyses controlled for age, gender, and stroke severity revealed that higher HR, lower HRV, and higher sympathovagal balance (low-frequency/high-frequency ratio of HRV) were associated with higher severity of depressive symptoms within the first week after stroke. Furthermore, higher sympathovagal balance in early phase predicted higher severity of depressive symptoms at the 3-month follow-up, whereas higher HR and lower HRV in early phase predicted lower global cognitive functioning at the 3-month follow-up. Resting HR measurements obtained in early poststroke phase could serve as an objective tool, applicable to patients unable to complete questionnaires, to help in the early prediction of PSD and PSCI. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  11. An efficient early phase 2 procedure to screen medications for efficacy in smoking cessation.

    PubMed

    Perkins, Kenneth A; Lerman, Caryn

    2014-01-01

    Initial screening of new medications for potential efficacy (i.e., Food and Drug Administration (FDA) early phase 2), such as in aiding smoking cessation, should be efficient in identifying which drugs do, or do not, warrant more extensive (and expensive) clinical testing. This focused review outlines our research on development, evaluation, and validation of an efficient crossover procedure for sensitivity in detecting medication efficacy for smoking cessation. First-line FDA-approved medications of nicotine patch, varenicline, and bupropion were tested as model drugs, in three separate placebo-controlled studies. We also tested specificity of our procedure in identifying a drug that lacks efficacy, using modafinil. This crossover procedure showed sensitivity (increased days of abstinence) during week-long "practice" quit attempts with each of the active cessation medications (positive controls) versus placebo, but not with modafinil (negative control) versus placebo, as hypothesized. Sensitivity to medication efficacy signal was observed only in smokers high in intrinsic quit motivation (i.e., already preparing to quit soon) and not smokers low in intrinsic quit motivation, even if monetarily reinforced for abstinence (i.e., given extrinsic motivation). A crossover procedure requiring less time and fewer subjects than formal trials may provide an efficient strategy for a go/no-go decision whether to advance to subsequent phase 2 randomized clinical trials with a novel drug. Future research is needed to replicate our results and evaluate this procedure with novel compounds, identify factors that may limit its utility, and evaluate its applicability to testing efficacy of compounds for treating other forms of addiction.

  12. Failures in Phase III: Causes and Consequences.

    PubMed

    Seruga, Bostjan; Ocana, Alberto; Amir, Eitan; Tannock, Ian F

    2015-10-15

    Phase III randomized controlled trials (RCT) in oncology fail to lead to registration of new therapies more often than RCTs in other medical disciplines. Most RCTs are sponsored by the pharmaceutical industry, which reflects industry's increasing responsibility in cancer drug development. Many preclinical models are unreliable for evaluation of new anticancer agents, and stronger evidence of biologic effect should be required before a new agent enters the clinical development pathway. Whenever possible, early-phase clinical trials should include pharmacodynamic studies to demonstrate that new agents inhibit their molecular targets and demonstrate substantial antitumor activity at tolerated doses in an enriched population of patients. Here, we review recent RCTs and found that these conditions were not met for most of the targeted anticancer agents, which failed in recent RCTs. Many recent phase III RCTs were initiated without sufficient evidence of activity from early-phase clinical trials. Because patients treated within such trials can be harmed, they should not be undertaken. The bar should also be raised when making decisions to proceed from phase II to III and from phase III to marketing approval. Many approved agents showed only better progression-free survival than standard treatment in phase III trials and were not shown to improve survival or its quality. Introduction of value-based pricing of new anticancer agents would dissuade the continued development of agents with borderline activity in early-phase clinical trials. When collaborating with industry, oncologists should be more critical and better advocates for cancer patients. ©2015 American Association for Cancer Research.

  13. 46 CFR 111.50-5 - Location of overcurrent protective devices.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... primary side of a single phase transformer (two wire with single-voltage secondary) also protects the... secondary conductor by the secondary to primary transformer voltage ratio, and this protection meets § 111...

  14. 46 CFR 111.50-5 - Location of overcurrent protective devices.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... primary side of a single phase transformer (two wire with single-voltage secondary) also protects the... secondary conductor by the secondary to primary transformer voltage ratio, and this protection meets § 111...

  15. 46 CFR 111.50-5 - Location of overcurrent protective devices.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... primary side of a single phase transformer (two wire with single-voltage secondary) also protects the... secondary conductor by the secondary to primary transformer voltage ratio, and this protection meets § 111...

  16. 46 CFR 111.50-5 - Location of overcurrent protective devices.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... primary side of a single phase transformer (two wire with single-voltage secondary) also protects the... secondary conductor by the secondary to primary transformer voltage ratio, and this protection meets § 111...

  17. 46 CFR 111.50-5 - Location of overcurrent protective devices.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... primary side of a single phase transformer (two wire with single-voltage secondary) also protects the... secondary conductor by the secondary to primary transformer voltage ratio, and this protection meets § 111...

  18. Tensor Network Wavefunctions for Topological Phases

    NASA Astrophysics Data System (ADS)

    Ware, Brayden Alexander

    The combination of quantum effects and interactions in quantum many-body systems can result in exotic phases with fundamentally entangled ground state wavefunctions--topological phases. Topological phases come in two types, both of which will be studied in this thesis. In topologically ordered phases, the pattern of entanglement in the ground state wavefunction encodes the statistics of exotic emergent excitations, a universal indicator of a phase that is robust to all types of perturbations. In symmetry protected topological phases, the entanglement instead encodes a universal response of the system to symmetry defects, an indicator that is robust only to perturbations respecting the protecting symmetry. Finding and creating these phases in physical systems is a motivating challenge that tests all aspects--analytical, numerical, and experimental--of our understanding of the quantum many-body problem. Nearly three decades ago, the creation of simple ansatz wavefunctions--such as the Laughlin fractional quantum hall state, the AKLT state, and the resonating valence bond state--spurred analytical understanding of both the role of entanglement in topological physics and physical mechanisms by which it can arise. However, quantitative understanding of the relevant phase diagrams is still challenging. For this purpose, tensor networks provide a toolbox for systematically improving wavefunction ansatz while still capturing the relevant entanglement properties. In this thesis, we use the tools of entanglement and tensor networks to analyze ansatz states for several proposed new phases. In the first part, we study a featureless phase of bosons on the honeycomb lattice and argue that this phase can be topologically protected under any one of several distinct subsets of the crystalline lattice symmetries. We discuss methods of detecting such phases with entanglement and without. In the second part, we consider the problem of constructing fixed-point wavefunctions for

  19. Improving the luteal phase after ovarian stimulation: reviewing new options.

    PubMed

    Yding Andersen, C; Vilbour Andersen, K

    2014-05-01

    The human chorionic gonadotrophin (HCG) trigger used for final follicular maturation in connection with assisted reproduction treatment combines ovulation induction and early luteal-phase stimulation of the corpora lutea. The use of a gonadotrophin-releasing hormone agonist (GnRHa) for final follicular maturation has, however, for the first time allowed a separation of the ovulatory signal from the early luteal-phase support. This has generated new information that may improve the currently employed luteal-phase support. Thus, combined results from a number of randomized controlled trials using the GnRHa trigger suggest an association between the reproductive outcome after IVF treatment and the mid-luteal-phase serum progesterone concentration. It appears that a minimum mid-luteal progesterone threshold of approximately 80-100 nmol/l exists, which, when surpassed, results in reduced early pregnancy loss and an increased live birth rate. Further, the trade off between the HCG bolus and the subsequent risk of ovarian hyperstimulation syndrome has resulted in a trend to reduce the HCG bolus from 10,000 IU to 6500-5000 IU, which augments the HCG/LH deficiency during the early/mid-luteal phase. The mid-luteal HCG/LH shortage results in an altered progesterone profile, showing the highest concentration during the early luteal phase, contrasting with the mid-luteal peak seen in the natural menstrual cycle. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  20. Use of activated protein C has no avail in the early phase of acute pancreatitis.

    PubMed

    Akay, Sinan; Ozutemiz, Omer; Yenisey, Cigdem; Simsek, Nilufer Genc; Yuce, Gul; Batur, Yucel

    2008-01-01

    Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancreatitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activities were collected, and blood for serum amylase, urea, creatinine, and interleukin-6 measurements was withdrawn. Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435+/-432 U/L vs. 27,426+/-118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970+/-323 pg/mL vs. 330+/-368 pg/mL, respectively). In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions.

  1. Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage.

    PubMed

    Li, Jianru; Chen, Jingsen; Mo, Hangbo; Chen, Jingyin; Qian, Cong; Yan, Feng; Gu, Chi; Hu, Qiang; Wang, Lin; Chen, Gao

    2016-05-01

    Minocycline has beneficial effects in early brain injury (EBI) following subarachnoid hemorrhage (SAH); however, the molecular mechanisms underlying these effects have not been clearly identified. This study was undertaken to determine the influence of minocycline on inflammation and neural apoptosis and the possible mechanisms of these effects in early brain injury following subarachnoid hemorrhage. SAH was induced by the filament perforation model of SAH in male Sprague-Dawley rats. Minocycline or vehicle was given via an intraperitoneal injection 1 h after SAH induction. Minocycline treatment markedly attenuated brain edema secondary to blood-brain barrier (BBB) dysfunction by inhibiting NLRP3 inflammasome activation, which controls the maturation and release of pro-inflammatory cytokines, especially interleukin-1β (IL-1β). Minocycline treatment also markedly reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells. To further identify the potential mechanisms, we demonstrated that minocycline increased Bcl2 expression and reduced the protein expression of P53, Bax, and cleaved caspase-3. In addition, minocycline reduced the cortical levels of reactive oxygen species (ROS), which are closely related to both NLRP3 inflammasome and P53 expression. Minocycline protects against NLRP3 inflammasome-induced inflammation and P53-associated apoptosis in early brain injury following SAH. Minocycline's anti-inflammatory and anti-apoptotic effect may involve the reduction of ROS. Minocycline treatment may exhibit important clinical potentials in the management of SAH.

  2. 40 CFR 26.123 - Early termination of research support: Evaluation of applications and proposals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Early termination of research support: Evaluation of applications and proposals. 26.123 Section 26.123 Protection of Environment ENVIRONMENTAL... Research Conducted or Supported by EPA § 26.123 Early termination of research support: Evaluation of...

  3. Effect of anabolic implants on adrenal cortisol synthesis in feedlot beef cattle implanted early or late in the finishing phase.

    PubMed

    Gifford, C A; Branham, K A; Ellison, J O; Gómez, B I; Lemley, C O; Hart, C G; Krehbiel, C R; Bernhard, B C; Maxwell, C L; Goad, C L; Hallford, D M; Hernandez Gifford, J A

    2015-01-01

    Implantation of anabolic steroids to increase growth rate in beef cattle impacts adrenal glucocorticoid production. The mechanism by which combination androgen and estrogen implants reduce cortisol biosynthesis in heifers is not clear. The objective of this study was to identify whether pituitary or adrenal gene expression and liver enzyme activity may contribute to altered serum cortisol concentrations in heifers receiving a combination implant. On d 0 of a 122-d finishing phase, 187 predominantly Angus heifers (361 kg) approximately 14 months old were randomly assigned to one of three implant groups: (1) non-implanted control, (2) implanted at the beginning of the finishing phase (d 0; early implant) with a combination implant (200mg TBA+20mg E2; Revalor 200®), and (3) implanted during the late stage of the finishing phase (d 56; late implant) with Revalor 200®. At d 56, body weight (BW) was greater (P<0.0001) for the early implanted heifers (456 ± 1.9 kg) compared to 437 and 435 (± 1.8) kg for control and late implanted heifers, respectively. Final BW (d 122) was similar between both implanted groups and heavier than non-implanted controls (P<0.0001). Serum cortisol was similar among groups at d 0 (P=0.86) however, by d 28 heifers receiving the combination implant had reduced (P<0.05) serum cortisol concentrations (31.2 ng/mL) compared to controls (49.4 ng/mL) and late (48.2 ng/mL) groups. On d 84 cortisol was similar (P=0.75) among implanted heifers and was less (P<0.01) than non-implanted heifers. Expression of pituitary and adrenal genes involved in glucocorticoid synthesis was evaluated at d 28/29 or 84/85; however, despite decreased serum cortisol in implanted heifers, no change in mRNA expression was demonstrated. Liver CYP3A enzyme activity at d 28/29 was decreased 59% in early implanted heifers compared to control heifers (P=0.01). Additionally, at d 84/85 AKR1C activity was greatest (P=0.01) in control heifers compared to both implanted groups. Data

  4. Indiana application for interim authorization, phase I, hazardous waste management program--Environmental Protection Agency. Notice of public hearing and public comment period.

    PubMed

    1982-04-12

    EPA regulations to protect human health and the environment from the improper management of hazardous waste were published in the Federal Register on May 19, 1980 (45 FR 33063). These regulations include provisions for authorization of State programs to operate in lieu of the Federal program. Today EPA is announcing the availability for public review of the Indiana application for Phase I Interim Authorization, inviting public comment, and giving notice of a public hearing to be held on the application.

  5. Portfolio management in early stage drug discovery - a traveler's guide through uncharted territory.

    PubMed

    Betz, Ulrich A K

    2011-07-01

    Portfolio management in drug development has become a best practice in the pharmaceutical industry. By contrast, early on in the value chain - the discovery phase - portfolio management is still in its infancy. Nevertheless, owing to the attrition of R&D projects from phase to phase and the cost of capital involved, these early phases of drug discovery play a significant part for the overall cost of bringing new, innovative drugs to the market. This paper describes various approaches to manage a portfolio of projects in early-stage drug discovery and provides crucial factors that determine the success of such an approach. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. 40 CFR 300.300 - Phase I-Discovery or notification.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 28 2014-07-01 2014-07-01 false Phase I-Discovery or notification. 300.300 Section 300.300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS NATIONAL OIL AND HAZARDOUS SUBSTANCES POLLUTION...

  7. 40 CFR 300.300 - Phase I-Discovery or notification.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 28 2011-07-01 2011-07-01 false Phase I-Discovery or notification. 300.300 Section 300.300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS NATIONAL OIL AND HAZARDOUS SUBSTANCES POLLUTION...

  8. 40 CFR 300.300 - Phase I-Discovery or notification.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Phase I-Discovery or notification. 300.300 Section 300.300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS NATIONAL OIL AND HAZARDOUS SUBSTANCES POLLUTION...

  9. 40 CFR 300.300 - Phase I-Discovery or notification.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Phase I-Discovery or notification. 300.300 Section 300.300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS NATIONAL OIL AND HAZARDOUS SUBSTANCES POLLUTION...

  10. Educational and emotional health outcomes in adolescence following maltreatment in early childhood: A population-based study of protective factors.

    PubMed

    Khambati, Nisreen; Mahedy, Liam; Heron, Jon; Emond, Alan

    2018-07-01

    Although childhood maltreatment is associated with long-term impairment, some children function well despite this adversity. This study aimed to identify the key protective factors for good educational attainment and positive emotional health in adolescents who experienced maltreatment in early childhood. Data were analyzed from the Avon Longitudinal Study of Parents and Children, a large UK prospective cohort study. The sample was defined by maternally reported exposure to physical or emotional maltreatment by a parent prior to 5 years. 1118 (8.0%) children were emotionally maltreated and 375 (2.7%) were physically maltreated before the age of 5. There were too few cases of sexual abuse to be considered. Positive outcomes were operationalized as achieving 5 or more grade A*-C GCSE exam grades at 16 years and scores above the cohort median on the self-report Warwick-Edinburgh Mental Wellbeing Scale and Bachmann Self-Esteem Scale at 17.5 years. The associations of individual, family and community covariates with successful adaptation to the adversity of maltreatment were investigated using logistic regression. School related factors, including engagement in extracurricular activities, satisfaction with school and not being bullied were the most important in facilitating resilience in educational attainment, self-esteem and wellbeing. Good communication and social skills was the most protective individual trait. There was insufficient evidence to suggest that family factors were associated with resilience to maltreatment. School-based interventions are recommended to promote positive adaptation following parental maltreatment. Future research should evaluate outcomes across the life-course to understand whether the protective influences of school persist into adulthood. Copyright © 2018. Published by Elsevier Ltd.

  11. Luteal phase deficiency: abnormal gonadotropin and progesterone secretion patterns.

    PubMed

    Soules, M R; Clifton, D K; Cohen, N L; Bremner, W J; Steiner, R A

    1989-10-01

    Luteal phase deficiency (LPD) is a reproductive disorder associated with infertility and spontaneous abortion. This study was undertaken to determine whether LPD might be related to an abnormal pattern of gonadotropin secretion. We tested this hypothesis by evaluating the pattern of pulsatile LH secretion in both the follicular and luteal phases of the menstrual cycle in normal women (n = 21) and women with LPD (n = 20), which was diagnosed on the basis of two out of phase endometrial biopsies. In addition, we sought to determine whether changes in progesterone (P) pulse patterns could account for the decrease in average serum P levels in women with LPD. To this end, we examined the pulse patterns of P and compared these patterns between normal women and those with LPD. Frequent blood sampling was performed in both groups to determine their respective hormone secretion patterns. In the follicular phase, blood samples were obtained every 10 min for 12 h; in the luteal phase the samples were obtained every 10 min for 12 h; in the luteal LH, FSH, and P were assayed in each sample. Pulse detection was performed by an adaptive threshold method of pulse analysis. The LH pulse frequency was significantly higher in the women with LPD than in the normal women in the early follicular phase [P less than 0.05; LPD, 12.8 +/- 1.4 (+/- SE); normal, 8.2 +/- 0.7 pulses/12 h]. LH pulse frequency was similar in the early and late follicular phases in the women with LPD, whereas it was higher in the late follicular phase in normal women. Mean serum FSH levels were not different between groups in both the early and late follicular phases. In the luteal phase the P pulse amplitude and mean serum P level were significantly lower in the LPD group than in the normal women (P less than 0.01). We conclude that 1) a too rapid LH pulse pattern in the early follicular phase may lead to inadequate LH support of the corpus luteum and become manifest as LPD; 2) the mechanism for inadequate P

  12. Metal Surface Modification for Obtaining Nano- and Sub-Nanostructured Protective Layers.

    PubMed

    Ledovskykh, Volodymyr; Vyshnevska, Yuliya; Brazhnyk, Igor; Levchenko, Sergiy

    2017-12-01

    Regularities of the phase protective layer formation in multicomponent systems involving inhibitors with different mechanism of protective action have been investigated. It was shown that optimization of the composition of the inhibition mixture allows to obtain higher protective efficiency owing to improved microstructure of the phase layer. It was found that mechanism of the film formation in the presence of NaNO 2 -PHMG is due to deposition of slightly soluble PHMG-Fe complexes on the metal surface. On the basis of the proposed mechanism, the advanced surface engineering methods for obtaining nanoscaled and sub-nanostructured functional coatings may be developed.

  13. Metal Surface Modification for Obtaining Nano- and Sub-Nanostructured Protective Layers

    NASA Astrophysics Data System (ADS)

    Ledovskykh, Volodymyr; Vyshnevska, Yuliya; Brazhnyk, Igor; Levchenko, Sergiy

    2017-03-01

    Regularities of the phase protective layer formation in multicomponent systems involving inhibitors with different mechanism of protective action have been investigated. It was shown that optimization of the composition of the inhibition mixture allows to obtain higher protective efficiency owing to improved microstructure of the phase layer. It was found that mechanism of the film formation in the presence of NaNO2-PHMG is due to deposition of slightly soluble PHMG-Fe complexes on the metal surface. On the basis of the proposed mechanism, the advanced surface engineering methods for obtaining nanoscaled and sub-nanostructured functional coatings may be developed.

  14. Planetary protection policy (U.S.A.)

    NASA Technical Reports Server (NTRS)

    Rummel, John D.

    1992-01-01

    Through existing treaty obligations of the United States, NASA is committed to exploring space while avoiding biological contamination of the planets, and to the protection of the earth against harm from materials returned from space. Because of the similarities between Mars and earth, plans for the exploration of Mars evoke discussions of these Planetary Protection issues. U.S. Planetary Protection Policy will be focused on the preservation of these goals in an arena that will change with the growth of scientific knowledge about the Martian environment. Early opportunities to gain the appropriate data will be used to guide later policy implementation. Because human presence on Mars will result in the end of earth's separation from the Martian environment, it is expected that precursor robotic missions will address critical planetary protection concerns before humans arrive.

  15. Webcam delivery of the Lidcombe program for early stuttering: a phase I clinical trial.

    PubMed

    O'Brian, Sue; Smith, Kylie; Onslow, Mark

    2014-06-01

    The Lidcombe Program is an operant treatment for early stuttering shown with meta-analysis to have a favorable odds ratio. However, many clients are unable to access the treatment because of distance and lifestyle factors. In this Phase I trial, we explored the potential efficacy, practicality, and viability of an Internet webcam Lidcombe Program service delivery model. Participants were 3 preschool children who stuttered and their parents, all of whom received assessment and treatment using webcam in their homes with no clinic attendance. At 6 months post-Stage 1 completion, all children were stuttering below 1.0% syllables stuttered. The webcam intervention was acceptable to the parents and appeared to be practical and viable, with only occasional audiovisual problems. At present, there is no reason to doubt that a webcam-delivered Lidcombe Program will be shown with clinical trials to have comparable efficacy with the clinic version. Webcam-delivered Lidcombe Program intervention is potentially efficacious, is practical and viable, and requires further exploration with comparative clinical trials and a qualitative study of parent and caregiver experiences.

  16. Biomechanical and neuromuscular adaptations during the landing phase of a stepping-down task in patients with early or established knee osteoarthritis.

    PubMed

    Sanchez-Ramirez, Diana C; Malfait, Bart; Baert, Isabel; van der Leeden, Marike; van Dieën, Jaap; Lems, Willem F; Dekker, Joost; Luyten, Frank P; Verschueren, Sabine

    2016-06-01

    To compare the knee joint kinematics, kinetics and EMG activity patterns during a stepping-down task in patients with knee osteoarthritis (OA) with control subjects. 33 women with knee OA (early OA, n=14; established OA n=19) and 14 female control subjects performed a stepping-down task from a 20cm step. Knee joint kinematics, kinetics and EMG activity were recorded on the stepping-down leg during the loading phase. During the stepping-down task patients with established knee OA showed greater normalized medial hamstrings activity (p=0.034) and greater vastus lateralis-medial hamstrings co-contraction (p=0.012) than controls. Greater vastus medialis-medial hamstrings co-contraction was found in patients with established OA compared to control subjects (p=0.040) and to patients with early OA (p=0.023). Self-reported knee instability was reported in 7% and 32% of the patients with early and established OA, respectively. The greater EMG co-activity found in established OA might suggest a less efficient use of knee muscles or an attempt to compensate for greater knee laxity usually present in patients with established OA. In the early stage of the disease, the biomechanical and neuromuscular control of stepping-down is not altered compared to healthy controls. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Design of a Protection Thermal Energy Storage Using Phase Change Material Coupled to a Solar Receiver

    NASA Astrophysics Data System (ADS)

    Verdier, D.; Falcoz, Q.; Ferrière, A.

    2014-12-01

    Thermal Energy Storage (TES) is the key for a stable electricity production in future Concentrated Solar Power (CSP) plants. This work presents a study on the thermal protection of the central receiver of CSP plant using a tower which is subject to considerable thermal stresses in case of cloudy events. The very high temperatures, 800 °C at design point, impose the use of special materials which are able to resist at high temperature and high mechanical constraints and high level of concentrated solar flux. In this paper we investigate a TES coupling a metallic matrix drilled with tubes of Phase Change Material (PCM) in order to store a large amount of thermal energy and release it in a short time. A numerical model is developed to optimize the arrangement of tubes into the TES. Then a methodology is given, based from the need in terms of thermal capacity, in order to help the choice of the geometry.

  18. Species-driven phases and increasing structure in early-successional plant communities.

    PubMed

    Zaplata, Markus K; Winter, Susanne; Fischer, Anton; Kollmann, Johannes; Ulrich, Werner

    2013-01-01

    Successional phases describe changes in ecological communities that proceed in steps rather than continuously. Despite their importance for the understanding of ecosystem development, there still exists no reliable definition of phases and no quantitative measure of phase transitions. In order to obtain these data, we investigated primary succession in an artificial catchment (6 ha) in eastern Germany over a period of 6 years. The data set consists of records of plant species and their cover values, and initial substrate properties, both from plots in a regular grid (20 m × 20 m) suitable for spatial data analysis. Community assembly was studied by analyses of species co-occurrence and nestedness. Additionally, we correlated lognormal and log series distributions of species abundance to each community. We here introduce a new general method for detection of successional phases based on the degree of transient spatial homogeneity in the study system. Spatially coherent vegetation patterns revealed nonoverlapping partitions within this sequence of primary succession and were characterized as two distinct ecological phases. Patterns of species co-occurrence were increasingly less random, and hence the importance of demographic stochasticity and neutral community assembly decreased during the study period. Our findings highlight the spatial dimension of successional phases and quantify the degree of change between these steps. They are an element for advancing a more reliable terminology of ecological successions.

  19. The Culture of Faith and Hope: Patients’ Justifications for Their High Estimations of Expected Therapeutic Benefit When Enrolling in Early-Phase Oncology Trials

    PubMed Central

    Sulmasy, Daniel P.; Astrow, Alan B.; He, M. Kai; Seils, Damon M.; Meropol, Neal J.; Micco, Ellyn; Weinfurt, Kevin P.

    2013-01-01

    Purpose Patients’ estimates of their chances of therapeutic benefit from participation in early-phase trials greatly exceed historical data. Ethicists worry that this “therapeutic misestimation” undermines the validity of informed consent. Patients and Methods We interviewed 45 patients enrolled in phase I or II oncology trials about their expectations of therapeutic benefit and their reasons for those expectations. We employed a phenomenological, qualitative approach with one primary coder to identify emergent themes, verified by 2 independent coders. Results Median expectations of therapeutic benefit varied from 50% to 80%, depending on how the question was asked. Justifications universally invoked hope and optimism, and 27/45 participants used one of these words. Three major themes emerged: (1) optimism as performative, that is, the notion that positive thoughts and expressions improve chances of benefit; (2) fighting cancer as a battle; and (3) faith in God, science, or both. Many participants described a culture in which optimism was encouraged and expected, such that trial enrollment became a way of reflecting this expectation. Many reported they had been told few patients would benefit and appeared to understand the uncertainties of clinical research, yet expressed high expected personal therapeutic benefit. More distressed participants were less likely to invoke performative justifications for their expectations (50% vs 84%; P = .04). Conclusion Expressions of high expected therapeutic benefit had little to do with reporting knowledge and more to do with expressing optimism. These results have implications for understanding how to obtain valid consent from participants in early-phase clinical trials. PMID:20564120

  20. Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide-a for early-stage cancer of the larynx: Phase Ib study.

    PubMed

    Shafirstein, Gal; Rigual, Nestor R; Arshad, Hassan; Cooper, Michele T; Bellnier, David A; Wilding, Gregory; Tan, Wei; Merzianu, Mihai; Henderson, Barbara W

    2016-04-01

    The purpose of this study was for us to report results regarding the safety of 3-(1'-hexyloxyethyl) pyropheophorbide-a (HPPH) mediated photodynamic therapy (PDT) in early laryngeal disease, and offer preliminary information on treatment responses. A single-institution, phase Ib, open label, noncomparative study of HPPH-PDT in patients with high-risk dysplasia, carcinoma in situ, and T1 squamous cell carcinoma (SCC) of the larynx. The primary outcomes were safety and maximum tolerated dose (MTD), and the secondary outcome was response. Twenty-nine patients and 30 lesions were treated. The most common adverse event (AE) was transient hoarseness of voice. Severe edema, requiring tracheostomy, was the most serious AE, which occurred in 2 patients within several hours of therapy. The MTD was 100 J/cm(2) . Patients with T1 SCC seemed to have good complete response rate (82%) to HPPH-PDT at MTD. HPPH-PDT can be safely used to treat early-stage laryngeal cancer, with potential efficacy. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E377-E383, 2016. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc.

  1. "Big Bang" as a result result of the curvature-driven first-order phase transition in the early cold Universe

    NASA Astrophysics Data System (ADS)

    Pashitskii, E. A.; Pentegov, V. I.

    We suggest that the "Big Bang" may be a result of the first-order phase transition driven by changing scalar curvature of the 4D space-time in the expanding cold Universe, filled with nonlinear scalar field φ and neutral matter with equation of state p = vɛ (where p and ɛ are pressure and energy density of matter). We consider a Lagrangian for scalar field in curved space-time with nonlinearity φ, which along with the quadratic term -ΣR|φ|2 (where Σ is interaction constant and R is scalar curvature) contains a term ΣR(φ +φ+) linear in φ. Due to this term the condition for the extrema of the potential energy of the scalar field is given by a cubic equation. Provided v > 1/3 the scalar curvature R = [κ(3v-1)ɛ - 4Γ (where κ and Γ are Einstein's gravitational and cosmological constants) decreases along with decreasing " in the process of the Universe's expansion, and at some critical value Rc < 0 a first-order phase transition occurs, driven by an "external field" parameter proportional to R. Given certain conditions the critical radius of the early Universe at the point of the first-order phase transition may reach arbitrary large values, so this scenario of unrestricted "inflation" of the Universe may be called "hyperinflation". Beyond the point of phase transition the system is rolling down into the potential minimum releasing the potential energy of scalar field with subsequent powerful heating of the Universe playing the role of "Big Bang".

  2. Floquet topological phases with symmetry in all dimensions

    NASA Astrophysics Data System (ADS)

    Roy, Rahul; Harper, Fenner

    2017-05-01

    Dynamical systems may host a number of remarkable symmetry-protected phases that are qualitatively different from their static analogs. In this work, we consider the phase space of symmetry-respecting unitary evolutions in detail and identify several distinct classes of evolution that host dynamical order. Using ideas from group cohomology, we construct a set of interacting Floquet drives that generate dynamical symmetry-protected topological order for each nontrivial cohomology class in every dimension, illustrating our construction with explicit two-dimensional examples. We also identify a set of symmetry-protected Floquet drives that lie outside of the group cohomology construction, and a further class of symmetry-respecting topological drives which host chiral edge modes. We use these special drives to define a notion of phase (stable to a class of local perturbations in the bulk) and the concepts of relative and absolute topological order, which can be applied to many different classes of unitary evolutions. These include fully many-body localized unitary evolutions and time crystals.

  3. Simplified spacecraft vulnerability assessments at component level in early design phase at the European Space Agency's Concurrent Design Facility

    NASA Astrophysics Data System (ADS)

    Kempf, Scott; Schäfer, Frank K.; Cardone, Tiziana; Ferreira, Ivo; Gerené, Sam; Destefanis, Roberto; Grassi, Lilith

    2016-12-01

    During recent years, the state-of-the-art risk assessment of the threat posed to spacecraft by micrometeoroids and space debris has been expanded to the analysis of failure modes of internal spacecraft components. This method can now be used to perform risk analyses for satellites to assess various failure levels - from failure of specific sub-systems to catastrophic break-up. This new assessment methodology is based on triple-wall ballistic limit equations (BLEs), specifically the Schäfer-Ryan-Lambert (SRL) BLE, which is applicable for describing failure threshold levels for satellite components following a hypervelocity impact. The methodology is implemented in the form of the software tool Particle Impact Risk and vulnerability Analysis Tool (PIRAT). During a recent European Space Agency (ESA) funded study, the PIRAT functionality was expanded in order to provide an interface to ESA's Concurrent Design Facility (CDF). The additions include a geometry importer and an OCDT (Open Concurrent Design Tool) interface. The new interface provides both the expanded geometrical flexibility, which is provided by external computer aided design (CAD) modelling, and an ease of import of existing data without the need for extensive preparation of the model. The reduced effort required to perform vulnerability analyses makes it feasible for application during early design phase, at which point modifications to satellite design can be undertaken with relatively little extra effort. The integration of PIRAT in the CDF represents the first time that vulnerability analyses can be performed in-session in ESA's CDF and the first time that comprehensive vulnerability studies can be applied cost-effectively in early design phase in general.

  4. Relation of Cardiac Complications in the Early Phase of Community-Acquired Pneumonia to Long-Term Mortality and Cardiovascular Events.

    PubMed

    Cangemi, Roberto; Calvieri, Camilla; Falcone, Marco; Bucci, Tommaso; Bertazzoni, Giuliano; Scarpellini, Maria G; Barillà, Francesco; Taliani, Gloria; Violi, Francesco

    2015-08-15

    Community-acquired pneumonia (CAP) is complicated by cardiac events in the early phase of the disease. Aim of this study was to assess if these intrahospital cardiac complications may account for overall mortality and cardiovascular events occurring during a long-term follow-up. Three hundred one consecutive patients admitted to the University-Hospital, Policlinico Umberto I, with community-acquired pneumonia were prospectively recruited and followed up for a median of 17.4 months. Primary end point was the occurrence of death for any cause, and secondary end point was the occurrence of cardiovascular events (cardiovascular death, nonfatal myocardial infarction [MI], and stroke). During the intrahospital stay, 55 patients (18%) experienced a cardiac complication. Of these, 32 had an MI (29 non-ST-elevation MI and 3 ST-elevation MI) and 30 had a new episode of atrial fibrillation (7 nonmutually exclusive events). During the follow-up, 89 patients died (51% of patients with an intrahospital cardiac complication and 26% of patients without, p <0.001) and 73 experienced a cardiovascular event (47% of patients with and 19% of patients without an intrahospital cardiac complication, p <0.001). A Cox regression analysis showed that intrahospital cardiac complications, age, and Pneumonia Severity Index were significantly associated with overall mortality, whereas intrahospital cardiac complications, age, hypertension, and diabetes were significantly associated with cardiovascular events during the follow-up. In conclusion, this prospective study shows that intrahospital cardiac complications in the early phase of pneumonia are associated with an enhanced risk of death and cardiovascular events during long-term follow-up. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Synergy of bone marrow transplantation and curcumin ensue protective effects at early onset of diabetes in mice.

    PubMed

    Arivazhagan, Arivarasan; Krishna, Soni; Yadav, Shivangi; Shah, Harshit Rajesh; Kumar, Pravir; Ambasta, Rashmi Kumar

    2015-07-01

    The aim of this study was to investigate the early onset effects of diabetes on pro-angiogenic signaling pathway, total number of bone marrow cells, organs (pancreas and kidney) damage and the reversal effect of diabetes by combinatorial treatment of curcumin and bone marrow transplantation in streptozotocin (STZ) induced diabetic mice. In the present study, Streptozotocin induced diabetic mice were transplanted with bone marrow cells (2 × 10(6) ) followed by the administration of curcumin (80 mg/kg bodyweight). Effect of diabetes on the different organs was studied by H&E, Western blotting and immunofluorescence using vascular endothelial growth factor (VEGF), platelet/endothelial cell adhesion molecule (PECAM), insulin, Caspase-9 and Caspase-3 antibodies. The effect of diabetes results in the reduction of the total cell number and viability of the bone marrow cells, organ degeneration and lower VEGF/PECAM expression. However, transplantation with normal bone marrow cells significantly reduced the blood glucose levels (above normal range) and initiated the organ regeneration via the VEGF/PECAM mediated manner. Curcumin treatment further reduced the blood glucose level (near normal); and accelerated the organ regeneration, enhanced VEGF/PECAM expression and decreased caspase expression level in the organs. Curcumin also had a protective role against the glucotoxicity test performed on the bone marrow cells. This study suggests that bone marrow transplantation and curcumin administration is an effective treatment in reversing the early onset effects of diabetes via the VEGF/PECAM signaling pathway. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  6. Dynamic interaction of two-phase debris flow with pyramidal defense structures: An optimal strategy to efficiently protecting the desired area

    NASA Astrophysics Data System (ADS)

    Kattel, Parameshwari; Kafle, Jeevan; Fischer, Jan-Thomas; Mergili, Martin; Tuladhar, Bhadra Man; Pudasaini, Shiva P.

    2017-04-01

    In this work we analyze the dynamic interaction of two phase debris flows with pyramidal obstacles. To simulate the dynamic interaction of two-phase debris flow (a mixture of solid particles and viscous fluid) with obstacles of different dimensions and orientations, we employ the general two-phase mass flow model (Pudasaini, 2012). The model consists of highly non-linear partial differential equations representing the mass and momentum conservations for both solid and fluid. Besides buoyancy, the model includes some dominant physical aspects of the debris flows such as generalized drag, virtual mass and non-Newtonian viscous stress as induced by the gradient of solid-volume-fraction. Simulations are performed with high-resolution numerical schemes to capture essential dynamics, including the strongly re-directed flow with multiple stream lines, mass arrest and debris-vacuum generation when the rapidly cascading debris mass suddenly encounters the obstacle. The solid and fluid phases show fundamentally different interactions with obstacles, flow spreading and dispersions, run-out dynamics, and deposition morphology. A forward-facing pyramid deflects the mass wider, and a rearward-facing pyramid arrests a portion of solid-mass at its front. Our basic study reveals that appropriately installed obstacles, their dimensions and orientations have a significant influence on the flow dynamics, material redistribution and redirection. The precise knowledge of the change in dynamics is of great importance for the optimal and effective protection of designated areas along the mountain slopes and the runout zones. Further important results are, that specific installations lead to redirect either solid, or fluid, or both, in the desired amounts and directions. The present method of the complex interactions of real two-phase mass flows with the obstacles may help us to construct defense structures and to design advanced and physics-based engineering solutions for the prevention

  7. Use of activated protein C has no avail in the early phase of acute pancreatitis

    PubMed Central

    Ozutemiz, Omer; Yenisey, Cigdem; Genc Simsek, Nilufer; Yuce, Gul; Batur, Yucel

    2008-01-01

    Objectives. Sepsis and acute pancreatitis have similar pathogenetic mechanisms that have been implicated in the progression of multiple organ failure. Drotrecogin alfa, an analogue of endogenous protein C, reduces mortality in clinical sepsis. Our objective was to evaluate the early therapeutic effects of activated protein C (APC) in a rat model of acute necrotizing pancreatitis. Subjects and method. Acute necrotizing pancreatitis was induced by intraductal injection of 5% Na taurocholate. Hourly bolus injections of saline or recombinant human APC (drotrecogin alfa) was commenced via femoral venous catheter four hours after the induction of acute pancreatitis. The experiment was terminated nine hours after pancratitis induction. Animals in group one (n=20) had a sham operation while animals in group two (n=20) received saline and animals in group three (n=20) received drotrecogin alfa boluses after acute pancreatitis induction. Pancreatic tissue for histopathologic scores and myeloperoxidase, glutathione reductase, glutathione peroxidase, and catalase activites were collected, and blood for serum amylase, urea, creatinine, and inleukin-6 measurements was withdrawn. Results. Serum amylase activity was significantly lower in the APC treated group than the untreated group (17,435±432 U/L vs. 27,426±118 U/L, respectively). While the serum interleukin-6 concentration in the APC untreated group was significantly lower than the treated group (970±323 pg/mL vs. 330±368 pg/mL, respectively). Conclusion. In the early phase of acute pancreatitis, drotrecogin alfa treatment did not result in a significant improvement in oxidative and inflammatory parameters or renal functions. PMID:19088933

  8. Protection of temperature sensitive biomedical products using molecular alloys as phase change material.

    PubMed

    Mondieig, Denise; Rajabalee, Fazil; Laprie, Alain; Oonk, Harry A J; Calvet, Thereza; Cuevas-Diarte, Miguel Angel

    2003-04-01

    In this paper we present an example of the application of molecular alloys for thermal protection of biomedical products during transport or storage. Particularly, thermal protection of blood elements have been considered at different temperatures. All steps from basic research to marketing have been addressed. The high latent heat of fusion of the components allows us to propose molecular alloys as materials for thermal energy storage and also for thermal protection over a large range of temperatures, which can be used in many industrial sectors.

  9. Machine protection system for rotating equipment and method

    DOEpatents

    Lakshminarasimha, Arkalgud N.; Rucigay, Richard J.; Ozgur, Dincer

    2003-01-01

    A machine protection system and method for rotating equipment introduces new alarming features and makes use of full proximity probe sensor information, including amplitude and phase. Baseline vibration amplitude and phase data is estimated and tracked according to operating modes of the rotating equipment. Baseline vibration and phase data can be determined using a rolling average and variance and stored in a unit circle or tracked using short term average and long term average baselines. The sensed vibration amplitude and phase is compared with the baseline vibration amplitude and phase data. Operation of the rotating equipment can be controlled based on the vibration amplitude and phase.

  10. 2004 Children's Health Protection Advisory Committee Meeting Agendas

    EPA Pesticide Factsheets

    Objectives for the three meetings in 2004 include discussing schools-related work, mercury regulation, the Food Quality Protection Act, Children's Health Indicators, early life exposure to carcinogens, and smart growth.

  11. ["Epistemic Negotiations" and the Pluralism of the Radiation Protection Regime: The Determination of Radiation Protection Standards for the General Population in the Early Years After World War II].

    PubMed

    Higuchi, Toshihiro

    2015-10-01

    Radiation protection standards for the general population have constituted one of the most controversial subjects in the history of atomic energy uses. This paper reexamines the process in which the first such standards evolved in the early postwar period. While the existing literature has emphasized a "collusion" between the standard-setters and users, the paper seeks to examine the horizontal relationship among the standard-setters. It first examines a series of expert consultations between the United States and the United Kingdom. Representing a different configuration of power and interest, the two failed to agree on the assessment of genetic damage and cancer induction whose occurrence might have no threshold and therefore be dependent on the population size. This stalemate prevented the International Commission on Radiological Protection (ICRP), established in 1950, from formulating separate guidelines for the general public. Situations radically changed when the Bikini incident in 1954 led to the creation of more scientific panels. One such panel under the U.S. Academy of Sciences enabled the geneticists to bridge their internal divide, unanimously naming 100 mSv as the genetically permissible dose for the general population. Not to be outdone, ICRP publicized its own guidelines for the same purpose. The case examined in this paper shows that the standard-setting process is best understood as a series of "epistemic negotiations" among and within the standard-setters, whose agendas were determined from the outset but whose outcomes were not.

  12. Fluctuation driven electroweak phase transition

    NASA Technical Reports Server (NTRS)

    Gleiser, Marcelo; Kolb, Edward W.

    1991-01-01

    We examine the dynamics of the electroweak phase transition in the early Universe. For Higgs masses in the range 46 less than or = M sub H less than or = 150 GeV and top quark masses less than 200 GeV, regions of symmetric and asymmetric vacuum coexist to below the critical temperature, with thermal equilibrium between the two phases maintained by fluctuations of both phases. We propose that the transition to the asymmetric vacuum is completed by percolation of these subcritical fluctuations. Our results are relevant to scenarios of baryogenesis that invoke a weakly first-order phase transition at the electroweak scale.

  13. 40 CFR 300.300 - Phase I-Discovery or notification.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Phase I-Discovery or notification. 300.300 Section 300.300 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND... person in charge of a vessel or a facility shall, as soon as he or she has knowledge of any discharge...

  14. A Comparison of Proposed Biosimilar LA-EP2006 and Reference Pegfilgrastim for the Prevention of Neutropenia in Patients With Early-Stage Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2), a Phase III, Randomized, Double-Blind Trial.

    PubMed

    Blackwell, Kimberly; Donskih, Roman; Jones, C Michael; Nixon, Allen; Vidal, Maria J; Nakov, Roumen; Singh, Pritibha; Schaffar, Gregor; Gascón, Pere; Harbeck, Nadia

    2016-07-01

    Pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. In highly regulated markets, there are currently no approved biosimilars of pegfilgrastim. Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare proposed biosimilar LA-EP2006 with reference pegfilgrastim (Neulasta, Amgen) in early-stage breast cancer patients receiving adjuvant or neoadjuvant myelosuppressive chemotherapy. A total of 308 patients were randomized to LA-EP2006 or reference pegfilgrastim. Each patient received TAC (intravenous docetaxel 75 mg/m(2), doxorubicin 50 mg/m(2), and cyclophosphamide 500 mg/m(2)) on day 1 of each cycle, for six or more cycles. Pegfilgrastim (LA-EP2006 or reference) was given subcutaneously (6 mg in 0.6 mL) on day 2 of each cycle. The primary endpoint was duration of severe neutropenia (DSN) during cycle 1 (number of consecutive days with an absolute neutrophil count <0.5 × 10(9)/L), with equivalence confirmed if 90% and 95% confidence intervals (CIs) were within a 1-day margin. Baseline characteristics were well balanced. DSN was equivalent between groups at mean ± SD 1.36 ± 1.13 (LA-EP2006, n = 155) and 1.19 ± 0.98 (reference, n = 153) in cycle 1. With a treatment difference (reference minus LA-EP2006) of -0.16 days (90% CI -0.36 to 0.04; 95% CI -0.40 to 0.08), LA-EP2006 was equivalent to reference pegfilgrastim. Secondary efficacy parameters were similar between groups during cycle 1 and across cycles. Safety profiles were also similar between groups. No neutralizing antibodies against pegfilgrastim, filgrastim, or polyethylene glycol were detected. LA-EP2006 and reference pegfilgrastim were therapeutically equivalent and comparable regarding efficacy and safety in the prevention of neutropenia in patients with early-stage breast cancer receiving TAC. The granulocyte colony-stimulating factor pegfilgrastim is widely used

  15. Influences on Turkish Early Childhood Teachers' Science Teaching Practices and the Science Content Covered in the Early Years

    ERIC Educational Resources Information Center

    Olgan, Refika

    2015-01-01

    The first rationale of the study was not only to determine the topics taught in Turkish early childhood settings but also to define the frequency and time allocation for teaching science (n?=?382). In the second phase, through semi-structured interview questions, the aim was to gain detailed information about Turkish early childhood teachers'…

  16. HRAS: a webserver for early warning of human health risk brought by aflatoxin.

    PubMed

    Hu, Ruifeng; Zeng, Xu; Gao, Weiwei; Wang, Qian; Liu, Zhihua

    2013-02-01

    Most people are aware that outdoor air pollution can damage their health, but many do not know that indoor air pollution can also exhibit significant negative health effects. Fungi parasitizing in air conditioning and ventilation systems can be one of indoor air pollution sources. Aflatoxin produced by Aspergillus flavus (A. flavus) became a central focus of indoor air pollution, especially in farmer markets. Therefore we developed an early warning system, Health Risk Assessment System, to estimate the growth rate of A. flavus, predict the amount of aflatoxin and provide early warning information. Firstly, the growth of A. flavus and the production of aflatoxin under different conditions were widely obtained through a comprehensive literature review. Secondly, three mathematical models were established to predict the A. flavus colony growth rate, lag phase duration and aflatoxin content, as functions of temperature and water activity based on present studies. Finally, all the results were evaluated by the user-supplied data using PHP programming language. We utilized the web page to show the results and display warning information. The JpGraph library was used to create a dynamic line chart, refreshing the warning information dynamically in real-time. The HARS provides accurate information for early warning purposes to let us take timely steps to protect ourselves.

  17. Assessment of Device-Related Thrombus and Associated Clinical Outcomes With the WATCHMAN Left Atrial Appendage Closure Device for Embolic Protection in Patients With Atrial Fibrillation (from the PROTECT-AF Trial).

    PubMed

    Main, Michael L; Fan, Dali; Reddy, Vivek Y; Holmes, David R; Gordon, Nicole T; Coggins, Tina R; House, John A; Liao, Lawrence; Rabineau, Dawn; Latus, George G; Huber, Kenneth C; Sievert, Horst; Wright, Richard F; Doshi, Shephal K; Douglas, Pamela S

    2016-04-01

    Left atrial appendage closure with the WATCHMAN device is an alternative to anticoagulation for stroke prevention in selected patients with atrial fibrillation (AF). LA device-related thrombus (DRT) is poorly defined and understood. We aimed to (1) develop consensus echocardiographic diagnostic criteria for DRT; (2) estimate the incidence of DRT; and (3) determine clinical event rates in patients with DRT. In phase 1 (training), a training manual was developed and reviewed by 3 echocardiographers with left atrial appendage closure device experience. All available transesophageal (TEE) studies in the WATCHMAN left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT-AF) trial patients with suspected DRT were reviewed in 2 subsequent phases. In phase 2 (primary blind read), each reviewer independently scored each study for DRT, and final echo criteria were developed. Unanimously scored studies were considered adjudicated, whereas all others were reevaluated by all reviewers in phase 3 (group adjudication read). DRT was suspected in 35 of 485 patients by the site investigator, the echocardiography core laboratory, or both; 93 of the individual TEE studies were available for review. In phase 2, 3 readers agreed on 67 (72%) of time points. Based on phases 1 and 2, 5 DRT criteria were developed. In phase 3, studies without agreement in phase 2 were adjudicated using these criteria. Overall, at least 1 TEE was DRT positive in 27 (5.7%) PROTECT-AF patients. Stroke, peripheral embolism, or cardiac/unexplained death occurred in subjects with DRT at a rate of 3.4 per 100 patient-years follow-up. In conclusion, DRT were identified on at least 1 TEE in 27 PROTECT-AF patients, indicating a DRT incidence of 5.7%. Primary efficacy events in patients with DRT occurred at a rate of 3.4 per 100 patient-years follow-up, intermediate in frequency between event rates previously reported for the overall device and warfarin arms in PROTECT

  18. Toward a clinically useful method of predicting early breast-feeding attrition.

    PubMed

    Lewallen, Lynne Porter; Dick, Margaret J; Wall, Yolanda; Zickefoose, Kimberly Taylor; Hannah, Susan Hensley; Flowers, Janet; Powell, Wanda

    2006-08-01

    The overall purpose of this study was to revise and test an instrument to identify, during the early postpartum period, women at risk for early breast-feeding attrition. This study was completed in two phases: the first phase tested a revision of the Breast-Feeding Attrition Prediction Tool (BAPT); the second, a new instrument, the Breast-Feeding Attitude Scale (BrAS), which was adapted from the BAPT. The two phases of this study involved 415 pregnant and postpartum women. Women answered questions either by phone (pregnant women) or in their hospital rooms after delivery (postpartum women). Data were analyzed using t tests and reliability analysis. The BAPT did not predict early breast-feeding attrition; however, the BrAS did differentiate between the attitudes of breast-feeding women and those of formula-feeding women and had adequate reliability. Women at risk for early breast-feeding attrition should be identified early so nursing interventions can be directed toward preventing early unintended weaning. Although the BrAS did not reliably identify women at risk in this sample, it did highlight important differences between breast-feeding and formula-feeding women that can be used in designing preconceptional or prenatal educational assessments and interventions.

  19. Early Program Development

    NASA Image and Video Library

    1969-01-01

    This 1969 artist's concept illustrates the use of three major elements of NASA's Integrated program, as proposed by President Nixon's Space Task Group. In Phases I and II, a Space Tug with a manipulator-equipped crew module removes a cargo module from an early Space Shuttle Orbiter and docks with it. In Phases III and IV, the Space Tug with attached cargo module flys toward a Nuclear Shuttle. As a result of the Space Task Group's recommendations for more commonality and integration in the American space program, Marshall Space Flight Center engineers studied many of the spacecraft depicted here.

  20. Identification of a transitional fibroblast function in very early rheumatoid arthritis

    PubMed Central

    Filer, Andrew; Ward, Lewis S C; Kemble, Samuel; Davies, Christopher S; Munir, Hafsa; Rogers, Rebekah; Raza, Karim; Buckley, Christopher Dominic; Nash, Gerard B; McGettrick, Helen M

    2017-01-01

    Objectives Synovial fibroblasts actively regulate the inflammatory infiltrate by communicating with neighbouring endothelial cells (EC). Surprisingly, little is known about how the development of rheumatoid arthritis (RA) alters these immunomodulatory properties. We examined the effects of phase of RA and disease outcome (resolving vs persistence) on fibroblast crosstalk with EC and regulation of lymphocyte recruitment. Methods Fibroblasts were isolated from patients without synovitis, with resolving arthritis, very early RA (VeRA; symptom ≤12 weeks) and established RA undergoing joint replacement (JRep) surgery. Endothelial-fibroblast cocultures were formed on opposite sides of porous filters. Lymphocyte adhesion from flow, secretion of soluble mediators and interleukin 6 (IL-6) signalling were assessed. Results Fibroblasts from non-inflamed and resolving arthritis were immunosuppressive, inhibiting lymphocyte recruitment to cytokine-treated endothelium. This effect was lost very early in the development of RA, such that fibroblasts no longer suppressed recruitment. Changes in IL-6 and transforming growth factor beta 1 (TGF-β1) signalling appeared critical for the loss of the immunosuppressive phenotype. In the absence of exogenous cytokines, JRep, but not VeRA, fibroblasts activated endothelium to support lymphocyte. Conclusions In RA, fibroblasts undergo two distinct changes in function: first a loss of immunosuppressive responses early in disease development, followed by the later acquisition of a stimulatory phenotype. Fibroblasts exhibit a transitional functional phenotype during the first 3 months of symptoms that contributes to the accumulation of persistent infiltrates. Finally, the role of IL-6 and TGF-β1 changes from immunosuppressive in resolving arthritis to stimulatory very early in the development of RA. Early interventions targeting ‘pathogenic’ fibroblasts may be required in order to restore protective regulatory processes. PMID:28847766

  1. Current Technology for Thermal Protection Systems

    NASA Technical Reports Server (NTRS)

    Scotti, Stephen J. (Compiler)

    1992-01-01

    Interest in thermal protection systems for high-speed vehicles is increasing because of the stringent requirements of such new projects as the Space Exploration Initiative, the National Aero-Space Plane, and the High-Speed Civil Transport, as well as the needs for improved capabilities in existing thermal protection systems in the Space Shuttle and in turbojet engines. This selection of 13 papers from NASA and industry summarizes the history and operational experience of thermal protection systems utilized in the national space program to date, and also covers recent development efforts in thermal insulation, refractory materials and coatings, actively cooled structures, and two-phase thermal control systems.

  2. Benzoate, a D-amino acid oxidase inhibitor, for the treatment of early-phase Alzheimer disease: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Lin, Chieh-Hsin; Chen, Ping-Kun; Chang, Yue-Cune; Chuo, Liang-Jen; Chen, Yan-Syun; Tsai, Guochuan E; Lane, Hsien-Yuan

    2014-05-01

    N-methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission is vital for learning and memory. Hypofunction of NMDAR has been reported to play a role in the pathophysiology of Alzheimer disease (AD), particularly in the early phase. Enhancing NMDAR activation might be a novel treatment approach. One of the methods to enhance NMDAR activity is to raise the levels of NMDA coagonists by blocking their metabolism. This study examined the efficacy and safety of sodium benzoate, a D-amino acid oxidase inhibitor, for the treatment of amnestic mild cognitive impairment and mild AD. We conducted a randomized, double-blind, placebo-controlled trial in four major medical centers in Taiwan. Sixty patients with amnestic mild cognitive impairment or mild AD were treated with 250-750 mg/day of sodium benzoate or placebo for 24 weeks. Alzheimer's Disease Assessment Scale-cognitive subscale (the primary outcome) and global function (assessed by Clinician Interview Based Impression of Change plus Caregiver Input) were measured every 8 weeks. Additional cognition composite was measured at baseline and endpoint. Sodium benzoate produced a better improvement than placebo in Alzheimer's Disease Assessment Scale-cognitive subscale (p = .0021, .0116, and .0031 at week 16, week 24, and endpoint, respectively), additional cognition composite (p = .007 at endpoint) and Clinician Interview Based Impression of Change plus Caregiver Input (p = .015, .016, and .012 at week 16, week 24, and endpoint, respectively). Sodium benzoate was well-tolerated without evident side-effects. Sodium benzoate substantially improved cognitive and overall functions in patients with early-phase AD. The preliminary results show promise for D-amino acid oxidase inhibition as a novel approach for early dementing processes. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  3. Insight as a social identity process in the evolution of psychosocial functioning in the early phase of psychosis.

    PubMed

    Klaas, H S; Clémence, A; Marion-Veyron, R; Antonietti, J-P; Alameda, L; Golay, P; Conus, P

    2017-03-01

    Awareness of illness (insight) has been found to have contradictory effects for different functional outcomes after the early course of psychosis. Whereas it is related to psychotic symptom reduction and medication adherence, it is also associated with increased depressive symptoms. In this line, the specific effects of insight on the evolution of functioning over time have not been identified, and social indicators, such as socio-occupational functioning have barely been considered. Drawing from social identity theory we investigated the impact of insight on the development of psychosocial outcomes and the interactions of these variables over time. The participants, 240 patients in early phase of psychosis from the Treatment and Early Intervention in Psychosis Program (TIPP) of the University Hospital of Lausanne, Switzerland, were assessed at eight time points over 3 years. Cross-lagged panel analyses and multilevel analyses were conducted on socio-occupational and general functioning [Social and Occupational Functioning Assessment Scale (SOFAS) and Global Assessment of Functioning (GAF)] with insight, time and depressive symptoms as independent variables. Results from multilevel analyses point to an overall positive impact of insight on psychosocial functioning, which increases over time. Yet the cross-lagged panel analysis did not reveal a systematic positive and causal effect of insight on SOFAS and GAF scores. Depressive symptoms seem only to be relevant in the beginning of the treatment process. Our results point to a complex process in which the positive impact of insight on psychosocial functioning increases over time, even when considering depressive symptoms. Future studies and treatment approaches should consider the procedural aspect of insight.

  4. 40 CFR 300.315 - Phase IV-Documentation and cost recovery.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 28 2014-07-01 2014-07-01 false Phase IV-Documentation and cost recovery. 300.315 Section 300.315 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS NATIONAL OIL AND HAZARDOUS SUBSTANCES...

  5. 40 CFR 300.315 - Phase IV-Documentation and cost recovery.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Phase IV-Documentation and cost recovery. 300.315 Section 300.315 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS NATIONAL OIL AND HAZARDOUS SUBSTANCES...

  6. 40 CFR 300.315 - Phase IV-Documentation and cost recovery.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Phase IV-Documentation and cost recovery. 300.315 Section 300.315 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SUPERFUND, EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS NATIONAL OIL AND HAZARDOUS SUBSTANCES...

  7. Central State University: Phase III Report

    ERIC Educational Resources Information Center

    Ohio Board of Regents, 2013

    2013-01-01

    This document is the final report on Central State University's implementation of Section 371 of Ohio Amended Substitute House Bill 153. Implementation of Phase I action items required that deliverables and timelines be shifted to give Central State the best opportunity for early success. In Phase II, Central State responded aggressively to a…

  8. 40 CFR 72.92 - Phase I unit allowance surrender.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... chapter) for all Phase I units in the dispatch system. (iii) Calculating percentage change in dispatch... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Phase I unit allowance surrender. 72... (CONTINUED) PERMITS REGULATION Compliance Certification § 72.92 Phase I unit allowance surrender. (a) Annual...

  9. 40 CFR 72.92 - Phase I unit allowance surrender.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... chapter) for all Phase I units in the dispatch system. (iii) Calculating percentage change in dispatch... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Phase I unit allowance surrender. 72... (CONTINUED) PERMITS REGULATION Compliance Certification § 72.92 Phase I unit allowance surrender. (a) Annual...

  10. Life cycle assessment based environmental impact estimation model for pre-stressed concrete beam bridge in the early design phase

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

    Kim, Kyong Ju, E-mail: kjkim@cau.ac.kr; Yun, Won Gun, E-mail: ogun78@naver.com; Cho, Namho, E-mail: nhc51@cau.ac.kr

    The late rise in global concern for environmental issues such as global warming and air pollution is accentuating the need for environmental assessments in the construction industry. Promptly evaluating the environmental loads of the various design alternatives during the early stages of a construction project and adopting the most environmentally sustainable candidate is therefore of large importance. Yet, research on the early evaluation of a construction project's environmental load in order to aid the decision making process is hitherto lacking. In light of this dilemma, this study proposes a model for estimating the environmental load by employing only the mostmore » basic information accessible during the early design phases of a project for the pre-stressed concrete (PSC) beam bridge, the most common bridge structure. Firstly, a life cycle assessment (LCA) was conducted on the data from 99 bridges by integrating the bills of quantities (BOQ) with a life cycle inventory (LCI) database. The processed data was then utilized to construct a case based reasoning (CBR) model for estimating the environmental load. The accuracy of the estimation model was then validated using five test cases; the model's mean absolute error rates (MAER) for the total environmental load was calculated as 7.09%. Such test results were shown to be superior compared to those obtained from a multiple-regression based model and a slab area base-unit analysis model. Henceforth application of this model during the early stages of a project is expected to highly complement environmentally friendly designs and construction by facilitating the swift evaluation of the environmental load from multiple standpoints. - Highlights: • This study is to develop the model of assessing the environmental impacts on LCA. • Bills of quantity from completed designs of PSC Beam were linked with the LCI DB. • Previous cases were used to estimate the environmental load of new case by CBR model. • CBR

  11. Protection against renal ischemia-reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ.

    PubMed

    Dare, Anna J; Bolton, Eleanor A; Pettigrew, Gavin J; Bradley, J Andrew; Saeb-Parsy, Kourosh; Murphy, Michael P

    2015-08-01

    Ischemia-reperfusion (IR) injury to the kidney occurs in a range of clinically important scenarios including hypotension, sepsis and in surgical procedures such as cardiac bypass surgery and kidney transplantation, leading to acute kidney injury (AKI). Mitochondrial oxidative damage is a significant contributor to the early phases of IR injury and may initiate a damaging inflammatory response. Here we assessed whether the mitochondria targeted antioxidant MitoQ could decrease oxidative damage during IR injury and thereby protect kidney function. To do this we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal vessels followed by reperfusion for up to 24h. This caused renal dysfunction, measured by decreased creatinine clearance, and increased markers of oxidative damage. Administering MitoQ to the mice intravenously 15 min prior to ischemia protected the kidney from damage and dysfunction. These data indicate that mitochondrial oxidative damage contributes to kidney IR injury and that mitochondria targeted antioxidants such as MitoQ are potential therapies for renal dysfunction due to IR injury. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  12. Protection against renal ischemia–reperfusion injury in vivo by the mitochondria targeted antioxidant MitoQ

    PubMed Central

    Dare, Anna J.; Bolton, Eleanor A.; Pettigrew, Gavin J.; Bradley, J. Andrew; Saeb-Parsy, Kourosh; Murphy, Michael P.

    2015-01-01

    Ischemia–reperfusion (IR) injury to the kidney occurs in a range of clinically important scenarios including hypotension, sepsis and in surgical procedures such as cardiac bypass surgery and kidney transplantation, leading to acute kidney injury (AKI). Mitochondrial oxidative damage is a significant contributor to the early phases of IR injury and may initiate a damaging inflammatory response. Here we assessed whether the mitochondria targeted antioxidant MitoQ could decrease oxidative damage during IR injury and thereby protect kidney function. To do this we exposed kidneys in mice to in vivo ischemia by bilaterally occluding the renal vessels followed by reperfusion for up to 24 h. This caused renal dysfunction, measured by decreased creatinine clearance, and increased markers of oxidative damage. Administering MitoQ to the mice intravenously 15 min prior to ischemia protected the kidney from damage and dysfunction. These data indicate that mitochondrial oxidative damage contributes to kidney IR injury and that mitochondria targeted antioxidants such as MitoQ are potential therapies for renal dysfunction due to IR injury. PMID:25965144

  13. Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C.

    PubMed

    Lee, Jae-Won; Kim, Won; Kwon, Eun-Kyung; Kim, Yuri; Shin, Hyun Mu; Kim, Dong-Hyun; Min, Chan-Ki; Choi, Ji-Yeob; Lee, Won-Woo; Choi, Myung-Sik; Kim, Byeong Gwan; Cho, Nam-Hyuk

    2017-01-01

    Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients.

  14. Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C

    PubMed Central

    Lee, Jae-Won; Kim, Won; Kwon, Eun-Kyung; Kim, Yuri; Shin, Hyun Mu; Kim, Dong-Hyun; Min, Chan-Ki; Choi, Ji-Yeob; Lee, Won-Woo; Choi, Myung-Sik; Kim, Byeong Gwan

    2017-01-01

    Type I interferons (IFNs) play an important role in antiviral immunity as well as immunopathogenesis of diverse chronic viral infections. However, the precise mechanisms regulating the multifaceted effects of type I IFNs on the immune system and pathological inflammation still remain unclear. In order to assess the immunological dynamics associated with rapid viral clearance in chronic hepatitis C patients during the acute phase of type I IFN therapy, we analyzed multiple parameters of virological and immunological responses in a cohort of 59 Korean hepatitis C patients who received pegylated IFN-α and ribavirin (IFN/RBV). Most of the Korean patients had favorable alleles in the IFN-λ loci for responsiveness to IFN/RBV (i.e., C/C in rs12979860, T/T in rs8099917, and TT/TT in rs368234815). Rapid virological response (RVR) was determined mainly by the hepatitis C virus genotype. Among the cytokines analyzed, higher plasma levels of IL-17A and FGF were observed in non-RVR patients infected with viral genotype 1 and IP-10 was consistently elevated in RVR group infected with genotype 2 during the early phase of antiviral therapy. In addition, these three cytokines were correlated each other, suggesting a functional linkage of the cytokines in antiviral responses during IFN/RBV therapy. A low baseline frequencies of regulatory T cells and γδ T cells, but high level of group 2 innate lymphoid cells, in peripheral bloods were also significantly associated with the RVR group, implicating a potential role of the cellular immunity during the early phase of IFN/RBV therapy. Therefore, the immunological programs established by chronic hepatitis C and rapid disruption of the delicate balance by exogenous type I IFN might be associated with the subsequent virological outcomes in chronic hepatitis C patients. PMID:28614389

  15. Layer Protecting the Surface of Zirconium Used in Nuclear Reactors.

    PubMed

    Ashcheulov, Petr; Skoda, Radek; Skarohlíd, Jan; Taylor, Andrew; Fendrych, Frantisek; Kratochvílová, Irena

    2016-01-01

    Zirconium alloys have very useful properties for nuclear facilities applications having low absorption cross-section of thermal electrons, high ductility, hardness and corrosion resistance. However, there is also a significant disadvantage: it reacts with water steam and during this (oxidative) reaction it releases hydrogen gas, which partly diffuses into the alloy forming zirconium hydrides. A new strategy for surface protection of zirconium alloys against undesirable oxidation in nuclear reactors by polycrystalline diamond film has been patented- Czech patent 305059: Layer protecting the surface of zirconium alloys used in nuclear reactors and PCT patent: Layer for protecting surface of zirconium alloys (Patent Number: WO2015039636-A1). The zirconium alloy surface was covered by polycrystalline diamond layer grown in plasma enhanced chemical vapor deposition apparatus with linear antenna delivery system. Substantial progress in the description and understanding of the polycrystalline diamond/ zirconium alloys interface and material properties under standard and nuclear reactors conditions (irradiation, hot steam oxidation experiments and heating-quenching cycles) was made. In addition, process technology for the deposition of protective polycrystalline diamond films onto the surface of zirconium alloys was optimized. Zircaloy2 nuclear fuel pins were covered by 300 nm thick protective polycrystalline diamond layer (PCD) using plasma enhanced chemical vapor deposition apparatus with linear antenna delivery system. The polycrystalline diamond layer protects the zirconium alloy surface against undesirable oxidation and consolidates its chemical stability while preserving its functionality. PCD covered Zircaloy2 and standard Zircaloy2 pins were for 30 min. oxidized in 1100°C hot steam. Under these conditions α phase of zirconium changes to β phase (more opened for oxygen/hydrogen diffusion). PCD anticorrosion protection of Zircaloy nuclear fuel assemblies can

  16. Dynamic CT for parathyroid disease: are multiple phases necessary?

    PubMed

    Raghavan, P; Durst, C R; Ornan, D A; Mukherjee, S; Wintermark, M; Patrie, J T; Xin, W; Shada, A L; Hanks, J B; Smith, P W

    2014-10-01

    A 4D CT protocol for detection of parathyroid lesions involves obtaining unenhanced, arterial, early, and delayed venous phase images. The aim of the study was to determine the ideal combination of phases that would minimize radiation dose without sacrificing diagnostic accuracy. With institutional review board approval, the records of 29 patients with primary hyperparathyroidism who had undergone surgical exploration were reviewed. Four neuroradiologists who were blinded to the surgical outcome reviewed the imaging studies in 5 combinations (unenhanced and arterial phase; unenhanced, arterial, and early venous; all 4 phases; arterial alone; arterial and early venous phases) with an interval of at least 7 days between each review. The accuracy of interpretation in lateralizing an abnormality to the side of the neck (right, left, ectopic) and localizing it to a quadrant in the neck (right or left upper, right or left lower) was evaluated. The lateralization and localization accuracy (90.5% and 91.5%, respectively) of the arterial phase alone was comparable with the other combinations of phases. There was no statistically significant difference among the different combinations of phases in their ability to lateralize or localize adenomas to a quadrant (P = .976 and .996, respectively). Assessment of a small group of patients shows that adequate diagnostic accuracy for parathyroid adenoma localization may be achievable by obtaining arterial phase images alone. If this outcome can be validated prospectively in a larger group of patients, then the radiation dose can potentially be reduced to one-fourth of what would otherwise be administered. © 2014 by American Journal of Neuroradiology.

  17. Farmers sun exposure, skin protection and public health campaigns: An Australian perspective.

    PubMed

    Smit-Kroner, Christel; Brumby, Susan

    2015-01-01

    Non-melanoma skin cancer is a common and costly cancer in agricultural populations. Prevention and early detection are an effective way to decrease the burden of disease and associated costs. To examine sun exposure and skin protection practices in agricultural workers and farmers a thematic review of the literature between 1983 and 2014 was undertaken. Comparison between studies was complicated by differences in study design, definitions of skin protection, and analytic methods used. Farmers are the most exposed to harmful ultraviolet (UV) radiation of all outdoor workers and the level of reported skin protection by farmers is suboptimal. Years of public health campaigns have failed to adequately address farmers' specific needs. Increased rates of skin cancer and subsequent higher costs are expected. Estimates of sun exposure and skin protection practice indicate that protective clothing is the most promising avenue to improve on farmers' skin protection. Early detection needs to be part of public health campaigns. This review explores the quantitative data about Australian farmers and their skin protective behaviours. We investigate what the documented measurable effect of the public health campaign Slip!Slop!Slap! has had on agricultural workers and farmers and make recommendations for future focus.

  18. Diverse roles of actin in C. elegans early embryogenesis

    PubMed Central

    Velarde, Nathalie; Gunsalus, Kristin C; Piano, Fabio

    2007-01-01

    Background The actin cytoskeleton plays critical roles in early development in Caenorhabditis elegans. To further understand the complex roles of actin in early embryogenesis we use RNAi and in vivo imaging of filamentous actin (F-actin) dynamics. Results Using RNAi, we found processes that are differentially sensitive to levels of actin during early embryogenesis. Mild actin depletion shows defects in cortical ruffling, pseudocleavage, and establishment of polarity, while more severe depletion shows defects in polar body extrusion, cytokinesis, chromosome segregation, and eventually, egg production. These defects indicate that actin is required for proper oocyte development, fertilization, and a wide range of important events during early embryogenesis, including proper chromosome segregation. In vivo visualization of the cortical actin cytoskeleton shows dynamics that parallel but are distinct from the previously described myosin dynamics. Two distinct types of actin organization are observed at the cortex. During asymmetric polarization to the anterior, or the establishment phase (Phase I), actin forms a meshwork of microfilaments and focal accumulations throughout the cortex, while during the anterior maintenance phase (Phase II) it undergoes a morphological transition to asymmetrically localized puncta. The proper asymmetric redistribution is dependent on the PAR proteins, while both asymmetric redistribution and morphological transitions are dependent upon PFN-1 and NMY-2. Just before cytokinesis, actin disappears from most of the cortex and is only found around the presumptive cytokinetic furrow. Finally, we describe dynamic actin-enriched comets in the early embryo. Conclusion During early C. elegans embryogenesis actin plays more roles and its organization is more dynamic than previously described. Morphological transitions of F-actin, from meshwork to puncta, as well as asymmetric redistribution, are regulated by the PAR proteins. Results from this study

  19. Symmetry-protected topological insulator and its symmetry-enriched topologically ordered boundary

    NASA Astrophysics Data System (ADS)

    Wang, Juven; Wen, Xiao-Gang; Witten, Edward

    We propose a mechanism for achieving symmetry-enriched topologically ordered boundaries for symmetry-protected topological states, including those of topological insulators. Several different boundary phases and their phase transitions are considered, including confined phases, deconfined phases, symmetry-breaking, gapped and gapless phases. National Science Foundation PHY-1606531, Corning Glass Works Foundation Fellowship, NSF Grant DMR- 1506475 and NSFC 11274192, the BMO Financial Group and the John Templeton Foundation No. 39901.

  20. Risks to Early Childhood Health and Development in the Postconflict Transition of Northern Uganda

    PubMed Central

    McElroy, Theresa A.; Atim, Stella; Larson, Charles P.; Armstrong, Robert W.

    2012-01-01

    Research from numerous fields of science has documented the critical importance of nurturing environments in shaping young children's future health and development. We studied the environments of early childhood (birth to 3 years) during postconflict, postdisplacement transition in northern Uganda. The aim was to better understand perceived needs and risks in order to recommend targeted policy and interventions. Methods. Applied ethnography (interview, focus group discussion, case study, observational methods, document review) in 3 sites over 1 year. Results. Transition was a prolonged and deeply challenging phase for families. Young children were exposed to a myriad of risk factors. Participants recognized risks as potential barriers to positive long-term life outcomes for children and society but circumstances generally rendered them unable to make substantive changes. Conclusions. Support structures were inadequate to protect the health and development of children during the transitional period placing infants and young children at risk. Specific policy and practice guidelines are required that focus on protecting hard-to-reach, vulnerable, children during what can be prolonged and extremely difficult periods of transition. PMID:22518183

  1. Simple uncertainty propagation for early design phase aircraft sizing

    NASA Astrophysics Data System (ADS)

    Lenz, Annelise

    Many designers and systems analysts are aware of the uncertainty inherent in their aircraft sizing studies; however, few incorporate methods to address and quantify this uncertainty. Many aircraft design studies use semi-empirical predictors based on a historical database and contain uncertainty -- a portion of which can be measured and quantified. In cases where historical information is not available, surrogate models built from higher-fidelity analyses often provide predictors for design studies where the computational cost of directly using the high-fidelity analyses is prohibitive. These surrogate models contain uncertainty, some of which is quantifiable. However, rather than quantifying this uncertainty, many designers merely include a safety factor or design margin in the constraints to account for the variability between the predicted and actual results. This can become problematic if a designer does not estimate the amount of variability correctly, which then can result in either an "over-designed" or "under-designed" aircraft. "Under-designed" and some "over-designed" aircraft will likely require design changes late in the process and will ultimately require more time and money to create; other "over-designed" aircraft concepts may not require design changes, but could end up being more costly than necessary. Including and propagating uncertainty early in the design phase so designers can quantify some of the errors in the predictors could help mitigate the extent of this additional cost. The method proposed here seeks to provide a systematic approach for characterizing a portion of the uncertainties that designers are aware of and propagating it throughout the design process in a procedure that is easy to understand and implement. Using Monte Carlo simulations that sample from quantified distributions will allow a systems analyst to use a carpet plot-like approach to make statements like: "The aircraft is 'P'% likely to weigh 'X' lbs or less, given the

  2. Logistics planning for phased programs.

    NASA Technical Reports Server (NTRS)

    Cook, W. H.

    1973-01-01

    It is pointed out that the proper and early integration of logistics planning into the phased program planning process will drastically reduce these logistics costs. Phased project planning is a phased approach to the planning, approval, and conduct of major research and development activity. A progressive build-up of knowledge of all aspects of the program is provided. Elements of logistics are discussed together with aspects of integrated logistics support, logistics program planning, and logistics activities for phased programs. Continuing logistics support can only be assured if there is a comprehensive sequential listing of all logistics activities tied to the program schedule and a real-time inventory of assets.

  3. The radial growth phase of malignant melanoma: multi-phase modelling, numerical simulations and linear stability analysis.

    PubMed

    Ciarletta, P; Foret, L; Ben Amar, M

    2011-03-06

    Cutaneous melanoma is disproportionately lethal despite its relatively low incidence and its potential for cure in the early stages. The aim of this study is to foster understanding of the role of microstructure on the occurrence of morphological changes in diseased skin during melanoma evolution. The authors propose a biomechanical analysis of its radial growth phase, investigating the role of intercellular/stromal connections on the initial stages of epidermis invasion. The radial growth phase of a primary melanoma is modelled within the multi-phase theory of mixtures, reproducing the mechanical behaviour of the skin layers and of the epidermal-dermal junction. The theoretical analysis takes into account those cellular processes that have been experimentally observed to disrupt homeostasis in normal epidermis. Numerical simulations demonstrate that the loss of adhesiveness of the melanoma cells both to the basal laminae, caused by deregulation mechanisms of adherent junctions, and to adjacent keratynocytes, consequent to a downregulation of E-cadherin, are the fundamental biomechanical features for promoting tumour initiation. Finally, the authors provide the mathematical proof of a long wavelength instability of the tumour front during the early stages of melanoma invasion. These results open the perspective to correlate the early morphology of a growing melanoma with the biomechanical characteristics of its micro-environment.

  4. The radial growth phase of malignant melanoma: multi-phase modelling, numerical simulations and linear stability analysis

    PubMed Central

    Ciarletta, P.; Foret, L.; Ben Amar, M.

    2011-01-01

    Cutaneous melanoma is disproportionately lethal despite its relatively low incidence and its potential for cure in the early stages. The aim of this study is to foster understanding of the role of microstructure on the occurrence of morphological changes in diseased skin during melanoma evolution. The authors propose a biomechanical analysis of its radial growth phase, investigating the role of intercellular/stromal connections on the initial stages of epidermis invasion. The radial growth phase of a primary melanoma is modelled within the multi-phase theory of mixtures, reproducing the mechanical behaviour of the skin layers and of the epidermal–dermal junction. The theoretical analysis takes into account those cellular processes that have been experimentally observed to disrupt homeostasis in normal epidermis. Numerical simulations demonstrate that the loss of adhesiveness of the melanoma cells both to the basal laminae, caused by deregulation mechanisms of adherent junctions, and to adjacent keratynocytes, consequent to a downregulation of E-cadherin, are the fundamental biomechanical features for promoting tumour initiation. Finally, the authors provide the mathematical proof of a long wavelength instability of the tumour front during the early stages of melanoma invasion. These results open the perspective to correlate the early morphology of a growing melanoma with the biomechanical characteristics of its micro-environment. PMID:20656740

  5. 34 CFR 97.123 - Early termination of research support: Evaluation of applications and proposals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROTECTION OF HUMAN SUBJECTS Federal Policy for the Protection of Human Subjects (Basic ED Policy for Protection of Human Research Subjects) § 97.123 Early termination of research support: Evaluation of... the protection of the rights and welfare of human subjects (whether or not the research was subject to...

  6. Study design and early result of a phase I study of SABR for early-stage glottic cancer.

    PubMed

    Yu, Tosol; Wee, Chan Woo; Choi, Noorie; Wu, Hong-Gyun; Kang, Hyun-Cheol; Park, Jong Min; Kim, Jung-In; Kim, Jin Ho; Kwon, Tack-Kyun; Chung, Eun-Jae

    2018-05-14

    Avoidance of organs at risk has become possible with advances in image-guided volumetric-modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level. Fraction size was increased from 3.5 gray (Gy) (total dose 59.5 Gy) to 9 Gy (total dose 45 Gy). Dose-limiting toxicities were defined as grade 3 or higher treatment-related toxicities. Voice outcome was assessed with electroglottography, and quality of life (QoL) was measured with the Head and Neck Cancer Inventory (HNCI). Seven patients received 59.5 Gy at 3.5 Gy per fraction as the first dose level, and five patients received 55 Gy at 5 Gy per fraction as the second dose level. None of the patients developed grade 3+ toxicity throughout a median follow-up of 17.5 months (range, 1.7-30.6 months). One patient in the second dose level recurred in the primary site at 4 months after radiotherapy (RT) and received total laryngectomy. The rest of participants were disease-free at locoregional and distant sites. Jitter, shimmer, mean phonation time, and noise-to-harmony ratio did not change significantly at 6 months after RT. HNCI scores between pretreatment and posttreatment were not significantly different (P = 0.221). This study revealed acceptable toxicity, voice outcome, and QoL in patients treated with hypofractionated VMAT of 3.5 Gy and 5 Gy per fraction. This phase I study is currently ongoing with a dose of 55 Gy in 11 fractions and 45 Gy in five fractions. 2b. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

  7. Gender-specific reduction of hepatic Mrp2 expression by high-fat diet protects female mice from ANIT toxicity

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

    Kong, Bo; Csanaky, Iván L.; Aleksunes, Lauren M.

    Emerging evidence suggests that feeding a high-fat diet (HFD) to rodents affects the expression of genes involved in drug transport. However, gender-specific effects of HFD on drug transport are not known. The multidrug resistance-associated protein 2 (Mrp2, Abcc2) is a transporter highly expressed in the hepatocyte canalicular membrane and is important for biliary excretion of glutathione-conjugated chemicals. The current study showed that hepatic Mrp2 expression was reduced by HFD feeding only in female, but not male, C57BL/6J mice. In order to determine whether down-regulation of Mrp2 in female mice altered chemical disposition and toxicity, the biliary excretion and hepatotoxicity ofmore » the Mrp2 substrate, α-naphthylisothiocyanate (ANIT), were assessed in male and female mice fed control diet or HFD for 4 weeks. ANIT-induced biliary injury is a commonly used model of experimental cholestasis and has been shown to be dependent upon Mrp2-mediated efflux of an ANIT glutathione conjugate that selectively injures biliary epithelial cells. Interestingly, HFD feeding significantly reduced early-phase biliary ANIT excretion in female mice and largely protected against ANIT-induced liver injury. In summary, the current study showed that, at least in mice, HFD feeding can differentially regulate Mrp2 expression and function and depending upon the chemical exposure may enhance or reduce susceptibility to toxicity. Taken together, these data provide a novel interaction between diet and gender in regulating hepatobiliary excretion and susceptibility to injury. -- Highlights: ► High-fat diet decreases hepatic Mrp2 expression only in female but not in male mice. ► HFD significantly reduces early-phase biliary ANIT excretion in female mice. ► HFD protects female mice against ANIT-induced liver injury.« less

  8. Unconventional transformation of spin Dirac phase across a topological quantum phase transition

    PubMed Central

    Xu, Su-Yang; Neupane, Madhab; Belopolski, Ilya; Liu, Chang; Alidoust, Nasser; Bian, Guang; Jia, Shuang; Landolt, Gabriel; Slomski, Batosz; Dil, J. Hugo; Shibayev, Pavel P.; Basak, Susmita; Chang, Tay-Rong; Jeng, Horng-Tay; Cava, Robert J.; Lin, Hsin; Bansil, Arun; Hasan, M. Zahid

    2015-01-01

    The topology of a topological material can be encoded in its surface states. These surface states can only be removed by a bulk topological quantum phase transition into a trivial phase. Here we use photoemission spectroscopy to image the formation of protected surface states in a topological insulator as we chemically tune the system through a topological transition. Surprisingly, we discover an exotic spin-momentum locked, gapped surface state in the trivial phase that shares many important properties with the actual topological surface state in anticipation of the change of topology. Using a spin-resolved measurement, we show that apart from a surface bandgap these states develop spin textures similar to the topological surface states well before the transition. Our results offer a general paradigm for understanding how surface states in topological phases arise from a quantum phase transition and are suggestive for the future realization of Weyl arcs, condensed matter supersymmetry and other fascinating phenomena in the vicinity of a quantum criticality. PMID:25882717

  9. Early marijuana initiation: The link between prenatal marijuana exposure, early childhood behavior, and negative adult roles.

    PubMed

    Goldschmidt, Lidush; Richardson, Gale A; Larkby, Cynthia; Day, Nancy L

    We investigated the associations among gestational factors including prenatal marijuana exposure (PME), child behavior at age 3, early age of onset of marijuana use (EAOM, <15years), and adult roles at 22years. Participants were drawn from the Maternal Health Practices and Child Development (MHPCD) Project, a longitudinal study of prenatal substance exposure in offspring who have been studied for over 22years since the prenatal phase. Data from the prenatal, birth, 3-, and 22-year phases (N=608) were used in the present study. Age of onset of offspring substance use was determined based on data from the 14-, 16-, and 22-year phases. The subjects were of lower socioeconomic status, 43% were Caucasian and the remaining were African-American, and 48% were males. Early childhood behavior was significantly (p<0.05) related to EAOM after controlling for PME, birth and childhood environmental risk factors, and Conduct Disorder. EAOM was significantly associated with negative adult roles including increased risk of being arrested (p<0.001), lower educational attainment (p<0.001), having a child without being married (p<0.05), and unemployment at 22years (p<0.001). The correlations between PME and negative adult roles and between early childhood behavior and negative adult roles were also statistically significant. Pathway analysis demonstrated that EAOM significantly mediated the associations between PME and fulfillment of adult roles and between early childhood behavior and adult roles. There are a number of intervention points that could be targeted that would have a long-term impact on lowering the probability of EAOM and less success in adult roles. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice.

    PubMed

    Seki, Ekihiro; Tsutsui, Hiroko; Tsuji, Noriko M; Hayashi, Nobuki; Adachi, Keishi; Nakano, Hiroki; Futatsugi-Yumikura, Shizue; Takeuchi, Osamu; Hoshino, Katsuaki; Akira, Shizuo; Fujimoto, Jiro; Nakanishi, Kenji

    2002-10-01

    Listeria monocytogenes (LM), a facultative intracellular Gram-positive bacterium, often causes lethal infection of the host. In this study we investigated the molecular mechanism underlying LM eradication in the early phase of infection. Upon infection with LM, both IL-12 and IL-18 were produced, and then they synergistically induced IFN-gamma production, leading to normal LM clearance in the host. IFN-gamma knockout (KO) mice were highly susceptible to LM infection. IL-12/IL-18 double knockout mice were also highly susceptible. Their susceptibility was less than that of IFN-gamma KO mice, but more than that of single IL-12 or IL-18 KO mice. Mice deficient in myeloid differentiation factor 88 (MyD88), an essential adaptor molecule used by signal transduction pathways of all members of the Toll-like receptor (TLR) family, showed an inability to produce IL-12 and IFN-gamma following LM infection and were most susceptible to LM. Furthermore, MyD88-deficient, but not IFN-gamma-deficient, Kupffer cells could not produce TNF-alpha in response to LM in vitro, indicating the importance of MyD88-dependent TNF-alpha production for host defense. As TLR2 KO, but not TLR4 KO, mice showed partial impairment in their capacity to produce IL-12, IFN-gamma, and TNF-alpha, TLR2 activation partly contributed to the induction of IL-12-mediated IFN-gamma production. These results indicated a critical role for TLRs/MyD88-dependent IL-12/TNF-alpha production and for IL-12- and IL-18-mediated IFN-gamma production in early phase clearance of LM.

  11. Temporal Genetic Dynamics of an Invasive Species, Frankliniella occidentalis (Pergande), in an Early Phase of Establishment.

    PubMed

    Yang, Xian-Ming; Lou, Heng; Sun, Jing-Tao; Zhu, Yi-Ming; Xue, Xiao-Feng; Hong, Xiao-Yue

    2015-07-03

    Many species can successfully colonize new areas despite their propagules having low genetic variation. We assessed whether the decreased genetic diversity could result in temporal fluctuations of genetic parameters of the new populations of an invasive species, western flower thrips, Frankliniella occidentalis, using mitochondrial and microsatellite markers. This study was conducted in eight localities from four climate regions in China, where F. occidentalis was introduced in the year 2000 and had lower genetic diversity than its native populations. We also tested the level of genetic differentiation in these introduced populations. The genetic diversity of the samples at different years in the same locality was not significantly different from each other in most localities. FST and STRUCTURE analysis also showed that most temporal population comparisons from the same sites were not significantly differentiated. Our results showed that the invasive populations of F. occidentalis in China can maintain temporal stability in genetic composition at an early phase of establishment despite having lower genetic diversity than in their native range.

  12. NHEXAS PHASE I MARYLAND STUDY

    EPA Science Inventory

    The National Human Exposure Assessment Survey (NHEXAS) is a federal interagency research effort coordinated by the Environmental Protection Agency (EPA), Office of Research and Development (ORD). Phase I consists of demonstration/scoping studies using probability-based sampling ...

  13. Illness versus substance use effects on the frontal white matter in early phase schizophrenia: A 4Tesla (1)H-MRS study.

    PubMed

    Bernier, Denise; Bartha, Robert; McAllindon, David; Hanstock, Christopher C; Marchand, Yannick; Dillen, Kim N H; Gallant, Michelle; Good, Kimberly P; Tibbo, Philip G

    2016-08-01

    Young adults with early phase schizophrenia often report a past or current pattern of illicit substance use and/or alcohol misuse. Still, little is known about the cumulative and separate effects of each stressor on white matter tissue, at this vulnerable period of brain development. Participants involved 24 healthy controls with a past or current history of sustained illicit drug use and/or alcohol misuse (users), 23 healthy controls without such history (normative data), and 27 users with early phase schizophrenia. (1)H-MRS data were acquired from a large frontal volume encompassing 95% of white matter, using a 4Tesla scanner (LASER sequence, TR/TE 3200/46ms). Reduced levels of choline-containing compounds (Cho) were specific to the effect of illness (Cohen's d=0.68), with 22% of the variance in Cho levels accounted for by duration of illness. Reduced levels of myoInositol (d=1.10) and creatine plus phosphocreatine (d=1.07) were specific to the effects of illness plus substance use. Effect of substance use on its own was revealed by reductions in levels of glutamate plus glutamine (d=0.83) in control users relative to normative data. The specific effect of illness on white matter might indicate a decreased synthesis of membrane phospholipids or alternatively, reduced membrane cellular density. In terms of limitations, this study did not include patients without a lifetime history of substance use (non-users), and the specific effect of each substance used could not be studied separately. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. 40 CFR 80.1275 - How are early benzene credits generated?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 16 2011-07-01 2011-07-01 false How are early benzene credits... PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Averaging, Banking and Trading (abt) Program § 80.1275 How are early benzene credits generated? (a) For each averaging period per...

  15. 40 CFR 80.1275 - How are early benzene credits generated?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 17 2013-07-01 2013-07-01 false How are early benzene credits... PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Averaging, Banking and Trading (abt) Program § 80.1275 How are early benzene credits generated? (a) For each averaging period per...

  16. 40 CFR 80.1275 - How are early benzene credits generated?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 17 2012-07-01 2012-07-01 false How are early benzene credits... PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Averaging, Banking and Trading (abt) Program § 80.1275 How are early benzene credits generated? (a) For each averaging period per...

  17. 40 CFR 80.1275 - How are early benzene credits generated?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false How are early benzene credits... PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Averaging, Banking and Trading (abt) Program § 80.1275 How are early benzene credits generated? (a) For each averaging period per...

  18. 40 CFR 80.1275 - How are early benzene credits generated?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 17 2014-07-01 2014-07-01 false How are early benzene credits... PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Averaging, Banking and Trading (abt) Program § 80.1275 How are early benzene credits generated? (a) For each averaging period per...

  19. Solid phase microextraction field kit

    DOEpatents

    Nunes, Peter J.; Andresen, Brian D.

    2005-08-16

    A field kit for the collection, isolation and concentration of trace amounts of high explosives (HE), biological weapons (BW) and chemical weapons (CW) residues in air, soil, vegetation, swipe, and liquid samples. The field kit includes a number of Solid Phase Microextraction (SPME) fiber and syringe assemblies in a hermetically sealed transportation container or tubes which includes a sampling port, a number of extra SPME fiber and syringe assemblies, the fiber and syringe assemblies including a protective cap for the fiber, and an extractor for the protective cap, along with other items including spare parts, protective glove, and an instruction manual, all located in an airtight container.

  20. Sickle cell protection from malaria.

    PubMed

    Eridani, Sandro

    2011-10-19

    A linkage between presence of Sickle Haemoglobin (HbS) and protection from malaria infection and clinical manifestations in certain areas was suspected from early observations and progressively elucidated by more recent studies. Research has confirmed the abovementioned connection, but also clarified how such protection may be abolished by coexistence of sickle cell trait (HbS trait) and alpha thalassemia, which may explain the relatively low incidence of HbS trait in the Mediterranean. The mechanisms of such protective effect are now being investigated: factors of genetic, molecular and immunological nature are prominent. As for genetic factors attention is given to the role of the red blood cell (RBC) membrane complement regulatory proteins as polymorphisms of these components seem to be associated with resistance to severe malaria; genetic ligands like the Duffy group blood antigen, necessary for erythrocytic invasion, and human protein CD36, a major receptor for P. falciparum-infected RBC's, are also under scrutiny: attention is focused also on plasmodium erythrocyte-binding antigens, which bind to RBC surface components. Genome-wide linkage and association studies are now carried out too, in order to identify genes associated with malaria resistance. Only a minor role is attributed to intravascular sickling, phagocytosis and haemolysis, while specific molecular mechanisms are the object of intensive research: among these a decisive role is played by a biochemical sequence, involving activation of haeme oxygenase (HMO-1), whose effect appears mediated by carbon monoxide (CO). A central role in protection from malaria is also played by immunological factors, which may stimulate antibody production to plasmodium antigens in the early years of life; the role of agents like pathogenic CD8 T-cells has been suggested while the effects of molecular actions on the immunity mechanism are presently investigated. It thus appears that protection from malaria can be