Sample records for undergoes major structural

  1. Surgical management of tumors invading the aorta and major arterial structures.

    PubMed

    Carpenter, Susanne G; Stone, William M; Bower, Thomas C; Fowl, Richard J; Money, Samuel R

    2011-11-01

    This study investigates surgical management of tumors arising from or involving the aorta and major arterial structures. A retrospective single institutional review was conducted of patients undergoing arterial resection for tumors involving the aorta or major arterial structures between January 1992 and May 2009 at a tertiary care center. Patients with tumors abutting arteries without necessitating resection and those involving only venous structures were excluded. Patients were analyzed in groups by vessel involvement: aorta, carotid, external/common iliac, internal iliac, superficial femoral, and miscellaneous. Sixty patients were identified and included for review. The iliac arteries were most often resected, and sarcomatous pathology was most common (37 patients, 62%). Twelve patients underwent aortic resection, with eight (67%) of these undergoing graft reconstruction, one (8%) graft patch, and two (17%) primary repair. None of the 17 patients undergoing internal iliac resection underwent reconstruction, whereas the majority of patients in all other groups underwent reconstruction. Thirty-day mortality (TDM) was 0% in all groups, except the aortic (2/12, 17% TDM), and internal iliac arteries (1/17, 6% TDM). Estimated blood loss varied widely and was not significantly different between vessel groups (p = 0.280). Overall, 44 of 60 (73%) patients had negative margins. Fourteen patients (23%) returned to the operating room, most for wound infection or dehiscence. Mean follow-up was 20.25 months (range: 0.5-122.0 months, SD: 23 months). Forty patients were followed up for more than 1 year. Thus, with an overall median follow-up of 12.25 months, overall survival was 60% with disease-free survival of 40%. Resection of tumors involving the aorta and major arterial structures provides a reasonable option for treatment, but with significant perioperative morbidity. In selected patients, this aggressive intervention should be considered. Copyright © 2011 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

  2. KSC-03pd0262

    NASA Image and Video Library

    2003-02-04

    KENNEDY SPACE CENTER, FLA. -- United Space Alliance (USA) technicians install thermal protection system tiles on Space Shuttle Discovery. Discovery is undergoing its Orbiter Major Modification Period, a regularly scheduled structural inspection and modification downtime, which began in September 2002. .

  3. Analysis of an industry in transition.

    PubMed

    Baliga, B R; Johnson, B

    1986-12-01

    The health care industry is undergoing major structural changes. The significance of these changes for individual competitors moving toward the 1990s is not yet clear. This article assesses the implications of the current changes by applying Porter's industry structure and generic strategy frameworks to the health care industry. Present trends are compared to this analysis to highlight areas where individual hospitals might improve their competitive positioning.

  4. Evidence for a Major Merger Origin of High-Redshift Submillimeter Galaxies

    NASA Astrophysics Data System (ADS)

    Conselice, Christopher J.; Chapman, Scott C.; Windhorst, Rogier A.

    2003-10-01

    Submillimeter-detected galaxies located at redshifts z>1 host a major fraction of the bolometric luminosity at high redshifts due to thermal emission from heated dust grains, yet the nature of these objects remains a mystery. The major problem in understanding their origin is whether the dust-heating mechanism is predominantly caused by star formation or active galactic nuclei and what triggered this activity. We address this issue by examining the structures of 11 submillimeter galaxies imaged with STIS on the Hubble Space Telescope. We argue that ~61%+/-21% of these submillimeter sources are undergoing an active major merger using the CAS (concentration, asymmetry, clumpiness) quantitative morphological system. We rule out at ~5 σ confidence that these submillimeter galaxies are normal Hubble types at high redshift. This merger fraction appears to be higher than for Lyman break galaxies undergoing mergers at similar redshifts. Using reasonable constraints on the stellar masses of Lyman break galaxies and these submillimeter sources, we further argue that at redshifts z~2-3, systems with high stellar masses are more likely than lower mass galaxies to be involved in major mergers.

  5. Structural Development of Finnish Universities: Achieving Competitiveness and Academic Excellence

    ERIC Educational Resources Information Center

    Tirronen, Jarkko; Nokkala, Terhi

    2009-01-01

    This paper discusses strategic instruments that are used to enhance the competitiveness of Finnish universities in the context of globalisation, internationalisation and commercialisation of research and education. The Finnish higher education system is currently undergoing a major policy reform, which aims to enhance the competitiveness of…

  6. A Stay-Rich View of the New Global Economy

    ERIC Educational Resources Information Center

    Trusteeship, 2011

    2011-01-01

    Major demographic changes around the world. Disproportionate sovereign debt. A shift from North America, Western Europe, and Japan to emerging economies as centers of growth. Unprecedented levels of market risk and volatility. The structure of the global economy is undergoing significant changes. Michael Oyster, managing principal of Fund…

  7. Envelope Structures of Gram-Positive Bacteria

    PubMed Central

    Rajagopal, Mithila; Walker, Suzanne

    2016-01-01

    Gram-positive organisms, including the pathogens Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus faecalis, have dynamic cell envelopes that mediate interactions with the environment and serve as the first line of defense against toxic molecules. Major components of the cell envelope include peptidoglycan, which is a well-established target for antibiotics, teichoic acids, capsular polysaccharides, surface proteins, and phospholipids. These components can undergo modification to promote pathogenesis, decrease susceptibility to antibiotics and host immune defenses, and enhance survival in hostile environments. This chapter will cover the structure, biosynthesis and important functions of major cell envelope components in Gram-positive bacteria. Possible targets for new antimicrobials will be noted. PMID:26919863

  8. Music is Beneficial for Awake Craniotomy Patients: A Qualitative Study.

    PubMed

    Jadavji-Mithani, Radhika; Venkatraghavan, Lashmi; Bernstein, Mark

    2015-01-01

    Patients undergoing awake craniotomy may experience high levels of stress. Minimizing anxiety benefits patients and surgeons. Music has many therapeutic effects in altering human mood and emotion. Tonality of music as conveyed by composition in major or minor keys can have an impact on patients' emotions and thoughts. Assessing the effects of listening to major and minor key musical pieces on patients undergoing awake craniotiomy could help in the design of interventions to alleviate anxiety, stress and tension. Twenty-nine patients who were undergoing awake craniotomy were recruited and randomly assigned into two groups: Group 1 subjects listened to major key music and Group 2 listened to minor key compositions. Subjects completed a demographics questionnaire, a pre- and post-operative Beck Anxiety Inventory (BAI) and a semi-structured open-ended interview. RESULTS were analyzed using modified thematic analysis through open and axial coding. Overall, patients enjoyed the music regardless of the key distinctions and stated they benefitted from listening to the music. No adverse reactions to the music were found. Subjects remarked that the music made them feel more at ease and less anxious before, during and after their procedure. Patients preferred either major key or minor key music but not a combination of both. Those who preferred major key pieces said it was on the basis of tonality while the individuals who selected minor key pieces stated that tempo of the music was the primary factor. Overall, listening to music selections was beneficial for the patients. Future work should further investigate the effects of audio interventions in awake surgery through narrative means.

  9. Priority research and management issues for the imperiled Great Basin of the western United States

    Treesearch

    Jeanne C. Chambers; Michael J. Wisdom

    2009-01-01

    Like many arid and semiarid regions, the Great Basin of the western United States is undergoing major ecological, social, and economic changes that are having widespread detrimental effects on the structure, composition, and function of native ecosystems. The causes of change are highly interactive and include urban, suburban, and exurban growth, past and present land...

  10. Stream Nitrate Response to Different Burning Treatments in Southern Appalachian Forests

    Treesearch

    Barton D. Clinton; James M. Vose; Jennifer D. Knoepp; Katherine J. Elliott

    2003-01-01

    Southern Appalachian forests are undergoing considerable change due to altered disturbance regimes. For example, fire exclusion has had a major impact on the structure and function of pine-hardwood ecosystems. Recently, fire has been prescribed for a variety of applications: 1) stand-replacement in the form of a mimicked wildfire, 2) site-preparation as part of a fell-...

  11. Detailed fetal anatomy assessment in the first trimester at 11, 12 and 13 weeks of gestation.

    PubMed

    Luchi, Carlo; Schifano, Martina; Sacchini, Clara; Nanini, Chiara; Sceusa, Francesca; Capriello, Patrizio; Genazzani, Andrea R

    2012-06-01

    The aim of the present observational study was to evaluate the feasibility of a morphological scan and determine the detection rate of fetal organs, structures and systems in the first trimester of pregnancy. 977 single pregnant women attending our Fetal Medicine Section to undergo first trimester screening for aneuploidies were enrolled and divided into three groups depending on gestational age and crown-rump-length measurement. Scans targeted on a total of 26 fetal anatomical structures were performed by a single operator. The overall detection rate was 96% at 11 weeks and reached 100% at 12 and 13 weeks, with a significant statistical difference between 11 and 12/13 weeks for the majority of the investigated fetal anatomical structures. Evaluation of most part of the fetal anatomical structures is feasible with high accuracy in the first trimester. Visualization of the majority of the targeted fetal organs improves from 11 to 13 weeks.

  12. The Feasibility of a Cadre Approach to Mobilization

    DTIC Science & Technology

    1990-05-01

    system, legislation was now required to structure and organize the force. Subsequentlythe Militia Act of 1792 was passsed and after being heavily...States was questioned. Thus, several legislative acts were passed between 1903 to 1933, which formulated the National Guard as it is known today, and...have to undergo major legislative revisions regarding the authority over the National Guard, its state versus national responsibilities, and the amount

  13. Structural Maturation of HIV-1 Reverse Transcriptase—A Metamorphic Solution to Genomic Instability

    PubMed Central

    London, Robert E.

    2016-01-01

    Human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT)—a critical enzyme of the viral life cycle—undergoes a complex maturation process, required so that a pair of p66 precursor proteins can develop conformationally along different pathways, one evolving to form active polymerase and ribonuclease H (RH) domains, while the second forms a non-functional polymerase and a proteolyzed RH domain. These parallel maturation pathways rely on the structural ambiguity of a metamorphic polymerase domain, for which the sequence–structure relationship is not unique. Recent nuclear magnetic resonance (NMR) studies utilizing selective labeling techniques, and structural characterization of the p66 monomer precursor have provided important insights into the details of this maturation pathway, revealing many aspects of the three major steps involved: (1) domain rearrangement; (2) dimerization; and (3) subunit-selective RH domain proteolysis. This review summarizes the major structural changes that occur during the maturation process. We also highlight how mutations, often viewed within the context of the mature RT heterodimer, can exert a major influence on maturation and dimerization. It is further suggested that several steps in the RT maturation pathway may provide attractive targets for drug development. PMID:27690082

  14. Polyreactive Antibodies Plus Complement Enhance the Phagocytosis of Cells Made Apoptotic by UV-Light or HIV

    PubMed Central

    Zhou, Zhao-hua; Wild, Teresa; Xiong, Ying; Sylvers, Peter; Zhang, Yahong; Zhang, Luxia; Wahl, Larry; Wahl, Sharon M.; Kozlowski, Steven; Notkins, Abner L.

    2013-01-01

    Polyreactive antibodies are a major component of the natural antibody repertoire and are capable of binding a variety of structurally unrelated antigens. Many of the properties attributed to natural antibodies, in fact, are turning out to be due to polyreactive antibodies. In humans, each day, billions of cells undergo apoptosis. In the present experiments, we show by ImageStream technology that although polyreactive antibodies do not bind to live T cells they bind to both the plasma membrane and cytoplasm of late apoptotic cells, fix complement, generate the anaphylatoxin C5a and increase by as much as 5 fold complement-mediated phagocytosis by macrophages. Of particular importance, T cells undergoing apoptosis following infection with HIV also bind polyreactive antibodies and are phagocytosed. We conclude that the polyreactive antibodies in the natural antibody repertoire contribute in a major way to the clearance of cells made apoptotic by a variety of natural and infectious processes. PMID:23881356

  15. From structure to mechanism—understanding initiation of DNA replication

    PubMed Central

    Riera, Alberto; Barbon, Marta; Noguchi, Yasunori; Reuter, L. Maximilian; Schneider, Sarah; Speck, Christian

    2017-01-01

    DNA replication results in the doubling of the genome prior to cell division. This process requires the assembly of 50 or more protein factors into a replication fork. Here, we review recent structural and biochemical insights that start to explain how specific proteins recognize DNA replication origins, load the replicative helicase on DNA, unwind DNA, synthesize new DNA strands, and reassemble chromatin. We focus on the minichromosome maintenance (MCM2–7) proteins, which form the core of the eukaryotic replication fork, as this complex undergoes major structural rearrangements in order to engage with DNA, regulate its DNA-unwinding activity, and maintain genome stability. PMID:28717046

  16. Human Resources Planning in the Republic of Korea. Improving Technical Education and Vocational Training. World Bank Staff Working Papers Number 554.

    ERIC Educational Resources Information Center

    Lee, Kye-Woo

    During the 1980s the Korean economy will have to undergo far-reaching structural changes. The major problems faced by the Korean labor market continue to be an excessive demand for college graduates and an excessive supply of high school graduates. Their solution requires a renewed national commitment to human resource development with emphasis on…

  17. Attitudes of Patients With Cancer About Personalized Medicine and Somatic Genetic Testing

    PubMed Central

    Gray, Stacy W.; Hicks-Courant, Katherine; Lathan, Christopher S.; Garraway, Levi; Park, Elyse R.; Weeks, Jane C.

    2012-01-01

    Purpose: Dramatic advances in genomic technology stand to revolutionize cancer care; however, little is known about patients' understanding and acceptance of personalized medicine and widespread genetic testing (GT). Patients and Methods: We conducted a formative, semi-structured interview study with a random sample of patients with lung, colorectal, and breast cancers to assess awareness of personalized medicine and GT and attitudes about somatic GT. Willingness to undergo GT was elicited through hypothetic scenarios. Results: Sixty-nine patients participated; 71% were women; 42% were black; median age was 59 years; and 42% had an education level ≥ college. We found that a majority of patients either were not aware of the term “personalized medicine” or defined it in unexpected ways. Although many patients identified relevant benefits of somatic testing (eg, informs treatment), many patients also expressed significant concerns (ie, psychological harm and discrimination). A majority of patients expressed a willingness to undergo somatic (predictive, 96%, prognostic, 93%) and germline (cancer risk without incidental information, 87%; cancer risk with incidental information, 81%; pharmacogenetic, 91%) testing; however, far fewer patients expressed a willingness to undergo full genome sequencing (62%). Reluctance was attributed to concerns over incidental findings, information overload, and the lack of a clear benefit. Conclusion: Many patients relayed misunderstandings about somatic testing and a reluctance to undergo full sequencing; oncologists must carefully consider how they present testing to patients so that concerns over discrimination and psychological harm do not hinder test uptake. More work is needed to identify effective ways to communicate complex genomic concepts to patients and research participants. PMID:23598841

  18. Numerical simulation of vehicle crashworthiness and occupant protection

    NASA Astrophysics Data System (ADS)

    Saha, Nripen K.

    1993-08-01

    Numerical simulation of vehicle crashworthiness and occupant protection are addressed. The vehicle crashworthiness design objectives are to design the vehicle structure for optimum impact energy absorption, and to design the restraint system (seatbelts, airbags, bolsters, etc.) for optimum occupant protection. The following approaches are taken; a major part of the impact energy is to be absorbed by the vehicle structure; the restraint components will provide protection against the remaining crash energy; certain vehicle components are designed to deform under specific types and speeds of impact in a desired mode for sound energy management; structural components such as front side rails, rear rails, door structure and pillars undergo large amounts of deformation; and with properly designed geometry and material these components assist in mitigating the effects of impact.

  19. Numerical simulation of vehicle crashworthiness and occupant protection

    NASA Technical Reports Server (NTRS)

    Saha, Nripen K.

    1993-01-01

    Numerical simulation of vehicle crashworthiness and occupant protection are addressed. The vehicle crashworthiness design objectives are to design the vehicle structure for optimum impact energy absorption, and to design the restraint system (seatbelts, airbags, bolsters, etc.) for optimum occupant protection. The following approaches are taken; a major part of the impact energy is to be absorbed by the vehicle structure; the restraint components will provide protection against the remaining crash energy; certain vehicle components are designed to deform under specific types and speeds of impact in a desired mode for sound energy management; structural components such as front side rails, rear rails, door structure and pillars undergo large amounts of deformation; and with properly designed geometry and material these components assist in mitigating the effects of impact.

  20. From structure to mechanism-understanding initiation of DNA replication.

    PubMed

    Riera, Alberto; Barbon, Marta; Noguchi, Yasunori; Reuter, L Maximilian; Schneider, Sarah; Speck, Christian

    2017-06-01

    DNA replication results in the doubling of the genome prior to cell division. This process requires the assembly of 50 or more protein factors into a replication fork. Here, we review recent structural and biochemical insights that start to explain how specific proteins recognize DNA replication origins, load the replicative helicase on DNA, unwind DNA, synthesize new DNA strands, and reassemble chromatin. We focus on the minichromosome maintenance (MCM2-7) proteins, which form the core of the eukaryotic replication fork, as this complex undergoes major structural rearrangements in order to engage with DNA, regulate its DNA-unwinding activity, and maintain genome stability. © 2017 Riera et al.; Published by Cold Spring Harbor Laboratory Press.

  1. DSSTOX (DISTRIBUTED STRUCTURE-SEARCHABLE ...

    EPA Pesticide Factsheets

    Distributed Structure-Searchable Toxicity Database Network Major trends affecting public toxicity information resources have the potential to significantly alter the future of predictive toxicology. Chemical toxicity screening is undergoing shifts towards greater use of more fundamental information on gene/protein expression patterns and bioactivity and bioassay profiles, the latter generated with highthroughput screening technologies. Curated, systematically organized, and webaccessible toxicity and biological activity data in association with chemical structures, enabling the integration of diverse data information domains, will fuel the next frontier of advancement for QSAR (quantitative structure-activity relationship) and data mining technologies. The DSSTox project is supporting progress towards these goals on many fronts, promoting the use of formalized and structure-annotated toxicity data models, helping to interface these efforts with QSAR modelers, linking data from diverse sources, and creating a large, quality reviewed, central chemical structure information resource linked to various toxicity data sources

  2. Site-specific genetic recombination: hops, flips, and flops.

    PubMed

    Sadowski, P D

    1993-06-01

    Genetic recombination plays a key role in the life of organisms as diverse as bacteriophages and humans. Contrary to our idea that chromosomes are stable structures, studies of recombination over the past few decades have shown that in fact DNA replicons are remarkably plastic, undergoing frequent recombination-induced rearrangements. This review summarizes our recent knowledge of the biochemistry of the two major classes of site-specific recombination: 1) transpositional recombination, and 2) conservative site-specific recombination.

  3. New metabolic pathway for N,N-dimethyltryptamine

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

    Hryhorczuk, L.M.; Rainey, J.M. Jr.; Frohman, C.E.

    1986-01-01

    N,N-Dimethyltryptamine (DMT) undergoes a major structural alteration when added to whole human blood or its red blood cells in vitro. A new high-pressure liquid chromatography (HPLC) peak is present in extracts of these treated tissues. The compound responsible for this peak has been identified by ultraviolet spectrophotometry and by mass spectrometry as dimethylkynuramine (DMK). The enzyme responsible for this appears to be different from tryptophan 2,3-dioxygenase and also from indoleamine 2,3-dioxygenase.

  4. Preliminary results for a higher-precision measurement of the helium n=2 triplet P fine structure

    NASA Astrophysics Data System (ADS)

    Kato, K.; Skinner, T. D. G.; George, M. C.; Fitzakerley, D. W.; Vutha, A. C.; Storry, C. H.; Bezginov, N.; Valdez, T.; Hessels, E. A.

    2017-04-01

    Preliminary results for a higher-precision measurement of the n=2 triplet P J=1 to J=2 fine-structure interval in atomic helium are presented. A beam of metastable helium atoms is created in a liquid-nitrogen-cooled dc-discharge source, and is intensified using a 2D-MOT. These atoms are excited to the 2 triplet P state, and undergo a frequency-offset separated-oscillatory-field (FOSOF) microwave experiment. Only atoms which undergo a microwave transition, in the time-separated microwave fields are laser-excited to a Rydberg state and then Stark ionized and counted. Our new experimental design has eliminated the major systematic effects of previous experiments, and has led to a substantial improvement in the signal-to-noise ratio of the collected data. Our final improved measurement (with an expected uncertainty of less than 100 Hz) will allow for a test of 2-electron QED-theory in the helium n=2 triplet P system, and will be an important step towards obtaining a precise determination of the fine-structure constant. This research is supported by NSERC, CRC, CFI and NIST.

  5. Concurrent risk-reduction surgery in patients with increased lifetime risk for breast and ovarian cancer: an analysis of the National Surgical Quality Improvement Program (NSQIP) database.

    PubMed

    Elmi, Maryam; Azin, Arash; Elnahas, Ahmad; McCready, David R; Cil, Tulin D

    2018-05-14

    Patients with genetic susceptibility to breast and ovarian cancer are eligible for risk-reduction surgery. Surgical morbidity of risk-reduction mastectomy (RRM) with concurrent bilateral salpingo-oophorectomy (BSO) is unknown. Outcomes in these patients were compared to patients undergoing RRM without BSO using a large multi-institutional database. A retrospective cohort analysis was conducted using the American College of Surgeon's National Surgical Quality Improvement Program (NSQIP) 2007-2016 datasets, comparing postoperative morbidity between patients undergoing RRM with patients undergoing RRM with concurrent BSO. Patients with genetic susceptibility to breast/ovarian cancer undergoing risk-reduction surgery were identified. The primary outcome was 30-day postoperative major morbidity. Secondary outcomes included surgical site infections, reoperations, readmissions, length of stay, and venous thromboembolic events. A multivariate analysis was performed to determine predictors of postoperative morbidity and the adjusted effect of concurrent BSO on morbidity. Of the 5470 patients undergoing RRM, 149 (2.7%) underwent concurrent BSO. The overall rate of major morbidity and postoperative infections was 4.5% and 4.6%, respectively. There was no significant difference in the rate of postoperative major morbidity (4.5% vs 4.7%, p = 0.91) or any of the secondary outcomes between patients undergoing RRM without BSO vs. those undergoing RRM with concurrent BSO. Multivariable analysis showed Body Mass Index (OR 1.05; p < 0.001) and smoking (OR 1.78; p = 0.003) to be the only predictors associated with major morbidity. Neither immediate breast reconstruction (OR 1.02; p = 0.93) nor concurrent BSO (OR 0.94; p = 0.89) were associated with increased postoperative major morbidity. This study demonstrated that RRM with concurrent BSO was not associated with significant additional morbidity when compared to RRM without BSO. Therefore, this joint approach may be considered for select patients at risk for both breast and ovarian cancer.

  6. Spatio-temporal patterns of major bacterial groups in alpine waters.

    PubMed

    Freimann, Remo; Bürgmann, Helmut; Findlay, Stuart E G; Robinson, Christopher T

    2014-01-01

    Glacial alpine landscapes are undergoing rapid transformation due to changes in climate. The loss of glacial ice mass has directly influenced hydrologic characteristics of alpine floodplains. Consequently, hyporheic sediment conditions are likely to change in the future as surface waters fed by glacial water (kryal) become groundwater dominated (krenal). Such environmental shifts may subsequently change bacterial community structure and thus potential ecosystem functioning. We quantitatively investigated the structure of major bacterial groups in glacial and groundwater-fed streams in three alpine floodplains during different hydrologic periods. Our results show the importance of several physico-chemical variables that reflect local geological characteristics as well as water source in structuring bacterial groups. For instance, Alpha-, Betaproteobacteria and Cytophaga-Flavobacteria were influenced by pH, conductivity and temperature as well as by inorganic and organic carbon compounds, whereas phosphorous compounds and nitrate showed specific influence on single bacterial groups. These results can be used to predict future bacterial group shifts, and potential ecosystem functioning, in alpine landscapes under environmental transformation.

  7. To Be or Not To Be T4: Evidence of a Complex Evolutionary Pathway of Head Structure and Assembly in Giant Salmonella Virus SPN3US

    PubMed Central

    Ali, Bazla; Desmond, Maxim I.; Mallory, Sara A.; Benítez, Andrea D.; Buckley, Larry J.; Weintraub, Susan T.; Osier, Michael V.; Black, Lindsay W.; Thomas, Julie A.

    2017-01-01

    Giant Salmonella phage SPN3US has a 240-kb dsDNA genome and a large complex virion composed of many proteins for which the functions of most are undefined. We recently determined that SPN3US shares a core set of genes with related giant phages and sequenced and characterized 18 amber mutants to facilitate its use as a genetic model system. Notably, SPN3US and related giant phages contain a bolus of ejection proteins within their heads, including a multi-subunit virion RNA polymerase (vRNAP), that enter the host cell with the DNA during infection. In this study, we characterized the SPN3US virion using mass spectrometry to gain insight into its head composition and the features that its head shares with those of related giant phages and with T4 phage. SPN3US has only homologs to the T4 proteins critical for prohead shell formation, the portal and major capsid proteins, as well as to the major enzymes essential for head maturation, the prohead protease and large terminase subunit. Eight of ~50 SPN3US head proteins were found to undergo proteolytic processing at a cleavage motif by the prohead protease gp245. Gp245 undergoes auto-cleavage of its C-terminus, suggesting this is a conserved activation and/or maturation feature of related phage proteases. Analyses of essential head gene mutants showed that the five subunits of the vRNAP must be assembled for any subunit to be incorporated into the prohead, although the assembled vRNAP must then undergo subsequent major conformational rearrangements in the DNA packed capsid to allow ejection through the ~30 Å diameter tail tube for transcription from the injected DNA. In addition, ejection protein candidate gp243 was found to play a critical role in head assembly. Our analyses of the vRNAP and gp243 mutants highlighted an unexpected dichotomy in giant phage head maturation: while all analyzed giant phages have a homologous protease that processes major capsid and portal proteins, processing of ejection proteins is not always a stable/defining feature. Our identification in SPN3US, and related phages, of a diverged paralog to the prohead protease further hints toward a complicated evolutionary pathway for giant phage head structure and assembly. PMID:29187846

  8. An unexpected twist in viral capsid maturation

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

    Gertsman, Ilya; Gan, Lu; Guttman, Miklos

    2009-04-14

    Lambda-like double-stranded (ds) DNA bacteriophage undergo massive conformational changes in their capsid shell during the packaging of their viral genomes. Capsid shells are complex organizations of hundreds of protein subunits that assemble into intricate quaternary complexes that ultimately are able to withstand over 50 atm of pressure during genome packaging. The extensive integration between subunits in capsids requires the formation of an intermediate complex, termed a procapsid, from which individual subunits can undergo the necessary refolding and structural rearrangements needed to transition to the more stable capsid. Although various mature capsids have been characterized at atomic resolution, no such procapsidmore » structure is available for a dsDNA virus or bacteriophage. Here we present a procapsid X-ray structure at 3.65 {angstrom} resolution, termed prohead II, of the lambda-like bacteriophage HK97, the mature capsid structure of which was previously solved to 3.44 {angstrom}. A comparison of the two largely different capsid forms has unveiled an unprecedented expansion mechanism that describes the transition. Crystallographic and hydrogen/deuterium exchange data presented here demonstrate that the subunit tertiary structures are significantly different between the two states, with twisting and bending motions occurring in both helical and -sheet regions. We also identified subunit interactions at each three-fold axis of the capsid that are maintained throughout maturation. The interactions sustain capsid integrity during subunit refolding and provide a fixed hinge from which subunits undergo rotational and translational motions during maturation. Previously published calorimetric data of a closely related bacteriophage, P22, showed that capsid maturation was an exothermic process that resulted in a release of 90 kJ mol{sup -1} of energy. We propose that the major tertiary changes presented in this study reveal a structural basis for an exothermic maturation process probably present in many dsDNA bacteriophage and possibly viruses such as herpesvirus, which share the HK97 subunit fold.« less

  9. Oxidation of a critical methionine modulates DNA binding of the Drosophila melanogaster high mobility group protein, HMG-D.

    PubMed

    Dow, L K; Changela, A; Hefner, H E; Churchill, M E

    1997-09-15

    HMG-D is a major high mobility group chromosomal protein present during early embryogenesis in Drosophila melanogaster. During overexpression and purification of HMG-D from E. coli, a key DNA binding residue, methionine 13, undergoes oxidation to methionine sulfoxide. Oxidation of this critical residue decreases the affinity of HMG-D for DNA by three-fold, altering the structure of the HMG-D-DNA complex without affecting the structure of the free protein. This work shows that minor modification of DNA intercalating residues may be used to fine tune the DNA binding affinity of HMG domain proteins.

  10. The development and plasticity of alveolar type 1 cells

    PubMed Central

    Yang, Jun; Hernandez, Belinda J.; Martinez Alanis, Denise; Narvaez del Pilar, Odemaris; Vila-Ellis, Lisandra; Akiyama, Haruhiko; Evans, Scott E.; Ostrin, Edwin J.; Chen, Jichao

    2016-01-01

    Alveolar type 1 (AT1) cells cover >95% of the gas exchange surface and are extremely thin to facilitate passive gas diffusion. The development of these highly specialized cells and its coordination with the formation of the honeycomb-like alveolar structure are poorly understood. Using new marker-based stereology and single-cell imaging methods, we show that AT1 cells in the mouse lung form expansive thin cellular extensions via a non-proliferative two-step process while retaining cellular plasticity. In the flattening step, AT1 cells undergo molecular specification and remodel cell junctions while remaining connected to their epithelial neighbors. In the folding step, AT1 cells increase in size by more than 10-fold and undergo cellular morphogenesis that matches capillary and secondary septa formation, resulting in a single AT1 cell spanning multiple alveoli. Furthermore, AT1 cells are an unexpected source of VEGFA and their normal development is required for alveolar angiogenesis. Notably, a majority of AT1 cells proliferate upon ectopic SOX2 expression and undergo stage-dependent cell fate reprogramming. These results provide evidence that AT1 cells have both structural and signaling roles in alveolar maturation and can exit their terminally differentiated non-proliferative state. Our findings suggest that AT1 cells might be a new target in the pathogenesis and treatment of lung diseases associated with premature birth. PMID:26586225

  11. Intracellular synthesis, processing, and transport of proteins encoded by ORFs 5 to 7 of porcine reproductive and respiratory syndrome virus.

    PubMed

    Mardassi, H; Massie, B; Dea, S

    1996-07-01

    Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a small enveloped virus containing a positive-strand RNA genome, possesses at least three major structural proteins designated N, M, and E. The N protein is considered as the major component of the nucleocapsid, whereas M and E are membrane-associated. Previous studies using peptide-specific antibodies assigned these proteins to ORFs 7, 6, and 5, respectively. In the present report, monospecific antisera raised against Escherichia coli-expressed ORFs 5, 6, and 7 products were used to study the synthesis and processing of PRRSV structural proteins in the highly permissive MARC-145 cell line. Treatment of viral proteins with various glycosidases showed that only E was modified by N-linked glycans. Pulse-chase experiments revealed that intracellular transport of the major envelope glycoprotein was delayed in the premedial Golgi compartment. During the first 30 min of chase, E undergoes a gradual downward shift of its apparent molecular weight, thought to result from trimming of the mannose-rich glycan structures. Once E is transported to the medial Golgi or proximal elements, some molecules undergo complete processing of all their high-mannose N-linked oligosaccharides to complex type, while in other molecules only a fraction of N-linked glycans are terminally glycosylated. These two differentially glycosylated forms of E were found to be incorporated into extracellular virions. In cells and virions, both M and E were shown to occur in heterodimeric complexes linked by disulfide bonds. The oligomerization process, as analyzed from pulse-chase experiments, showed that M and E are incorporated into M-E complexes with different kinetics and efficiencies, in a fashion similar to their counterparts in equine arteritis virus. Apparently, all steps of E protein N-glycans processing proceed after its association with M which occurs in the endoplasmic reticulum (ER). In the infected cells, E and M appear highly membrane-associated, while N is predominantly cytosolic.

  12. Signal Transduction in Histidine Kinases: Insights from New Structures

    PubMed Central

    Bhate, Manasi P.; Molnar, Kathleen S.; Goulian, Mark; DeGrado, William F.

    2015-01-01

    Histidine kinases (HKs) are major players in bacterial signaling. There has been an explosion of new HK crystal structures in the last five years. We globally analyze the structures of HKs to yield insights into the mechanisms by which signals are transmitted to and across protein structures in this family. We interpret known enzymological data in the context of new structural data to show how asymmetry across the dimer interface is a key feature of signal transduction in HKs, and discuss how different HK domains undergo asymmetric-to-symmetric transitions during signal transduction and catalysis. A thermodynamic framework for signaling that encompasses these various properties is presented and the consequences of weak thermodynamic coupling are discussed. The synthesis of observations from enzymology, structural biology, protein engineering and thermodynamics paves the way for a deeper molecular understanding of histidine kinase signal transduction. PMID:25982528

  13. Metamorphic Proteins: Emergence of Dual Protein Folds from One Primary Sequence.

    PubMed

    Lella, Muralikrishna; Mahalakshmi, Radhakrishnan

    2017-06-20

    Every amino acid exhibits a different propensity for distinct structural conformations. Hence, decoding how the primary amino acid sequence undergoes the transition to a defined secondary structure and its final three-dimensional fold is presently considered predictable with reasonable certainty. However, protein sequences that defy the first principles of secondary structure prediction (they attain two different folds) have recently been discovered. Such proteins, aptly named metamorphic proteins, decrease the conformational constraint by increasing flexibility in the secondary structure and thereby result in efficient functionality. In this review, we discuss the major factors driving the conformational switch related both to protein sequence and to structure using illustrative examples. We discuss the concept of an evolutionary transition in sequence and structure, the functional impact of the tertiary fold, and the pressure of intrinsic and external factors that give rise to metamorphic proteins. We mainly focus on the major components of protein architecture, namely, the α-helix and β-sheet segments, which are involved in conformational switching within the same or highly similar sequences. These chameleonic sequences are widespread in both cytosolic and membrane proteins, and these folds are equally important for protein structure and function. We discuss the implications of metamorphic proteins and chameleonic peptide sequences in de novo peptide design.

  14. Effects of parenteral structured lipid emulsion on modulating the inflammatory response in rats undergoing a total gastrectomy.

    PubMed

    Lin, Ming-Tsan; Yeh, Sung-Ling; Tsou, Shung-Sheng; Wang, Ming-Yang; Chen, Wei-Jao

    2009-01-01

    Structured lipid emulsion improves the nitrogen balance and is rapidly cleared from the blood of moderately catabolic patients. However, the effects of structured lipids on inflammatory reactions during major surgery are not clear. This study investigated the effect of a parenteral structured triacylglycerol emulsion on leukocyte adhesion molecule expression and inflammatory mediator production in rats undergoing a total gastrectomy. Normal rats with internal jugular catheters were assigned to three experimental groups and received total parenteral nutrition. At the same time, a total gastrectomy was performed on the experimental groups. The total parenteral nutrition solutions were isonitrogenous and identical in nutrient compositions except for differences in the composition of the fat emulsion. Group 1 received a conventional fat emulsion with long-chain triacylglycerols (LCTs), group 2 received a physical mixture of medium-chain triacylglycerols (MCTs) and LCTs (MCT/LCT), and group 3 received structured lipids composed of MCTs and LCTs (STG). Half of the rats in each respective group were sacrificed 1 d and the other half 3 d after surgery to examine the analytical parameters. Plasma cholesterol and free fatty acid levels in the STG group were lower than those in the other groups after surgery. The STG group had lower leukocyte CD11a/CD18 expressions than the MCT/LCT group 3 d after surgery, and CD11b/CD18 expressions in the STG group were lower than those in the LCT group on postoperative days. The STG group had higher monocyte chemotactic protein-1 and macrophage inflammatory protein-2 levels in peritoneal lavage fluid than did the other two groups. These results suggest that, compared with the LCT and MCT/LCT groups, rats administered STG had lower plasma lipid concentrations and leukocyte integrin expressions. In addition, STG administration may cause increased recruiting of neutrophils and monocytes at the site of injury and enhance antipathogenicity in rats undergoing a total gastrectomy.

  15. KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, one of two orbital maneuvering system (OMS) pods removed from Endeavour is lowered toward a transporter. The OMS pods are attached to the upper aft fuselage left and right sides. Fabricated primarily of graphite epoxy composite and aluminum, each pod is 21.8 feet long and 11.37 feet wide at its aft end and 8.41 feet wide at its forward end, with a surface area of approximately 435 square feet. Each pod houses the Reaction Control System propulsion components used for inflight maneuvering and is attached to the aft fuselage with 11 bolts. OMS pods are removed during Orbiter Major Modifications. Once removed, the OMS pods undergo in-depth structural inspections, system checks and the thrusters are changed out.

    NASA Image and Video Library

    2003-09-05

    KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, one of two orbital maneuvering system (OMS) pods removed from Endeavour is lowered toward a transporter. The OMS pods are attached to the upper aft fuselage left and right sides. Fabricated primarily of graphite epoxy composite and aluminum, each pod is 21.8 feet long and 11.37 feet wide at its aft end and 8.41 feet wide at its forward end, with a surface area of approximately 435 square feet. Each pod houses the Reaction Control System propulsion components used for inflight maneuvering and is attached to the aft fuselage with 11 bolts. OMS pods are removed during Orbiter Major Modifications. Once removed, the OMS pods undergo in-depth structural inspections, system checks and the thrusters are changed out.

  16. KENNEDY SPACE CENTER, FLA. - Technicians in the Orbiter Processing Facility oversee removal of one of two orbital maneuvering system (OMS) pods from Endeavour. The OMS pods are attached to the upper aft fuselage left and right sides. Fabricated primarily of graphite epoxy composite and aluminum, each pod is 21.8 feet long and 11.37 feet wide at its aft end and 8.41 feet wide at its forward end, with a surface area of approximately 435 square feet. Each pod houses the Reaction Control System propulsion components used for inflight maneuvering and is attached to the aft fuselage with 11 bolts. OMS pods are removed during Orbiter Major Modifications. Once removed, the OMS pods undergo in-depth structural inspections, system checks and the thrusters are changed out.

    NASA Image and Video Library

    2003-09-05

    KENNEDY SPACE CENTER, FLA. - Technicians in the Orbiter Processing Facility oversee removal of one of two orbital maneuvering system (OMS) pods from Endeavour. The OMS pods are attached to the upper aft fuselage left and right sides. Fabricated primarily of graphite epoxy composite and aluminum, each pod is 21.8 feet long and 11.37 feet wide at its aft end and 8.41 feet wide at its forward end, with a surface area of approximately 435 square feet. Each pod houses the Reaction Control System propulsion components used for inflight maneuvering and is attached to the aft fuselage with 11 bolts. OMS pods are removed during Orbiter Major Modifications. Once removed, the OMS pods undergo in-depth structural inspections, system checks and the thrusters are changed out.

  17. KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility prepare to remove one of two orbital maneuvering system (OMS) pods from Endeavour. The OMS pods are attached to the upper aft fuselage left and right sides. Fabricated primarily of graphite epoxy composite and aluminum, each pod is 21.8 feet long and 11.37 feet wide at its aft end and 8.41 feet wide at its forward end, with a surface area of approximately 435 square feet. Each pod houses the Reaction Control System propulsion components used for inflight maneuvering and is attached to the aft fuselage with 11 bolts. OMS pods are removed during Orbiter Major Modifications. Once removed, the OMS pods undergo in-depth structural inspections, system checks and the thrusters are changed out.

    NASA Image and Video Library

    2003-09-05

    KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility prepare to remove one of two orbital maneuvering system (OMS) pods from Endeavour. The OMS pods are attached to the upper aft fuselage left and right sides. Fabricated primarily of graphite epoxy composite and aluminum, each pod is 21.8 feet long and 11.37 feet wide at its aft end and 8.41 feet wide at its forward end, with a surface area of approximately 435 square feet. Each pod houses the Reaction Control System propulsion components used for inflight maneuvering and is attached to the aft fuselage with 11 bolts. OMS pods are removed during Orbiter Major Modifications. Once removed, the OMS pods undergo in-depth structural inspections, system checks and the thrusters are changed out.

  18. KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, one of two orbital maneuvering system (OMS) pods removed from Endeavour is suspended overhead. The OMS pods are attached to the upper aft fuselage left and right sides. Fabricated primarily of graphite epoxy composite and aluminum, each pod is 21.8 feet long and 11.37 feet wide at its aft end and 8.41 feet wide at its forward end, with a surface area of approximately 435 square feet. Each pod houses the Reaction Control System propulsion components used for inflight maneuvering and is attached to the aft fuselage with 11 bolts. OMS pods are removed during Orbiter Major Modifications. Once removed, the OMS pods undergo in-depth structural inspections, system checks and the thrusters are changed out.

    NASA Image and Video Library

    2003-09-05

    KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, one of two orbital maneuvering system (OMS) pods removed from Endeavour is suspended overhead. The OMS pods are attached to the upper aft fuselage left and right sides. Fabricated primarily of graphite epoxy composite and aluminum, each pod is 21.8 feet long and 11.37 feet wide at its aft end and 8.41 feet wide at its forward end, with a surface area of approximately 435 square feet. Each pod houses the Reaction Control System propulsion components used for inflight maneuvering and is attached to the aft fuselage with 11 bolts. OMS pods are removed during Orbiter Major Modifications. Once removed, the OMS pods undergo in-depth structural inspections, system checks and the thrusters are changed out.

  19. KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, one of two orbital maneuvering system (OMS) pods removed from Endeavour is lowered onto a transporter. The OMS pods are attached to the upper aft fuselage left and right sides. Fabricated primarily of graphite epoxy composite and aluminum, each pod is 21.8 feet long and 11.37 feet wide at its aft end and 8.41 feet wide at its forward end, with a surface area of approximately 435 square feet. Each pod houses the Reaction Control System propulsion components used for inflight maneuvering and is attached to the aft fuselage with 11 bolts. OMS pods are removed during Orbiter Major Modifications. Once removed, the OMS pods undergo in-depth structural inspections, system checks and the thrusters are changed out.

    NASA Image and Video Library

    2003-09-05

    KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, one of two orbital maneuvering system (OMS) pods removed from Endeavour is lowered onto a transporter. The OMS pods are attached to the upper aft fuselage left and right sides. Fabricated primarily of graphite epoxy composite and aluminum, each pod is 21.8 feet long and 11.37 feet wide at its aft end and 8.41 feet wide at its forward end, with a surface area of approximately 435 square feet. Each pod houses the Reaction Control System propulsion components used for inflight maneuvering and is attached to the aft fuselage with 11 bolts. OMS pods are removed during Orbiter Major Modifications. Once removed, the OMS pods undergo in-depth structural inspections, system checks and the thrusters are changed out.

  20. Retrospective Review of the Anaesthetic Management of Maxillectomies and Mandibulectomies for Benign Tumours in Sub-Saharan Africa.

    PubMed

    White, Michelle C; Horner, Katherine C; Lai, Peggy S

    2016-01-01

    Safe anaesthesia is a crucial component of safe surgical care, yet anaesthetic complications are common in resource-limited settings. We describe differences in anaesthetic needs for Mandibulectomy vs. Maxillectomy in three sub-Saharan African countries. Retrospective review of patients undergoing minor Mandibulectomy, major Mandibulectomy, or Maxillectomy in Togo, Guinea and Republic of the Congo. Surgeries were performed on the Africa Mercy, an international non-governmental hospital ship. Primary outcomes were need for advanced airway management and intra-operative blood loss. Secondary outcomes were time under general anaesthesia and hospital length of stay. Multivariate regression determined the association between operation type and each outcome measure. 105 patients were included (25 minor Mandibulectomy, 58 major Mandibulectomy, 22 Maxillectomy procedures). In-hospital mortality was 0%. 44/105 (41.9%) required an advanced airway management technique to achieve intubation, although in all cases this was anticipated prior to the procedure; no differences were noted between surgical procedure (p = 0.72). Operative procedure was a significant risk factor for intra-operative blood loss. Patients undergoing Maxillectomy lost on average 851.5 (413.3, 1289.8, p = 0.0003) mL more blood than patients undergoing minor Mandibulectomy, and 507.3 (150.3, 864.3, p = 0.007) mL more blood than patients undergoing major Mandibulectomy. Patients undergoing Maxillectomy had a significantly higher time under general anaesthesia than those undergoing minor Mandibulectomy. There was no significant difference in hospital length of stay between operation type. Anaesthetic considerations for minor Mandibulectomy, major Mandibulectomy, and Maxillectomy differ with respect to intra-operative blood loss and time under general anaesthesia, but not need for advanced airway management or length of stay. Although advanced airway management was required in 41.9% of patients, there were no unanticipated difficult airways. With appropriate training and resources, safe anaesthesia can be delivered to patients from low-income countries requiring major head and neck surgery.

  1. Retrospective Review of the Anaesthetic Management of Maxillectomies and Mandibulectomies for Benign Tumours in Sub-Saharan Africa

    PubMed Central

    White, Michelle C.; Horner, Katherine C.; Lai, Peggy S.

    2016-01-01

    Background Safe anaesthesia is a crucial component of safe surgical care, yet anaesthetic complications are common in resource-limited settings. We describe differences in anaesthetic needs for Mandibulectomy vs. Maxillectomy in three sub-Saharan African countries. Materials and Methods Retrospective review of patients undergoing minor Mandibulectomy, major Mandibulectomy, or Maxillectomy in Togo, Guinea and Republic of the Congo. Surgeries were performed on the Africa Mercy, an international non-governmental hospital ship. Primary outcomes were need for advanced airway management and intra-operative blood loss. Secondary outcomes were time under general anaesthesia and hospital length of stay. Multivariate regression determined the association between operation type and each outcome measure. Results 105 patients were included (25 minor Mandibulectomy, 58 major Mandibulectomy, 22 Maxillectomy procedures). In-hospital mortality was 0%. 44/105 (41.9%) required an advanced airway management technique to achieve intubation, although in all cases this was anticipated prior to the procedure; no differences were noted between surgical procedure (p = 0.72). Operative procedure was a significant risk factor for intra-operative blood loss. Patients undergoing Maxillectomy lost on average 851.5 (413.3, 1289.8, p = 0.0003) mL more blood than patients undergoing minor Mandibulectomy, and 507.3 (150.3, 864.3, p = 0.007) mL more blood than patients undergoing major Mandibulectomy. Patients undergoing Maxillectomy had a significantly higher time under general anaesthesia than those undergoing minor Mandibulectomy. There was no significant difference in hospital length of stay between operation type. Conclusion Anaesthetic considerations for minor Mandibulectomy, major Mandibulectomy, and Maxillectomy differ with respect to intra-operative blood loss and time under general anaesthesia, but not need for advanced airway management or length of stay. Although advanced airway management was required in 41.9% of patients, there were no unanticipated difficult airways. With appropriate training and resources, safe anaesthesia can be delivered to patients from low-income countries requiring major head and neck surgery. PMID:27788172

  2. A pragmatic multi-centre randomised controlled trial of fluid loading and level of dependency in high-risk surgical patients undergoing major elective surgery: trial protocol

    PubMed Central

    2010-01-01

    Background Patients undergoing major elective or urgent surgery are at high risk of death or significant morbidity. Measures to reduce this morbidity and mortality include pre-operative optimisation and use of higher levels of dependency care after surgery. We propose a pragmatic multi-centre randomised controlled trial of level of dependency and pre-operative fluid therapy in high-risk surgical patients undergoing major elective surgery. Methods/Design A multi-centre randomised controlled trial with a 2 * 2 factorial design. The first randomisation is to pre-operative fluid therapy or standard regimen and the second randomisation is to routine intensive care versus high dependency care during the early post-operative period. We intend to recruit 204 patients undergoing major elective and urgent abdominal and thoraco-abdominal surgery who fulfil high-risk surgical criteria. The primary outcome for the comparison of level of care is cost-effectiveness at six months and for the comparison of fluid optimisation is the number of hospital days after surgery. Discussion We believe that the results of this study will be invaluable in determining the future care and clinical resource utilisation for this group of patients and thus will have a major impact on clinical practice. Trial Registration Trial registration number - ISRCTN32188676 PMID:20398378

  3. Multidrug efflux transporter, AcrB--the pumping mechanism.

    PubMed

    Murakami, Satoshi

    2008-08-01

    Resistance nodulation cell division (RND) transporters are one of the main causes of the bacterial multidrug resistance. They pump a wide range of antibiotics out of the cell by proton motive force. AcrB is the major RND transporter in Escherichia coli. Recently, the crystal structures of AcrB have been determined by different space groups. All these structures are consistent with asymmetric trimer. Each monomer has different conformation corresponding to one of the three functional states of the transport cycle. Transporting hydrophobic drug was bound in the periplasmic domain on one of the three monomers. The transport pathway with alternating access mechanism is located at the hydrophilic domain protruded into the periplasmic space while this mechanism of other transporter families like ATP binding cassette (ABC) and major facilitator superfamily (MFS) transporter is located in the membrane-embedded region. For the RND, protonation might also take place asymmetrically at the functionally important charged residues in the transmembrane (TM) region. The structures indicate that drugs are transported by a three-step functional rotation in which substrates undergo ordered binding change.

  4. Recent findings in cardiovascular physiology with space travel.

    PubMed

    Hughson, Richard L

    2009-10-01

    The cardiovascular system undergoes major changes in stress with space flight primarily related to the elimination of the head-to-foot gravitational force. A major observation has been that the central venous pressure is not elevated early in space flight yet stroke volume is increased at least early in flight. Recent observations demonstrate that heart rate remains lower during the normal daily activities of space flight compared to Earth-based conditions. Structural and functional adaptations occur in the vascular system that could result in impaired response with demands of physical exertion and return to Earth. Cardiac muscle mass is reduced after flight and contractile function may be altered. Regular and specific countermeasures are essential to maintain cardiovascular health during long-duration space flight.

  5. Magnetic Protostars

    NASA Astrophysics Data System (ADS)

    Glagolevskij, Yu. V.

    2015-09-01

    A possible variant of the evolution of magnetic protostars "before the Hayashi phase" is discussed. Arguments are given in support of the following major properties of magnetic stars: (1) global magnetic dipole fields with predominant orientation of the magnetic lines of force in the plane of the equator of revolution; (2) slow rotation; (3) complex, two and three dipole structures of the magnetic field in a large part of the stars; (4) partition of stars into magnetic and normal in a proportion of 1:10 occurs during the period when the protostellar clouds undergo gravitational collapse "before the Hayashi phase."

  6. Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis.

    PubMed

    Nepogodiev, Dmitri

    2018-06-13

    Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major post-operative complications in an international cohort and to present a meta-analysis of all available prospective data. This prospective, multi-centre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma, or formation of stoma. The primary endpoint was 30-day major complications (Clavien-Dindo grades III-V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis (IPMA) was used to analyse pooled results. This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese versus normal weight patients (13.0% versus 16.2%, respectively), but this did not reach statistical significance (p=0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. IPMA demonstrated that obese patients undergoing surgery for malignancy were at increased risk of major complications (odds ratio 2.10, 95% confidence interval 1.49-2.96, p<0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46-0.75, p<0.001), compared to normal weight patients. In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Juggling Act: Re-Planning and Building on Observatory...Simultaneously!

    NASA Technical Reports Server (NTRS)

    Zavala, Eddie; Daws, Patricia

    2011-01-01

    SOFIA (Stratospheric Observatory for Infrared Astronomy) is a major SMD program that has been required to meet several requirements and implement major planning and business initiatives overthe past 1 1/2 years, in the midst of system development and flight test phases. The program was required to implementing JCL and EVM simultaneously, as well as undergo a major replan and Standing Review Board - and all without impacting technical schedule progress. The team developed innovative processes that met all the requirements, and improved Program Management process toolsets. The SOFIA team, being subject to all the typical budget constraints, found ways to leverage existing roles in new ways to meet the requirements without creating unmanageable overhead. The team developed strategies and value added processes - such as improved risk identification, structured reserves management, cost/risk integration - so that the effort expended resulted in a positive return to the program.

  8. The Molecular Dynamics Study of the Structural Conversions in the Transformer Protein RfaH

    NASA Astrophysics Data System (ADS)

    Gc, Jeevan; Gerstman, Bernard; Chapagain, Prem

    Recently, a class of multi-domain proteins such as RfaH transcription factor are labelled as the transformer proteins as they undergo major conformational transformation for performing multiple functions. In the absence of the inter-domain contacts, the C-terminal domain of RfaH transforms from its alpha-helix conformation to a beta-barrel structure. Each of these states have their own functional role: in its alpha-helx state, RfaH-CTD inhibits the transcription by masking the binding site of RNAP, but in its beta state it facilitates the translation. We used various molecular dynamics simulations to study its transformer-like behavior of full-RfaH and identified key amino acid residues that are important in modulating such behavior. Our results show that the inter domain interactions constitute the major barrier in the alpha-helix to beta-barrel conversion. Once the interfacial interactions are broken, structural conversion is easier. The structural conversion from beta-barrel to alpha-helix proceeds with the rearrangement of the hydrophobic residues followed by the inter domain contacts formation via non-native, transient salt-bridge formation, leading to the formation of the native inter domain salt-bridge and hydrophobic contacts to give the final alpha-helix structure.

  9. The elusive indigo precursors in woad (Isatis tinctoria L.)--identification of the major indigo precursor, isatan A, and a structure revision of isatan B.

    PubMed

    Oberthür, Christine; Schneider, Bernd; Graf, Heidemarie; Hamburger, Matthias

    2004-01-01

    A metabolite-profiling study of shock-frozen leaves of Isatis tinctoria L., an old indigo dye plant and medicinal herb, revealed a complex pattern of indigo-forming compounds with higher polarities than the known indigo precursors isatan B and indican. These highly unstable compounds underwent rapid post-harvest transformation and were not detected in air-dried leaves. The major indigo precursor, named isatan A (4), was isolated by rapid normal-phase and gel chromatography, along with isatan B (3). A full spectral data set of 3 showed that the previous structure assignment as 'indoxyl-5-ketogluconate' has to be revised to 1H-indol-3-yl beta-D-ribohex-3-ulopyranoside. Isatan A (4) was identified as 1H-indol-3-yl 6'-O-(carboxyacetyl)-beta-D-ribohex-3'-ulopyranoside. In aqueous solution, glycosides 3 and 4 occur as hydrates and undergo rapid hydrolysis under very mild acidic or basic conditions.

  10. Hierarchical Porous Interlocked Polymeric Microcapsules: Sulfonic Acid Functionalization as Acid Catalysts

    NASA Astrophysics Data System (ADS)

    Wang, Xiaomei; Gu, Jinyan; Tian, Lei; Zhang, Xu

    2017-03-01

    Owing to their unique structural and surface properties, mesoporous microspheres are widely applied in the catalytic field. Generally, increasing the surface area of the specific active phase of the catalyst is a good method, which can achieve a higher catalytic activity through the fabrication of the corresponding catalytic microspheres with the smaller size and hollow structure. However, one of the major challenges in the use of hollow microspheres (microcapsules) as catalysts is their chemical and structural stability. Herein, the grape-like hypercrosslinked polystyrene hierarchical porous interlocked microcapsule (HPIM-HCL-PS) is fabricated by SiO2 colloidal crystals templates, whose structure is the combination of open mouthed structure, mesoporous nanostructure and interlocked architecture. Numerous microcapsules assembling together and forming the roughly grape-like microcapsule aggregates can enhance the structural stability and recyclability of these microcapsules. After undergoing the sulfonation, the sulfonated HPIM-HCL-PS is served as recyclable acid catalyst for condensation reaction between benzaldehyde and ethylene glycol (TOF = 793 h-1), moreover, exhibits superior activity, selectivity and recyclability.

  11. Irradiation induced structural change in Mo 2Zr intermetallic phase

    DOE PAGES

    Gan, J.; Keiser, Jr., D. D.; Miller, B. D.; ...

    2016-05-14

    The Mo 2Zr phase has been identified as a major interaction product at the interface of U-10Mo and Zr. Transmission electron microscopy in-situ irradiation with Kr ions at 200 °C with doses up to 2.0E+16 ions/cm 2 was carried out to investigate the radiation stability of the Mo 2Zr. The Mo 2Zr undergoes a radiation-induced structural change, from a large cubic (cF24) to a small cubic (cI2), along with an estimated 11.2% volume contraction without changing its composition. The structural change begins at irradiation dose below 1.0E+14 ions/cm 2. Furthermore, the transformed Mo 2Zr phase demonstrates exceptional radiation tolerance withmore » the development of dislocations without bubble formation.« less

  12. Tools to reduce first year nursing students' anxiety levels prior to undergoing objective structured clinical assessment (OSCA) and how this impacts on the student's experience of their first clinical placement.

    PubMed

    Stunden, Annette; Halcomb, Elizabeth; Jefferies, Diana

    2015-09-01

    One form of assessment that tests students' theoretical skills and confidence in their clinical practice is known as the Objective Structured Clinical Assessment (OSCA). Traditionally it was first launched from medical education, and is now being incorporated by other disciplines, such as nursing. This review seeks to present the best available evidence into strategies that help reduce first year nursing students' anxiety levels prior to undergoing OSCA and clinical placement. A systematic literature search was performed using Medline and CINAHL. This review considered any English language original research published between 2005 and 2013. A literature search located 117 articles. Eight articles were identified as meeting the inclusion in criteria. Majority of studies reported simulation session prior to the OSCA increased students confidence and reduced their anxiety levels. This resulted in students' reporting that they valued the OSCA as a worthwhile assessment. However there were four major themes: that students were anxious about attending the OSCA; that adequate preparation was seen as a coping strategy; that simulation was a further cause for anxiety; and that the simulation experience could also be used as an OSCA tool. Students who have been exposed to simulation scenarios before the OSCA are able to cope much better during the OSCA. Therefore, it is highly recommended to incorporate simulation scenarios into the nursing curricula for first year nursing students' clinical units to help reduce their anxiety levels prior to OCSA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Do patients fear undergoing general anesthesia for oral surgery?

    PubMed

    Elmore, Jasmine R; Priest, James H; Laskin, Daniel M

    2014-01-01

    Many patients undergoing major surgery have more fear of the general anesthesia than the procedure. This appears to be reversed with oral surgery. Therefore, patients need to be as well informed about this aspect as the surgical operation.

  14. Molecular dynamics analysis of conformational change of paramyxovirus F protein during the initial steps of membrane fusion

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

    Martin-Garcia, Fernando; Mendieta-Moreno, Jesus Ignacio; Mendieta, Jesus

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Initial conformational change of paramyxovirus F protein is caused only by mechanical forces. Black-Right-Pointing-Pointer HRA region undergoes a structural change from a beta + alpha conformation to an extended coil and then to an all-alpha conformation. Black-Right-Pointing-Pointer HRS domains of F protein form three single {alpha}-helices prior to generation of the coiled coil. -- Abstract: The fusion of paramyxovirus to the cell membrane is mediated by fusion protein (F protein) present in the virus envelope, which undergoes a dramatic conformational change during the process. Unlike hemagglutinin in orthomyxovirus, this change is not mediated by an alteration of environmentalmore » pH, and its cause remains unknown. Steered molecular dynamics analysis leads us to suggest that the conformational modification is mediated only by stretching mechanical forces once the transmembrane fusion peptide of the protein is anchored to the cell membrane. Such elongating forces will generate major secondary structure rearrangement in the heptad repeat A region of the F protein; from {beta}-sheet conformation to an elongated coil and then spontaneously to an {alpha}-helix. In addition, it is proposed that the heptad repeat A region adopts a final three-helix coiled coil and that this structure appears after the formation of individual helices in each monomer.« less

  15. [In-depth assessment of work-related stress in a major company undergoing restructuring].

    PubMed

    Magrini, Andrea; Pelagalli, Maria Felicia; Pietroiusti, Antonio; Livigni, Lucilla; Guidi, Stefano; Moscatelli, Maurizia; Mascioli, Marco; D'Orsi, Fulvio; Zolla, Antonella; Bagnara, Sebastiano

    2015-07-08

    An in-depth assessment of work-related stress was conducted in a major national telecommunications company undergoing major changes. The assessment was made on three homogeneous groups of workers and covered a large representative sample of the corresponding populations. To identify the main sources of stress for the three populations of workers, stimulate a discussion on the possible corrective actions, and assess the impact of the on-going organizational changes on workers' health. The assessment started with an analysis of the objective stress indicators listed in the INAIL (National Insurance Institute for Occupational Diseases and Accidents) Checklist. This was followed by a combination of qualitative and quantitative investigations on work context and tasks and on the subjective perceptions of workers, which were carried out by using: semi-structured interviews with management, field observations of work tasks, focus groups and questionnaires (GHQ-12, HSE Indicator Tool, ad-hoc questionnaire). The assessment allowed identification of the critical areas to be addressed with specific interventions: relationship with the company, work performance, work organization, and equipment. the investigation allowed to identification of specific practical actions (improvement of technological tools; professional development through training courses) as well as strategic actions ( re-establish relationship of trust with the company) so as to mitigate the workers' level of stress. Analysis of the results also showed that the three targeted populations differed in the degree of acceptance and understanding of the organizational changes.

  16. Spatial Mapping of Structural and Connectional Imaging Data for the Developing Human Brain with Diffusion Tensor Imaging

    PubMed Central

    Ouyang, Austin; Jeon, Tina; Sunkin, Susan M.; Pletikos, Mihovil; Sedmak, Goran; Sestan, Nenad; Lein, Ed S.; Huang, Hao

    2014-01-01

    During human brain development from fetal stage to adulthood, the white matter (WM) tracts undergo dramatic changes. Diffusion tensor imaging (DTI), a widely used magnetic resonance imaging (MRI) modality, offers insight into the dynamic changes of WM fibers as these fibers can be noninvasively traced and three-dimensionally (3D) reconstructed with DTI tractography. The DTI and conventional T1 weighted MRI images also provide sufficient cortical anatomical details for mapping the cortical regions of interests (ROIs). In this paper, we described basic concepts and methods of DTI techniques that can be used to trace major WM tracts noninvasively from fetal brain of 14 postconceptional weeks (pcw) to adult brain. We applied these techniques to acquire DTI data and trace, reconstruct and visualize major WM tracts during development. After categorizing major WM fiber bundles into five unique functional tract groups, namely limbic, brain stem, projection, commissural and association tracts, we revealed formation and maturation of these 3D reconstructed WM tracts of the developing human brain. The structural and connectional imaging data offered by DTI provides the anatomical backbone of transcriptional atlas of the developing human brain. PMID:25448302

  17. Study of the interactions between a proline-rich protein and a flavan-3-ol by NMR: residual structures in the natively unfolded protein provides anchorage points for the ligands.

    PubMed

    Pascal, Christine; Paté, Franck; Cheynier, Véronique; Delsuc, Marc-André

    2009-09-01

    Astringency is one of the major organoleptic properties of food and beverages that are made from plants, such as tea, chocolate, beer, or red wine. This sensation is thought to be due to interactions between tannins and salivary proline-rich proteins, which are natively unfolded proteins. A human salivary proline-rich protein, namely IB-5, was produced by the recombinant method. Its interactions with a model tannin, epigallocatechin gallate (EGCG), the major flavan-3-ol in green tea, were studied here. Circular dichroism experiments showed that IB-5 presents residual structures (PPII helices) when the ionic strength is close to that in saliva. In the presence of these residual structures, IB-5 undergoes an increase in structural content upon binding to EGCG. NMR data corroborated the presence of preformed structural elements within the protein prior to binding and a partial assignment was proposed, showing partial structuration. TOCSY experiments showed that amino acids that are involved in PPII helices are more likely to interact with EGCG than those in random coil regions, as if they were anchorage points for the ligand. The signal from IB-5 in the DOSY NMR spectrum revealed an increase in polydispersity upon addition of EGCG while the mean hydrodynamic radius remained unchanged. This strongly suggests the formation of IB-5/EGCG aggregates.

  18. Management of hyperphosphataemia: practices and perspectives amongst the renal care community.

    PubMed

    Nagel, Christina Johanna Maria; Casal, María Cruz; Lindley, Elizabeth; Rogers, Susan; Pancířová, Jitka; Kernc, Jennifer; Copley, J Brian; Fouque, Denis

    2014-12-01

    Protein-rich foods are a major source of dietary phosphorus; therefore, helping patients to increase their dietary protein intake, while simultaneously managing their hyperphosphataemia, poses a significant challenge for renal care professionals. To examine the clinical recommendations and practice perceptions of renal care professionals providing nutrition and phosphate control advice to patients with chronic kidney disease (CKD). Renal care professionals from four European countries completed an online survey on the clinical management of hyperphosphataemia. The majority of responders recommended a protein intake of less than 1.0 g/kg/day for pre-dialysis patients, 1.2 g/kg/day for patients undergoing peritoneal dialysis (PD) and 1.1-1.2 g/kg/day for patients undergoing haemodialysis (HD). The most common perception was that maintaining dietary protein intake and reducing dietary phosphorus intake are equally important for hyperphosphataemia management. For patients in the pre-dialysis stage, the majority of responders (59%) reported that their first-line management recommendation would be reduction of dietary phosphorus. For patients undergoing PD and HD, the majority of responders (53% and 59%, respectively) reported a first-line management recommendation of both reduction of dietary phosphorus and phosphate binder therapy. More renal nurses than dietitians perceived reducing dietary phosphorus to be more important than maintaining protein intake (for patients undergoing PD, 23% vs. 0%, respectively; for patients undergoing HD, 34% vs. 0%, respectively). This renal care community followed professionally accepted guidelines for patient nutrition and management of hyperphosphataemia. There was disparity in the perceptions and recommendations between nurses and dietitians, highlighting the need to standardise management practices amongst renal care professionals. © 2014 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  19. 10,000 - A reason to study granular heat convection

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

    Einav, I.; Rognon, P.; Gan, Y.

    2013-06-18

    In sheared granular media, particle motion is characterized by vortex-like structures; here this is demonstrated experimentally for disks system undergoing indefinite deformation during simple shear, as often imposed by the rock masses hosting earthquake fault gouges. In traditional fluids it has been known for years that vortices represent a major factor of heat transfer enhancement via convective internal mixing, but in analyses of heat transfer through earthquake faults and base planes of landslides this has been continuously neglected. Can research proceed by neglecting heat convection by internal mixing? Our answer is astonishingly far from being yes.

  20. Maintaining Weight Loss by Decreasing Sedentary Time: A Patient and Physician's Perspective.

    PubMed

    Montoya, Christopher; Lazarus, Ethan

    2017-04-01

    This article, co-authored by a patient living with obesity and his obesity medicine specialist, reviews how the patient has successfully lost 200 lb and maintained that loss for over a decade. This was achieved primarily with a behavioral intervention including support visits, a structured food plan, and changes in his physical activity. He did not undergo bariatric surgery. For the majority of this time, he was not treated with anti-obesity medication. This article will review how the patient lost the weight and kept it off, particularly in relationship to the importance of decreasing sedentary time.

  1. Cangrelor use prior to left ventricular assist device surgery: a case series.

    PubMed

    Washam, Jeffrey B; Yerokun, Babatunde; Patel, Chetan B; Welsby, Ian J; Milano, Carmelo A; DeVore, Adam D

    2018-06-02

    Bleeding frequently occurs in patients undergoing placement of a left ventricular assist device (LVAD). Clinical factors that have been identified as contributing to peri-procedural bleeding include LVAD implantation after an acute myocardial infarction and preoperative use of antiplatelet agents. In this report, we describe the use of cangrelor for preoperative antiplatelet bridging to LVAD in five post myocardial infarction patients with cardiogenic shock that had recently undergone percutaneous coronary intervention. During the cangrelor bridging period, no cases of thrombotic or major bleeding events occurred. During the first week following LVAD implantation, two patients experienced a major bleeding (each case required chest exploration for suspected hemorrhage). To our knowledge, this is the first series describing cangrelor use for antiplatelet bridging in patients undergoing LVAD implantation. While this series suggest cangrelor could possibly be a safe and effective antiplatelet bridging strategy, further research is needed to identify the optimal antithrombotic strategy in cardiogenic shock patients undergoing LVAD implantation who have recently undergoing percutaneous coronary intervention.

  2. 46 CFR 176.600 - Drydock and internal structural examination intervals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... States port, it must undergo the required examination before sailing. (c) If your vessel is not operated... exclusively by divers, the vessel must undergo two alternate hull exams and two internal structural exams within any five-year period. If a vessel completes a satisfactory alternate hull exam, with the...

  3. KENNEDY SPACE CENTER, FLA. - Launch Pad 39A undergoes sandblasting of its metal structures and surfaces. Routine maintenance includes sandblasting and repainting as preventive means to minimize corrosion.

    NASA Image and Video Library

    2003-09-12

    KENNEDY SPACE CENTER, FLA. - Launch Pad 39A undergoes sandblasting of its metal structures and surfaces. Routine maintenance includes sandblasting and repainting as preventive means to minimize corrosion.

  4. Hypovitaminosis D in patients undergoing kidney transplant: the importance of sunlight exposure

    PubMed Central

    Vilarta, Cristiane F.; Unger, Marianna D.; dos Reis, Luciene M.; Dominguez, Wagner V.; David-Neto, Elias; Moysés, Rosa M.; Titan, Silvia; Custodio, Melani R.; Hernandez, Mariel J.; Jorgetti, Vanda

    2017-01-01

    OBJECTIVES: Recent studies have shown a high prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D level less than 30 ng/ml, in both healthy populations and patients with chronic kidney disease. Patients undergoing kidney transplant are at an increased risk of skin cancer and are advised to avoid sunlight exposure. Therefore, these patients might share two major risk factors for hypovitaminosis D: chronic kidney disease and low sunlight exposure. This paper describes the prevalence and clinical characteristics of hypovitaminosis D among patients undergoing kidney transplant. METHODS: We evaluated 25-hydroxyvitamin D serum levels in a representative sample of patients undergoing kidney transplant. We sought to determine the prevalence of hypovitaminosis D, compare these patients with a control group, and identify factors associated with hypovitaminosis D (e.g., sunlight exposure and dietary habits). RESULTS: Hypovitaminosis D was found in 79% of patients undergoing kidney transplant, and the major associated factor was low sunlight exposure. These patients had higher creatinine and intact parathyroid hormone serum levels, with 25-hydroxyvitamin D being inversely correlated with intact parathyroid hormone serum levels. Compared with the control group, patients undergoing kidney transplant presented a higher prevalence of 25-hydroxyvitamin D deficiency and lower serum calcium, phosphate and albumin but higher creatinine and intact parathyroid hormone levels. CONCLUSIONS: Our results confirmed the high prevalence of hypovitaminosis D in patients undergoing kidney transplant. Therapeutic strategies such as moderate sunlight exposure and vitamin D supplementation should be seriously considered for this population. PMID:28793001

  5. Hypovitaminosis D in patients undergoing kidney transplant: the importance of sunlight exposure.

    PubMed

    Vilarta, Cristiane F; Unger, Marianna D; Dos Reis, Luciene M; Dominguez, Wagner V; David-Neto, Elias; Moysés, Rosa M; Titan, Silvia; Custodio, Melani R; Hernandez, Mariel J; Jorgetti, Vanda

    2017-07-01

    Recent studies have shown a high prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D level less than 30 ng/ml, in both healthy populations and patients with chronic kidney disease. Patients undergoing kidney transplant are at an increased risk of skin cancer and are advised to avoid sunlight exposure. Therefore, these patients might share two major risk factors for hypovitaminosis D: chronic kidney disease and low sunlight exposure. This paper describes the prevalence and clinical characteristics of hypovitaminosis D among patients undergoing kidney transplant. We evaluated 25-hydroxyvitamin D serum levels in a representative sample of patients undergoing kidney transplant. We sought to determine the prevalence of hypovitaminosis D, compare these patients with a control group, and identify factors associated with hypovitaminosis D (e.g., sunlight exposure and dietary habits). Hypovitaminosis D was found in 79% of patients undergoing kidney transplant, and the major associated factor was low sunlight exposure. These patients had higher creatinine and intact parathyroid hormone serum levels, with 25-hydroxyvitamin D being inversely correlated with intact parathyroid hormone serum levels. Compared with the control group, patients undergoing kidney transplant presented a higher prevalence of 25-hydroxyvitamin D deficiency and lower serum calcium, phosphate and albumin but higher creatinine and intact parathyroid hormone levels. Our results confirmed the high prevalence of hypovitaminosis D in patients undergoing kidney transplant. Therapeutic strategies such as moderate sunlight exposure and vitamin D supplementation should be seriously considered for this population.

  6. On the Origin of Banded Structure in Dusty Protoplanetary Discs: HL Tau and TW Hya

    NASA Astrophysics Data System (ADS)

    Boley, Aaron C.

    2017-10-01

    We present simulations of planet-planetesimal interactions that can reproduce major and minor banded structure in the HL Tau and TW Hya discs provided that small grains trace the dynamically cold planetesimal population. The consequences of the model and its limitations will be discussed. In particular, the model requires that planetesimals form throughout the disc at early times, that planetesimal-planetesimal collisions are predominately among the cold population, and that pebble accretion leads to mass redistribution of the small grains onto planetesimals before the grains can undergo significant radial drift. The meteortic record may suggest that a similar process occurred in the Solar System. The model implies that grain size distributions inferred from submm/mm studies may reflect early debris processes rather than grain growth.

  7. Development of a core outcome set for studies involving patients undergoing major lower limb amputation for peripheral arterial disease: study protocol for a systematic review and identification of a core outcome set using a Delphi survey.

    PubMed

    Ambler, Graeme K; Bosanquet, David C; Brookes-Howell, Lucy; Thomas-Jones, Emma; Waldron, Cherry-Ann; Edwards, Adrian G K; Twine, Christopher P

    2017-12-28

    The development of a standardised reporting set is important to ensure that research is directed towards the most important outcomes and that data is comparable. To ensure validity, the set must be agreed by a consensus of stakeholders including patients, healthcare professionals and lay representatives. There is currently no agreed core outcome set for patients undergoing major lower limb amputation for peripheral arterial disease (PAD) for either short- or medium-term research outcomes. By developing these sets we aim to rationalise future trial outcomes, facilitate meta-analysis and improve the quality and applicability of amputation research. We will undertake a comprehensive systematic review of studies of patients undergoing major lower limb amputation for PAD. Data regarding all primary and secondary outcomes reported in relevant studies will be extracted and summarised as outcome domains. We will then undertake focus groups with key stakeholders (patients, carers, health and social care workers) to collect qualitative data to identify the main short- and medium-term research outcomes for patients undergoing major lower limb amputation. Results of the systematic review and focus groups will be combined to create a comprehensive list of potential key outcomes. Stakeholders (patients, researchers and health and social care workers) will then be polled to determine which of the outcomes are considered to be important in a general context using a three-phase Delphi process. After preliminary analysis, results will be presented at a face-to-face meeting of key stakeholders for discussion and voting on the final set of core outcomes. This project is being run in parallel with a feasibility trial assessing perineural catheters in patients undergoing lower limb amputation (the PLACEMENT trial). Full ethical approval has been granted for the study (Wales REC 3 reference number 16/WA/0353). Core outcome sets will be developed for short- and medium-term outcomes of research involving patients undergoing major lower limb amputation for PAD. This will help with the design of future trials and facilitate meta-analyses of trial data. PROSPERO: CRD42017059329 . Registered on 30 March 2017. 975 . Registered on 5 April 2017.

  8. Racial/Ethnic Disparities in Perioperative Outcomes of Major Procedures: Results From the National Surgical Quality Improvement Program.

    PubMed

    Ravi, Praful; Sood, Akshay; Schmid, Marianne; Abdollah, Firas; Sammon, Jesse D; Sun, Maxine; Klett, Dane E; Varda, Briony; Peabody, James O; Menon, Mani; Kibel, Adam S; Nguyen, Paul L; Trinh, Quoc-Dien

    2015-12-01

    To determine the association between race/ethnicity and perioperative outcomes in individuals undergoing major oncologic and nononcologic surgical procedures in the United States. Prior work has shown that there are significant racial/ethnic disparities in perioperative outcomes after several types of major cardiac, general, vascular, orthopedic, and cancer surgical procedures. However, recent evidence suggests attenuation of these racial/ethnic differences, particularly at academic institutions. We utilized the American College of Surgeons National Surgical Quality Improvement Program database to identify 142,344 patients undergoing one of the 16 major cancer and noncancer surgical procedures between 2005 and 2011. Eighty-five percent of the cohort was white, with black and Hispanic individuals comprising 8% and 4%, respectively. In multivariable analyses, black patients had greater odds of experiencing prolonged length of stay after 10 of the 16 procedures studied (all P < 0.05), though there was no disparity in odds of 30-day mortality after any surgery. Hispanics were more likely to experience prolonged length of stay after 5 surgical procedures (all P < 0.04), and were at greater odds of dying within 30 days after colectomy, heart valve repair/replacement, or abdominal aortic aneurysm repair (all P < 0.03). Fewer disparities were observed for Hispanics, than for black patients, and also for cancer, than for noncancer surgical procedures. Important racial/ethnic disparities in perioperative outcomes were observed among patients undergoing major cancer and noncancer surgical procedures at American College of Surgeons National Surgical Quality Improvement Program institutions. There were fewer disparities among individuals undergoing cancer surgery, though black patients, in particular, were more likely to experience prolonged length of stay.

  9. Global incidence and case fatality rate of pulmonary embolism following major surgery: a protocol for a systematic review and meta-analysis of cohort studies.

    PubMed

    Temgoua, Mazou N; Tochie, Joel Noutakdie; Noubiap, Jean Jacques; Agbor, Valirie Ndip; Danwang, Celestin; Endomba, Francky Teddy A; Nkemngu, Njinkeng J

    2017-12-04

    Pulmonary embolism (PE) is a life-threatening condition common after major surgery. Although the high incidence (0.3-30%) and mortality rate (16.9-31%) of PE in patients undergoing major surgical procedures is apparent from findings of contemporary observational studies, there is a lack of a summary and meta-analysis data on the epidemiology of postoperative PE in this same regard. Hence, we propose to conduct the first systematic review to summarise existing data on the global incidence, determinants and case fatality rate of PE following major surgery. Electronic databases including MEDLINE, EMBASE, SCOPUS, WHO global health library (including LILACS), Web of Science and Google scholar from inception to April 30, 2017, will be searched for cohort studies reporting on the incidence, determinants and case fatality rate of PE occurring after major surgery. Data from grey literature will also be assessed. Two investigators will independently perform study selection and data extraction. Included studies will be evaluated for risk of bias. Appropriate meta-analytic methods will be used to pool incidence and case fatality rate estimates from studies with identical features, globally and by subgroups of major surgical procedures. Random-effects and risk ratio with 95% confidence interval will be used to summarise determinants and predictors of mortality of PE in patients undergoing major surgery. This systematic review and meta-analysis will provide the most up-to-date epidemiology of PE in patients undergoing major surgery to inform health authorities and identify further research topics based on the remaining knowledge gaps. PROSPERO CRD42017065126.

  10. Effects of ECT in treatment of depression: study protocol for a prospective neuroradiological study of acute and longitudinal effects on brain structure and function.

    PubMed

    Oltedal, Leif; Kessler, Ute; Ersland, Lars; Grüner, Renate; Andreassen, Ole A; Haavik, Jan; Hoff, Per Ivar; Hammar, Åsa; Dale, Anders M; Hugdahl, Kenneth; Oedegaard, Ketil J

    2015-05-01

    Major depression can be a serious and debilitating condition. For some patients in a treatment resistant depressive episode, electroconvulsive treatment (ECT) is the only treatment that is effective. Although ECT has shown efficacy in randomized controlled trials, the treatment is still controversial and stigmatized. This can in part be attributed to our lack of knowledge of the mechanisms of action. Some reports also suggest potential harmful effects of ECT treatment and memory related side effects have been documented. The present study will apply state of the art radiology through advanced magnetic resonance imaging (MRI) techniques to investigate structural and functional brain effects of ECT. As a multi-disciplinary collaboration, imaging findings will be correlated to psychiatric response parameters, neuropsychological functioning as well as neurochemical and genetic biomarkers that can elucidate the underlying mechanisms. The aim is to document both treatment effects and potential harmful effects of ECT. n = 40 patients in a major depressive episode (bipolar and major depressive disorder). Two control groups with n = 15 in each group: age and gender matched healthy volunteers not receiving ECT and patients undergoing electrical cardioversion (ECV) for atrial fibrillation (AF). Observation time: six months. The study will contribute to our understanding of the pathophysiology of major depression as well as mechanisms of action for the most effective treatment for the disorder; ECT.

  11. Cryo-EM structure of aerolysin variants reveals a novel protein fold and the pore-formation process

    NASA Astrophysics Data System (ADS)

    Iacovache, Ioan; de Carlo, Sacha; Cirauqui, Nuria; Dal Peraro, Matteo; van der Goot, F. Gisou; Zuber, Benoît

    2016-07-01

    Owing to their pathogenical role and unique ability to exist both as soluble proteins and transmembrane complexes, pore-forming toxins (PFTs) have been a focus of microbiologists and structural biologists for decades. PFTs are generally secreted as water-soluble monomers and subsequently bind the membrane of target cells. Then, they assemble into circular oligomers, which undergo conformational changes that allow membrane insertion leading to pore formation and potentially cell death. Aerolysin, produced by the human pathogen Aeromonas hydrophila, is the founding member of a major PFT family found throughout all kingdoms of life. We report cryo-electron microscopy structures of three conformational intermediates and of the final aerolysin pore, jointly providing insight into the conformational changes that allow pore formation. Moreover, the structures reveal a protein fold consisting of two concentric β-barrels, tightly kept together by hydrophobic interactions. This fold suggests a basis for the prion-like ultrastability of aerolysin pore and its stoichiometry.

  12. Neogene to recent contraction and basin inversion along the Nubia-Iberia boundary in SW Iberia

    NASA Astrophysics Data System (ADS)

    Ramos, Adrià; Fernández, Oscar; Terrinha, Pedro; Muñoz, Josep Anton

    2017-02-01

    The SW of Iberia is currently undergoing compression related to the convergence between Nubia and Iberia. Multiple compressive structures, and their related seismic activity, have been documented along the diffuse Nubia-Iberia plate boundary, including the Gorringe bank west of the Gulf of Cadiz, and the Betic-Rif orogen to the east. Despite seismic activity indicating a dominant compressive stress along the Algarve margin in the Gulf of Cadiz, the structures at the origin of this seismicity remain elusive. This paper documents the contractional structures that provide linkage across the Gulf of Cadiz and play a major role in defining the present-day seismicity and bathymetry of this area. The structures described in this paper caused the Neogene inversion of the Jurassic oblique passive margin that formed between the central Atlantic and the Ligurian Tethys. This example of a partially inverted margin provides insights into the factors that condition the inversion of passive margins.

  13. Cryo-EM visualization of the protein machine that replicates the chromosome

    NASA Astrophysics Data System (ADS)

    Li, Huilin

    Structural knowledge is key to understanding biological functions. Cryo-EM is a physical method that uses transmission electron microscopy to visualize biological molecules that are frozen in vitreous ice. Due to recent advances in direct electron detector and image processing algorithm, cryo-EM has become a high-resolution technique. Cryo-EM field is undergoing a rapid expansion and vast majority research institutions and research universities around the world are setting up cryo-EM research. Indeed, the method is revolutionizing structural and molecular biology. We have been using cryo-EM to study the structure and mechanism of eukaryotic chromosome replication. Despite an abundance of cartoon drawings found in review articles and biology textbooks, the structure of the eukaryotic helicase that unwinds the double stranded DNA has been unknown. It has also been unknown how the helicase works with DNA polymerases to accomplish the feat of duplicating the genome. In my presentation, I will show how we have used cryo-EM to derive at structures of the eukaryotic chromosome replication machinery and describe mechanistic insights we have gleaned from the structures.

  14. Molecular dynamics simulations of DNA-polycation complexes

    NASA Astrophysics Data System (ADS)

    Ziebarth, Jesse; Wang, Yongmei

    2008-03-01

    A necessary step in the preparation of DNA for use in gene therapy is the packaging of DNA with a vector that can condense DNA and provide protection from degrading enzymes. Because of the immunoresponses caused by viral vectors, there has been interest in developing synthetic gene therapy vectors, with polycations emerging as promising candidates. Molecular dynamics simulations of the DNA duplex CGCGAATTCGCG in the presence of 20 monomer long sequences of the polycations, poly-L-lysine (PLL) and polyethyleneimine (PEI), with explicit counterions and TIP3P water, are performed to provide insight into the structure and formation of DNA polyplexes. After an initial separation of approximately 50 å, the DNA and polycation come together and form a stable complex within 10 ns. The DNA does not undergo any major structural changes upon complexation and remains in the B-form. In the formed complex, the charged amine groups of the polycation mainly interact with DNA phosphate groups, and rarely occupy electronegative sites in either the major or minor grooves. Differences between complexation with PEI and PLL will be discussed.

  15. Structural control of weathering processes within exhumed granitoids: Compartmentalisation of geophysical properties by faults and fractures

    NASA Astrophysics Data System (ADS)

    Place, J.; Géraud, Y.; Diraison, M.; Herquel, G.; Edel, J.-B.; Bano, M.; Le Garzic, E.; Walter, B.

    2016-03-01

    In the latter stages of exhumation processes, rocks undergo weathering. Weathering halos have been described in the vicinity of structures such as faults, veins or dykes, with a lateral size gradually narrowing with depth, symmetrically around the structures. In this paper, we describe the geophysical characterisation of such alteration patterns on two granitoid outcrops of the Catalan Coastal Ranges (Spain), each of which is affected by one major fault, as well as minor faults and fractures. Seismic, electric and ground penetrating radar surveys were carried out to map the spatial distribution of P-wave velocity, electrical resistivity and to identify reflectors of electromagnetic waves. The analysis of this multi-method and complementary dataset revealed that, at shallow depth, geophysical properties of the materials are compartmentalised and asymmetric with respect to major and subsidiary faults affecting the rock mass. This compartmentalisation and asymmetry both tend to attenuate with depth, whereas the effect of weathering is more symmetric with respect to the major structure of the outcrops. We interpret such compartmentalisation as resulting from the role of hydraulic and mechanical boundaries played by subsidiary faults, which tend to govern both the chemical and physical alterations involved in weathering. Thus, the smoothly narrowing halo model is not always accurate, as weathering halos can be strongly asymmetrical and present highly irregular contours delimiting sharp contrasts of geophysical properties. These results should be considered when investigating and modelling fluid storage and transfer in top crystalline rock settings for groundwater applications, hydrocarbon or geothermal reservoirs, as well as mineral deposits.

  16. In situ Studies of Phase Evolution in (Pr 1-x Nd x) 2 NiO 4 Electrodes with Various Interlayer Chemistries

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

    Dogdibegovic, Emir; Alabri, Nawf Saif; Wright, Christopher J.

    The interest in Pr2NiO4 (PNO) electrode stems from the necessity to develop active and stable oxygen electrodes (1-6) for solid oxide fuel cells (SOFCs) (7-9). PNO is known for its highly active nature (7,8,10), originating from its superior oxygen ion diffusion, surface exchange coefficient (2,7,9-11) and structural flexibility over a wide temperature region (from 500 to 900oC) (3,12). PNO electrode, however, does undergo structural evolution to form a higher order phase (Pr3Ni2O7) and Pr6O11 (PrOx) (8). The structural change has been a major concern because it possibly links with the performance degradation over long-term operation (7,8) Conventional x-ray diffraction (XRD)more » has been extensively used to investigate the structural evolution in nickelates in the form of powders or planar electrodes (8,10). This method has two major limitations due to its low flux and low resolution: (1) it might overlook the presence of additional phases in the system, which is especially true for praseodymium nickelates where XRD diffraction patterns of higher order phase(s) (e.g. Pr3Ni2O7) may overlap with the parent PNO phase, making quantification challenging (8); and (2) the quantification of phase evolution in electrochemically operated PNO electrode may show major structural change with almost 100% of the parent phase transition from the conventional XRD analysis, while the transmission electron microscopy (TEM) studies clearly show the regions of preserved PNO phase (7).« less

  17. In situ Studies of Phase Evolution in (Pr1-xNdx)2NiO4 Electrodes with Various Interlayer Chemistries

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

    Dogdibegovic, Emir; Alabri, Nawf S.; Wright, Christopher J.

    2017-07-24

    The interest in Pr2NiO4 (PNO) electrode stems from the necessity to develop active and stable oxygen electrodes (1-6) for solid oxide fuel cells (SOFCs) (7-9). PNO is known for its highly active nature (7,8,10), originating from its superior oxygen ion diffusion, surface exchange coefficient (2,7,9-11) and structural flexibility over a wide temperature region (from 500 to 900oC) (3,12). PNO electrode, however, does undergo structural evolution to form a higher order phase (Pr3Ni2O7) and Pr6O11 (PrOx) (8). The structural change has been a major concern because it possibly links with the performance degradation over long-term operation (7,8) Conventional x-ray diffraction (XRD)more » has been extensively used to investigate the structural evolution in nickelates in the form of powders or planar electrodes (8,10). This method has two major limitations due to its low flux and low resolution: (1) it might overlook the presence of additional phases in the system, which is especially true for praseodymium nickelates where XRD diffraction patterns of higher order phase(s) (e.g. Pr3Ni2O7) may overlap with the parent PNO phase, making quantification challenging (8); and (2) the quantification of phase evolution in electrochemically operated PNO electrode may show major structural change with almost 100% of the parent phase transition from the conventional XRD analysis, while the transmission electron microscopy (TEM) studies clearly show the regions of preserved PNO phase (7).« less

  18. Emergency General Surgery in the Elderly: Too Old or Too Frail?

    PubMed

    Joseph, Bellal; Zangbar, Bardiya; Pandit, Viraj; Fain, Mindy; Mohler, Martha Jane; Kulvatunyou, Narong; Jokar, Tahereh Orouji; O'Keeffe, Terence; Friese, Randal S; Rhee, Peter

    2016-05-01

    Assessment of operative risk in geriatric patients undergoing emergency general surgery (EGS) is challenging. Frailty is an established measure for risk assessment in elective surgical cases. Emerging literature suggests the superiority of frailty measurements to chronological age in predicting outcomes. The aim of this study was to assess the outcomes in elderly patients undergoing EGS using an established Rockwood frailty index. We prospectively measured preadmission frailty in all geriatric (aged 65 years and older) patients undergoing EGS at our institution during a 2-year period. Frailty index (FI) was calculated using the modified 50-variable Rockwood Preadmission FI. Frail patients were defined by FI ≥ 0.25. Outcomes measures were in-hospital complications, development of major complications, and mortality. Multivariate regression analysis was performed. A total of 220 patients were enrolled, of which 82 (37%) were frail. Frailty index score did not correlate with age (R = 0.64; R(2) = 0.53; p = 0.1) and poorly correlated with American Society of Anesthesiologists score (R = 0.51; R(2) = 0.44; p = 0.045). Thirty-five percent (n = 77) of patients had postoperative complications and 19% (n = 42) had major complications. Frailty index was an independent predictor for development of in-hospital complications (odds ratio = 2.13; 95% CI, 1.09-4.16; p = 0.02) and major complications (odds ratio = 3.87; 95% CI, 1.69-8.84; p = 0.001). Age and American Society of Anesthesiologists score were not predictive of postoperative and major complications. Our FI model had 80% sensitivity, 72% specificity, and area under the curve of 0.75 in predicting complications in geriatric patients undergoing EGS. The overall mortality rate was 3.2% (n = 7) and all patients who died were frail. Frailty index independently predicts postoperative complications, major complications, and hospital length of stay in elderly patients undergoing emergency general surgery. Use of FI will provide insight into the hospital course of elderly patients, allowing for identification of patients in need and more efficient allocation of hospital resources. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Sulfoquinovose in the biosphere: occurrence, metabolism and functions.

    PubMed

    Goddard-Borger, Ethan D; Williams, Spencer J

    2017-02-20

    The sulfonated carbohydrate sulfoquinovose (SQ) is produced in quantities estimated at some 10 billion tonnes annually and is thus a major participant in the global sulfur biocycle. SQ is produced by most photosynthetic organisms and incorporated into the sulfolipid sulfoquinovosyl diacylglycerol (SQDG), as well as within some archaea for incorporation into glycoprotein N-glycans. SQDG is found mainly within the thylakoid membranes of the chloroplast, where it appears to be important for membrane structure and function and for optimal activity of photosynthetic protein complexes. SQDG metabolism within the sulfur cycle involves complex biosynthetic and catabolic processes. SQDG biosynthesis is largely conserved within plants, algae and bacteria. On the other hand, two major sulfoglycolytic pathways have been discovered for SQDG degradation, the sulfo-Embden-Meyerhof-Parnas (sulfo-EMP) and sulfo-Entner-Doudoroff (sulfo-ED) pathways, which mirror the major steps in the glycolytic EMP and ED pathways. Sulfoglycolysis produces C3-sulfonates, which undergo biomineralization to inorganic sulfur species, completing the sulfur cycle. This review discusses the discovery and structural elucidation of SQDG and archaeal N-glycans, the occurrence, distribution, and speciation of SQDG, and metabolic pathways leading to the biosynthesis of SQDG and its catabolism through sulfoglycolytic and biomineralization pathways to inorganic sulfur. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  20. Determining Surgical Complications in the Overweight (DISCOVER): a multicentre observational cohort study to evaluate the role of obesity as a risk factor for postoperative complications in general surgery.

    PubMed

    Nepogodiev, Dmitri; Chapman, Stephen J; Glasbey, James; Kelly, Michael; Khatri, Chetan; Drake, Thomas M; Kong, Chia Yew; Mitchell, Harriet; Harrison, Ewen M; Fitzgerald, J Edward; Bhangu, Aneel

    2015-07-20

    Obesity is increasingly prevalent among patients undergoing surgery. Conflicting evidence exists regarding the impact of obesity on postoperative complications. This multicentre study aims to determine whether obesity is associated with increased postoperative complications following general surgery. This prospective, multicentre cohort study will be performed utilising a collaborative methodology. Consecutive adults undergoing open or laparoscopic, elective or emergency, gastrointestinal, bariatric or hepatobiliary surgery will be included. Day case patients will be excluded. The primary end point will be the overall 30-day major complication rate (Clavien-Dindo grade III-V complications). Data will be collected to risk-adjust outcomes for potential confounding factors, such as preoperative cardiac risk. This study will be disseminated through structured medical student networks using established collaborative methodology. The study will be powered to detect a two-percentage point increase in the major postoperative complication rate in obese versus non-obese patients. Following appropriate assessment, an exemption from full ethics committee review has been received, and the study will be registered as a clinical audit or service evaluation at each participating hospital. Dissemination will take place through national and local research collaborative networks. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Mapping flexible protein domains at subnanometer resolution with the atomic force microscope.

    PubMed

    Müller, D J; Fotiadis, D; Engel, A

    1998-06-23

    The mapping of flexible protein domains with the atomic force microscope is reviewed. Examples discussed are the bacteriorhodopsin from Halobacterium salinarum, the head-tail-connector from phage phi29, and the hexagonally packed intermediate layer from Deinococcus radiodurans which all were recorded in physiological buffer solution. All three proteins undergo reversible structural changes that are reflected in standard deviation maps calculated from aligned topographs of individual protein complexes. Depending on the lateral resolution (up to 0.8 nm) flexible surface regions can ultimately be correlated with individual polypeptide loops. In addition, multivariate statistical classification revealed the major conformations of the protein surface.

  2. KSC-99pp0413

    NASA Image and Video Library

    1999-04-15

    The Space Shuttle orbiter Columbia sits outside the Orbiter Processing Facility bay 1 after transfer from the Vehicle Assembly Building. Columbia will undergo processing for mission STS-93, targeted for launch in July 1999. The STS-93 mission will deploy the Chandra X-ray Observatory (formerly AXAF) which comprises three major elements: the spacecraft, the telescope, and the science instrument module (SIM). Chandra will allow scientists from around the world to obtain unprecedented X-ray images of a variety of high-energy objects to help understand the structure and evolution of the universe. The STs-93 mission commander is Eileen M. Collins, the first woman to serve in that capacity

  3. TDRS-L NASA Social Tour

    NASA Image and Video Library

    2014-01-23

    CAPE CANAVERAL, Fla. -- At NASA's Kennedy Space Center in Florida, social media participants were given an opportunity to go inside the spaceport's Vehicle Assembly Building. After serving through the Apollo and Space Shuttle Programs, the structure now is undergoing renovations to accommodate future launch vehicles and to continue as a major part of America's efforts to explore space. The social media participants gathered at the Florida spaceport for the launch of the Tracking and Data Relay Satellite, or TDRS-L spacecraft. Their visit included tours of key facilities and participating in presentations by key NASA leaders who updated the space agency's current efforts. Photo credit: NASA/Dan Casper

  4. RNA-modifying proteins as anticancer drug targets.

    PubMed

    Boriack-Sjodin, P Ann; Ribich, Scott; Copeland, Robert A

    2018-06-01

    All major biological macromolecules (DNA, RNA, proteins and lipids) undergo enzyme-catalysed covalent modifications that impact their structure, function and stability. A variety of covalent modifications of RNA have been identified and demonstrated to affect RNA stability and translation to proteins; these mechanisms of translational control have been termed epitranscriptomics. Emerging data suggest that some epitranscriptomic mechanisms are altered in human cancers as well as other human diseases. In this Review, we examine the current understanding of RNA modifications with a focus on mRNA methylation, highlight their possible roles in specific cancer indications and discuss the emerging potential of RNA-modifying proteins as therapeutic targets.

  5. A multi-institutional analysis of 429 patients undergoing major hepatectomy for colorectal cancer liver metastases: The impact of concomitant bile duct resection on survival.

    PubMed

    Postlewait, Lauren M; Squires, Malcolm H; Kooby, David A; Weber, Sharon M; Scoggins, Charles R; Cardona, Kenneth; Cho, Clifford S; Martin, Robert C G; Winslow, Emily R; Maithel, Shishir K

    2015-10-01

    Data are lacking on long-term outcomes of patients undergoing major hepatectomy requiring bile duct resection (BDR) for the treatment of colorectal cancer liver metastases. Patients who underwent major hepatectomy (≥3 segments) for metastatic colorectal cancer from 2000-2010 at three US academic institutions were included. The primary outcome was disease-specific survival (DSS). Of 429 patients, nine (2.1%) underwent BDR, which was associated with pre-operative portal vein embolization (25.0% vs. 4.3%; P = 0.049). There were no significant differences in age, ASA class, margin status, number of lesions, tumor size, cirrhosis, perineural invasion, or lymphovascular invasion. BDR was independently associated with increased postoperative major complications (OR: 6.22; 95%CI:1.44-26.97; P = 0.015). There were no differences in length of stay, reoperation, readmission, or 30-day mortality. Patients who underwent BDR had markedly decreased DSS (9.3 vs. 39.9 mo; P = 0.002). When accounting for differences between the two groups, the need for BDR was independently associated with reduced DSS (HR: 3.06; 95%CI:1.12-8.34; P = 0.029). Major hepatectomy with concomitant bile duct resection is seldom performed in patients undergoing resection of colorectal cancer liver metastases and is associated with higher major morbidity and reduced disease-specific survival compared to major hepatectomy alone. Stringent selection criteria should be applied when patients may need bile duct resection during hepatectomy for colorectal cancer liver metastases. © 2015 Wiley Periodicals, Inc.

  6. Development of immature stomata: evidence for epigenetic selection of a spacing pattern.

    PubMed

    Kagan, M L; Sachs, T

    1991-07-01

    In Sansevieria trifasciata as many as half the potential stomata remain immature. The development of all stomatal structures started at the same time and the early stages of the development of immature stomata had no special characteristics. Statistical analysis showed that the mature stomata were more evenly spaced than all potential stomata, both mature and immature. Furthermore, the distribution of mature stomata per unit area was more predictable or orderly than comparable structures of a random model that developed in the same way. These facts indicate that a nonrandom loss of many stomata by "immaturity" is a major determinant, acting during rather than preceding development, of the distribution of the mature, functional stomata. Thus in Sansevieria there is a selection of an epidermal pattern from an excess of cells that undergo the early stages of stomatal development.

  7. Children with chronic renal disease undergoing dialysis or conservative treatment--differences in structural and functional echocardiographic parameters.

    PubMed

    Scavarda, Valeska Tavares; Pinheiro, Aurelio Carvalho; Costa, Symône Damasceno; de Andrade, Zélia Maria; Carvalhaes, João Tomás de Abreu; Campos, Orlando; Carvalho, Antonio Carlos; Moises, Valdir Ambrosio

    2014-10-01

    Cardiac disease frequently occurs in children with chronic kidney disease (CKD) undergoing dialysis (DI), but it is not well studied in patients undergoing conservative treatment (CT). The aim of our study was to use echocardiography to analyze and compare the cardiac involvement of children with CKD undergoing DI or CT. Seventy-one children with CKD were included; 41 undergoing DI and 30 undergoing CT. There were 33 controls. Measurements of arterial pressure and structural and functional echocardiographic variables were obtained; the children were followed up for 18 months. Tests of comparison and multiple regression were used; significant if P < 0.05. Arterial hypertension (AH) was present in 37 of 71 (52%) children with CKD: 27 (65.8%) in DI and 10 (33.3%) in CT (X2 = 8.7; P = 0.003). An abnormal left ventricular geometric pattern was present in 37/41 (90.3%) undergoing DI, 33 had left ventricular hypertrophy (LVH), and in 14/30 (46.7%) undergoing CT, 5 had LVH. Ejection fraction was normal in all groups; diastolic function alteration (DFA) occurred in 28/41 (68.3%) children on DI and in 10/30 (33.3%) on CT (X2 = 9.2; P = 0.002). For children with CKD, DI (P = 0.002) and hypertension (P = 0.04) were associated with LVH; among those on DI, only AH was associated with LVH (P = 0.02). During the follow-up, 18 (43.9%) children undergoing DI had at least one cardiovascular event. Children with CKD undergoing CT had less cardiac involvement than those undergoing DI. LVH was associated with DI and AH in all children with CKD and with AH in those on DI.

  8. Interventional radiology in living donor liver transplant

    PubMed Central

    Cheng, Yu-Fan; Ou, Hsin-You; Yu, Chun-Yen; Tsang, Leo Leung-Chit; Huang, Tung-Liang; Chen, Tai-Yi; Hsu, Hsien-Wen; Concerjero, Allan M; Wang, Chih-Chi; Wang, Shih-Ho; Lin, Tsan-Shiun; Liu, Yueh-Wei; Yong, Chee-Chien; Lin, Yu-Hung; Lin, Chih-Che; Chiu, King-Wah; Jawan, Bruno; Eng, Hock-Liew; Chen, Chao-Long

    2014-01-01

    The shortage of deceased donor liver grafts led to the use of living donor liver transplant (LDLT). Patients who undergo LDLT have a higher risk of complications than those who undergo deceased donor liver transplantation (LT). Interventional radiology has acquired a key role in every LT program by treating the majority of vascular and non-vascular post-transplant complications, improving graft and patient survival and avoiding, in the majority of cases, surgical revision and/or re-transplant. The aim of this paper is to review indications, diagnostic modalities, technical considerations, achievements and potential complications of interventional radiology procedures after LDLT. PMID:24876742

  9. Telemedicine at sea and onshore: divergences and convergences.

    PubMed

    Guitton, Matthieu J

    2015-01-01

    Telemedical Maritime Assistance Service (TMAS) is one of the fundamental components of medical assistance delivery at sea. However, while onshore telemedicine is undergoing a fast growth, these research and clinical investments unfortunately did not yet benefit for telemedicine at sea. While telemedicine aims at providing distant health care, telemedicine at sea and onshore bear major differences, particularly for merchant vessels, and to a lesser extent for passenger vessels, which can be divided between structural differences, differences of practices, and policy differences. Despite the existence of important divergences between telemedicine at sea and telemedicine onshore, these two major branches of distant health care delivery still converge in some respects. Identifying the convergences between telemedicine at sea and telemedicine onshore might contribute to increase and optimise the transfer from research on onshore telemedicine to maritime telemedicine, and to overcome the relatively low amount of research performed on telemedicine at sea compared to its onshore counterpart.

  10. Psychometric properties and factor structure of the Fertility Problem Inventory in a sample of infertile women undergoing fertility treatment.

    PubMed

    Gourounti, K; Anagnostopoulos, F; Vaslamatzis, G

    2011-10-01

    to examine the psychometric properties of the Fertility Problem Inventory (FPI) originally developed by Newton et al. (1999); as there are no data concerning the factorial structure of the FPI, a special focus is placed on construct validity through factor analysis. public hospital in Athens, Greece. a cross-sectional study. 108 women undergoing fertility treatment with in-vitro fertilisation. the FPI was 'forward-backward' translated from English to Greek. The translated instrument was then administered to a set of infertile women for pilot testing. Principal axis factoring with promax rotation was used to test the factor structure of the FPI. Measures of anxiety State Trait Anxiety Inventory, depression (Center for Epidemiologic Studies--Depression Scale) and mood states Profile of Mood States were used to assess the convergent validity of the FPI. Cronbach's α was used to measure internal consistency of the FPI scales. exploratory factor analysis suggested four factors. The majority of relationship and sexual concern items grouped into one solid factor, named 'spousal concern'. The original scales of social concern, need for parenthood and rejection of childfree lifestyle were reproduced after rearranging nine cross-loading items. Construct validity was confirmed by computing correlations between the derived FPI scales and conceptually similar constructions of anxiety, depression and mood states. Internal consistency reliability was satisfactory. the FPI was found to have a relatively stable factor structure and satisfactory reliability, and convergent and discriminant validity. The FPI may enable researchers and clinicians to apply a reliable measure that focuses on various/many dimensions of infertility-related stress. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Gender-based outcomes of bivalirudin versus heparin in patients undergoing percutaneous coronary interventions: Meta-analysis of randomized controlled trials.

    PubMed

    Mina, George S; Firouzbakht, Tina; Modi, Kalgi; Dominic, Paari

    2017-11-01

    We aimed to perform a gender-based meta-analysis of the outcome of bivalirudin versus heparin in patients undergoing percutaneous coronary interventions (PCI). Bivalirudin has been shown to decrease major bleeding when compared to heparin ± glycoprotein IIb/IIIa inhibitors (GPI) in patients undergoing PCI. It is unclear, however, if those differences in outcomes are the same for men and women. We included randomized controlled trials (RCTs) that compared bivalirudin to heparin with or without GPI in patients undergoing PCI and reported outcome data that were stratified by gender. Random effect model was used to pool odds ratio (OR) and 95% confidence intervals (CI). We included 9 trials with 33,224 patients. Bivalirudin decreased major bleeding when compared to heparin plus routine GPI in both men (OR: 0.51, P < 0.001) and women (OR: 0.55, P < 0.001). However, when GPI were used selectively with heparin, the bleeding lowering effect of bivalirudin was statistically significant in men (OR: 0.69, P = 0.02) but not in women (OR: 0.71, P = 0.21). When compared to heparin ± GPI, there was a nonstatistically significant trend toward lower all-cause mortality with bivalirudin in both men (OR: 0.76, P = 0.055) and women (OR: 0.79, P = 0.21). There were no significant differences in major adverse cardiovascular events between heparin and bivalirudin in both men and women. Bivalirudin decreases major bleeding in both men and women when compared to heparin plus routine GPI. However, when compared to heparin alone, the bleeding lowering benefit of bivalirudin is less evident in women. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. In-hospital management and outcome of patients on warfarin undergoing coronary stent implantation: results of the multicenter, prospective WARfarin and coronary STENTing (WAR-STENT) registry.

    PubMed

    Rubboli, Andrea; Sciahbasi, Alessandro; Briguori, Carlo; Saia, Francesco; Palmieri, Cataldo; Moroni, Luigi Andrea; Calabrò, Paolo; Leone, Antonio Maria; Franco, Nicoletta; Valgimigli, Marco; Varani, Elisabetta; Santi, Michela; Pasqualini, Paola; Capecchi, Alessandro; Piccalò, Giacomo; Margheri, Massimo; di Pasquale, Giuseppe; Galvani, Marcello; Bolognese, Leonardo; Gonzini, Lucio; Maggioni, Aldo Pietro

    2013-04-01

    The in-hospital management of patients on warfarin undergoing coronary stent implantation (PCI-S) is variable, and the in-hospital outcome incompletely defined. To determine the adherence to the current recommendations, and the incidence of adverse events, we carried out the prospective, multicenter, observational WARfarin and coronary STENTing (WAR-STENT) registry (ClinicalTrials.gov identifier NCT00722319). All consecutive patients on warfarin undergoing PCI-S at 37 Italian centers were enrolled and followed for 12 months. Outcome measures were: major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, need for urgent revascularization, stroke, and venous thromboembolism, and major and minor bleeding. In this paper, we report the in-hospital findings. Out of the 411 patients enrolled, 92% were at non-low (ie, moderate or high) thromboembolic risk. The radial approach and bare-metal stents were used in 61% and 60% of cases, respectively. Drug-eluting stents were essentially reserved to patients with diabetes, which in turn, significantly predicted the implantation of drug-eluting stents (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.29-3.17; P=.002). The in-hospital MACE and major bleeding rates were 2.7% and 2.1%, respectively. At discharge, triple therapy (TT) of warfarin, aspirin, and clopidogrel was prescribed to 76% of patients. Prescription of TT was significantly more frequent in the non-low thromboembolic risk group. Non-low thromboembolic risk, in turn, was a significant predictor of TT prescription (OR, 11.2; 95% CI, 4.83-26.3; P<.0001). In conclusion, real-world warfarin patients undergoing PCI-S are largely managed according to the current recommendations. As a consequence, the risk of in-hospital MACE and major bleedings appears limited and acceptable.

  13. Use of tailored loading-dose clopidogrel in patients undergoing selected percutaneous coronary intervention based on adenosine diphosphate-mediated platelet aggregation.

    PubMed

    Meng, Kang; Lü, Shu-Zheng; Zhu, Hua-Gang; Chen, Xin; Ge, Chang-Jiang; Song, Xian-Tao

    2010-12-01

    Adenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to assess whether an adjusted loading dose of clopidogrel could more effectively inhibit platelet aggregation in patients undergoing selected percutaneous coronary intervention. A total of 205 patients undergoing selected percutaneous coronary intervention were enrolled in this multicenter, prospective, randomized study. Patients receiving domestic clopidogrel (n = 104) served as the Talcom (Taijia) group; others (n = 101) received Plavix, the Plavix group. Patients received up to 3 additional 300-mg loading doses of clopidogrel to decrease the adenosine phosphate-mediated platelet aggregation index by more than 50% (the primary endpoint) compared with the baseline. The secondary endpoint was major adverse cardiovascular events at 12 months. Compared with the rational loading dosage, the tailored loading dosage better inhibited platelet aggregation based on a > 50% decrease in adenosine phosphate-mediated platelet aggregation (rational loading dosage vs. tailored loading dosage, 48% vs. 73%, P = 0.028). There was no significant difference in the eligible index between the Talcom and Plavix groups (47% vs. 49% at 300 mg; 62% vs. 59% at 600 mg; 74% vs. 72% at 900 mg; P > 0.05) based on a standard adenosine diphosphate-mediated platelet aggregation decrease of > 50%. After 12 months of follow-up, there were no significant differences in major adverse cardiac events (2.5% vs. 2.9%, P = 5.43). No acute or subacute stent thrombosis events occurred. An adjusted loading dose of clopidogrel could have significant effects on antiplatelet aggregation compared with a rational dose, decreasing 1-year major adverse cardiac events in patients undergoing percutaneous coronary interventions based on adenosine phosphate-mediated platelet aggregation with no increase in bleeding.

  14. Notch-modifying xylosyltransferase structures support an S Ni-like retaining mechanism

    DOE PAGES

    Yu, Hongjun; Li, Huilin; Takeuchi, Megumi; ...

    2015-09-28

    A major question remaining in glycobiology is how a glycosyltransferase (GT) that retains the anomeric linkage of a sugar catalyzes the reaction. Xyloside α-1,3-xylosyltransferase (XXYLT1) is a retaining GT that regulates Notch receptor activation by adding xylose to the Notch extracellular domain. Here, using natural acceptor and donor substrates and active Mus musculus XXYLT1, we report a series of crystallographic snapshots along the reaction, including an unprecedented natural and competent Michaelis reaction complex for retaining enzymes. These structures strongly support the SNi-like reaction as the retaining mechanism for XXYLT1. Unexpectedly, the epidermal growth factor–like repeat acceptor substrate undergoes a largemore » conformational change upon binding to the active site, providing a structural basis for substrate specificity. As a result, our improved understanding of this retaining enzyme will accelerate the design of retaining GT inhibitors that can modulate Notch activity in pathological situations in which Notch dysregulation is known to cause cancer or developmental disorders.« less

  15. Notch-modifying xylosyltransferase structures support an S Ni-like retaining mechanism

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

    Yu, Hongjun; Li, Huilin; Takeuchi, Megumi

    A major question remaining in glycobiology is how a glycosyltransferase (GT) that retains the anomeric linkage of a sugar catalyzes the reaction. Xyloside α-1,3-xylosyltransferase (XXYLT1) is a retaining GT that regulates Notch receptor activation by adding xylose to the Notch extracellular domain. Here, using natural acceptor and donor substrates and active Mus musculus XXYLT1, we report a series of crystallographic snapshots along the reaction, including an unprecedented natural and competent Michaelis reaction complex for retaining enzymes. These structures strongly support the SNi-like reaction as the retaining mechanism for XXYLT1. Unexpectedly, the epidermal growth factor–like repeat acceptor substrate undergoes a largemore » conformational change upon binding to the active site, providing a structural basis for substrate specificity. As a result, our improved understanding of this retaining enzyme will accelerate the design of retaining GT inhibitors that can modulate Notch activity in pathological situations in which Notch dysregulation is known to cause cancer or developmental disorders.« less

  16. Beyond the five-year horizon: long-term outcome of high-risk and inoperable patients undergoing TAVR with first-generation devices.

    PubMed

    Deutsch, Marcus-André; Erlebach, Magdalena; Burri, Melchior; Hapfelmeier, Alexander; Witt, Olivia Ganga; Ziegelmueller, Johannes Amadeus; Wottke, Michael; Ruge, Hendrik; Krane, Markus; Piazza, Nicolo; Bleiziffer, Sabine; Lange, Rüdiger

    2018-05-20

    We sought to determine the long-term outcome of high-risk patients who underwent transcatheter aortic valve replacement (TAVR) with first-generation devices with a focus on the identification of predictors for mortality and valve durability. Consecutive patients in our prospective single-centre registry undergoing TAVR with first-generation devices (n=214 CoreValve; n=86 SAPIEN) between 06/2007 and 07/2009 were retrospectively analysed (n=300, mean age 81.43±6.55 years, mean STS score 6.5±4.5%). Kaplan-Meier estimates of survival and the Cox proportional hazards model were used to identify independent predictors of all-cause-mortality. At 1, 5, and 7 years, estimated survival rates were 76.0%, 40.2%, and 23.2%, respectively. Age-adjusted baseline predictors of mortality included atrial fibrillation, impaired kidney function, peripheral artery disease, and mitral regurgitation (≥moderate). Baseline risk-adjusted procedure-related predictors for all-cause mortality included acute kidney injury, neurological events, major vascular complications, and major/life-threatening bleeding. At both five and six years, 78.2% of surviving patients were in NYHA Class I or II. PVL was ≤mild in the majority of patients at discharge and throughout follow-up. At seven years, the overall crude cumulative incidence of structural valve deterioration according to the 2017 EAPCI/ESC/EACTS definition was 14.9% (CoreValve 11.8% vs. SAPIEN 22.6%; p=0.01). Seven years after TAVR, 23.2% of high-risk patients were still alive. Independent predictors of all-cause mortality included both patient- and procedure-related factors. With a cumulative incidence of 14.9% at seven years, there is some suggestion that SVD post TAVR may become increasingly relevant during longer-term follow-up.

  17. Psychological effects of amniocentesis on women and their spouses: importance of the testing period and genetic counseling.

    PubMed

    Kukulu, Kamile; Buldukoglu, Kadriye; Keser, Ibrahim; Keser, Ilkay; Simşek, Mehmet; Mendilcioğlu, Inanç; Lüleci, Güven

    2006-03-01

    To evaluate both women's and their spouses' reasons for undergoing amniocentesis, their concerns relating to the procedure as well as their psychological reactions and coping mechanisms during the testing period. Eighty-five women undergoing amniocentesis and their spouses took part in the study. The couples completed a questionnaire that provided demographic data and insights into their experiences of amniocentesis. Age was the main reason for undergoing amniocentesis. When they first learned that they were going to undergo amniocentesis, women were more concerned about the potential danger to their fetus than their spouses. Most of participants believed that their pregnancy would continue after amniocentesis. However, they also stated that they were prepared for an abortion. Uncertainty and tension were two significant emotions experienced by couples while waiting for the test results. For the majority of women (80%) and men (42.3%) the strongest support was provided by their spouses during this period. In summary, we can conclude that the test did have a major psychological impact on both women and their spouses, but did not have a negative impact on their coping mechanisms. The psychological impact of amniocentesis on women and their spouses does not constitute a major obstacle to their ability to cope. However, a certain number of couples reported feelings of uncertainty, tension and anxiety about fetal injury. We strongly suggest that counseling should be given to high-risk families and that prenatal/antenatal care units must be established.

  18. Uncertainty, the Overbearing Lived Experience of the Elderly People Undergoing Hemodialysis: A Qualitative Study.

    PubMed

    Sahaf, Robab; Sadat Ilali, Ehteram; Peyrovi, Hamid; Akbari Kamrani, Ahmad Ali; Spahbodi, Fatemeh

    2017-01-01

    The chronic kidney disease is a major health concern. The number of the elderly people with chronic renal failure has increased across the world. Dialysis is an appropriate therapy for the elderly, but it involves certain challenges. The present paper reports uncertainty as part of the elderly experiences of living with hemodialysis. This qualitative study applied Max van Manen interpretative phenomenological analysis to explain and explore experiences of the elderly with hemodialysis. Given the study inclusion criteria, data were collected using in-depth unstructured interviews with nine elderly undergoing hemodialysis, and then analyzed according to Van Manen 6-stage methodological approach. One of the most important findings emerging in the main study was "uncertainty", which can be important and noteworthy, given other aspects of the elderly life (loneliness, despair, comorbidity of diseases, disability, and mental and psychosocial problems). Uncertainty about the future is the most psychological concerns of people undergoing hemodialysis. The results obtained are indicative of the importance of paying attention to a major aspect in the life of the elderly undergoing hemodialysis, uncertainty. A positive outlook can be created in the elderly through education and increased knowledge about the disease, treatment and complications.

  19. Managing direct oral anticoagulants in patients undergoing dentoalveolar surgery.

    PubMed

    Patel, J P; Woolcombe, S A; Patel, R K; Obisesan, O; Roberts, L N; Bryant, C; Arya, R

    2017-02-24

    Our objective was to describe our experience of managing a cohort of adult patients prescribed direct oral anticoagulants (DOACs) undergoing dentoalveolar procedures between November 2012 and May 2016. Prior to conducting a procedure a formal assessment was made of each patient's anticoagulation treatment. A specific plan was then formulated, balancing the risk of bleeding with the risk of thrombosis. Patients received a telephone consultation one week following treatment to assess any post-operative bleeding. Eighty-two patients underwent 111 oral surgical procedures, the majority of which were dental extractions. In the case of 35 (32%) procedures, advice was given to omit the DOAC, either before or after treatment. There was no bleeding following the majority of procedures. Persistent bleeding followed 15 (13.5%) procedures, of which 7 (6.3%) procedures required specific intervention. The majority of patients prescribed DOACs can undergo dentoalveolar procedures safely. Important considerations when planning treatment are: (i) when the patient usually takes their dose of DOAC, (ii) the time the procedure is performed and, (iii) when the DOAC is taken post-procedure. In our experience, if these factors are considered carefully, omission of DOAC doses is unlikely to be required for most patients.

  20. Drastic stabilization of parallel DNA hybridizations by a polylysine comb-type copolymer with hydrophilic graft chain.

    PubMed

    Miyoshi, Daisuke; Ueda, Yu-Mi; Shimada, Naohiko; Nakano, Shu-Ichi; Sugimoto, Naoki; Maruyama, Atsushi

    2014-09-01

    Electrostatic interactions play a major role in protein-DNA interactions. As a model system of a cationic protein, herein we focused on a comb-type copolymer of a polycation backbone and dextran side chains, poly(L-lysine)-graft-dextran (PLL-g-Dex), which has been reported to form soluble interpolyelectrolyte complexes with DNA strands. We investigated the effects of PLL-g-Dex on the conformation and thermodynamics of DNA oligonucleotides forming various secondary structures. Thermodynamic analysis of the DNA structures showed that the parallel conformations involved in both DNA duplexes and triplexes were significantly and specifically stabilized by PLL-g-Dex. On the basis of thermodynamic parameters, it was further possible to design DNA switches that undergo structural transition responding to PLL-g-Dex from an antiparallel duplex to a parallel triplex even with mismatches in the third strand hybridization. These results suggest that polycationic molecules are able to induce structural polymorphism of DNA oligonucleotides, because of the conformation-selective stabilization effects. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Increased major bleeding complications related to triple antithrombotic therapy usage in patients with atrial fibrillation undergoing percutaneous coronary artery stenting.

    PubMed

    Manzano-Fernández, Sergio; Pastor, Francisco J; Marín, Francisco; Cambronero, Francisco; Caro, Cesar; Pascual-Figal, Domingo A; Garrido, Iris P; Pinar, Eduardo; Valdés, Mariano; Lip, Gregory Y H

    2008-09-01

    The optimal antithrombotic therapy strategy for atrial fibrillation (AF) patients who undergo percutaneous coronary intervention with stent implantation (PCI-S) is unknown. We assessed the safety of antithrombotic therapy strategies in AF patients with indication for oral anticoagulation (OAC) undergoing PCI-S. We studied consecutive AF patients with indication for OAC who underwent PCI-S. We compared patients that received triple antithrombotic therapy (TT) [aspirin, clopidogrel, and coumadin] against other regimes (non-TT) after PCI-S. The primary end point was defined as the occurrence of major bleeding complications that were termed as early major bleeding (EMB) [< or = 48 h] or late major bleeding (LMB) [> 48 h]. Clinical follow-up was performed, and complications were recorded. We studied 104 patients (mean age +/- SD, 72 +/- 8 years; 70% men); TT was used in 51 patients (49%). TT was associated with a higher incidence of LMB (21.6% vs non-TT, 3.8%; p = 0.006) but not of EMB (5.8% vs non-TT, 11.3%; p = 0.33). In multivariate analyses, glycoprotein (GP) IIb/IIIa inhibitor use (hazard ratio [HR], 13.5; 95% confidence interval [CI], 1.7 to 108.3; p = 0.014) and PCI-S of three vessels or left main artery disease (HR, 7.9; 95% CI, 1.6 to 39.2; p = 0.01) were independent predictors for EMB. TT use (HR, 7.1; 95% CI, 1.5 to 32.4; p = 0.012), the occurrence of EMB (HR, 6.7; 95% CI, 1.8 to 25.3; p = 0.005), and baseline anemia (HR, 3.8; 95% CI, 1.2 to 12.5; p = 0.027) were independent predictors for LMB. No differences in major cardiovascular events were observed in patients treated with TT vs non-TT (25.5% vs 21.0%; p = 0.53). A high rate of major bleeding is observed in AF patients with indication for OAC undergoing PCI-S who receive TT. GP IIb/IIIa inhibitor use and multivessel/left main artery disease during PCI-S were independent predictors for EMB, while TT use, occurrence of EMB, and baseline anemia were independent predictors for LMB.

  2. Integration of XNAT/PACS, DICOM, and Research Software for Automated Multi-modal Image Analysis.

    PubMed

    Gao, Yurui; Burns, Scott S; Lauzon, Carolyn B; Fong, Andrew E; James, Terry A; Lubar, Joel F; Thatcher, Robert W; Twillie, David A; Wirt, Michael D; Zola, Marc A; Logan, Bret W; Anderson, Adam W; Landman, Bennett A

    2013-03-29

    Traumatic brain injury (TBI) is an increasingly important public health concern. While there are several promising avenues of intervention, clinical assessments are relatively coarse and comparative quantitative analysis is an emerging field. Imaging data provide potentially useful information for evaluating TBI across functional, structural, and microstructural phenotypes. Integration and management of disparate data types are major obstacles. In a multi-institution collaboration, we are collecting electroencephalogy (EEG), structural MRI, diffusion tensor MRI (DTI), and single photon emission computed tomography (SPECT) from a large cohort of US Army service members exposed to mild or moderate TBI who are undergoing experimental treatment. We have constructed a robust informatics backbone for this project centered on the DICOM standard and eXtensible Neuroimaging Archive Toolkit (XNAT) server. Herein, we discuss (1) optimization of data transmission, validation and storage, (2) quality assurance and workflow management, and (3) integration of high performance computing with research software.

  3. Integration of XNAT/PACS, DICOM, and research software for automated multi-modal image analysis

    NASA Astrophysics Data System (ADS)

    Gao, Yurui; Burns, Scott S.; Lauzon, Carolyn B.; Fong, Andrew E.; James, Terry A.; Lubar, Joel F.; Thatcher, Robert W.; Twillie, David A.; Wirt, Michael D.; Zola, Marc A.; Logan, Bret W.; Anderson, Adam W.; Landman, Bennett A.

    2013-03-01

    Traumatic brain injury (TBI) is an increasingly important public health concern. While there are several promising avenues of intervention, clinical assessments are relatively coarse and comparative quantitative analysis is an emerging field. Imaging data provide potentially useful information for evaluating TBI across functional, structural, and microstructural phenotypes. Integration and management of disparate data types are major obstacles. In a multi-institution collaboration, we are collecting electroencephalogy (EEG), structural MRI, diffusion tensor MRI (DTI), and single photon emission computed tomography (SPECT) from a large cohort of US Army service members exposed to mild or moderate TBI who are undergoing experimental treatment. We have constructed a robust informatics backbone for this project centered on the DICOM standard and eXtensible Neuroimaging Archive Toolkit (XNAT) server. Herein, we discuss (1) optimization of data transmission, validation and storage, (2) quality assurance and workflow management, and (3) integration of high performance computing with research software.

  4. Integration of XNAT/PACS, DICOM, and Research Software for Automated Multi-modal Image Analysis

    PubMed Central

    Gao, Yurui; Burns, Scott S.; Lauzon, Carolyn B.; Fong, Andrew E.; James, Terry A.; Lubar, Joel F.; Thatcher, Robert W.; Twillie, David A.; Wirt, Michael D.; Zola, Marc A.; Logan, Bret W.; Anderson, Adam W.; Landman, Bennett A.

    2013-01-01

    Traumatic brain injury (TBI) is an increasingly important public health concern. While there are several promising avenues of intervention, clinical assessments are relatively coarse and comparative quantitative analysis is an emerging field. Imaging data provide potentially useful information for evaluating TBI across functional, structural, and microstructural phenotypes. Integration and management of disparate data types are major obstacles. In a multi-institution collaboration, we are collecting electroencephalogy (EEG), structural MRI, diffusion tensor MRI (DTI), and single photon emission computed tomography (SPECT) from a large cohort of US Army service members exposed to mild or moderate TBI who are undergoing experimental treatment. We have constructed a robust informatics backbone for this project centered on the DICOM standard and eXtensible Neuroimaging Archive Toolkit (XNAT) server. Herein, we discuss (1) optimization of data transmission, validation and storage, (2) quality assurance and workflow management, and (3) integration of high performance computing with research software. PMID:24386548

  5. Rescue from replication stress during mitosis.

    PubMed

    Fragkos, Michalis; Naim, Valeria

    2017-04-03

    Genomic instability is a hallmark of cancer and a common feature of human disorders, characterized by growth defects, neurodegeneration, cancer predisposition, and aging. Recent evidence has shown that DNA replication stress is a major driver of genomic instability and tumorigenesis. Cells can undergo mitosis with under-replicated DNA or unresolved DNA structures, and specific pathways are dedicated to resolving these structures during mitosis, suggesting that mitotic rescue from replication stress (MRRS) is a key process influencing genome stability and cellular homeostasis. Deregulation of MRRS following oncogene activation or loss-of-function of caretaker genes may be the cause of chromosomal aberrations that promote cancer initiation and progression. In this review, we discuss the causes and consequences of replication stress, focusing on its persistence in mitosis as well as the mechanisms and factors involved in its resolution, and the potential impact of incomplete replication or aberrant MRRS on tumorigenesis, aging and disease.

  6. Rescue from replication stress during mitosis

    PubMed Central

    Naim, Valeria

    2017-01-01

    ABSTRACT Genomic instability is a hallmark of cancer and a common feature of human disorders, characterized by growth defects, neurodegeneration, cancer predisposition, and aging. Recent evidence has shown that DNA replication stress is a major driver of genomic instability and tumorigenesis. Cells can undergo mitosis with under-replicated DNA or unresolved DNA structures, and specific pathways are dedicated to resolving these structures during mitosis, suggesting that mitotic rescue from replication stress (MRRS) is a key process influencing genome stability and cellular homeostasis. Deregulation of MRRS following oncogene activation or loss-of-function of caretaker genes may be the cause of chromosomal aberrations that promote cancer initiation and progression. In this review, we discuss the causes and consequences of replication stress, focusing on its persistence in mitosis as well as the mechanisms and factors involved in its resolution, and the potential impact of incomplete replication or aberrant MRRS on tumorigenesis, aging and disease. PMID:28166452

  7. Steady State Structural Analysis of High Pressure Gas Turbine Blade using Finite Element Analysis

    NASA Astrophysics Data System (ADS)

    Mazarbhuiya, Hussain Mahamed Sahed Mostafa; Murari Pandey, Krishna

    2017-08-01

    In gas turbines the major portion of performance dependency lies upon turbine blade design. Turbine blades experience very high centrifugal, axial and tangential force during power generation. While withstanding these forces blades undergo elongation. Different methods have proposed for better enhancement of the mechanical properties of blade to withstand in extreme condition. Present paper describes the stress and elongation for blades having properties of different materials. Steady state structural analysis have performed in the present work for different materials (In 625, In 718, In 738, In 738 LC, MAR M246, Ni-Cr, Ti-alloy, Ti-Al, Ti-T6, U500). Remarkable finding is that the root of the blade is subjected to maximum stress for all blade materials and the blade made of MAR M246 has less stress and deformation among all other blade materials which can be selected as a suitable material for gas turbine blade.

  8. How to Make a Heart Valve: From Embryonic Development to Bioengineering of Living Valve Substitutes

    PubMed Central

    MacGrogan, Donal; Luxán, Guillermo; Driessen-Mol, Anita; Bouten, Carlijn; Baaijens, Frank; de la Pompa, José Luis

    2014-01-01

    Cardiac valve disease is a significant cause of ill health and death worldwide, and valve replacement remains one of the most common cardiac interventions in high-income economies. Despite major advances in surgical treatment, long-term therapy remains inadequate because none of the current valve substitutes have the potential for remodeling, regeneration, and growth of native structures. Valve development is coordinated by a complex interplay of signaling pathways and environmental cues that cause disease when perturbed. Cardiac valves develop from endocardial cushions that become populated by valve precursor mesenchyme formed by an epithelial–mesenchymal transition (EMT). The mesenchymal precursors, subsequently, undergo directed growth, characterized by cellular compartmentalization and layering of a structured extracellular matrix (ECM). Knowledge gained from research into the development of cardiac valves is driving exploration into valve biomechanics and tissue engineering directed at creating novel valve substitutes endowed with native form and function. PMID:25368013

  9. Universal spectral signatures in pnictides and cuprates: the role of quasiparticle-pair coupling.

    PubMed

    Sacks, William; Mauger, Alain; Noat, Yves

    2017-11-08

    Understanding the physical properties of a large variety of high-T c superconductors (SC), the cuprate family as well as the more recent iron-based superconductors, is still a major challenge. In particular, these materials exhibit the 'peak-dip-hump' structure in the quasiparticle density of states (DOS). The origin of this structure is explained within our pair-pair interaction (PPI) model: The non-superconducting state consists of incoherent pairs, a 'Cooper-pair glass' which, due to the PPI, undergoes a Bose-like condensation below T c to the coherent SC state. We derive the equations of motion for the quasiparticle operators showing that the DOS 'peak-dip-hump' is caused by the coupling between quasiparticles and excited pair states, or 'super-quasiparticles'. The renormalized SC gap function becomes energy-dependent and non retarded, reproducing accurately the experimental spectra of both pnictides and cuprates, despite the large difference in gap value.

  10. Identifying intrinsically disordered protein regions likely to undergo binding-induced helical transitions.

    PubMed

    Glover, Karen; Mei, Yang; Sinha, Sangita C

    2016-10-01

    Many proteins contain intrinsically disordered regions (IDRs) lacking stable secondary and ordered tertiary structure. IDRs are often implicated in macromolecular interactions, and may undergo structural transitions upon binding to interaction partners. However, as binding partners of many protein IDRs are unknown, these structural transitions are difficult to verify and often are poorly understood. In this study we describe a method to identify IDRs that are likely to undergo helical transitions upon binding. This method combines bioinformatics analyses followed by circular dichroism spectroscopy to monitor 2,2,2-trifluoroethanol (TFE)-induced changes in secondary structure content of these IDRs. Our results demonstrate that there is no significant change in the helicity of IDRs that are not predicted to fold upon binding. IDRs that are predicted to fold fall into two groups: one group does not become helical in the presence of TFE and includes examples of IDRs that form β-strands upon binding, while the other group becomes more helical and includes examples that are known to fold into helices upon binding. Therefore, we propose that bioinformatics analyses combined with experimental evaluation using TFE may provide a general method to identify IDRs that undergo binding-induced disorder-to-helix transitions. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. The epidemiology of upper airway injury in patients undergoing major surgical procedures.

    PubMed

    Hua, May; Brady, Joanne; Li, Guohua

    2012-01-01

    Airway injury is a potentially serious and costly adverse event of anesthesia care. The epidemiologic characteristics of airway injury have not been well documented. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) is a multicenter, prospective, outcome-oriented database for patients undergoing major surgical procedures. Using the NSQIP data for the years 2005 to 2008, we examined the incidence of, and risk factors for, airway injury. Of the 563,190 patients studied, 1202 (0.2%) sustained airway injury. The most common airway injury was lip laceration/hematoma (61.4%), followed by tooth injury (26.1%), tongue laceration (5.7%), pharyngeal laceration (4.7%), and laryngeal laceration (2.1%). Multivariable logistic modeling revealed an increased risk of airway injury in patients with Mallampati class III (adjusted odds ratio [OR], 1.69; 99% confidence interval [CI], 1.36-2.11, relative to patients with Mallampati classes I and II) or class IV (adjusted OR, 2.6; 99% CI, 1.52-4.02), and in patients aged 80 years or older (adjusted OR, 1.50; 99% CI, 1.02-2.19, relative to patients aged 40 to 49 years). The risk of airway injury for patients undergoing major surgical procedures is approximately 1 in 500. Patients with difficult airways as indicated by Mallampati classes III and IV are at significantly increased risk of sustaining airway injury during anesthesia for major surgical procedures.

  12. A Complete NMR Spectral Assignment of the Lipid-free Mouse Apolipoprotein A-I (ApoAI) C-terminal Truncation Mutant, ApoAI(1-216)

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

    Yang, Yunhuang; Hoyt, David W.; Wang, Jianjun

    2007-07-28

    Apolipoprotein A-I (apoAI) is the major protein component of the high-density lipoprotein (HDL) that has been a hot subject of interests because of its anti-atherogenic properties. Upon lipid-binding, apoAI undergoes conformational changes from lipid-free to several different HDL-associated states (1). These different conformational states regulate HDL formation, maturation and transportation. Recent crystal structure of lipid-free human apoAI represents a major progress of structural study of lipid-free apoAI (2). However, no structural is available for lipid-free mouse apoAI (240-residues). Since mouse HDL is homogenous with only HDL2-like size, whereas human HDL is heterogeneous, containing HDL2/HDL3 as its main species, a structuralmore » comparison between human and mouse apoAI may allow us to identify structure basis of HDL size distribution difference between human and mouse. We carried out an NMR structure determination of lipid-free mouse apoAI (1-216) and completely assigned backbone atoms (except backbone amide proton and nitrogen atoms for residues D1, N48, W107, K108, K132, E135, F147, R148, M169 and K203). Secondary structure prediction using backbone NMR parameters indicates that lipid-free mouse apoAI consists of a four helical segments in the N-terminal domain, residues 1-180. In addition, two short helices are also observed between residues 190-195 and 210-215. The helix locations are significantly different from those in the crystal structure of human apoAI, suggesting that mouse apoAI may have a different conformational adaptation upon lipid-binding. BMRB deposit with accession number: 15091.« less

  13. Triple antithrombotic therapy versus dual antiplatelet therapy in patients with atrial fibrillation undergoing drug-eluting stent implantation.

    PubMed

    Kang, Dong Oh; Yu, Cheol Woong; Kim, Hee Dong; Cho, Jae Young; Joo, Hyung Joon; Choi, Rak Kyong; Park, Jin Sik; Lee, Hyun Jong; Kim, Je Sang; Park, Jae Hyung; Hong, Soon Jun; Lim, Do-Sun

    2015-08-01

    The optimal antithrombotic regimen in patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation for complex coronary artery disease is unclear. We compared the net clinical outcomes of triple antithrombotic therapy (TAT; aspirin, thienopyridine, and warfarin) and dual antiplatelet therapy (DAPT; aspirin and thienopyridine) in AF patients who had undergone DES implantation. A total of 367 patients were enrolled and analyzed retrospectively; 131 patients (35.7%) received TAT and 236 patients (64.3%) received DAPT. DAPT and warfarin were maintained for a minimum of 12 and 24 months, respectively. The primary endpoint was the 2-year net clinical outcomes, a composite of major bleeding and major adverse cardiac and cerebral events (MACCE). Propensity score-matching analysis was carried out in 99 patient pairs. The 2-year net clinical outcomes of the TAT group were worse than those of the DAPT group (34.3 vs. 21.1%, P=0.006), which was mainly due to the higher incidence of major bleeding (16.7 vs. 4.6%, P<0.001), without any significant increase in MACCE (22.1 vs. 17.7%, P=0.313). In the multivariate analysis, TAT was an independent predictor of worse net clinical outcomes (odds ratio 1.63, 95% confidence interval 1.06-2.50) and major bleeding (odds ratio 3.54, 95% confidence interval 1.65-7.58). After propensity score matching, the TAT group still had worse net clinical outcomes and a higher incidence of major bleeding compared with the DAPT group. In AF patients undergoing DES implantation, prolonged administration of TAT may be harmful due to the substantial increase in the risk for major bleeding without any reduction in MACCE.

  14. Impaired thrombin generation and fibrin clot formation in patients with dilutional coagulopathy during major surgery.

    PubMed

    Schols, S E M; Lancé, M D; Feijge, M A H; Damoiseaux, J; Marcus, M A; Hamulyák, K; Ten Cate, H; Heemskerk, J W M; van Pampus, E C M

    2010-02-01

    Patients subjected to haemodilution during surgery are at increased risk of bleeding. We hypothesised that, in the acquired dilutional coagulopathy, insufficient haemostasis is due to either insufficient thrombin generation or insufficient fibrin clot formation. In tissue factor-activated plasmas from patients with coagulation deficiency, we measured time curves of thrombin generation and fibrin clot formation (thromboelastography). Investigated were in study A: 10 patients treated with vitamin K antagonist and five healthy subjects; in study B: 30 patients undergoing cardiopulmonary bypass (CPB) surgery and infused with on average 2,000 ml crystalloids and colloids (no major bleeding); in study C: 58 patients undergoing major general surgery, and transfused with >5,000 ml crystalloids, colloids and red cell concentrates, who experienced major bleeding and were post-transfused with fresh frozen plasma. The treatment with vitamin K antagonist led to a progressive reduction in thrombin generation but not fibrin clot formation. In CPB patients, plasma factor levels post-surgery were 53-60% of normal. This was accompanied by moderate reduction in both haemostatic processes. In plasmas from patients undergoing major surgery, factor levels were 38-41% of normal, and these levels increased after plasma transfusion. Taking preset thresholds for normal thrombin generation and fibrin clot formation, at least one of these processes was low in 88-93% of the patients with (persistent) bleeding, but only in 40-53% of the patients without bleeding. In conclusion, the ability of thrombin generation and fibrin clot formation is independently reduced in acquired dilutional coagulopathy, while minimal levels of both are required for adequate haemostasis.

  15. Omitting chest tube drainage after thoracoscopic major lung resection.

    PubMed

    Ueda, Kazuhiro; Hayashi, Masataro; Tanaka, Toshiki; Hamano, Kimikazu

    2013-08-01

    Absorbable mesh and fibrin glue applied to prevent alveolar air leakage contribute to reducing the length of chest tube drainage, length of hospitalization and the rate of pulmonary complications. This study investigated the feasibility of omitting chest tube drainage in selected patients undergoing thoracoscopic major lung resection. Intraoperative air leakages were sealed with fibrin glue and absorbable mesh in patients undergoing thoracoscopic major lung resection. The chest tube was removed just after tracheal extubation if no air leakages were detected in a suction-induced air leakage test, which is an original technique to confirm pneumostasis. Patients with bleeding tendency or extensive thoracic adhesions were excluded. Chest tube drainage was omitted in 29 (58%) of 50 eligible patients and was used in 21 (42%) on the basis of suction-induced air leakage test results. Male gender and compromised pulmonary function were significantly associated with the failure to omit chest tube drainage (both, P < 0.05). Regardless of omitting the chest tube drainage, there were no adverse events during hospitalization, such as subcutaneous emphysema, pneumothorax, pleural effusion or haemothorax, requiring subsequent drainage. Furthermore, there was no prolonged air leakage in any patients: The mean length of chest tube drainage was only 0.9 days. Omitting the chest tube drainage was associated with reduced pain on the day of the operation (P = 0.046). The refined strategy for pneumostasis allowed the omission of chest tube drainage in the majority of patients undergoing thoracoscopic major lung resection without increasing the risk of adverse events, which may contribute to a fast-track surgery.

  16. Structural transition in sputter-deposited amorphous germanium films by aging at ambient temperature

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

    Okugawa, M.; Nakamura, R., E-mail: nakamura@mtr.osakafu-u.ac.jp; Numakura, H.

    The structure of amorphous Ge (a-Ge) films prepared by sputter-deposition and the effects of aging at ambient temperature and pressure were studied by pair-distribution-function (PDF) analysis from electron scattering and molecular dynamics simulations. The PDFs of the as-deposited and aged samples for 3–13 months showed that the major peaks for Ge-Ge bonds decrease in intensity and broaden with aging for up to 7 months. In the PDFs of a-Ge of molecular dynamics simulation obtained by quenching liquid at different rates, the major peak intensities of a slowly cooled model are higher than those of a rapidly cooled model. Analyses onmore » short- and medium-range configurations show that the slowly cooled model includes a certain amount of medium-range ordered (MRO) clusters, while the rapidly cooled model includes liquid-like configurations rather than MRO clusters. The similarity between experimental and computational PDFs implies that as-deposited films are similar in structure to the slowly cooled model, whereas the fully aged films are similar to the rapidly cooled model. It is assumed that as they undergo room-temperature aging, the MRO clusters disintegrate and transform into liquid-like regions in the same matrix. This transition in local configurations is discussed in terms of instability and the non-equilibrium of nanoclusters produced by a vapor-deposition process.« less

  17. Enzymatic and Structural Characterization of the Major Endopeptidase in the Venus Flytrap Digestion Fluid*

    PubMed Central

    Risør, Michael W.; Thomsen, Line R.; Sanggaard, Kristian W.; Nielsen, Tania A.; Thøgersen, Ida B.; Lukassen, Marie V.; Rossen, Litten; Garcia-Ferrer, Irene; Guevara, Tibisay; Scavenius, Carsten; Meinjohanns, Ernst; Gomis-Rüth, F. Xavier; Enghild, Jan J.

    2016-01-01

    Carnivorous plants primarily use aspartic proteases during digestion of captured prey. In contrast, the major endopeptidases in the digestive fluid of the Venus flytrap (Dionaea muscipula) are cysteine proteases (dionain-1 to -4). Here, we present the crystal structure of mature dionain-1 in covalent complex with inhibitor E-64 at 1.5 Å resolution. The enzyme exhibits an overall protein fold reminiscent of other plant cysteine proteases. The inactive glycosylated pro-form undergoes autoprocessing and self-activation, optimally at the physiologically relevant pH value of 3.6, at which the protective effect of the pro-domain is lost. The mature enzyme was able to efficiently degrade a Drosophila fly protein extract at pH 4 showing high activity against the abundant Lys- and Arg-rich protein, myosin. The substrate specificity of dionain-1 was largely similar to that of papain with a preference for hydrophobic and aliphatic residues in subsite S2 and for positively charged residues in S1. A tentative structure of the pro-domain was obtained by homology modeling and suggested that a pro-peptide Lys residue intrudes into the S2 pocket, which is more spacious than in papain. This study provides the first analysis of a cysteine protease from the digestive fluid of a carnivorous plant and confirms the close relationship between carnivorous action and plant defense mechanisms. PMID:26627834

  18. Active vibration control of structures undergoing bending vibrations

    NASA Technical Reports Server (NTRS)

    Pla, Frederic G. (Inventor); Rajiyah, Harindra (Inventor)

    1995-01-01

    An active vibration control subassembly for a structure (such as a jet engine duct or a washing machine panel) undergoing bending vibrations caused by a source (such as the clothes agitator of the washing machine) independent of the subassembly. A piezoceramic actuator plate is vibratable by an applied electric AC signal. The plate is connected to the structure such that vibrations in the plate induced by the AC signal cause canceling bending vibrations in the structure and such that the plate is compressively pre-stressed along the structure when the structure is free of any bending vibrations. The compressive prestressing increases the amplitude of the canceling bending vibrations before the critical tensile stress level of the plate is reached. Preferably, a positive electric DC bias is also applied to the plate in its poling direction.

  19. Reform of health care in Germany

    PubMed Central

    Hurst, Jeremy W.

    1991-01-01

    For the past 45 years Germany has had two health care systems: one in the former Federal Republic of Germany and one in the former German Democratic Republic. The system in the Federal Republic was undergoing some important reforms when German reunification took place in October 1990. Now the system in eastern Germany is undergoing a major transformation to bring it more into line with that in western Germany. PMID:10110879

  20. The Role of Palliative Surgery in Gynecologic Cancer Cases

    PubMed Central

    Hope, Joanie Mayer

    2013-01-01

    The decision to undergo major palliative surgery in end-stage gynecologic cancer is made when severe disease symptoms significantly hinder quality of life. Malignant bowel obstruction, unremitting pelvic pain, fistula formation, tumor necrosis, pelvic sepsis, and chronic hemorrhage are among the reasons patients undergo palliative surgeries. This review discusses and summarizes the literature on surgical management of malignant bowel obstruction and palliative pelvic exenteration in gynecologic oncology. PMID:23299775

  1. Actigraphy for Measurement of Sleep and Sleep-Wake Rhythms in Relation to Surgery

    PubMed Central

    Madsen, Michael T.; Rosenberg, Jacob; Gögenur, Ismail

    2013-01-01

    Study Objectives: Patients undergoing surgery have severe sleep and sleep-wake rhythm disturbances resulting in increased morbidity. Actigraphy is a tool that can be used to quantify these disturbances. The aim of this manuscript was to present the literature where actigraphy has been used to measure sleep and sleep-wake rhythms in relation to surgery. Methods: A systematic review was performed in 3 databases (Medline, Embase, and Psycinfo), including all literature until July 2012. Results: Thirty-two studies were included in the review. Actigraphy could demonstrate that total sleep time and sleep efficiency was reduced after surgery and number of awakenings was increased in patients undergoing major surgery. Disturbances were less severe in patients undergoing minor surgery. Actigraphy could be used to differentiate between delirious and non-delirious patients after major surgery. Actigraphy measurements could determine a differential effect of surgery based on the patient's age. The effect of pharmacological interventions (chronobiotics and hypnotics) in surgical patients could also be demonstrated by actigraphy. Conclusion: Actigraphy can be used to measure sleep and sleep-wake rhythms in patients undergoing surgery. Citation: Madsen MT; Rosenberg J; Gögenur I. Actigraphy for measurement of sleep and sleep-wake rhythms in relation to surgery. J Clin Sleep Med 2013;9(4):387-394. PMID:23585756

  2. Uncertainty, the Overbearing Lived Experience of the Elderly People Undergoing Hemodialysis: A Qualitative Study

    PubMed Central

    Sahaf, Robab; Sadat Ilali, Ehteram; Peyrovi, Hamid; Akbari Kamrani, Ahmad Ali; Spahbodi, Fatemeh

    2017-01-01

    ABSTRACT Background: The chronic kidney disease is a major health concern. The number of the elderly people with chronic renal failure has increased across the world. Dialysis is an appropriate therapy for the elderly, but it involves certain challenges. The present paper reports uncertainty as part of the elderly experiences of living with hemodialysis. Methods: This qualitative study applied Max van Manen interpretative phenomenological analysis to explain and explore experiences of the elderly with hemodialysis. Given the study inclusion criteria, data were collected using in-depth unstructured interviews with nine elderly undergoing hemodialysis, and then analyzed according to Van Manen 6-stage methodological approach. Results: One of the most important findings emerging in the main study was “uncertainty”, which can be important and noteworthy, given other aspects of the elderly life (loneliness, despair, comorbidity of diseases, disability, and mental and psychosocial problems). Uncertainty about the future is the most psychological concerns of people undergoing hemodialysis. Conclusion: The results obtained are indicative of the importance of paying attention to a major aspect in the life of the elderly undergoing hemodialysis, uncertainty. A positive outlook can be created in the elderly through education and increased knowledge about the disease, treatment and complications. PMID:28097174

  3. Patients with glycogen storage diseases undergoing anesthesia: a case series.

    PubMed

    Gurrieri, Carmelina; Sprung, Juraj; Weingarten, Toby N; Warner, Mary E

    2017-10-06

    Glycogen storage diseases are rare genetic disorders of glycogen synthesis, degradation, or metabolism regulation. When these patients are subjected to anesthesia, perioperative complications can develop, including hypoglycemia, rhabdomyolysis, myoglobinuria, acute renal failure, and postoperative fatigue. The objective of this study was to describe the perioperative course of a cohort of patients with glycogen storage diseases. This is a retrospective review of patients with glycogen storage diseases undergoing anesthetic care at our institution from January 1, 1990, through June 30, 2015 to assess perioperative management and outcomes. We identified 30 patients with a glycogen storage disease who underwent 41 procedures under anesthesia management. Intraoperative lactic acidosis developed during 4 major surgeries (3 liver transplants, 1 myectomy), and in all cases resolved within 24 postoperative hours. Lactated Ringer solution was used frequently. Preoperative and intraoperative hypoglycemia was noted in some patients with glycogen storage disease type I, all of which responded to administration of dextrose-containing solutions. No serious postoperative complications occurred. Patients with glycogen storage disease, despite substantial comorbid conditions, tolerates the anesthetic management without major complications. Several patients who experienced self-limited metabolic acidosis were undergoing major surgical procedures, during which acidosis could be anticipated. Close monitoring and management of blood glucose levels of patients with glycogen storage disease type I is prudent.

  4. A bleeding assessment tool correlates with intraoperative blood loss in children and adolescents undergoing major spinal surgery.

    PubMed

    Anadio, Jennifer M; Sturm, Peter F; Forslund, Johan M; Agarwal, Sunil; Lane, Adam; Tarango, Cristina; Palumbo, Joseph S

    2017-04-01

    Screening laboratory studies for bleeding disorders are of little predictive value for operative bleeding risk in adults. Predicting perioperative bleeding in pediatric patients is particularly difficult as younger patients often have not had significant hemostatic challenges. This issue is distinctly important for high bleeding risk surgeries, such as major spinal procedures. The aim of this study was to determine if the score of a detailed bleeding questionnaire (BQ) correlated with surgical bleeding in pediatric patients undergoing major spinal surgery. A total of 220 consecutive pediatric patients (mean age 14.2years) undergoing major spinal surgery were administered the BQ preoperatively, as well as having routine screening laboratory studies (i.e., PT, aPTT, PFA) drawn. A retrospective analysis was conducted to determine if there was a correlation between either the results of the BQ and/or laboratory studies with operative outcomes. A BQ score>2 showed a strong positive correlation with intraoperative bleeding based on both univariate and multivariate analyses. In contrast, abnormalities in screening laboratory studies showed no significant correlation with operative bleeding outcomes. Relying on screening laboratory studies alone is inadequate. The BQ used here correlated with increased intraoperative hemorrhage, suggesting this tool may be useful for assessing pediatric surgical bleeding risk, and may also be useful in identifying a subset of patients with a very low bleeding risk that may not require laboratory screening. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Gender differences in risk profile and outcome of Middle Eastern patients undergoing percutaneous coronary intervention.

    PubMed

    Jarrah, Mohamad I; Hammoudeh, Ayman J; Al-Natour, Dalal B; Khader, Yousef S; Tabbalat, Ramzi A; Alhaddad, Imad A; Kullab, Susan M

    2017-02-01

    To determine the gender differences in cardiovascular risk profile and outcomes among patients undergoing percutaneous coronary intervention (PCI). Methods: In a prospective multicenter study of consecutive Middle Eastern patients managed with PCI from January 2013 to February 2014 in 12 tertiary care centers in Amman and Irbid, Jordan. Clinical and coronary angiographic features, and major cardiovascular events were assessed for both genders from hospital stay to 1 year. Results: Women comprised 20.6% of 2426 enrolled patients, were older (mean age 62.9 years versus 57.2 years), had higher prevalence of hypertension (81% versus 57%), diabetes (66% versus 44%), dyslipidemia (58% versus 46%), and obesity (44% versus 25%) compared with men, p less than 0.001. The PCI for ST-segment elevation myocardial infarction was indicated for fewer women than men (23% versus 33%; p=0.001). Prevalence of single or multi-vessel coronary artery disease was similar in women and men. More women than men had major bleeding during hospitalization (2.2% versus 0.6%; p=0.003) and at one year (2.5% versus 0.9%; p=0.007). There were no significant differences between women and men in mortality (3.1% versus 1.7%) or stent thrombosis (2.1% versus 1.8%) at 1 year. Conclusion: Middle Eastern women undergoing PCI had worse baseline risk profile compared with men.Except for major bleeding, no gender differences in the incidence of major adverse cardiovascular events were demonstrated.

  6. Biological and nonbiological modifications of carbamates

    PubMed Central

    Knaak, James B.

    1971-01-01

    Methylcarbamate insecticides undergo hydrolysis, oxidation, dealkylation, and conjugation in animals, plants, and insects to form similar or identical products. Carbaryl is hydroxylated in biological systems to form hydroxy, dihydro-dihydroxy, and N-hydroxymethyl carbaryl and is hydrolysed to form 1-naphthol. The products are conjugated, stored, or excreted. Carbofuran is hydroxylated at the 3 position and propoxur at the 5 position to form hydroxylated derivatives. N-hydroxymethyl derivatives of these two carbamates may also be formed. Hydrolysis appears to be the major metabolic pathway of carbofuran in the animal. Aldicarb is oxidized to its sulfoxide and then hydrolysed to the oxime sulfoxide in animals and plants. Plants hydrolyse the oxime sulfoxide to form the corresponding aldehyde, which is an intermediate in the formation of 2-methyl-2-(methyl-sulfinyl)propanol. Methomyl, which is structurally similar to aldicarb, is metabolized in plants to acetonitrile, carbon dioxide, and methylamine. Bux and Meobal undergo hydrolysis and hydroxylation to form N-hydroxy methylcarbamates, as well as hydroxybutylphenyl and hydroxymethylphenyl methylcarbamates. Zectran, which contains a dimethylamino group, is converted to the methylamino, amino, and methylformamido derivatives by insects and plants. In soil and water, methylcarbamate insecticides are hydrolysed to their respective phenols or oximes. PMID:4999481

  7. Epilepsy surgery in patients with malformations of cortical development.

    PubMed

    Lüders, Hans; Schuele, Stephan U

    2006-04-01

    Patients with malformations of cortical development often suffer from intractable focal epilepsy. This review considers recent progress in the selection and seizure outcome of patients undergoing resective epilepsy surgery for this condition. Patients with malformations of cortical development restricted to part or even a whole hemisphere may be candidates for epilepsy surgery even when, due to microscopic malformations, magnetic resonance imaging shows no detectable lesion. Despite recent advances in structural and functional imaging, the majority of patients with this condition undergo invasive evaluation. Patients with focal cortical dysplasia, with and without a detectable lesion on magnetic resonance imaging, often have a favorable outcome with epilepsy surgery. The underlying pathological substrate seems to be a better predictor for surgical outcome in patients with focal cortical dysplasia than the presence of a lesion on magnetic resonance imaging. Epilepsy surgery can be offered in a highly selected subgroup of patients with unilateral nodular heterotopia. Seizures in hemimegalencephaly may respond favorably to hemispherectomy, although most children will continue to have seizures and significant functional impairments. Patients with focal epilepsy due to malformations of cortical development are often intractable to medical management. Resective epilepsy surgery can be beneficial, particularly for patients with focal cortical dysplasia and unilateral hemispheric malformations.

  8. History and evolution of TMD concepts.

    PubMed

    McNeill, C

    1997-01-01

    Historically the field of temporomandibular disorders (TMD) has been based on testimonials, clinical opinion, and blind faith rather than on science. Reparative procedures to the joints, jaws, or occlusal surfaces of the teeth to develop idealized structural relationships that may be required for dental health and function are less likely to be required for the management of chronic musculoskeletal disorders. Because of the concerns of many people today regarding professional credibility and intellectual honesty, the need for a scientific foundation to support the various belief systems is of paramount importance. In fact, therapeutic approaches for TMD are undergoing a major evolution away from the traditional mechanistic dental concepts of the past to the more current biopsychosocial medical concepts that emphasize multidisciplinary approaches. Recent advances in the understanding of pain mechanisms and management of chronic pain have improved long-term treatment outcome. The emphasis is on treatment that involves the patient in the physical and behavioral management of their own problem. The majority of patients with TMD achieve good relief of their symptoms with noninvasive, conservative therapy.

  9. Inflexibility and independence: Phase transitions in the majority-rule model.

    PubMed

    Crokidakis, Nuno; de Oliveira, Paulo Murilo Castro

    2015-12-01

    In this work we study opinion formation in a population participating in a public debate with two distinct choices. We consider three distinct mechanisms of social interactions and individuals' behavior: conformity, nonconformity, and inflexibility. The conformity is ruled by the majority-rule dynamics, whereas the nonconformity is introduced in the population as an independent behavior, implying the failure of attempted group influence. Finally, the inflexible agents are introduced in the population with a given density. These individuals present a singular behavior, in a way that their stubbornness makes them reluctant to change their opinions. We consider these effects separately and all together, with the aim to analyze the critical behavior of the system. We perform numerical simulations in some lattice structures and for distinct population sizes. Our results suggest that the different formulations of the model undergo order-disorder phase transitions in the same universality class as the Ising model. Some of our results are complemented by analytical calculations.

  10. On the analytical modeling of the nonlinear vibrations of pretensioned space structures

    NASA Technical Reports Server (NTRS)

    Housner, J. M.; Belvin, W. K.

    1983-01-01

    Pretensioned structures are receiving considerable attention as candidate large space structures. A typical example is a hoop-column antenna. The large number of preloaded members requires efficient analytical methods for concept validation and design. Validation through analyses is especially important since ground testing may be limited due to gravity effects and structural size. The present investigation has the objective to present an examination of the analytical modeling of pretensioned members undergoing nonlinear vibrations. Two approximate nonlinear analysis are developed to model general structural arrangements which include beam-columns and pretensioned cables attached to a common nucleus, such as may occur at a joint of a pretensioned structure. Attention is given to structures undergoing nonlinear steady-state oscillations due to sinusoidal excitation forces. Three analyses, linear, quasi-linear, and nonlinear are conducted and applied to study the response of a relatively simple cable stiffened structure.

  11. KSC-99pc0191

    NASA Image and Video Library

    1999-02-10

    In the Vertical Processing Facility (VPF), workers prepare the shrouded Chandra X-ray Observatory for its lift to a vertical position. The telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  12. KSC-99pc0195

    NASA Image and Video Library

    1999-02-10

    In the Vertical Processing Facility (VPF), the shrouded Chandra X-ray Observatory achieves a vertical position via the overhead crane. The telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  13. Unusual structural transition of antimicrobial VP1 peptide.

    PubMed

    Shanmugam, Ganesh; Phambu, Nsoki; Polavarapu, Prasad L

    2011-05-01

    VP1 peptide, an active domain of m-calpain enzyme with antimicrobial activity is found to undergo an unusual conformational transition in trifluoroethanol (TFE) solvent. The nature of, and time dependent variations in, circular dichroism associated with the amide I vibrations, suggest that VP1 undergoes self-aggregation forming anti-parallel β-sheet structure in TFE. Transmission electron micrograph (TEM) images revealed that β-sheet aggregates formed by VP1 possess fibril-like assemblies. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Outcomes after elective abdominal aortic aneurysm repair in obese versus nonobese patients.

    PubMed

    Locham, Satinderjit; Rizwan, Muhammad; Dakour-Aridi, Hanaa; Faateh, Muhammad; Nejim, Besma; Malas, Mahmoud

    2018-06-07

    Obesity is a worldwide epidemic, particularly in Western society. It predisposes surgical patients to an increased risk of adverse outcomes. The aim of our study was to use a nationally representative vascular database and to compare in-hospital outcomes in obese vs nonobese patients undergoing elective open aortic repair (OAR) and endovascular aneurysm repair (EVAR). All patients undergoing elective abdominal aortic aneurysm repair were identified in the Vascular Quality Initiative database (2003-2017). Obesity was defined as body mass index ≥30 kg/m 2 . Univariable (Student t-test and χ 2  test) and multivariable (logistic regression) analyses were implemented to compare in-hospital mortality and any major complications (wound infection, renal failure, and cardiopulmonary failure) in obese vs nonobese patients. We identified a total of 33,082 patients undergoing elective OAR (nonobese, n = 4605 [72.4%]; obese, n = 1754 [27.6%]) and EVAR (nonobese, n = 18,338 [68.6%]; obese, n = 8385 [31.4%]). Obese patients undergoing OAR and EVAR were relatively younger compared with nonobese patients (mean age [standard deviation], 67.55 [8.26] years vs 70.27 [8.30] years and 71.06 [8.22] years vs 74.55 [8.55] years), respectively; (both P < .001). Regardless of approach, obese patients had slightly longer operative time (OAR, 259.02 [109.97] minutes vs 239.37 [99.78] minutes; EVAR, 138.27 [70.64] minutes vs 134.34 [69.98] minutes) and higher blood loss (OAR, 2030 [1823] mL vs 1619 [1642] mL; EVAR, 228 [354] mL vs 207 [312] mL; both P < .001). There was no significant difference in mortality between the two groups undergoing OAR and EVAR (OAR, 2.9% vs 3.2% [P = .50]; EVAR, 0.5% vs 0.6% [P = .76]). On multivariable analysis, obese patients undergoing OAR had 33% higher odds of renal failure (adjusted odds ratio [OR], 1.33; 95% confidence interval [CI], 1.09-1.63; P = .006) and 75% higher odds of wound infections (adjusted OR, 1.75; 95% CI, 1.11-2.76; P = .02) compared with nonobese patients. However, in patients undergoing EVAR, no association was seen between obesity and any major complications. A significant interaction was found between obesity and surgical approach in the event of renal failure, in which obese patients undergoing OAR had significantly higher odds of renal failure compared with those in the EVAR group (OR interaction , 1.36; 95% CI, 1.05-1.75; P = .02). Using a large nationally representative database, we demonstrated an increased risk of renal failure and wound infections in obese patients undergoing OAR compared with nonobese patients. On the other hand, obesity did not seem to increase the odds of major adverse outcomes in patients undergoing EVAR. Further long-term prospective studies are needed to verify the effects of obesity after abdominal aortic aneurysm repair and the implications of these findings in clinical decision-making. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  15. Structural Basis for the Histone Chaperone Activity of Asf1

    PubMed Central

    English, Christine M.; Adkins, Melissa W.; Carson, Joshua J.; Churchill, Mair E.A.; Tyler, Jessica K.

    2010-01-01

    SUMMARY Asf1 is a highly conserved chaperone of histones H3/H4 that assembles or disassembles chromatin during transcription, replication, and repair. The structure of the globular domain of Asf1 bound to H3/H4 determined by X-ray crystallography to a resolution of 1.7 Å shows how Asf1 binds the H3/H4 heterodimer, enveloping the C-terminus of histone H3 and physically blocking formation of the H3/H4 heterotetramer. Unexpectedly, the C-terminus of histone H4 that forms a mini-beta sheet with histone H2A in the nucleosome, undergoes a major conformational change upon binding to Asf1 and adds a beta strand to the Asf1 beta-sheet sandwich. Interactions with both H3 and H4 were required for Asf1 histone chaperone function in vivo and in vitro. The Asf1-H3/H4 structure suggests a “strand-capture” mechanism whereby the H4 tail acts as a lever to facilitate chromatin disassembly / assembly that may be used ubiquitously by histone chaperones. PMID:17081973

  16. Drugs from the Oceans: Marine Natural Products as Leads for Drug Discovery.

    PubMed

    Altmann, Karl-Heinz

    2017-10-25

    The marine environment harbors a vast number of species that are the source of a wide array of structurally diverse bioactive secondary metabolites. At this point in time, roughly 27'000 marine natural products are known, of which eight are (were) at the origin of seven marketed drugs, mostly for the treatment of cancer. The majority of these drugs and also of drug candidates currently undergoing clinical evaluation (excluding antibody-drug conjugates) are unmodified natural products, but synthetic chemistry has played a central role in the discovery and/or development of all but one of the approved marine-derived drugs. More than 1000 new marine natural products have been isolated per year over the last decade, but the pool of new and unique structures is far from exhausted. To fully leverage the potential offered by the structural diversity of marine-produced secondary metabolites for drug discovery will require their broad assessment for different bioactivities and the productive interplay between new fermentation technologies, synthetic organic chemistry, and medicinal chemistry, in order to secure compound supply and enable lead optimization.

  17. Structure and dynamics of AMPA receptor GluA2 in resting, pre-open and desensitized states

    PubMed Central

    Dürr, Katharina L.; Chen, Lei; Stein, Richard A.; De Zorzi, Rita; MihaelaFolea, I.; Walz, Thomas; Mchaourab, Hassane S.; Gouaux, Eric

    2014-01-01

    Summary Ionotropic glutamate receptors (iGluRs) mediate the majority of fast excitatory signaling in the nervous system. Despite the profound importance of iGluRs in the nervous system, little is known about the structures and dynamics of intact receptors in distinct functional states. Here we elucidate the structures of the intact GluA2 AMPA receptor in an apo resting/closed state, in an activated/pre-open state bound with the partial agonists and a positive allosteric modulator and in a desensitized/closed state in complex with FW alone. To probe the conformational properties of these states, we carried out double electron-electron resonance experiments on cysteine mutants and cryo-electron microscopy studies. We show how agonist binding modulates the conformation of the ligand binding domain 'layer' of the intact receptors and how, upon desensitization, the receptor undergoes large conformational rearrangements of amino-terminal and ligand-binding domains. We define mechanistic principles by which to understand antagonism, activation and desensitization in AMPA iGluRs. PMID:25109876

  18. Calmodulin fishing with a structurally disordered bait triggers CyaA catalysis

    PubMed Central

    O’Brien, Darragh P.; Durand, Dominique; Voegele, Alexis; Hourdel, Véronique; Davi, Marilyne; Chamot-Rooke, Julia; Vachette, Patrice; Brier, Sébastien; Ladant, Daniel

    2017-01-01

    Once translocated into the cytosol of target cells, the catalytic domain (AC) of the adenylate cyclase toxin (CyaA), a major virulence factor of Bordetella pertussis, is potently activated by binding calmodulin (CaM) to produce supraphysiological levels of cAMP, inducing cell death. Using a combination of small-angle X-ray scattering (SAXS), hydrogen/deuterium exchange mass spectrometry (HDX-MS), and synchrotron radiation circular dichroism (SR-CD), we show that, in the absence of CaM, AC exhibits significant structural disorder, and a 75-residue-long stretch within AC undergoes a disorder-to-order transition upon CaM binding. Beyond this local folding, CaM binding induces long-range allosteric effects that stabilize the distant catalytic site, whilst preserving catalytic loop flexibility. We propose that the high enzymatic activity of AC is due to a tight balance between the CaM-induced decrease of structural flexibility around the catalytic site and the preservation of catalytic loop flexibility, allowing for fast substrate binding and product release. The CaM-induced dampening of AC conformational disorder is likely relevant to other CaM-activated enzymes. PMID:29287065

  19. Issues in the deregulation of the electric industry

    NASA Astrophysics Data System (ADS)

    Tyler, Cleve Brent

    The electric industry is undergoing a major restructuring which allows competition in the generation portion of the industry. This dissertation explores several pricing issues relevant to this restructuring. First, an extensive overview examines the industry's history, discusses major regulation theories, and relays the major issues of deregulation. Second, a literature review recounts major works in the economics literature on price discrimination, pricing efficiency, and cost estimation. Then, customer specific generation, transmission, distribution, and general and administration costs are estimated for each company. The customer classes are residential, general service, large general service, and large industrial, representing a finer division of customer classes than found in previous studies. Average prices are compiled and marginal prices are determined from a set of utility schedules. Average and marginal price/cost ratios are computed for each customer class. These ratios show that larger use customers face relative price discrimination but operate under more efficient price structures than small use consumers. Finally, issues in peak load pricing are discussed using a model which predicts inefficient capital choice by regulated utilities. Efficiency losses are estimated to be $620 million dollars a year from the lack of peak load prices under regulation. This result is based on the time-of-use pricing predictions from the Department of Energy.

  20. Multifilament Cable Wire versus Conventional Wire for Sternal Closure in Patients Undergoing Major Cardiac Surgery.

    PubMed

    Oh, You Na; Ha, Keong Jun; Kim, Joon Bum; Jung, Sung-Ho; Choo, Suk Jung; Chung, Cheol Hyun; Lee, Jae Won

    2015-08-01

    Stainless steel wiring remains the most popular technique for primary sternal closure. Recently, a multifilament cable wiring system (Pioneer Surgical Technology Inc., Marquette, MI, USA) was introduced for sternal closure and has gained wide acceptance due to its superior resistance to tension. We aimed to compare conventional steel wiring to multifilament cable fixation for sternal closure in patients undergoing major cardiac surgery. Data were collected retrospectively on 1,354 patients who underwent sternal closure after major cardiac surgery, using either the multifilament cable wiring system or conventional steel wires between January 2009 and October 2010. The surgical outcomes of these two groups of patients were compared using propensity score matching based on 18 baseline patient characteristics. Propensity score matching yielded 392 pairs of patients in the two groups whose baseline profiles showed no significant differences. No significant differences between the two groups were observed in the rates of early mortality (2.0% vs. 1.3%, p=0.578), major wound complications requiring reconstruction (1.3% vs. 1.3%, p>0.99), minor wound complications (3.6% vs. 2.0%, p=0.279), or mediastinitis (0.8% vs. 1.0%, p=1.00). Patients in the multifilament cable group had fewer sternal bleeding events than those in the conventional wire group, but this tendency was not statistically significant (4.3% vs. 7.4%, p=0.068). The surgical outcomes of sternal closure using multifilament cable wires were comparable to those observed when conventional steel wires were used. Therefore, the multifilament cable wiring system may be considered a viable option for sternal closure in patients undergoing major cardiac surgery.

  1. Analysis of National Trends in Hospital Acquired Conditions Following Major Urological Surgery Before and After Implementation of the Hospital Acquired Condition Reduction Program,,✰✰✰.

    PubMed

    Rude, Tope L; Donin, Nicholas M; Cohn, Matthew R; Meeks, William; Gulig, Scott; Patel, Samir N; Wysock, James S; Makarov, Danil V; Bjurlin, Marc A

    2018-06-07

    To define the rates of common Hospital Acquired Conditions (HACs) in patients undergoing major urological surgery over a period of time encompassing the implementation of the Hospital Acquired Condition Reduction program, and to evaluate whether implementation of the HAC reimbursement penalties in 2008 was associated with a change in the rate of HACs. Using American College of Surgeons National Surgical Quality Improvement Program (NSQIP) data, we determined rates of HACs in patients undergoing major inpatient urological surgery from 2005 to 2012. Rates were stratified by procedure type and approach (open vs. laparoscopic/robotic). Multivariable logistic regression was used to determine the association between year of surgery and HACs. We identified 39,257 patients undergoing major urological surgery, of whom 2300 (5.9%) had at least one hospital acquired condition. Urinary tract infection (UTI, 2.6%) was the most common, followed by surgical site infection (SSI, 2.5%) and venous thrombotic events (VTE, 0.7%). Multivariable logistic regression analysis demonstrated that open surgical approach, diabetes, congestive heart failure, chronic obstructive pulmonary disease, weight loss, and ASA class were among the variables associated with higher likelihood of HAC. We observed a non-significant secular trend of decreasing rates of HAC from 7.4% to 5.8% HACs during the study period, which encompassed the implementation of the Hospital Acquired Condition Reduction Program. HACs occurred at a rate of 5.9% after major urological surgery, and are significantly affected by procedure type and patient health status. The rate of HAC appeared unaffected by national reduction program in this cohort. Better understanding of the factors associated with HACs is critical in developing effective reduction programs. Copyright © 2018. Published by Elsevier Inc.

  2. Immunocytochemical localization of the major polypeptides of the nuclear pore complex-lamina fraction. Interphase and mitotic distribution

    PubMed Central

    1978-01-01

    This laboratory has previously isolated a fraction from rat liver nuclei consisting of nuclear pore complexes associated with the proteinaceous lamina which underlies the inner nuclear membrane. Using protein eluted from sodium dodecyl sulfate (SDS) gels, we have prepared antibodies in chickens to each of the three predominant pore complex- lamina bands. Ouchterlony double diffusion analysis shows that each of these individual bands cross-reacts strongly with all three antisera. In immunofluorescence localization performed on tissue culture cells with these antibodies, we obtain a pattern of intense staining at the periphery of the interphase nucleus, with little or no cytoplasmic reaction. Electron microscope immunoperoxidase staining of rat liver nuclei with these antibodies labels exclusively the nuclear periphery. Furthermore, reaction occurs in areas which contain the lamina, but not at the pore complexes. While our isolation procedure extracts the internal contents of nuclei completely, semiquantitative Ouchterlony analysis shows that it releases negligible amounts of these lamina antigens. Considered together, our results indicate that these three bands represent major components of a peripheral nuclear lamina, and are not structural elements of an internal "nuclear protein matrix." Fluorescence microscopy shows that the perinuclear interphase localization of these lamina proteins undergoes dramatic changes during mitosis. Concomitant with nuclear envelope disassembly in prophase, these antigens assume a diffuse localization throughout the cell. This distribution persists until telophase, when the antigens become progressively and completely localized at the surface of the daughter chromosome masses. We propose that the lamina is a biological polymer which can undergo reversible disassembly during mitosis. PMID:102651

  3. Optomechanics of two- and three-dimensional soft photonic crystals

    NASA Astrophysics Data System (ADS)

    Krishnan, Dwarak

    Soft photonic crystals are a class of periodic dielectric structures that undergo highly nonlinear deformation due to strain or other external stimulus such as temperature, pH etc. This can in turn dramatically affect optical properties such as light transmittance. Moreover certain classes of lithographically fabricated structures undergo some structural distortion due to the effects of processing, eventually affecting the optical properties of the final photonic crystal. In this work, we study the deformation mechanics of soft photonic crystal structures using realistic physics-based models and leverage that understanding to explain the optomechanics of actual 2-D and 3-D soft photonic crystals undergoing similar symmetry breaking nonlinear deformations. We first study the optomechanics of two classes of 3-D soft photonic crystals: (1) hydrogel and (2) elastomer based material systems. The hydrogel based inverse face-centered-cubic structure undergoes swelling with change in pH of the surrounding fluid. The inverse structure is a network of bulky domains with thin ligament-like connections, and it undergoes a pattern transformation from FCC to L11 as a result of swelling. A continuum scale poroelasticity based coupled fluid-diffusion FEM model is developed to accurately predict this mechanical behavior. Light transmittance simulation results qualitatively explain the experimentally observed trends in the optical behavior with pH change. The elastomer based, lithographically fabricated material experiences shrinkage induced distortion upon processing. This behavior is modeled using FEM with the material represented by a neo-Hookean constitutive law. The light transmittance calculations for normal incidence are carried out using the transfer matrix method and a good comparison is obtained for the positions of first and second order reflectance peaks. A unit cell based approach is taken to compute the photonic bandstructure to estimate light propagation through the structure for other angles of light incidence. To obtain a detailed picture of the change in optical properties due to a pattern transformation, we study simple 2-D elastomer photonic crystals which undergo an interesting structural pattern transformation from simple circular holes to alternately oriented ellipses in a square lattice due to uniaxial compression. The incident light does not have any effect on the properties of the elastomer material. A decomposition of the deformation gradient quickly shows that the pattern transformation is induced by alternating rotations of the interstitial regions and the bending of interconnecting ligaments. Numerical simulations of light transmittance using vector element based FEM analysis of Maxwells equations shows changes in the light energy localization within the material especially in the high energy/low wavelength regions of the spectra. Additionally, with bandstructure calculations on a unit cell of the structure, the optomechanical behavior is completely explained. Finally, computational evidence is provided for a hypothetical 2-D photonic crystal made of a light-sensitive material, which undergoes a structural pattern transformation primarily due to the effect of incident light. The model takes into account the order kinetics of optically induced isomerization (of trans to cis configuration) in the azobenzene-liquid crystal elastomer to compute the transformational strain. This strain, in turn, deforms the structure and hence changes its periodicity and dielectric properties and thus affects the manner in which light gets localized within the material system. This consequently changes the profile of the imposed transformational strain on the deformed structure. The macroscopic strain history shows that prior to the mechanical instability that causes the pattern transformation, there is a period of structural relaxation which initiates the pattern transformation. After the symmetry breaking pattern transformation, the photonic bandstructure is altered significantly. Light does not get localized in the spot regions anymore and stress relaxation dominates. Due to this, the compressive macroscopic strain of the pattern transformed structure starts to decrease indicating a possible cyclical behavior.

  4. Thrombosis prevention in lower extremity arthroplasty: mobile compression device or pharmacological therapy.

    PubMed

    Colwell, Clifford W

    2014-11-01

    Venous thromboembolic (VTE) events, either deep vein thromboses (DVT) or pulmonary emboli (PE), are important complications in patients undergoing knee or hip arthroplasty. Symptomatic VTE rates observed in total joint arthroplasty patients using the mobile compression device with home use capability were non-inferior to rates reported for pharmacological prophylaxis, including warfarin, enoxaparin, rivaroxaban, and dabigatran. Major bleeding in total hip arthroplasty was less using the mobile compression device than using low molecular weight heparin. A cost analysis demonstrated a cost savings based on decreased major bleeding. Use of a mobile compression device with or without aspirin for patients undergoing total joint arthroplasty provides a non-inferior risk for developing VTE compared with current pharmacological protocols.

  5. Interventional radiology: a half century of innovation.

    PubMed

    Baum, Richard A; Baum, Stanley

    2014-11-01

    The evolution of modern interventional radiology began over half century ago with a simple question. Was it possible to use the same diagnostic imaging tools that had revolutionized the practice of medicine to guide the real-time treatment of disease? This disruptive concept led to rapid treatment advances in every organ system of the body. It became clear that by utilizing imaging some patients could undergo targeted procedures, eliminating the need for major surgery, while others could undergo procedures for previously unsolvable problems. The breadth of these changes now encompasses all of medicine and has forever changed the way we think about disease. In this brief review article, major advances in the field, as chronicled in the pages of Radiology, will be described.

  6. Systemic Inflammatory Response Syndrome After Major Abdominal Surgery Predicted by Early Upregulation of TLR4 and TLR5.

    PubMed

    Lahiri, Rajiv; Derwa, Yannick; Bashir, Zora; Giles, Edward; Torrance, Hew D T; Owen, Helen C; O'Dwyer, Michael J; O'Brien, Alastair; Stagg, Andrew J; Bhattacharya, Satyajit; Foster, Graham R; Alazawi, William

    2016-05-01

    To study innate immune pathways in patients undergoing hepatopancreaticobiliary surgery to understand mechanisms leading to enhanced inflammatory responses and identifying biomarkers of adverse clinical consequences. Patients undergoing major abdominal surgery are at risk of life-threatening systemic inflammatory response syndrome (SIRS) and sepsis. Early identification of at-risk patients would allow tailored postoperative care and improve survival. Two separate cohorts of patients undergoing major hepatopancreaticobiliary surgery were studied (combined n = 69). Bloods were taken preoperatively, on day 1 and day 2 postoperatively. Peripheral blood mononuclear cells and serum were separated and immune phenotype and function assessed ex vivo. Early innate immune dysfunction was evident in 12 patients who subsequently developed SIRS (postoperative day 6) compared with 27 who did not, when no clinical evidence of SIRS was apparent (preoperatively or days 1 and 2). Serum interleukin (IL)-6 concentration and monocyte Toll-like receptor (TLR)/NF-κB/IL-6 functional pathways were significantly upregulated and overactive in patients who developed SIRS (P < 0.0001). Interferon α-mediated STAT1 phosphorylation was higher preoperatively in patients who developed SIRS. Increased TLR4 and TLR5 gene expression in whole blood was demonstrated in a separate validation cohort of 30 patients undergoing similar surgery. Expression of TLR4/5 on monocytes, particularly intermediate CD14CD16 monocytes, on day 1 or 2 predicted SIRS with accuracy 0.89 to 1.0 (areas under receiver operator curves). These data demonstrate the mechanism for IL-6 overproduction in patients who develop postoperative SIRS and identify markers that predict patients at risk of SIRS 5 days before the onset of clinical signs.

  7. Loss of H2 and CO from protonated aldehydes in electrospray ionization mass spectrometry.

    PubMed

    Neta, Pedatsur; Simón-Manso, Yamil; Liang, Yuxue; Stein, Stephen E

    2014-09-15

    Electrospray ionization mass spectrometry (ESI-MS) of many protonated aldehydes shows loss of CO as a major fragmentation pathway. However, we find that certain aldehydes undergo loss of H2 followed by reaction with water in the collision cell. This complicates interpretation of tandem mass (MS/MS) spectra and affects multiple reaction monitoring (MRM) results. 3-Formylchromone and other aldehydes were dissolved in acetonitrile/water/formic acid and studied by ESI-MS to record their MS(2) and MS(n) spectra in several mass spectrometers (QqQ, QTOF, ion trap (IT), and Orbitrap HCD). Certain product ions were found to react with water and the rate of reaction was determined in the IT instrument using zero collision energy and variable activation times. Theoretical calculations were performed to help with the interpretation of the fragmentation mechanism. Protonated 3-formylchromones and 3-formylcoumarins undergo loss of H2 as a major fragmentation route to yield a ketene cation, which reacts with water to form a protonated carboxylic acid. In general, protonated aldehydes which contain a vicinal group that forms a hydrogen bridge with the formyl group undergo significant loss of H2. Subsequent losses of CO and C3O are also observed. Theoretical calculations suggest mechanistic details for these losses. Loss of H2 is a major fragmentation channel for protonated 3-formychromones and certain other aldehydes and it is followed by reaction with water to produce a protonated carboxylic acid, which undergoes subsequent fragmentation. This presents a problem for reference libraries and raises concerns about MRM results. Published in 2014. This article is a U.S. Government work and is in the public domain in the USA.

  8. Breaking Symmetry in Viral Icosahedral Capsids as Seen through the Lenses of X-ray Crystallography and Cryo-Electron Microscopy

    PubMed Central

    Parent, Kristin N.; Schrad, Jason R.; Cingolani, Gino

    2018-01-01

    The majority of viruses on Earth form capsids built by multiple copies of one or more types of a coat protein arranged with 532 symmetry, generating an icosahedral shell. This highly repetitive structure is ideal to closely pack identical protein subunits and to enclose the nucleic acid genomes. However, the icosahedral capsid is not merely a passive cage but undergoes dynamic events to promote packaging, maturation and the transfer of the viral genome into the host. These essential processes are often mediated by proteinaceous complexes that interrupt the shell’s icosahedral symmetry, providing a gateway through the capsid. In this review, we take an inventory of molecular structures observed either internally, or at the 5-fold vertices of icosahedral DNA viruses that infect bacteria, archea and eukaryotes. Taking advantage of the recent revolution in cryo-electron microscopy (cryo-EM) and building upon a wealth of crystallographic structures of individual components, we review the design principles of non-icosahedral structural components that interrupt icosahedral symmetry and discuss how these macromolecules play vital roles in genome packaging, ejection and host receptor-binding. PMID:29414851

  9. Palisade is required in the Drosophila ovary for assembly and function of the protective vitelline membrane.

    PubMed

    Elalayli, Maggie; Hall, Jacklyn D; Fakhouri, Mazen; Neiswender, Hannah; Ellison, Tambrea T; Han, Zhe; Roon, Penny; LeMosy, Ellen K

    2008-07-15

    The innermost layer of the Drosophila eggshell, the vitelline membrane, provides structural support and positional information to the embryo. It is assembled in an incompletely understood manner from four major proteins to form a homogeneous, transparent extracellular matrix. Here we show that RNAi knockdown or genetic deletion of a minor constituent of this matrix, Palisade, results in structural disruptions during the initial synthesis of the vitelline membrane by somatic follicle cells surrounding the oocyte, including wide size variation among the precursor vitelline bodies and disorganization of follicle cell microvilli. Loss of Palisade or the microvillar protein Cad99C results in abnormal uptake into the oocyte of sV17, a major vitelline membrane protein, and defects in non-disulfide cross-linking of sV17 and sV23, while loss of Palisade has additional effects on processing and disulfide cross-linking of these proteins. Embryos surrounded by the abnormal vitelline membranes synthesized when Palisade is reduced are fertilized but undergo developmental arrest, usually during the first 13 nuclear divisions, with a nuclear phenotype of chromatin margination similar to that described for wild-type embryos subjected to anoxia. Our results demonstrate that Palisade is involved in coordinating assembly of the vitelline membrane and is required for functional properties of the eggshell.

  10. Palisade is required in the Drosophila ovary for assembly and function of the protective vitelline membrane

    PubMed Central

    Elalayli, Maggie; Hall, Jacklyn D.; Fakhouri, Mazen; Neiswender, Hannah; Ellison, Tambrea T.; Han, Zhe; Roon, Penny; LeMosy, Ellen K.

    2008-01-01

    The innermost layer of the Drosophila eggshell, the vitelline membrane, provides structural support and positional information to the embryo. It is assembled in an incompletely understood manner from four major proteins to form a homogeneous, transparent extracellular matrix. Here we show that RNAi knockdown or genetic deletion of a minor constituent of this matrix, Palisade, results in structural disruptions during the initial synthesis of the vitelline membrane by somatic follicle cells surrounding the oocyte, including wide size variation among the precursor vitelline bodies and disorganization of follicle cell microvilli. Loss of Palisade or the microvillar protein Cad99C results in abnormal uptake into the oocyte of sV17, a major vitelline membrane protein, and defects in non-disulfide cross-linking of sV17 and sV23, while loss of Palisade has additional effects on processing and disulfide cross-linking of these proteins. Embryos surrounded by the abnormal vitelline membranes synthesized when Palisade is reduced are fertilized but undergo developmental arrest, usually during the first 13 nuclear divisions, with a nuclear phenotype of chromatin margination similar to that described for wild-type embryos subjected to anoxia. Our results demonstrate that Palisade is involved in coordinating assembly of the vitelline membrane and is required for functional properties of the eggshell. PMID:18514182

  11. The centrosomin CM2 domain is a multi-functional binding domain with distinct cell cycle roles.

    PubMed

    Citron, Y Rose; Fagerstrom, Carey J; Keszthelyi, Bettina; Huang, Bo; Rusan, Nasser M; Kelly, Mark J S; Agard, David A

    2018-01-01

    The centrosome serves as the main microtubule-organizing center in metazoan cells, yet despite its functional importance, little is known mechanistically about the structure and organizational principles that dictate protein organization in the centrosome. In particular, the protein-protein interactions that allow for the massive structural transition between the tightly organized interphase centrosome and the highly expanded matrix-like arrangement of the mitotic centrosome have been largely uncharacterized. Among the proteins that undergo a major transition is the Drosophila melanogaster protein centrosomin that contains a conserved carboxyl terminus motif, CM2. Recent crystal structures have shown this motif to be dimeric and capable of forming an intramolecular interaction with a central region of centrosomin. Here we use a combination of in-cell microscopy and in vitro oligomer assessment to show that dimerization is not necessary for CM2 recruitment to the centrosome and that CM2 alone undergoes significant cell cycle dependent rearrangement. We use NMR binding assays to confirm this intramolecular interaction and show that residues involved in solution are consistent with the published crystal structure and identify L1137 as critical for binding. Additionally, we show for the first time an in vitro interaction of CM2 with the Drosophila pericentrin-like-protein that exploits the same set of residues as the intramolecular interaction. Furthermore, NMR experiments reveal a calcium sensitive interaction between CM2 and calmodulin. Although unexpected because of sequence divergence, this suggests that centrosomin-mediated assemblies, like the mammalian pericentrin, may be calcium regulated. From these results, we suggest an expanded model where during interphase CM2 interacts with pericentrin-like-protein to form a layer of centrosomin around the centriole wall and that at the onset of mitosis this population acts as a nucleation site of intramolecular centrosomin interactions that support the expansion into the metaphase matrix.

  12. Survey on Restoration of Endodontically Treated Anterior Teeth: A Questionnaire Based Study

    PubMed Central

    Ratnakar, P; Bhosgi, Rashmi; Metta, Kiran Kumar; Aggarwal, Kanika; Vinuta, S; Singh, Navneet

    2014-01-01

    Background: The aim of endodontic and restorative dentistry is the conservation of natural tooth structure. Endodontically treated tooth (ETT) undergoes loss of tooth structure and changes in physical characteristics. Therefore, proper selection of restoration for ETT is mandatory. The clinical approach of restoring ETT needs taking into considerations several issues. However, the best way to restore teeth after root canal treatment has long been and still a controversial subject to debate. Therefore, this study was carried out to detect the frequency of preferred methods of restoring ETT under different conditions. Materials and Methods: A questionnaire was framed and distributed among prosthodontists, endodontist and general practitioners of north India region to find out the frequency of best suitable material and method regarding restoration of ETT. 220 questionnaires were sent by electronic mail out of which 110 were received back. The questionnaire contained different methods of restoration of endodontically treated anterior teeth at different conditions (percentages) of remaining sound tooth structure. Respondents were asked to indicate their preferred method of restoration of those teeth. Results: Results showed that majority of respondents (51.82%) preferred to restore the tooth only with a tooth-color restorative material in condition A. In condition B, majority of respondents preferred to use tooth colored crown (44.55%) and prefabricated post and tooth colored restoration (24.5%). Whereas in condition C, most of the respondents preferred to use a cast post and core/crown (80.91%). Conclusion: From the findings of the present study, it can be concluded that the unrestored ETT is susceptible to fracture, which could lead to loss of tooth and that the maximum preservation of healthy tooth structure and use of restorative materials with mechanical properties similar to dental structure favor greater longevity of tooth restoration complex. PMID:25628482

  13. Structural organisation and lipid composition of the epicuticular accessory layer of infective larvae of Trichinella spiralis.

    PubMed

    Gounaris, K; Smith, V P; Selkirk, M E

    1996-05-22

    The epicuticle of infective larvae of Trichinella spiralis represents the interface between this intracellular nematode parasite and the cytosol of mammalian skeletal muscle. The macromolecular structures that make up the epicuticle were studied by freeze-fracture electron microscopy and compositional analysis. Three fracture planes were observed: one with a typical plasma membrane-type bilayer organisation which was overlaid by two extended layers of lipid in an inverted cylindrical configuration. This overall structure remained unchanged in response to variations in temperature between 20 degrees C and 45 degrees C. The lipid cylinders were on average 6.8 nm in diameter, with randomly-associated particles that were not dissociated by high-salt treatment, indicative of hydrophobically associated proteins. The majority of the lipids were non-polar, consisting of cholesterol, cholesterol esters, mono- and tri-glycerides, and free fatty acids. Three major classes of phospholipids were identified: phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine. Total lipid extracts did not adopt an inverted cylindrical or micellar configuration on isolation, but formed flat sheets of lamellae as did the purified polar and non-polar fractions of the lipids. Isolated lipids did not undergo thermally-induced polymorphism between 20 degrees C and 60 degrees C and there was no pH dependency of the structures adopted. The fatty acid saturation levels of the phospholipids were compatible with the observation that they did not form polymorphic structures on isolation. We suggest that this unusual configuration is probably stabilised by the associated (glyco)proteins and may be required for selective permeation of nutrients from the host cell cytosol and/or for maintaining the high curvature of the parasite within the cell.

  14. Comparison of onboard low-field magnetic resonance imaging versus onboard computed tomography for anatomy visualization in radiotherapy.

    PubMed

    Noel, Camille E; Parikh, Parag J; Spencer, Christopher R; Green, Olga L; Hu, Yanle; Mutic, Sasa; Olsen, Jeffrey R

    2015-01-01

    Onboard magnetic resonance imaging (OB-MRI) for daily localization and adaptive radiotherapy has been under development by several groups. However, no clinical studies have evaluated whether OB-MRI improves visualization of the target and organs at risk (OARs) compared to standard onboard computed tomography (OB-CT). This study compared visualization of patient anatomy on images acquired on the MRI-(60)Co ViewRay system to those acquired with OB-CT. Fourteen patients enrolled on a protocol approved by the Institutional Review Board (IRB) and undergoing image-guided radiotherapy for cancer in the thorax (n = 2), pelvis (n = 6), abdomen (n = 3) or head and neck (n = 3) were imaged with OB-MRI and OB-CT. For each of the 14 patients, the OB-MRI and OB-CT datasets were displayed side-by-side and independently reviewed by three radiation oncologists. Each physician was asked to evaluate which dataset offered better visualization of the target and OARs. A quantitative contouring study was performed on two abdominal patients to assess if OB-MRI could offer improved inter-observer segmentation agreement for adaptive planning. In total 221 OARs and 10 targets were compared for visualization on OB-MRI and OB-CT by each of the three physicians. The majority of physicians (two or more) evaluated visualization on MRI as better for 71% of structures, worse for 10% of structures, and equivalent for 14% of structures. 5% of structures were not visible on either. Physicians agreed unanimously for 74% and in majority for > 99% of structures. Targets were better visualized on MRI in 4/10 cases, and never on OB-CT. Low-field MR provides better anatomic visualization of many radiotherapy targets and most OARs as compared to OB-CT. Further studies with OB-MRI should be pursued.

  15. Associations between relationship support and psychological reactions of participants and partners to BRCA1 and BRCA2 testing in a clinic-based sample.

    PubMed

    Manne, Sharon; Audrain, Janet; Schwartz, Marc; Main, David; Finch, Clinton; Lerman, Caryn

    2004-12-01

    Despite the potential importance of communication about genetic testing between test participants and their significant others, little is known about social support and communication between women undergoing BRCA1 and BRCA2 testing and their partners. The aims of this longitudinal study were to examine communication about genetic testing during and following testing and to evaluate whether communication is associated with psychological distress reported by test participants and their partners. Participants were 153 women who were undergoing genetic testing and 118 partners of women undergoing testing. Relationship communication and distress were evaluated at the time of pretest education and 6 months postdisclosure. Overall, the decision to undergo testing was discussed by the majority of test participants and partners, and most couples felt their partners were supportive. Most women disclosed their results to their partners. Longitudinal analyses suggested that less support and protective buffering were associated with greater distress 6 months postdisclosure among test participants, whereas lower comfort in sharing concerns and partner support were associated with lower distress 6 months postdisclosure among partners. The results of this study suggest that the majority of couples respond supportively during the test experience, but for a small subset of couples the process can strain the relationship. Partner support during this process is important, particularly for test participants dealing with an uninformative test result.

  16. In-Hospital Outcomes of Dual Loading Antiplatelet Therapy in Patients 75 Years and Older With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Findings From the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) Project.

    PubMed

    Zhao, Guanqi; Zhou, Mengge; Ma, Changsheng; Huo, Yong; Smith, Sidney C; Fonarow, Gregg C; Ge, Junbo; Han, Yaling; Liu, Jing; Hao, Yongchen; Liu, Jun; Wang, Xiao; Taubert, Kathryn A; Morgan, Louise; Zhao, Dong; Nie, Shaoping

    2018-03-30

    Elderly patients with acute coronary syndrome (ACS) are at high risk for ischemic and bleeding events. This study aimed to evaluate the clinical effectiveness and safety of dual loading antiplatelet therapy for patients 75 years and older undergoing percutaneous coronary intervention for ACS. The Improving Care for Cardiovascular Disease in China-ACS project was a collaborative study of the American Heart Association and Chinese Society of Cardiology. A total of 5887 patients 75 years and older with ACS who had percutaneous coronary intervention and received dual antiplatelet therapy with aspirin and P2Y 12 inhibitors (clopidogrel or ticagrelor) between November 2014 and June 2017 were enrolled. The primary effectiveness and safety outcomes were in-hospital major adverse cardiovascular events and major bleeding. Hazard ratios (HRs) of in-hospital outcomes with different loading statuses of antiplatelet therapy were estimated using Cox proportional hazard models with multivariate adjustment. A propensity score-matched analysis was also conducted. Compared with patients receiving a dual nonloading dose, patients taking a dual loading dose had increased risks of both major adverse cardiovascular events (HR, 1.66, 95% confidence interval, 1.13-2.44; [ P =0.010]) and major bleeding (HR, 2.34, 95% confidence interval, 1.75-3.13; [ P <0.001]). Among 3284 propensity score-matched patients, a dual loading dose was associated with a 1.36-fold risk of major adverse cardiovascular events (HR, 1.36; 95% confidence interval, 0.88-2.11 [ P =0.168]) and a 2.08-fold risk of major bleeding (HR, 2.08; 95% confidence interval, 1.47-2.93 [ P <0.001]). A dual loading dose of antiplatelet therapy was associated with increased major bleeding risk but not with decreased major adverse cardiovascular events risk among patients 75 years and older undergoing percutaneous coronary intervention for ACS in China. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT02306616. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  17. Genetic and pharmacological intervention for treatment/prevention of hearing loss

    PubMed Central

    Cotanche, Douglas A.

    2008-01-01

    Twenty years ago it was first demonstrated that birds could regenerate their cochlear hair cells following noise damage or aminoglycoside treatment. An understanding of how this structural and functional regeneration occurred might lead to the development of therapies for treatment of sensorineural hearing loss in humans. Recent experiments have demonstrated that noise exposure and aminoglycoside treatment lead to apoptosis of the hair cells. In birds, this programmed cell death induces the adjacent supporting cells to undergo regeneration to replace the lost hair cells. Although hair cells in the mammalian cochlea undergo apoptosis in response to noise damage and ototoxic drug treatment, the supporting cells do not possess the ability to undergo regeneration. However, current experiments on genetic manipulation, gene therapy, and stem cell transplantation suggest that regeneration in the mammalian cochlea may eventually be possible and may 1 day provide a therapeutic tool for hearing loss in humans. Learning outcomes The reader should be able to: (1) Describe the anatomy of the avian and mammalian cochlea, identify the individual cell types in the organ of Corti, and distinguish major features that participate in hearing function, (2) Demonstrate a knowledge of how sound damage and aminoglycoside poisoning induce apoptosis of hair cells in the cochlea, (3) Define how hair cell loss in the avian cochlea leads to regeneration of new hair cells and distinguish this from the mammalian cochlea where there is no regeneration following damage, and (4) Interpret the potential for new approaches, such as genetic manipulation, gene therapy and stem cell transplantation, could provide a therapeutic approach to hair cell loss in the mammalian cochlea. PMID:18455177

  18. Genetic and pharmacological intervention for treatment/prevention of hearing loss.

    PubMed

    Cotanche, Douglas A

    2008-01-01

    Twenty years ago it was first demonstrated that birds could regenerate their cochlear hair cells following noise damage or aminoglycoside treatment. An understanding of how this structural and functional regeneration occurred might lead to the development of therapies for treatment of sensorineural hearing loss in humans. Recent experiments have demonstrated that noise exposure and aminoglycoside treatment lead to apoptosis of the hair cells. In birds, this programmed cell death induces the adjacent supporting cells to undergo regeneration to replace the lost hair cells. Although hair cells in the mammalian cochlea undergo apoptosis in response to noise damage and ototoxic drug treatment, the supporting cells do not possess the ability to undergo regeneration. However, current experiments on genetic manipulation, gene therapy, and stem cell transplantation suggest that regeneration in the mammalian cochlea may eventually be possible and may 1 day provide a therapeutic tool for hearing loss in humans. The reader should be able to: (1) Describe the anatomy of the avian and mammalian cochlea, identify the individual cell types in the organ of Corti, and distinguish major features that participate in hearing function, (2) Demonstrate a knowledge of how sound damage and aminoglycoside poisoning induce apoptosis of hair cells in the cochlea, (3) Define how hair cell loss in the avian cochlea leads to regeneration of new hair cells and distinguish this from the mammalian cochlea where there is no regeneration following damage, and (4) Interpret the potential for new approaches, such as genetic manipulation, gene therapy and stem cell transplantation, could provide a therapeutic approach to hair cell loss in the mammalian cochlea.

  19. Outcomes in Patients With Hemophilia and von Willebrand Disease Undergoing Invasive or Surgical Procedures.

    PubMed

    Chapin, John; Bamme, Jaqueline; Hsu, Fraustina; Christos, Paul; DeSancho, Maria

    2017-03-01

    Adults with hemophilia A (HA), hemophilia B (HB), and von Willebrand disease (VWD) frequently require surgery and invasive procedures. However, there is variability in perioperative management guidelines. We describe our periprocedural outcomes in this setting. A retrospective chart review from January 2006 to December 2012 of patients with HA, HB, and VWD undergoing surgery or invasive procedures was conducted. Type of procedures, management including the use of continuous factor infusion, and administration of antifibrinolytics were reviewed. Adverse outcomes were defined as acute bleeding (<48 hours), delayed bleeding (≥48 hours), transfusion, inhibitor development, and thrombosis. We identified 59 patients with HA and HB. In all, 24 patients had severe hemophilia and 12 had mild/moderate hemophilia. Twelve patients had inhibitors. There were also 5 female carriers of HA and 6 patients with VWD. There were 34 major surgeries (26 orthopedic, 8 nonorthopedic) and 129 minor surgeries. Continuous infusion was used in 55.9% of major surgeries versus 8.5% of minor surgeries. Antifibrinolytics were administered in 14.7% of major surgeries versus 23.2% of minor surgeries. In all, 4 patients developed acute bleeding and 10 patients developed delayed bleeding. Delayed bleeding occurred in 28.6% of genitourinary procedures and in 16.1% of dental procedures. Five patients acquired an inhibitor and 2 had thrombosis. In conclusion, patients with HA, HB, or VWD had similar rates of adverse outcomes when undergoing minor surgeries or major surgeries. This finding underscores the importance of an interdisciplinary management and procedure-specific guidelines for patients with hemophilia and VWD prior to even minor invasive procedures.

  20. K-Ras protein as a drug target.

    PubMed

    McCormick, Frank

    2016-03-01

    K-Ras proteins are major drivers of human cancers, playing a direct causal role in about one million cancer cases/year. In cancers driven by mutant K-Ras, the protein is locked in the active, GTP-bound state constitutively, through a defect in the off-switch mechanism. As such, the mutant protein resembles the normal K-Ras protein from a structural perspective, making therapeutic attack extremely challenging. K-Ras is a member of a large family of related proteins, which share very similar GDP/GTP-binding domains, making specific therapies more difficult. Furthermore, Ras proteins lack pockets to which small molecules can bind with high affinity, with a few interesting exceptions. However, new insights into the structure and function of K-Ras proteins reveal opportunities for intervention that were not appreciated many years ago, when efforts were launched to develop K-Ras therapies. Furthermore, K-Ras undergoes post-translational modification and interactions with cellular signaling proteins that present additional therapeutic opportunities, such as specific binding to calmodulin and regulation of non-canonical Wnt signaling.

  1. Cultural Psychiatry: A Spotlight on the Experience of Clinical Social Workers' Encounter with Jewish Ultra-Orthodox Mental Health Clients.

    PubMed

    Freund, Anat; Band-Winterstein, Tova

    2017-07-01

    Community is a complex issue, especially in two particular populations overlap: Haredi society, which embraces cultural codes common to closed communities, and the mental health population characterized by its own unique needs. The present study explores the encounter experience of social workers with the cultural perceptions of mental health clients in the Haredi community in light of Community Cultural Psychiatry. A qualitative-phenomenological approach was adopted. In-depth semi-structured interviews were conducted with 27 social workers, mental health professionals, who are in contact with ultra-Orthodox Jewish clients. Three major themes emerged from the data analysis: (1) Exclusion vs. grace and compassion. (2) Mental health: A professional or cultural arena? (3) Mental health help-seeking changing processes. This study shows that the attitude in the Haredi community toward mental health therapy undergoes a process of change. It is important to strengthen this process, together with preserving existing community informal structures of help.

  2. Long-term biopersistence of tangled oxidized carbon nanotubes inside and outside macrophages in rat subcutaneous tissue

    NASA Astrophysics Data System (ADS)

    Sato, Yoshinori; Yokoyama, Atsuro; Nodasaka, Yoshinobu; Kohgo, Takao; Motomiya, Kenichi; Matsumoto, Hiroaki; Nakazawa, Eiko; Numata, Tomoko; Zhang, Minfang; Yudasaka, Masako; Hara, Hideyuki; Araki, Rikita; Tsukamoto, Osamu; Saito, Hiroaki; Kamino, Takeo; Watari, Fumio; Tohji, Kazuyuki

    2013-08-01

    Because of their mechanical strength, chemical stability, and low molecular weight, carbon nanotubes (CNTs) are attractive biological implant materials. Biomaterials are typically implanted into subcutaneous tissue or bone; however, the long-term biopersistence of CNTs in these tissues is unknown. Here, tangled oxidized multi-walled CNTs (t-ox-MWCNTs) were implanted into rat subcutaneous tissues and structural changes in the t-ox-MWCNTs located inside and outside of macrophages were studied for 2 years post-implantation. The majority of the large agglomerates were present in the intercellular space, maintained a layered structure, and did not undergo degradation. By contrast, small agglomerates were found inside macrophages, where they were gradually degraded in lysosomes. None of the rats displayed symptoms of cancer or severe inflammatory reactions such as necrosis. These results indicate that t-ox-MWCNTs have high biopersistence and do not evoke adverse events in rat subcutaneous tissue in vivo, demonstrating their potential utility as implantable biomaterials.

  3. Notch-modifying xylosyltransferase-substrate complexes support an SNi-like retaining mechanism

    PubMed Central

    Yu, Hongjun; Takeuchi, Megumi; LeBarron, Jamie; Kantharia, Joshua; London, Erwin; Bakker, Hans; Haltiwanger, Robert S.; Li, Huilin; Takeuchi, Hideyuki

    2015-01-01

    A major remaining question in glycobiology is how a glycosyltransferase (GT) that retains the anomeric linkage of a sugar catalyzes the reaction. Xylosideα1–3 Xylosyltransferase (XXYLT1) is a retaining GT that regulates Notch receptor activation by adding xylose to the Notch extracellular domain. Here, using natural acceptor and donor substrates and active Mus musculus XXYLT1, we report a series of crystallographic snapshots along the reaction, including an unprecedented natural and competent Michaelis reaction complex for retaining enzymes. These structures strongly support the SNi-like reaction as the retaining mechanism for XXYLT1. Unexpectedly the Epidermal Growth Factor-like repeat acceptor substrate undergoes a large conformational change upon binding to the active site, providing a structural basis for substrate specificity. Our improved understanding of this retaining enzyme will accelerate the design of retaining GT inhibitors that can modulate Notch activity in pathological situations where dysregulation of Notch is known to cause cancer or developmental disorders. PMID:26414444

  4. Reduction in cardiac mortality with bivalirudin in patients with and without major bleeding: The HORIZONS-AMI trial (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction).

    PubMed

    Stone, Gregg W; Clayton, Tim; Deliargyris, Efthymios N; Prats, Jayne; Mehran, Roxana; Pocock, Stuart J

    The purpose of this study was to determine whether, in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), the reduction in cardiac mortality in those taking bivalirudin compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor (UFH+GPI) can be fully attributed to reduced bleeding. The association between hemorrhagic complications and mortality may explain the survival benefit with bivalirudin. A total of 3,602 STEMI patients undergoing primary PCI were randomized to bivalirudin versus UFH+GPI. Three-year cardiac mortality was analyzed in patients with and without major bleeding. When compared with UFH+GPI, bivalirudin resulted in lower 3-year rates of major bleeding (6.9% vs. 10.5%, hazard ratio [HR]: 0.64 [95% confidence interval (CI): 0.51 to 0.80], p < 0.0001) and cardiac mortality (2.9% vs. 5.1%, HR: 0.56 [95% CI: 0.40 to 0.80], p = 0.001). Three-year cardiac mortality was reduced in bivalirudin-treated patients with major bleeding (20 fewer deaths with bivalirudin; 5.8% vs. 14.6%, p = 0.025) and without major bleeding (18 fewer deaths with bivalirudin; 2.6% vs. 3.8%, p = 0.048). In a fully-adjusted multivariable model accounting for major bleeding and other adverse events, bivalirudin was still associated with a 43% reduction in 3-year cardiac mortality (adjusted HR: 0.57 [95% CI: 0.39 to 0.83], p = 0.003). Bivalirudin reduces cardiac mortality in patients with STEMI undergoing primary PCI, an effect that can only partly be attributed to prevention of bleeding. Further studies are required to identify the nonhematologic benefits of bivalirudin. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. Implementation of a finite element analysis procedure for structural analysis of shape memory behaviour of fibre reinforced shape memory polymer composites

    NASA Astrophysics Data System (ADS)

    Azzawi, Wessam Al; Epaarachchi, J. A.; Islam, Mainul; Leng, Jinsong

    2017-12-01

    Shape memory polymers (SMPs) offer a unique ability to undergo a substantial shape deformation and subsequently recover the original shape when exposed to a particular external stimulus. Comparatively low mechanical properties being the major drawback for extended use of SMPs in engineering applications. However the inclusion of reinforcing fibres in to SMPs improves mechanical properties significantly while retaining intrinsic shape memory effects. The implementation of shape memory polymer composites (SMPCs) in any engineering application is a unique task which requires profound materials and design optimization. However currently available analytical tools have critical limitations to undertake accurate analysis/simulations of SMPC structures and slower derestrict transformation of breakthrough research outcomes to real-life applications. Many finite element (FE) models have been presented. But majority of them require a complicated user-subroutines to integrate with standard FE software packages. Furthermore, those subroutines are problem specific and difficult to use for a wider range of SMPC materials and related structures. This paper presents a FE simulation technique to model the thermomechanical behaviour of the SMPCs using commercial FE software ABAQUS. Proposed technique incorporates material time-dependent viscoelastic behaviour. The ability of the proposed technique to predict the shape fixity and shape recovery was evaluated by experimental data acquired by a bending of a SMPC cantilever beam. The excellent correlation between the experimental and FE simulation results has confirmed the robustness of the proposed technique.

  6. Efficacy and safety of recombinant activated factor vii in major surgical procedures: systematic review and meta-analysis of randomized clinical trials.

    PubMed

    Ranucci, Marco; Isgrò, Giuseppe; Soro, Giorgio; Conti, Daniela; De Toffol, Barbara

    2008-03-01

    To investigate the efficacy and safety of recombinant activated factor VII (rFVIIa) treatment in patients undergoing major surgical procedures. Relevant studies were searched in BioMedCentral, CENTRAL, PubMed, and PubMed Central. Only randomized controlled trials on humans undergoing major surgery were included. Efficacy was determined as the rate of patients receiving allogeneic packed red blood cells; safety was assessed in terms of thromboembolic complications and mortality rate. We followed the Cochrane Collaboration method for data extraction and internal validity procedures, as well as the Quality of Reporting of Meta-analyses statement. Seven randomized controlled trials met the inclusion criteria. Treatment with rFVIIa is associated with a reduced risk of receiving allogeneic packed red blood cells (odds ratio, 0.29; 95% confidence interval, 0.10-0.80). In a subgroup analysis, only patients receiving at least 50 mug/kg of rFVIIa had a significant benefit (odds ratio, 0.43; 95% confidence interval, 0.23-0.78). No differences in thromboembolic complications and mortality rates were observed. Treatment with rFVIIa is effective in reducing the rate of patients undergoing transfusion with allogeneic packed red blood cells. However, the cost-benefit ratio is favorable only in patients who need a huge number of packed red blood cell units. No safety concerns arise from the present study.

  7. The effect of perioperative beta-blockade on the pulmonary function of patients undergoing major arterial surgery.

    PubMed

    Kieran, S M; Cahill, R A; Browne, I; Sheehan, S J; Mehigan, D; Barry, M C

    2006-09-01

    Concern about the potential detrimental side-effects of beta-blockade on pulmonary function often dissuades against their perioperative use in patients undergoing major arterial surgery (especially in those with chronic obstructive pulmonary disease (COPD)). In this study we aimed to establish prospectively the clinical relevance of these concerns. After ethics committee approval and individual informed consent, the pulmonary function of twenty patients (mean age 68.7 years (range 43-82), 11 males) scheduled to undergo non-emergency major vascular surgery was studied by recording symptoms and spirometry before and after institution of effective beta-blockade. Fifteen patients (75%) had significant smoking histories (mean pack years/patient=50), while 12 (60%) had COPD. All patients tolerated effective beta-blockade satisfactorily without developing either subjective deterioration in symptoms or significant change on spirometry. The mean change in FEV1 following adequate beta-blockade was 0.05+/-0.24 liters (95% CI -0.06 to +1.61), p=0.35, giving a mean percentage change of 3.18%+/-11.66 (95% CI -2.26 to 8.62). Previously held concerns about worsening pulmonary function through the short-term use of beta-blockers should not dissuade their perioperative usage in patients with peripheral vascular disease. Furthermore, the accuracy of pulmonary function tests in preoperative assessment and risk stratification also appears unaffected by this therapy.

  8. Dual antiplatelet therapy versus aspirin alone in patients undergoing transcatheter aortic valve implantation.

    PubMed

    Ussia, Gian Paolo; Scarabelli, Marilena; Mulè, Massimiliano; Barbanti, Marco; Sarkar, Kunal; Cammalleri, Valeria; Immè, Sebastiano; Aruta, Patrizia; Pistritto, Anna Maria; Gulino, Simona; Deste, Wanda; Capodanno, Davide; Tamburino, Corrado

    2011-12-15

    Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely accepted strategy in patients undergoing transcatheter aortic valve implantation (TAVI), but this approach is not evidence based. The goal of the present study was to determine whether DAPT in patients undergoing TAVI is associated with improved outcomes compared to aspirin alone. From May 2009 to August 2010, consecutive patients were randomized to receive a 300-mg loading dose of clopidogrel on the day before TAVI followed by a 3-month maintenance daily dose of 75 mg plus aspirin 100 mg lifelong (DAPT group) or aspirin 100 mg alone (ASA group). The primary end point was the composite of major adverse cardiac and cerebrovascular events, defined as death from any cause, myocardial infarction, major stroke, urgent or emergency conversion to surgery, or life-threatening bleeding. The cumulative incidence of major adverse cardiac and cerebrovascular events at 30 days and 6 months was 14% and 16%, respectively. No significant differences between the DAPT and ASA groups were noted at both 30 days (13% vs 15%, p = 0.71) and 6 months (18% vs 15%; p = 0.85). In conclusion, the strategy of adding clopidogrel to aspirin for 3 months after TAVI was not found to be superior to aspirin alone. These results must be confirmed in a larger randomized trial. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Spectroscopic studies on the conformational transitions of a bovine growth hormone releasing factor analog

    NASA Astrophysics Data System (ADS)

    Sarver, Ronald W.; Friedman, Alan R.; Thamann, Thomas J.

    1997-10-01

    The secondary structure of the bovine growth hormone releasing factor analog, [Ile 2, Ser 8,28, Ala 15, Leu 27, Hse 30] bGRF(1-30)-NH-Ethyl, acetate salt (U-90699F) was studied in solution by Fourier transform infrared and Raman spectroscopies. Spectroscopic studies revealed that concentrated aqueous solutions of U-90699F (100 mg ml -1) undergo a secondary structure transition from disordered coil/α-helix to intermolecular β-sheet. Disordered coil and α-helical structure were grouped together in the infrared and Raman studies since the amide I vibrations are close in frequency and overlap in assignments was possible. Before the conformational transition, the facile exchange of the peptide's amide hydrogens for deuterium indicated that the majority of amide hydrogens were readily accessible to solvent. The kinetics of the conformational transition coincided with an increase in solution viscosity and turbidity. An initiation phase preceded the conformational transition during which only minor spectral changes were observed by infrared spectroscopy. The initiation phase and reaction kinetics were consistent with a highly cooperative nucleation ultimately leading to a network of intermolecular β-sheet structure and gel formation. Increased temperature accelerated the conformational transition. The conformational transition was thermally irreversible but the β-sheet structure of aggregated or gelled peptide could be disrupted by dilution and agitation.

  10. Atomic resolution structure of the cytoplasmic domain of Yersinia pestis YscU, a regulatory switch involved in type III secretion

    PubMed Central

    Lountos, George T; Austin, Brian P; Nallamsetty, Sreedevi; Waugh, David S

    2009-01-01

    Crystal structures of cleaved and uncleaved forms of the YscU cytoplasmic domain, an essential component of the type III secretion system (T3SS) in Yersinia pestis, have been solved by single-wavelength anomolous dispersion and refined with X-ray diffraction data extending up to atomic resolution (1.13 Å). These crystallographic studies provide structural insights into the conformational changes induced upon auto-cleavage of the cytoplasmic domain of YscU. The structures indicate that the cleaved fragments remain bound to each other. The conserved NPTH sequence that contains the site of the N263-P264 peptide bond cleavage is found on a β-turn which, upon cleavage, undergoes a major reorientation of the loop away from the catalytic N263, resulting in altered electrostatic surface features at the site of cleavage. Additionally, a significant conformational change was observed in the N-terminal linker regions of the cleaved and noncleaved forms of YscU which may correspond to the molecular switch that influences substrate specificity. The YscU structures determined here also are in good agreement with the auto-cleavage mechanism described for the flagellar homolog FlhB and E. coli EscU. PMID:19165725

  11. iATTRACT: simultaneous global and local interface optimization for protein-protein docking refinement.

    PubMed

    Schindler, Christina E M; de Vries, Sjoerd J; Zacharias, Martin

    2015-02-01

    Protein-protein interactions are abundant in the cell but to date structural data for a large number of complexes is lacking. Computational docking methods can complement experiments by providing structural models of complexes based on structures of the individual partners. A major caveat for docking success is accounting for protein flexibility. Especially, interface residues undergo significant conformational changes upon binding. This limits the performance of docking methods that keep partner structures rigid or allow limited flexibility. A new docking refinement approach, iATTRACT, has been developed which combines simultaneous full interface flexibility and rigid body optimizations during docking energy minimization. It employs an atomistic molecular mechanics force field for intermolecular interface interactions and a structure-based force field for intramolecular contributions. The approach was systematically evaluated on a large protein-protein docking benchmark, starting from an enriched decoy set of rigidly docked protein-protein complexes deviating by up to 15 Å from the native structure at the interface. Large improvements in sampling and slight but significant improvements in scoring/discrimination of near native docking solutions were observed. Complexes with initial deviations at the interface of up to 5.5 Å were refined to significantly better agreement with the native structure. Improvements in the fraction of native contacts were especially favorable, yielding increases of up to 70%. © 2014 Wiley Periodicals, Inc.

  12. Embedding memories in colloidal gels though oscillatory shear

    NASA Astrophysics Data System (ADS)

    Schwen, Eric; Ramaswamay, Meera; Jan, Linda; Cheng, Chieh-Min; Cohen, Itai

    While gels are ubiquitous in applications from food products to filtration, their mechanical properties are usually determined by self-assembly. We use oscillatory shear to train colloidal gels, embedding memories of the training protocol in rheological responses such as the yield strain and the gel network structures. When our gels undergo shear, the particles are forced to rearrange until they organize into structures that can locally undergo reversible shear cycles. We utilize a high-speed confocal microscope and a shear cell to image a colloidal gel while simultaneously straining the gel and measuring its shear stresses. By comparing stroboscopic images of the gel, we quantify the decrease in particle rearrangement as the gel develops reversible structures. We analyze and construct a model for the rates at which different regions in the gel approach reversible configurations. Through characterizing the gel network, we determine the structural origins of these shear training memories in gels. These results may allow us to use shear training protocols to produce gels with controllable yield strains and to better understand changes in the microstructure and rheology of gels that undergo repeated shear through mixing or flowing. This research was supported in part by NSF CBET 1509308 and Xerox Corporation.

  13. Structural and Functional Plasticity in the Maternal Brain Circuitry

    ERIC Educational Resources Information Center

    Pereira, Mariana

    2016-01-01

    Parenting recruits a distributed network of brain structures (and neuromodulators) that coordinates caregiving responses attuned to the young's affect, needs, and developmental stage. Many of these structures and connections undergo significant structural and functional plasticity, mediated by the interplay between maternal hormones and social…

  14. Qualitative study of patients’ decision-making when accepting second-line treatment after failure of first-line chemotherapy

    PubMed Central

    Roch, Benoît; Roth, Caroline; Mérel, Jean-Pierre

    2018-01-01

    Objective Treatment failures in advanced lung cancer are frequent events affecting patients during or after first-line chemotherapy. International guidelines recommend second-line chemotherapy. However, around one half of patients who experience disease progression enter a systemic second-line therapy. In the herein qualitative study, we investigated patients' thoughts and attitudes determining the decision to undergo a second-line chemotherapy. Methods Thirty-three purposively selected patients who recently accepted second-line or palliative chemotherapy were invited to participate in this survey consisting of semi-structured in-depth interviews. Grounded theory was applied to investigate participants’ perceptions of the context that have surrounded their decision to undergo palliative chemotherapy. Results For most patients, tumor burden and reduced quality of life in relation with lung cancer itself were major drivers of the decision-making process. There was a balance between two different attitudes: making a decision to undergo a new line of chemotherapy or starting a psychological process in order to accept end of life. Choosing between these two attitudes allowed the patient to keep the matter of palliative care at a distance. Even in case of low chance of success, many patients who worried about their life partner's future would accept a new chemotherapy line. Some patients experienced ambivalent thoughts regarding social network, particularly about their family as daily function impairment required an increased need for relative's support. The initial "Worrying about others" thoughts left place to in an increasing self-need of care as those provided by relatives; this phenomenon might increase patients' self- perception of being a burden for others. Confidence previously established with formal caregiver support was another major decision driver: some patients with sustained confidence in their medical staff may have privileged this formal support rather than family support when the latter was perceived as weak, insufficient or intrusive. Conclusion This study identified three domains involved into a complex interplay for lung cancer patients’ decision regarding second-line palliative chemotherapy: (i) perception of the definitive loss of health, (ii) interactions between idiosyncrasy (hope, disease burden) and environment (healthcare and social network support), and (iii) patient's subjective evaluation of chemotherapy benefit–risk. PMID:29799879

  15. Study of improved modeling and solution procedures for nonlinear analysis. [aircraft-like structures

    NASA Technical Reports Server (NTRS)

    Kamat, M. P.

    1979-01-01

    An evaluation of the ACTION computer code on an aircraft like structure is presented. This computer program proved adequate in predicting gross response parameters in structures which undergo severe localized cross sectional deformations.

  16. National survey of the current management of endometriomas in women undergoing assisted reproductive treatment.

    PubMed

    Raffi, F; Shaw, R W; Amer, S A

    2012-09-01

    What is the current management of women with ovarian endometriomas undergoing assisted reproductive treatment (ART) in the UK? It appears that the majority of gynaecologists in the UK offer surgery (mostly cystectomy) for endometriomas prior to ART, regardless of the presence of symptoms. The ideal management of endometriomas in women undergoing ART remains controversial and presents a dilemma to reproductive specialists. This was a national cross-sectional survey. A total of 388 gynaecologists completed the questionnaire. All clinicians fully registered with the Royal College of Obstetricians and Gynaecologists were contacted. An 11-item survey was administered electronically using Survey Monkey software. Quantitative data were analysed using descriptive and comparative statistics. The majority of responders were consultants (65%), 25% practiced ART and 65% performed laparoscopic surgery. Overall, 95% of responders would offer surgery for endometriomas in women undergoing ART, either on the basis of the size (>3-5 cm) of the endometrioma (52%), the presence of symptoms (16%), the presence of multiple/bilateral endometriomas (2%), regardless of the size and symptoms (19%) or only to women undergoing IVF (6%). The remaining 5% of responders would not offer surgery before ART. Excision was the most common surgical modality (68%), followed by ablation (25%). Laparoscopic surgeons were almost twice as likely to 'offer surgery to all patients with endometriomas prior to ART' compared with clinicians performing laparotomy (22 versus 12%, P < 0.001). Our overall response rate, with answers to the questionnaire, was low (15%). However, the response rate amongst reproductive specialists was estimated at 60%. It is possible that there might have been an element of bias towards over-representation of responders who are more concerned about 'normalization' of the pelvic anatomy. Furthermore, our survey relied on self-reporting of practice and it is possible that being presented with a list of 'ideal' options may have resulted in respondent bias. Despite the available evidence that surgery for endometriomas does not improve the outcome of ART and may damage ovarian reserve, it seems that the majority of gynaecologists in the UK offer ovarian cystectomy to their patients.

  17. Preoperative oral carbohydrate therapy.

    PubMed

    Nygren, Jonas; Thorell, Anders; Ljungqvist, Olle

    2015-06-01

    Management of the postoperative response to surgical stress is an important issue in major surgery. Avoiding preoperative fasting using preoperative oral carbohydrates (POC) has been suggested as a measure to prevent and reduce the extent to which such derangements occur. This review summarizes the current evidence and rationale for this treatment. A recent review from the Cochrane Collaboration reports enhanced gastrointestinal recovery and shorter hospital stay with the use of POC with no effect on postoperative complication rates. Multiple randomized controlled trials demonstrate improved postoperative metabolic response after POC administration, including reduced insulin resistance, protein sparing, improved muscle function and preserved immune response. Cohort studies in patients undergoing major abdominal surgery have shown that the use of POC as part of an enhanced recovery after surgery protocol is a significant predictor for improved clinical outcomes. Avoiding preoperative fasting with POC is associated with attenuated postoperative insulin resistance, improved metabolic response, enhanced perioperative well-being, and better clinical outcomes. The impact is greatest for patients undergoing major surgeries.

  18. Assessing infertility-related stress: the factor structure of the Fertility Problem Inventory in Italian couples undergoing infertility treatment.

    PubMed

    Donarelli, Zaira; Gullo, Salvatore; Lo Coco, Gianluca; Marino, Angelo; Scaglione, Piero; Volpes, Aldo; Allegra, Adolfo

    2015-01-01

    The factor structure of the Fertility Problem Inventory (FPI) and its invariance across gender were examined in Italian couples undergoing infertility treatment. About 1000 subjects (both partners of 500 couples) completed two questionnaires prior to commencing infertility treatment at a private Clinic in Palermo, Italy. Confirmatory Factor Analysis demonstrated that the original factor structure of the FPI was partially confirmed. Two correlated factors (Infertility Life Domains and Importance of Parenthood) were obtained via a post hoc Exploratory Factor Analysis. Finally, the invariance of this factor structure across gender was confirmed. The study supported the relevance of two interrelated factors specific to infertility stress which could help clinicians to focus on the core infertility-related stress domains of infertile couples.

  19. Does omphalocele major undergo spontaneous closure?

    PubMed Central

    Emordi, Victor C.; Osifo, David O.

    2017-01-01

    Abstract The early surgical management of omphalocele major in Africa predisposes neonates to surgical complications which are often worsened by the presence of associated anomalies. Conservative management using available escharotics results in early skin cover by secondary wound healing. This delays the need for fascial closure and avoids neonatal surgical risks thus improving survival. We present a case of omphalocele major that underwent spontaneous closure during conservative management with honey dressing without surgical intervention. PMID:28928917

  20. WebCT: A Major Shift of Emphasis

    ERIC Educational Resources Information Center

    Morningstar, Barbara; Schubert, Jeremy; Thibeault, Kristine

    2004-01-01

    The evaluation reports in this series usually feature several products at once. The current review, however, comes at a time when one of the most widely used (and expensive) online learning management systems is undergoing a major change in its marketing strategy and corporate focus. "WebCT" is currently evolving to a new version ("WebCT Vista"),…

  1. Clinical decision making by nurses when faced with third-space fluid shift. How well do they fare?

    PubMed

    Redden, M; Wotton, K

    2001-01-01

    Nurses' use of knowledge, the connection of this knowledge to treatment decisions and information actually used to reach such decisions, delineates nurses' level of expertise. Previous research has shown that nurses in their clinical decision-making use the hypothetico-deductive method and intuitive judgment or pattern recognition. This interpretive study explored experienced critical care nurses' (n = 5) and gastrointestinal surgical nurses' (n = 5) clinical decision-making processes through ascertaining their knowledge and understanding of third-space fluid shift in elderly patients undergoing major gastrointestinal surgery. Both groups of nurses, because of their experience with elderly patients undergoing gastrointestinal surgery, were assumed to be experts. Data collection techniques included semi-structured interviews and the use of think aloud protocol for clinical scenario analysis. The findings demonstrated that the gastrointestinal surgical nurses used the hypothetico-deductive method to recognize critical cues and the existence of a problem but could not name the problem. The critical care nurses, on the other hand, used a combination of the hypothetico-deductive method and pattern recognition as a basis for identification of critical cues. The critical care nurses also possessed in depth knowledge of third-space fluid shift and were able to use pivotal cues to identify the actual phenomenon. Ultimately, it would appear that the structure of critical care nurses' work, their increased educational qualifications and the culture of the critical care unit promote a more proactive approach to reasoning in the physiological domain. The findings have implications for the development of practice guidelines and curriculum development in both tertiary and continuing nurse education.

  2. SELECTIVE ADVANTAGE OF RECOMBINATION IN EVOLVING PROTEIN POPULATIONS: A LATTICE MODEL STUDY

    PubMed Central

    WILLIAMS, PAUL D.; POLLOCK, DAVID D.

    2010-01-01

    Recent research has attempted to clarify the contributions of several mutational processes, such as substitutions or homologous recombination. Simplistic, tractable protein models, which determine the compact native structure phenotype from the sequence genotype, are well-suited to such studies. In this paper, we use a lattice-protein model to examine the effects of point mutation and homologous recombination on evolving populations of proteins. We find that while the majority of mutation and recombination events are neutral or deleterious, recombination is far more likely to be beneficial. This results in a faster increase in fitness during evolution, although the final fitness level is not significantly changed. This transient advantage provides an evolutionary advantage to subpopulations that undergo recombination, allowing fixation of recombination to occur in the population. PMID:25473139

  3. Navigation in head and neck oncological surgery: an emerging concept.

    PubMed

    Gangloff, P; Mastronicola, R; Cortese, S; Phulpin, B; Sergeant, C; Guillemin, F; Eluecque, H; Perrot, C; Dolivet, G

    2011-01-01

    Navigation surgery, initially applied in rhinology, neurosurgery and orthopaedic cases, has been developed over the last twenty years. Surgery based on computed tomography data has become increasingly important in the head and neck region. The technique for hardware fusion between RMI and computed tomography is also becoming more useful. We use such device since 2006 in head and neck carcinologic situation. Navigation allows control of the resection in order to avoid and protect the precise anatomical structures (vessels and nerves). It also guides biopsy and radiofrequency. Therefore, quality of life is much more increased and morbidity is decreased for these patients who undergo major and mutilating head and neck surgery. Here we report the results of 33 navigation procedures performed for 31 patients in our institution.

  4. KSC-99pc0193

    NASA Image and Video Library

    1999-02-10

    In the Vertical Processing Facility (VPF), workers keep watch on the crane lifting the shrouded Chandra X-ray Observatory to a vertical position. The telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  5. KSC-99pc0172

    NASA Image and Video Library

    1999-02-08

    Inside the Vertical Processing Facility (VPF), the overhead crane lifts Chandra X-ray Observatory completely out of its protective container. While in the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  6. KSC-99pc0194

    NASA Image and Video Library

    1999-02-10

    In the Vertical Processing Facility (VPF), workers guide the final stages as the overhead crane lifts the shrouded Chandra X-ray Observatory to a vertical position. The telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  7. KSC-99pc0196

    NASA Image and Video Library

    1999-02-10

    In the Vertical Processing Facility (VPF), workers move the shrouded Chandra X-ray Observatory on its workstand to the scaffolding behind it. The telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  8. KSC-99pc0170

    NASA Image and Video Library

    1999-02-08

    Inside the Vertical Processing Facility (VPF), workers check the overhead cable that will lift the Chandra X-ray Observatory out of its protective container. While in the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  9. KSC-99pc0169

    NASA Image and Video Library

    1999-02-08

    Inside the Vertical Processing Facility (VPF), workers attach the overhead cable to the Chandra X-ray Observatory to lift it out of its protective container. While in the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  10. KSC-99pc0192

    NASA Image and Video Library

    1999-02-10

    In the Vertical Processing Facility (VPF), workers watch as the overhead crane starts lifting the shrouded Chandra X-ray Observatory to a vertical position. The telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  11. KSC-99pc0171

    NASA Image and Video Library

    1999-02-08

    Inside the Vertical Processing Facility (VPF), workers begin lifting the Chandra X-ray Observatory out of its protective container. While in the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  12. Analysis of the thermal reaction products of para polyphenylene by combined gas chromatography-mass spectrometry

    NASA Technical Reports Server (NTRS)

    Fewell, L. L.

    1976-01-01

    Analysis of the volatiles and sublimate produced when para-polyphenylene is pyrolyzed to constant weight under vacuum in the temperature range from 380 to 1000 C indicates that the polymer undergoes thermal degradation in two stages. The first stage involved dehydrohalogenation, which is essentially a curing reaction that produces crosslinking between polyphenylene chains resulting from the loss of chlorine from the polymer in the form of hydrogen chloride. The second stage of the thermal degradation is dehydrogenation because hydrogen is the major volatile species. Increasing amounts of polycyclic aromatic hydrocarbons (phenanthrene and 9, 10 benzphenanthrene) in the sublimate, concomitant with increasing C/H ratios of the polymeric residue with pyrolysis temperature, is consistent with the buildup of polynuclear structures in the polymer matrix.

  13. Selective Advantage of Recombination in Evolving Protein Populations:. a Lattice Model Study

    NASA Astrophysics Data System (ADS)

    Williams, Paul D.; Pollock, David D.; Goldstein, Richard A.

    Recent research has attempted to clarify the contributions of several mutational processes, such as substitutions or homologous recombination. Simplistic, tractable protein models, which determine the compact native structure phenotype from the sequence genotype, are well-suited to such studies. In this paper, we use a lattice-protein model to examine the effects of point mutation and homologous recombination on evolving populations of proteins. We find that while the majority of mutation and recombination events are neutral or deleterious, recombination is far more likely to be beneficial. This results in a faster increase in fitness during evolution, although the final fitness level is not significantly changed. This transient advantage provides an evolutionary advantage to subpopulations that undergo recombination, allowing fixation of recombination to occur in the population.

  14. The economic implications of a multimodal analgesic regimen for patients undergoing major orthopedic surgery: a comparative study of direct costs.

    PubMed

    Duncan, Christopher M; Hall Long, Kirsten; Warner, David O; Hebl, James R

    2009-01-01

    Total knee and total hip arthoplasty (THA) are 2 of the most common surgical procedures performed in the United States and represent the greatest single Medicare procedural expenditure. This study was designed to evaluate the economic impact of implementing a multimodal analgesic regimen (Total Joint Regional Anesthesia [TJRA] Clinical Pathway) on the estimated direct medical costs of patients undergoing lower extremity joint replacement surgery. An economic cost comparison was performed on Mayo Clinic patients (n = 100) undergoing traditional total knee or total hip arthroplasty using the TJRA Clinical Pathway. Study patients were matched 1:1 with historical controls undergoing similar procedures using traditional anesthetic (non-TJRA) techniques. Matching criteria included age, sex, surgeon, type of procedure, and American Society of Anesthesiologists (ASA) physical status (PS) classification. Hospital-based direct costs were collected for each patient and analyzed in standardized inflation-adjusted constant dollars using cost-to-charge ratios, wage indexes, and physician services valued using Medicare reimbursement rates. The estimated mean direct hospital costs were compared between groups, and a subgroup analysis was performed based on ASA PS classification. The estimated mean direct hospital costs were significantly reduced among TJRA patients when compared with controls (cost difference, 1999 dollars; 95% confidence interval, 584-3231 dollars; P = 0.0004). A significant reduction in hospital-based (Medicare Part A) costs accounted for the majority of the total cost savings. Use of a comprehensive, multimodal analgesic regimen (TJRA Clinical Pathway) in patients undergoing lower extremity joint replacement surgery provides a significant reduction in the estimated total direct medical costs. The reduction in mean cost is primarily associated with lower hospital-based (Medicare Part A) costs, with the greatest overall cost difference appearing among patients with significant comorbidities (ASA PS III-IV patients).

  15. Femoral Access PCI in a Default Radial Center Identifies High-Risk Patients With Poor Outcomes.

    PubMed

    Uddin, Muezz; Bundhoo, Shantu; Mitra, Rito; Ossei-Gerning, Nicholas; Morris, Keith; Anderson, Richard; Kinnaird, Tim

    2015-10-01

    Increasingly the trans-radial route (TRR) is preferred over the trans-femoral route (TFR) for PCI. However, even in high volume default TRR centers a cohort of patients undergo TFR PCI. We examined the demographics, procedural characteristics, and outcomes of patients undergoing PCI via the TF. The patient demographics, procedural data, and outcomes of 5,379 consecutive patients undergoing PCI at a default radial center between 2009 and 2012 were examined. Major bleeding (MB) was classified by ACUITY and BARC definitions. A total of 559 (10.4%) patients underwent PCI via the TFR and 4,820 patients via the TRR (89.6%). Baseline variables associated with TFR were shock, previous CABG, chronic total occlusion intervention, rotablation/laser use, female sex, and renal failure. Sixty-five patients of the TFR cohort (11.6%) experienced MB with 27 (41.5%) being access site related. MB was significantly more frequent than in the radial cohort. The variables independently associated with MB in the TFR cohort were renal failure, acute presentation, shock, and age. In the TFR, patients with MB mortality was high at 30 days (17.2% vs 2.6% for no MB, P < 0.0001) and at 1 year (37.6% vs 5.0%, P < 0.0001). Shock and MB were highly predictive of 30 day and 12 month mortality. In a default radial PCI center 10% of patients undergo PCI via the femoral artery. These patients have high baseline bleeding risk and undergo complex interventions. As a result the incidence of major bleeding, transfusion and death are high. Alternative strategies are required to optimize outcomes in this select group. © 2015, Wiley Periodicals, Inc.

  16. Flavonoids: hemisynthesis, reactivity, characterization and free radical scavenging activity.

    PubMed

    Es-Safi, Nour-Eddine; Ghidouche, Souhila; Ducrot, Paul Henri

    2007-09-26

    Phenolic compounds form one of the main classes of secondary metabolites. They display a large range of structures and they are responsible for the major organoleptic characteristics of plant-derived-foods and beverages, particularly color and taste properties and they also contribute to the nutritional qualities of fruits and vegetables. Phenolic compounds are also highly unstable compounds which undergo numerous enzymatic and chemical reactions during postharvest food storage and processing thus adding to the complexity of plant polyphenol composition. Among these compounds flavonoids constitute one of the most ubiquitous groups of all plant phenolics. Owing to their importance in food organoleptic properties and in human health, a better understanding of their structures, their reactivity and chemical properties in addition to the mechanisms generating them appears essential to predict and control food quality. The purpose of this work is an overview of our findings concerning the hemisynthesis, the reactivity and the enzymatic oxidation of some flavonoids and shed light on the mechanisms involved in some of these processes and the structures of the resulting products. The free radical scavenging activity of some of the synthesized compounds is also presented and a structure-activity relationship is discussed. The first part of this review concerns the synthesis and structural characterization of modified monomeric flavanols. The use of these compounds as precursor for the preparation of natural and modified dimeric procyanidin derivatives was then explored through different coupling reactions. The full characterization of the synthesized compounds was achieved by concerted use of NMR and ESI-MS techniques. The free radical scavenging activity of some of the synthesized compounds was investigated. The second part of this review concerns the enzymatic oxidation of several flavonols by Trametes versicolor laccase. Most of the major oxidation products have been isolated as pure compounds and their structures unambiguously established through spectroscopic methods. Correlation between the structure of the oxidation product and the substitution pattern of the starting materials allows mechanistic features of this transformation to be elucidated.

  17. Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 2: changes in spermatid organelles associated with development of spermatozoa.

    PubMed

    Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

    2010-04-01

    Spermiogenesis is a long process whereby haploid spermatids derived from the meiotic divisions of spermatocytes undergo metamorphosis into spermatozoa. It is subdivided into distinct steps with 19 being identified in rats, 16 in mouse and 8 in humans. Spermiogenesis extends over 22.7 days in rats and 21.6 days in humans. In this part, we review several key events that take place during the development of spermatids from a structural and functional point of view. During early spermiogenesis, the Golgi apparatus forms the acrosome, a lysosome-like membrane bound organelle involved in fertilization. The endoplasmic reticulum undergoes several topographical and structural modifications including the formation of the radial body and annulate lamellae. The chromatoid body is fully developed and undergoes structural and functional modifications at this time. It is suspected to be involved in RNA storing and processing. The shape of the spermatid head undergoes extensive structural changes that are species-specific, and the nuclear chromatin becomes compacted to accommodate the stream-lined appearance of the sperm head. Microtubules become organized to form a curtain or manchette that associates with spermatids at specific steps of their development. It is involved in maintenance of the sperm head shape and trafficking of proteins in the spermatid cytoplasm. During spermiogenesis, many genes/proteins have been implicated in the diverse dynamic events occurring at this time of development of germ cells and the absence of some of these have been shown to result in subfertility or infertility. Copyright 2009 Wiley-Liss, Inc.

  18. Preconditioning Shields Against Vascular Events in Surgery (SAVES), a multicentre feasibility trial of preconditioning against adverse events in major vascular surgery: study protocol for a randomised control trial.

    PubMed

    Healy, Donagh; Clarke-Moloney, Mary; Gaughan, Brendan; O'Daly, Siobhan; Hausenloy, Derek; Sharif, Faisal; Newell, John; O'Donnell, Martin; Grace, Pierce; Forbes, John F; Cullen, Walter; Kavanagh, Eamon; Burke, Paul; Cross, Simon; Dowdall, Joseph; McMonagle, Morgan; Fulton, Greg; Manning, Brian J; Kheirelseid, Elrasheid A H; Leahy, Austin; Moneley, Daragh; Naughton, Peter; Boyle, Emily; McHugh, Seamus; Madhaven, Prakash; O'Neill, Sean; Martin, Zenia; Courtney, Donal; Tubassam, Muhammed; Sultan, Sherif; McCartan, Damian; Medani, Mekki; Walsh, Stewart

    2015-04-23

    Patients undergoing vascular surgery procedures constitute a 'high-risk' group. Fatal and disabling perioperative complications are common. Complications arise via multiple aetiological pathways. This mechanistic redundancy limits techniques to reduce complications that target individual mechanisms, for example, anti-platelet agents. Remote ischaemic preconditioning (RIPC) induces a protective phenotype in at-risk tissue, conferring protection against ischaemia-reperfusion injury regardless of the trigger. RIPC is induced by repeated periods of upper limb ischaemia-reperfusion produced using a blood pressure cuff. RIPC confers some protection against cardiac and renal injury during major vascular surgery in proof-of-concept trials. Similar trials suggest benefit during cardiac surgery. Several uncertainties remain in advance of a full-scale trial to evaluate clinical efficacy. We propose a feasibility trial to fully evaluate arm-induced RIPC's ability to confer protection in major vascular surgery, assess the incidence of a proposed composite primary efficacy endpoint and evaluate the intervention's acceptability to patients and staff. Four hundred major vascular surgery patients in five Irish vascular centres will be randomised (stratified for centre and procedure) to undergo RIPC or not immediately before surgery. RIPC will be induced using a blood pressure cuff with four cycles of 5 minutes of ischaemia followed by 5 minutes of reperfusion immediately before the start of operations. There is no sham intervention. Participants will undergo serum troponin measurements pre-operatively and 1, 2, and 3 days post-operatively. Participants will undergo 12-lead electrocardiograms pre-operatively and on the second post-operative day. Predefined complications within one year of surgery will be recorded. Patient and staff experiences will be explored using qualitative techniques. The primary outcome measure is the proportion of patients who develop elevated serum troponin levels in the first 3 days post-operatively. Secondary outcome measures include length of hospital and critical care stay, unplanned critical care admissions, death, myocardial infarction, stroke, mesenteric ischaemia and need for renal replacement therapy (within 30 days of surgery). RIPC is novel intervention with the potential to significantly improve perioperative outcomes. This trial will provide the first evaluation of RIPC's ability to reduce adverse clinical events following major vascular surgery. www.clinicaltrials.gov NCT02097186 Date Registered: 24 March 2014.

  19. Tapered structure construction

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

    Smith, Eric D.; Takata, Rosalind K.; Slocum, Alexander H.

    Feeding stock used to form a tapered structure into a curving device such that each point on the stock undergoes rotational motion about a peak location of the tapered structure; and the stock meets a predecessor portion of stock along one or more adjacent edges.

  20. Anesthetic Considerations in Patients Undergoing Bariatric Surgery: A Review Article

    PubMed Central

    Soleimanpour, Hassan; Safari, Saeid; Sanaie, Sarvin; Nazari, Mehdi; Alavian, Seyed Moayed

    2017-01-01

    Context This article discusses the anesthetic considerations in patients undergoing bariatric surgery in the preoperative, intraoperative, and postoperative phases of surgery. Evidence Acquisition This review includes studies involving obese patients undergoing bariatric surgery. Searches have been conducted in PubMed, MEDLINE, EMBASE, Google Scholar, Scopus, and Cochrane Database of Systematic Review using the terms obese, obesity, bariatric, anesthesia, perioperative, preoperative, perioperative, postoperative, and their combinations. Results Obesity is a major worldwide health problem associated with many comorbidities. Bariatric surgery has been proposed as the best alternative treatment for extreme obese patients when all other therapeutic options have failed. Conclusions Anesthetists must completely assess the patients before the surgery to identify anesthesia- related potential risk factors and prepare for management during the surgery. PMID:29430407

  1. Electrical impedance tomography during major open upper abdominal surgery: a pilot-study

    PubMed Central

    2014-01-01

    Background Electrical impedance tomography (EIT) of the lungs facilitates visualization of ventilation distribution during mechanical ventilation. Its intraoperative use could provide the basis for individual optimization of ventilator settings, especially in patients at risk for ventilation-perfusion mismatch and impaired gas exchange, such as patients undergoing major open upper abdominal surgery. EIT throughout major open upper abdominal surgery could encounter difficulties in belt positioning and signal quality. Thus, we conducted a pilot-study and tested whether EIT is feasible in patients undergoing major open upper abdominal surgery. Methods Following institutional review board’s approval and written informed consent, we included patients scheduled for major open upper abdominal surgery of at least 3 hours duration. EIT measurements were conducted prior to intubation, at the time of skin incision, then hourly during surgery until shortly prior to extubation and after extubation. Number of successful intraoperative EIT measurements and reasons for failures were documented. From the valid measurements, a functional EIT image of changes in tidal impedance was generated for every time point. Regions of interest were defined as horizontal halves of the picture. Monitoring of ventilation distribution was assessed using the center of ventilation index, and also using the total and dorsal ventilated lung area. All parameter values prior to and post intubation as well as extubation were compared. A p < 0.05 was considered statistically significant. Results A total of 120 intraoperative EIT measurements during major abdominal surgery lasting 4-13 hours were planned in 14 patients. The electrode belt was attached between the 2nd and 4th intercostal space. Consecutive valid measurements could be acquired in 13 patients (93%). 111 intraoperative measurements could be retrieved as planned (93%). Main obstacle was the contact of skin electrodes. Despite the high belt position, distribution of tidal volume showed a significant shift of ventilation towards ventral lung regions after intubation. This was reversed after weaning from mechanical ventilation. Conclusions Despite a high belt position, monitoring of ventilation distribution is feasible in patients undergoing major open upper abdominal surgery lasting from 4 to 13 hours. Therefore, further interventional trials in order to optimize ventilatory management should be initiated. PMID:25018668

  2. Structural Insights of Glucan Phosphatase Dynamics using Amide Hydrogen/Deuterium Exchange Mass Spectrometry

    PubMed Central

    Hsu, Simon; Kim, Youngjun; Li, Sheng; Durrant, Eric S.; Pace, Rachel M.; Woods, Virgil L.; Gentry, Matthew S.

    2009-01-01

    Laforin and Starch Excess 4 (SEX4) are founding members of a class of phosphatases that dephosphorylate phosphoglucans. Each protein contains a carbohydrate binding module (CBM) and a dual specificity phosphatase (DSP) domain. The gene encoding laforin is mutated in a fatal neurodegenerative disease called Lafora disease (LD). In the absence of laforin function, insoluble glucans accumulate that are hyperphosphorylated and exhibit sparse branching. It is hypothesized that these accumulations trigger the neurodegeneration and premature death of LD patients. We recently demonstrated that laforin removes phosphate from phosphoglucans and hypothesized that this function inhibits insoluble glucan accumulation. Loss of SEX4 function in plants yields a similar cellular phenotype; cells accumulate an excess amount of insoluble, hyperphosphorylated glucans. While multiple groups have shown that these phosphatases dephosphorylate phosphoglucans, there is no structure of a glucan phosphatase and little is known about the mechanism whereby they perform this action. We utilized hydrogen-deuterium exchange mass spectrometry (DXMS) and structural modeling to probe the conformational and structural dynamics of the glucan phosphatase SEX4. We found that the enzyme does not undergo a global conformational change upon glucan binding, but instead undergoes minimal rearrangement upon binding. The CBM undergoes increased protection from deuteration when bound to glucans, confirming its role in glucan binding. More interestingly, we identified structural components of the DSP that also undergo increased protection from deuteration upon glucan addition. To determine the position of these regions, we generated a homology model of the SEX4 DSP. The homology model shows that all of these regions are adjacent the DSP active site. Therefore, our results suggest that these regions of the DSP participate in presenting the phosphoglucan to the active site and provide the first structural analysis and mode of action of this unique class of phosphatases. PMID:19754155

  3. UV-damaged DNA binding protein-1 and de-etiolated-1 regulate golden 2-like transcription factor by assembling a cullin 4-based ubiquitin ligase in tomato

    USDA-ARS?s Scientific Manuscript database

    Fleshy fruit undergo a novel developmental program that ends in the irreversible process of ripening and eventual tissue senescence. During these maturation processes, fruit undergo numerous physiological, biochemical and structural alterations, making them more attractive to seed dispersal organism...

  4. A randomized trial of therapies for type 2 diabetes and coronary artery disease.

    PubMed

    Frye, Robert L; August, Phyllis; Brooks, Maria Mori; Hardison, Regina M; Kelsey, Sheryl F; MacGregor, Joan M; Orchard, Trevor J; Chaitman, Bernard R; Genuth, Saul M; Goldberg, Suzanne H; Hlatky, Mark A; Jones, Teresa L Z; Molitch, Mark E; Nesto, Richard W; Sako, Edward Y; Sobel, Burton E

    2009-06-11

    Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established. We randomly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. Primary end points were the rate of death and a composite of death, myocardial infarction, or stroke (major cardiovascular events). Randomization was stratified according to the choice of percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) as the more appropriate intervention. At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin-provision group (9.2%) than in the insulin-sensitization group (5.9%, P=0.003). Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision. (ClinicalTrials.gov number, NCT00006305.) 2009 Massachusetts Medical Society

  5. Single molecule analysis of Thermus thermophilus SSB protein dynamics on single-stranded DNA.

    PubMed

    Zhang, Jichuan; Zhou, Ruobo; Inoue, Jin; Mikawa, Tsutomu; Ha, Taekjip

    2014-04-01

    Single-stranded (ss) DNA binding (SSB) proteins play central roles in DNA replication, recombination and repair in all organisms. We previously showed that Escherichia coli (Eco) SSB, a homotetrameric bacterial SSB, undergoes not only rapid ssDNA-binding mode transitions but also one-dimensional diffusion (or migration) while remaining bound to ssDNA. Whereas the majority of bacterial SSB family members function as homotetramers, dimeric SSB proteins were recently discovered in a distinct bacterial lineage of extremophiles, the Thermus-Deinococcus group. Here we show, using single-molecule fluorescence resonance energy transfer (FRET), that homodimeric bacterial SSB from Thermus thermophilus (Tth) is able to diffuse spontaneously along ssDNA over a wide range of salt concentrations (20-500 mM NaCl), and that TthSSB diffusion can help transiently melt the DNA hairpin structures. Furthermore, we show that two TthSSB molecules undergo transitions among different DNA-binding modes while remaining bound to ssDNA. Our results extend our previous observations on homotetrameric SSBs to homodimeric SSBs, indicating that the dynamic features may be shared among different types of SSB proteins. These dynamic features of SSBs may facilitate SSB redistribution and removal on/from ssDNA, and help recruit other SSB-interacting proteins onto ssDNA for subsequent DNA processing in DNA replication, recombination and repair.

  6. The influence of dispositional optimism on decision regret to undergo major breast reconstructive surgery.

    PubMed

    Zhong, Toni; Bagher, Shaghayegh; Jindal, Kunaal; Zeng, Delong; O'Neill, Anne C; MacAdam, Sheina; Butler, Kate; Hofer, Stefan O P; Pusic, Andrea; Metcalfe, Kelly A

    2013-12-01

    It is not known if optimism influences regret following major reconstructive breast surgery. We examined the relationship between dispositional optimism, major complications and decision regret in patients undergoing microsurgical breast reconstruction. A consecutive series of 290 patients were surveyed. Independent variables were: (1) dispositional optimism and (2) major complications. The primary outcome was Decision Regret. A multivariate regression analysis determined the relationship between the independent variables, confounders and decision regret. Of the 181 respondents, 63% reported no regret after breast reconstruction, 26% had mild regret, and 11% moderate to severe regret. Major complications did not have a significant effect on decision regret, and the impact of dispositional optimism was not significant in Caucasian women. There was a significant effect in non-Caucasian women with less optimism who had significantly higher levels of mild regret 1.36 (CI 1.02-1.97) and moderate to severe regret 1.64 (CI 1.0-93.87). This is the first paper to identify a subgroup of non-Caucasian patients with low dispositional optimism who may be at risk for developing regret after microsurgical breast reconstruction. Possible strategies to ameliorate regret may involve addressing cultural and language barriers, setting realistic expectations, and providing more support during the pre-operative decision-making phase. © 2013 Wiley Periodicals, Inc.

  7. Predicting Precession Rates from Secular Dynamics for Extra-solar Multi-planet Systems

    NASA Astrophysics Data System (ADS)

    Van Laerhoven, Christa

    2015-12-01

    Considering the secular dynamics of multi-planet systems provides substantial insight into the interactions between planets in those systems. Secular interactions are those that don't involve knowing where a planet is along its orbit, and they dominate when planets are not involved in mean motion resonances. These interactions exchange angular momentum among the planets, evolving their eccentricities and inclinations. To second order in the planets' eccentricities and inclinations, the eccentricity and inclination perturbations are decoupled. Given the right variable choice, the relevant differential equations are linear and thus the eccentricity and inclination behaviors can be described as a sum of eigenmodes. Since the underlying structure of the secular eigenmodes can be calculated using only the planets' masses and semi-major axes, one can elucidate the eccentricity and inclination behavior of planets in exoplanet systems even without knowing the planets' current eccentricities and inclinations. I have calculated both the eccentricity and inclination secular eigenmodes for the population of known multi-planet systems whose planets have well determined masses and periods and have used this to predict what range of pericenter precession (and nodal regression) rates the planets may have. One might have assumed that in any given system the planets with shorter periods would have faster precession rates, but I show that this is not necessarily the case. Planets that are 'loners' have narrow ranges of possible precession rates, while planets that are 'groupies' can have a wider range of possible precession rates. Several planets are expected to undergo significant precession on few-year timescales and many planets (though not the majority of planets) will undergo significant precession on decade timescales.

  8. Potential impacts of global warming on the diversity and distribution of stream insects in South Korea.

    PubMed

    Li, Fengqing; Kwon, Yong-Su; Bae, Mi-Jung; Chung, Namil; Kwon, Tae-Sung; Park, Young-Seuk

    2014-04-01

    Globally, the East Asian monsoon region is one of the richest environments in terms of biodiversity. The region is undergoing rapid human development, yet its river ecosystems have not been well studied. Global warming represents a major challenge to the survival of species in this region and makes it necessary to assess and reduce the potential consequences of warming on species of conservation concern. We projected the effects of global warming on stream insect (Ephemeroptera, Odonata, Plecoptera, and Trichoptera [EOPT]) diversity and predicted the changes of geographical ranges for 121 species throughout South Korea. Plecoptera was the most sensitive (decrease of 71.4% in number of species from the 2000s through the 2080s) order, whereas Odonata benefited (increase of 66.7% in number of species from the 2000s through the 2080s) from the effects of global warming. The impact of global warming on stream insects was predicted to be minimal prior to the 2060s; however, by the 2080s, species extirpation of up to 20% in the highland areas and 2% in the lowland areas were predicted. The projected responses of stream insects under global warming indicated that species occupying specific habitats could undergo major reductions in habitat. Nevertheless, habitat of 33% of EOPT (including two-thirds of Odonata and one-third of Ephemeroptera, Plecoptera, and Trichoptera) was predicted to increase due to global warming. The community compositions predicted by generalized additive models varied over this century, and a large difference in community structure in the highland areas was predicted between the 2000s and the 2080s. However, stream insect communities, especially Odonata, Plecoptera, and Trichoptera, were predicted to become more homogenous under global warming. © 2013 Society for Conservation Biology.

  9. Exercise induced left bundle branch block in isotopic exercise test. Findings and prognostic value.

    PubMed

    Gomez, M V; Lorente Castro, B C; Jané, P; García-Zoghby, L; Martínez-Lorca, A; Pérez, J A

    2018-04-18

    Exercise-induced left bundle branch block (EI-LBBB) is a rare circumstance of unknown significance. The purpose of this paper is to describe the scintigraphic features and the prognostic value of this finding. We reviewed the features of 1,885 patients who had visited our department to undergo GATED-SPECT ergometry to diagnose ischaemic heart disease. Seven patients showed EI-LBBB throughout the exercise testing. Coronary angiography was performed in 4 of them. Patients were followed-up over an average period of time of 30±8 months. The onset of major cardiovascular events was recorded during the follow-up period. The prevalence of EI-LBBB was 0.37%. Six out of 7 patients were women. Myocardial function and perfusion were normal in 3 patients. Three patients had fixed perfusion defects and one patient had a reversible defect. Two out of the 4 patients showing perfusion defects presented a moderate-severe decrease of the left ventricular ejection fraction. None of the 4 patients with perfusion defects were found to have coronary disease on coronary angiography. The prevalence of EI-LBBB among the patients that came to undergo GATED-SPECT ergometry was very low. The finding was more frequent in women. In our series, 2 patients presented non-ischaemic structural heart disease, but no patient was diagnosed with coronary artery disease. In our patients the presence of EI-LBBB did not relate to a greater risk of experiencing a major cardiovascular event. Copyright © 2018 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Human auditory evoked potentials in the assessment of brain function during major cardiovascular surgery.

    PubMed

    Rodriguez, Rosendo A

    2004-06-01

    Focal neurologic and intellectual deficits or memory problems are relatively frequent after cardiac surgery. These complications have been associated with cerebral hypoperfusion, embolization, and inflammation that occur during or after surgery. Auditory evoked potentials, a neurophysiologic technique that evaluates the function of neural structures from the auditory nerve to the cortex, provide useful information about the functional status of the brain during major cardiovascular procedures. Skepticism regarding the presence of artifacts or difficulty in their interpretation has outweighed considerations of its potential utility and noninvasiveness. This paper reviews the evidence of their potential applications in several aspects of the management of cardiac surgery patients. The sensitivity of auditory evoked potentials to the effects of changes in brain temperature makes them useful for monitoring cerebral hypothermia and rewarming during cardiopulmonary bypass. The close relationship between evoked potential waveforms and specific anatomic structures facilitates the assessment of the functional integrity of the central nervous system in cardiac surgery patients. This feature may also be relevant in the management of critical patients under sedation and coma or in the evaluation of their prognosis during critical care. Their objectivity, reproducibility, and relative insensitivity to learning effects make auditory evoked potentials attractive for the cognitive assessment of cardiac surgery patients. From a clinical perspective, auditory evoked potentials represent an additional window for the study of underlying cerebral processes in healthy and diseased patients. From a research standpoint, this technology offers opportunities for a better understanding of the particular cerebral deficits associated with patients who are undergoing major cardiovascular procedures.

  11. Preparation for Retrievals from Sellafield Legacy Ponds Installation of the Gantry Refurbishment System

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

    Ellison, M.

    2008-07-01

    Retrieval of sludge and fuel from the First Generation Magnox Fuel Storage Pond, and its safe long term storage is one of the NDA's top priorities in the UK clean up programme. The plant is currently undergoing a series of major modifications in preparation for the retrievals operations. The most visible example of these modifications is the Gantry Refurbishment System (GRS), a major work platform which has recently been lifted onto the pond long travel girders used by the Skip Handler. This paper describes the design, manufacture, works test, and site installation of this major piece of equipment. The installationmore » lift, involving the use of an 800Te crane was one of the largest lifts undertaken at Sellafield. The GRS is a mobile platform structure which is designed to be pushed or pulled along the long travel girders by the Skip Handler. Its principle function is to provide a safe and shielded working platform from which to undertake refurbishment of the Skip Handler long travel girders and support structure. The potential hazards and consequences resulting from the modification were fully understood and controls were put in place to ensure that the risk of carrying out the work was as low as reasonably practicable. The work was authorised by the NII, Sellafield Nuclear Safety Committee and an independent readiness review panel. Despite less than perfect weather in the run up to the lift, the GRS was successfully and safely lifted onto the pond on 18 October 2006, the culmination of three years of planning, engineering and construction. (authors)« less

  12. Structures of Ebola virus GP and sGP in complex with therapeutic antibodies.

    PubMed

    Pallesen, Jesper; Murin, Charles D; de Val, Natalia; Cottrell, Christopher A; Hastie, Kathryn M; Turner, Hannah L; Fusco, Marnie L; Flyak, Andrew I; Zeitlin, Larry; Crowe, James E; Andersen, Kristian G; Saphire, Erica Ollmann; Ward, Andrew B

    2016-08-08

    The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. We also provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses towards differently structured products of the GP gene.

  13. Effects of Pre-Existing Liver Disease on Acute Pain Management Using Patient-Controlled Analgesia Fentanyl With Parecoxib After Major Liver Resection: A Retrospective, Pragmatic Study.

    PubMed

    Lim, K I; Chiu, Y C; Chen, C L; Wang, C H; Huang, C J; Cheng, K W; Wu, S C; Shih, T H; Yang, S C; Juang, S E; Huang, C E; Jawan, B; Lee, Y E

    2016-05-01

    The aim of this study was to compare the outcomes of pain management with the use of patient-controlled analgesia (PCA) fentanyl with IV parecoxib between patients with healthy liver with patients with diseased liver undergoing major liver resection. Patients with healthy liver undergoing partial hepatectomy as liver donors for liver transplantation (group 1) and patients with liver cirrhosis (Child's criteria A) undergoing major liver resection for hepatoma (group 2) were identified retrospectively. Both groups routinely received post-operative IV PCA fentanyl and a single dose of parecoxib 40 mg. They were followed up for 3 days or until PCA fentanyl was discontinued post-operatively. Daily Visual Analog Scale, PCA fentanyl usage, rescue attempts, and common drug side effects were collected and analyzed with the use of SPSS version 20. One hundred one patients were included in the study: 54 in group 1, and 47 in group 2. There were no statistical differences between the two groups in terms of the daily and total fentanyl usage, VAS resting, and incidence of itchiness. The rate of rescue analgesia on post-operative day (POD) 1 was lower in group 2, with a value of P = .045. VAS dynamics were better on POD 1 and 2 for group 2, with P = .05 and P = .012, respectively. We found that combining a single dose of IV parecoxib 40 mg with PCA fentanyl is an easy and effective method of acute pain control after major liver resection. We propose the careful usage of post-operative fentanyl and parecoxib in patients with diseased liver, given the difference in effect as compared with healthy liver. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Liberal perioperative fluid administration is an independent risk factor for morbidity and is associated with longer hospital stay after rectal cancer surgery.

    PubMed

    Boland, M R; Reynolds, I; McCawley, N; Galvin, E; El-Masry, S; Deasy, J; McNamara, D A

    2017-02-01

    INTRODUCTION Recent studies have advocated the use of perioperative fluid restriction in patients undergoing major abdominal surgery as part of an enhanced recovery protocol. Series reported to date include a heterogenous group of high- and low-risk procedures but few studies have focused on rectal cancer surgery alone. The aim of this study was to assess the effects of perioperative fluid volumes on outcomes in patients undergoing elective rectal cancer resection. METHODS A prospectively maintained database of patients with rectal cancer who underwent elective surgery over a 2-year period was reviewed. Total volume of fluid received intraoperatively was calculated, as well as blood products required in the perioperative period. The primary outcome was postoperative morbidity (Clavien-Dindo grade I-IV) and the secondary outcomes were length of stay and major morbidity (Clavien-Dindo grade III-IV). RESULTS Over a 2-year period (2012-2013), 120 patients underwent elective surgery with curative intent for rectal cancer. Median total intraoperative fluid volume received was 3680ml (range 1200-9670ml); 65/120 (54.1%) had any complications, with 20/120 (16.6%) classified as major (Clavien-Dindo grade III-IV). Intraoperative volume >3500ml was an independent risk factor for the development of postoperative all-cause morbidity (P=0.02) and was associated with major morbidity (P=0.09). Intraoperative fluid volumes also correlated with length of hospital stay (Pearson's correlation coefficient 0.33; P<0.01). CONCLUSIONS Intraoperative fluid infusion volumes in excess of 3500ml are associated with increased morbidity and length of stay in patients undergoing elective surgery for rectal cancer.

  15. Does Travel Distance Affect Readmission Rates after Cardiac Surgery?

    PubMed

    Juo, Yen-Yi; Woods, Alexis; Ou, Ryan; Ramos, Gianna; Shemin, Richard; Benharash, Peyman

    2017-10-01

    With emphasis on value-based health care, empiric models are used to estimate expected readmission rates for individual institutions. The aim of this study was to determine the relationship between distance traveled to seek surgical care and likelihood of readmission in adult patients undergoing cardiac operations at a single medical center. All adults undergoing major cardiac surgeries from 2008 to 2015 were included. Patients were stratified by travel distance into regional and distant travel groups. Multivariable logistic regression models were developed to assess the impact of distance traveled on odds of readmission. Of the 4232 patients analyzed, 29 per cent were in the regional group and 71 per cent in the distant. Baseline characteristics between the two groups were comparable except mean age (62 vs 61 years, P < 0.01) and Caucasian race (59 vs 73%, P < 0.01). Distant travel was associated with a significantly longer hospital length of stay (11.8 vs 10.5 days, P < 0.01) and lower risk of readmission (9.5 vs 13.4%, P < 0.01). Odds of readmission was inversely associated with logarithm of distance traveled (odds ratio 0.75). Travel distance in patients undergoing major cardiac surgeries was inversely associated with odds of readmission.

  16. Epidemiology, natural history, and management of urinary tract infections in pregnancy.

    PubMed

    Andriole, V T; Patterson, T F

    1991-03-01

    The urinary tract undergoes profound physiologic and anatomic changes during pregnancy that facilitate the development of symptomatic UTIs in women with bacteriuria. Although the adverse effects of asymptomatic bacteriuria on maternal and fetal health continue to be debated, it is clear that asymptomatic bacteriuria is the major risk factor for developing symptomatic UTI and that symptomatic infections are associated with significant maternal and fetal risks. Because the majority of symptomatic UTIs develop in women with bacteriuria earlier in pregnancy, treatment of bacteriuria is undertaken to prevent symptomatic infections. All women should be screened at the first antenatal visit, which is reliably and inexpensively done with a dipstick culture. Short-course therapy is as effective as prolonged therapy and should be followed with a repeat culture to document clearing of the bacteriuria. Failure to eliminate bacteriuria with repeated therapy or recurrence with the same organism is indicative of renal parenchymal infection or a structural abnormality. All women with persistent bacteriuria or recurrent infection should have follow-up cultures and a complete urologic evaluation after delivery.

  17. Prevalence of major depressive disorder in patients receiving beta-blocker therapy versus other medications.

    PubMed

    Carney, R M; Rich, M W; teVelde, A; Saini, J; Clark, K; Freedland, K E

    1987-08-01

    Depression is believed to be a common side effect in patients receiving beta-blocker therapy. However, diagnoses of depression defined by current diagnostic criteria may not be more common in patients receiving beta-blockers than in patients with the same medical disorder receiving other medications. Seventy-seven patients undergoing elective cardiac catheterization for evaluation of chest pain received a semi-structured diagnostic psychiatric interview. Twenty-one percent of the patients receiving beta-blockers and 33 percent of the patients receiving medications other than beta-blockers met the current American Psychiatric Association criteria for major depressive disorder (DSM-III) (p = NS). The mean heart rate and state anxiety scores for patients taking beta-blockers were significantly lower than those measured in patients taking medications other than beta-blockers. No other medical or demographic differences were observed between the two groups. Despite the methodologic limitations of the study, there does not appear to be a difference in the point prevalence of depression between patients receiving beta-blockers and those receiving other medications.

  18. Relationship between Cell Surface Carbohydrates and Intrastrain Variation on Opsonophagocytosis of Streptococcus pneumoniae

    PubMed Central

    Kim, Jean O.; Romero-Steiner, Sandra; Sørensen, Uffe B. Skov; Blom, Jens; Carvalho, M.; Barnard, S.; Carlone, George; Weiser, Jeffrey N.

    1999-01-01

    Streptococcus pneumoniae undergoes spontaneous phase variation between a transparent and an opaque colony phenotype, the latter being more virulent in a murine model of sepsis. Opaque pneumococci have previously been shown to express lower amounts of C polysaccharide (cell wall teichoic acid) and in this study were shown to have a higher content of capsular polysaccharide by immunoelectron microscopy. This report then examined the relationship between expression of these two cell surface carbohydrate structures and their relative contribution to the increased virulence of opaque variants. Comparison of genetically related strains showed that the differential content of capsular polysaccharide did not affect the amount of teichoic acid as measured by a capture enzyme-linked immunosorbent assay (ELISA). In contrast, when the teichoic acid structure was altered by replacing choline in the growth medium with structural analogs, the quantity of capsular polysaccharide as measured by a capture ELISA was decreased, demonstrating a linkage in the expression of the two surface carbohydrate structures. A standardized assay was used to assess the relative contribution of cell surface carbohydrates to opsonophagocytosis. The opaque variants required 1.2- to 30-fold more immune human serum to achieve 50% opsonophagocytic killing than did related transparent variants (types 6B and 9V). The opsonophagocytic titer was proportional to the quantity of capsular polysaccharide rather than teichoic acid. The major factor in binding of the opsonin, C-reactive protein (CRP), was also the amount of capsular polysaccharide rather than the teichoic acid ligand. Only for the transparent variant (type 6B), which bound more CRP, was there enhanced opsonophagocytic killing in the presence of this serum protein. Increased expression of capsular polysaccharide, therefore, appeared to be the major factor in the decreased opsonophagocytic killing of opaque pneumococci. PMID:10225891

  19. Mitochondrial motility and vascular smooth muscle proliferation.

    PubMed

    Chalmers, Susan; Saunter, Christopher; Wilson, Calum; Coats, Paul; Girkin, John M; McCarron, John G

    2012-12-01

    Mitochondria are widely described as being highly dynamic and adaptable organelles, and their movement is thought to be vital for cell function. Yet, in various native cells, including those of heart and smooth muscle, mitochondria are stationary and rigidly structured. The significance of the differences in mitochondrial behavior to the physiological function of cells is unclear and was studied in single myocytes and intact resistance-sized cerebral arteries. We hypothesized that mitochondrial dynamics is controlled by the proliferative status of the cells. High-speed fluorescence imaging of mitochondria in live vascular smooth muscle cells shows that the organelle undergoes significant reorganization as cells become proliferative. In nonproliferative cells, mitochondria are individual (≈ 2 μm by 0.5 μm), stationary, randomly dispersed, fixed structures. However, on entering the proliferative state, mitochondria take on a more diverse architecture and become small spheres, short rod-shaped structures, long filamentous entities, and networks. When cells proliferate, mitochondria also continuously move and change shape. In the intact pressurized resistance artery, mitochondria are largely immobile structures, except in a small number of cells in which motility occurred. When proliferation of smooth muscle was encouraged in the intact resistance artery, in organ culture, the majority of mitochondria became motile and the majority of smooth muscle cells contained moving mitochondria. Significantly, restriction of mitochondrial motility using the fission blocker mitochondrial division inhibitor prevented vascular smooth muscle proliferation in both single cells and the intact resistance artery. These results show that mitochondria are adaptable and exist in intact tissue as both stationary and highly dynamic entities. This mitochondrial plasticity is an essential mechanism for the development of smooth muscle proliferation and therefore presents a novel therapeutic target against vascular disease.

  20. Community College Leadership: A Multidimensional Model for Leading Change

    ERIC Educational Resources Information Center

    Eddy, Pamela L.

    2010-01-01

    Two-year colleges are facing major change. The majority will undergo a turnover in college presidencies in the next ten years, at a time when they are being asked to be engines for economic growth, enable more students--and a greater diversity of students--to gain 21st century qualifications, and provide a pathway to higher degrees, all with…

  1. Skylab

    NASA Image and Video Library

    1971-06-01

    The Apollo Telescope Mount (ATM), one of four major components comprising the Skylab, was designed and developed by the Marshall Space Flight Center. In this image, the ATM is shown undergoing horizontal vibration testing in a vibration test unit.

  2. The risk of venous thromboembolism, myocardial infarction, stroke, major bleeding and death in patients undergoing total hip and knee replacement: a 15-year retrospective cohort study of routine clinical practice.

    PubMed

    Pedersen, A B; Mehnert, F; Sorensen, H T; Emmeluth, C; Overgaard, S; Johnsen, S P

    2014-04-01

    We examined the risk of thrombotic and major bleeding events in patients undergoing total hip and knee replacement (THR and TKR) treated with thromboprophylaxis, using nationwide population-based databases. We identified 83 756 primary procedures performed between 1997 and 2011. The outcomes were symptomatic venous thromboembolism (VTE), myocardial infarction (MI), stroke, death and major bleeding requiring hospitalisation within 90 days of surgery. A total of 1114 (1.3%) and 483 (0.6%) patients experienced VTE and bleeding, respectively. The annual risk of VTE varied between 0.9% and 1.6%, and of bleeding between 0.4% and 0.8%. The risk of VTE and bleeding was unchanged over a 15-year period. A total of 0.7% of patients died within 90 days, with a decrease from 1% in 1997 to 0.6% in 2011 (p < 0.001). A high level of comorbidity and general anaesthesia were strong risk factors for both VTE and bleeding, with no difference between THR and TKR patients. The risk of both MI and stroke was 0.5%, which remained unchanged during the study period. In this cohort study of patients undergoing THR and TKR patients in routine clinical practice, approximately 3% experienced VTE, MI, stroke or bleeding. These risks did not decline during the 15-year study period, but the risk of dying fell substantially.

  3. Comparison of different antithrombotic regimens for patients with atrial fibrillation undergoing drug-eluting stent implantation.

    PubMed

    Gao, Fei; Zhou, Yu Jie; Wang, Zhi Jian; Shen, Hua; Liu, Xiao Li; Nie, Bin; Yan, Zhen Xian; Yang, Shi Wei; Jia, De An; Yu, Miao

    2010-04-01

    The optimal antithrombotic strategy for patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation is unknown. The 622 consecutive AF patients undergoing DES implantation were prospectively enrolled. Among them, 142 patients (TT group) continued triple antithrombotic therapy comprising aspirin, clopidogrel and warfarin after discharge; 355 patients (DT group) had dual antiplatelet therapy; 125 patients (WS group) were discharged with warfarin and a single antiplatelet agent. Target INR was set as 1.8-2.5 and was regularly monitored after discharge. The TT group had a significant reduction in stroke and major adverse cardiac and cerebral events (MACCE) (8.8% vs 20.1% vs 14.9%, P=0.010) as compared with either the DT or WS group. In the Cox regression analysis, administration with warfarin (hazard ratio (HR) 0.49; 95% confidence interval (CI) 0.31-0.77; P=0.002) and baseline CHADS(2) score >or=2 (HR 2.09; 95%CI 1.27-3.45; P=0.004) were independent predictors of MACCE. Importantly, the incidence of major bleeding was comparable among 3 groups (2.9% vs 1.8% vs 2.5%, P=0.725), although the overall bleeding rate was increased in the TT group. Kaplan-Meier analysis indicated that the TT group was associated with the best net clinical outcome. The cardiovascular benefits of triple antithrombotic therapy were confirmed by reducing the MACCE rate, and its major bleeding risk might be acceptable if the INR is closely monitored.

  4. Use of rectus sheath catheters for pain relief in patients undergoing major pelvic urological surgery.

    PubMed

    Dutton, Thomas J; McGrath, John S; Daugherty, Mark O

    2014-02-01

    To report on the safety and efficacy of rectus sheath blocks, 'topped-up' using bilateral rectus sheath catheters (RSCs), in patients undergoing major open urological surgery. The RSCs were inserted under ultrasound guidance into 200 patients between April 2008 and August 2011, of whom 106 patients underwent radical retropubic prostatectomy (RRP) and 94 underwent open radical cystectomy (ORC). A retrospective case-note review was undertaken. Outcomes included technical success and complication rates of the insertion and use of RSC, visual analogue pain scores, additional analgesia requirements and length of hospital stay (LOS). All RSCs were successfully placed without complication and used for a mean of 3.6 days for ORC and 2.1 days for RRP. Early removal occurred in 6.49% of patients. Low overall pain scores were reported in both groups. Patients were more likely to require a patient-controlled analgesia system in the ORC group but the overall need for additional analgesia was low in both groups, reducing significantly after the initial 24 h. In combination with an enhanced recovery programme, LOS reduced from 17.0 to 10.8 days in the ORC group and from 6.2 to 2.8 days in the RRP group. The use of RSCs appears to offer an effective and safe method of peri-operative analgesia in patients undergoing major open urological pelvic surgery. © 2013 The Authors. BJU International © 2013 BJU International.

  5. Non-Elective Paraesophageal Hernia Repair Portends Worse Outcomes in Comparable Patients: a Propensity-Adjusted Analysis.

    PubMed

    Tam, Vernissia; Luketich, James D; Winger, Daniel G; Sarkaria, Inderpal S; Levy, Ryan M; Christie, Neil A; Awais, Omar; Shende, Manisha R; Nason, Katie S

    2017-01-01

    Patients undergoing non-elective paraesophageal hernia repair (PEHR) have worse perioperative outcomes. Because they are usually older and sicker, however, these patients may be more prone to adverse events, independent of surgical urgency. Our study aimed to determine whether non-elective PEHR is associated with differential postoperative outcome compared to elective repair, using propensity-score weighting. We abstracted data for patients undergoing PEHR (n = 924; non-elective n = 171 (19 %); 1997-2010). Using boosted regression, we generated a propensity-weighted dataset. Odds of 30-day/in-hospital mortality and major complications after non-elective surgery were determined. Patients undergoing non-elective repair were significantly older, had more adverse prognostic factors, and significantly more major complications (38 versus 18 %; p < 0.001) and death (8 versus 1 %; p < 0.001). After propensity weighting, median absolute percentage bias across 28 propensity-score variables improved from 19 % (significant imbalance) to 5.6 % (well-balanced). After adjusting propensity-weighted data for age and comorbidity score, odds of major complications were still nearly two times greater (OR 1.67, CI 1.07-2.61) and mortality nearly three times greater (OR 2.74, CI 0.93-8.1) than for elective repair. Even after balancing significant differences in baseline characteristics, non-elective PEHR was associated with worse outcomes than elective repair. Symptomatic patients should be referred for elective repair by experienced surgeons.

  6. A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery--the FOCCUS study.

    PubMed

    Cuthbertson, Brian H; Campbell, Marion K; Stott, Stephen A; Elders, Andrew; Hernández, Rodolfo; Boyers, Dwayne; Norrie, John; Kinsella, John; Brittenden, Julie; Cook, Jonathan; Rae, Daniela; Cotton, Seonaidh C; Alcorn, David; Addison, Jennifer; Grant, Adrian

    2011-01-01

    Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Prospective Clinical Trials, ISRCTN32188676.

  7. A pragmatic multi-centre randomised controlled trial of fluid loading in high-risk surgical patients undergoing major elective surgery - the FOCCUS study

    PubMed Central

    2011-01-01

    Introduction Fluid strategies may impact on patient outcomes in major elective surgery. We aimed to study the effectiveness and cost-effectiveness of pre-operative fluid loading in high-risk surgical patients undergoing major elective surgery. Methods This was a pragmatic, non-blinded, multi-centre, randomised, controlled trial. We sought to recruit 128 consecutive high-risk surgical patients undergoing major abdominal surgery. The patients underwent pre-operative fluid loading with 25 ml/kg of Ringer's solution in the six hours before surgery. The control group had no pre-operative fluid loading. The primary outcome was the number of hospital days after surgery with cost-effectiveness as a secondary outcome. Results A total of 111 patients were recruited within the study time frame in agreement with the funder. The median pre-operative fluid loading volume was 1,875 ml (IQR 1,375 to 2,025) in the fluid group compared to 0 (IQR 0 to 0) in controls with days in hospital after surgery 12.2 (SD 11.5) days compared to 17.4 (SD 20.0) and an adjusted mean difference of 5.5 days (median 2.2 days; 95% CI -0.44 to 11.44; P = 0.07). There was a reduction in adverse events in the fluid intervention group (P = 0.048) and no increase in fluid based complications. The intervention was less costly and more effective (adjusted average cost saving: £2,047; adjusted average gain in benefit: 0.0431 quality adjusted life year (QALY)) and has a high probability of being cost-effective. Conclusions Pre-operative intravenous fluid loading leads to a non-significant reduction in hospital length of stay after high-risk major surgery and is likely to be cost-effective. Confirmatory work is required to determine whether these effects are reproducible, and to confirm whether this simple intervention could allow more cost-effective delivery of care. Trial registration Prospective Clinical Trials, ISRCTN32188676 PMID:22177541

  8. Measuring the dynamic structure factor of a quantum gas undergoing a structural phase transition

    PubMed Central

    Landig, Renate; Brennecke, Ferdinand; Mottl, Rafael; Donner, Tobias; Esslinger, Tilman

    2015-01-01

    The dynamic structure factor is a central quantity describing the physics of quantum many-body systems, capturing structure and collective excitations of a material. In condensed matter, it can be measured via inelastic neutron scattering, which is an energy-resolving probe for the density fluctuations. In ultracold atoms, a similar approach could so far not be applied because of the diluteness of the system. Here we report on a direct, real-time and nondestructive measurement of the dynamic structure factor of a quantum gas exhibiting cavity-mediated long-range interactions. The technique relies on inelastic scattering of photons, stimulated by the enhanced vacuum field inside a high finesse optical cavity. We extract the density fluctuations, their energy and lifetime while the system undergoes a structural phase transition. We observe an occupation of the relevant quasi-particle mode on the level of a few excitations, and provide a theoretical description of this dissipative quantum many-body system. PMID:25944151

  9. Structural Evidence of a Major Conformational Change Triggered by Substrate Binding in DapE Enzymes: Impact on the Catalytic Mechanism

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

    Nocek, Boguslaw; Reidl, Cory; Starus, Anna

    In this paper, the X-ray crystal structure of the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase from Haemophilus influenzae (HiDapE) bound by the products of hydrolysis, succinic acid and l,l-DAP, was determined at 1.95 Å. Surprisingly, the structure bound to the products revealed that HiDapE undergoes a significant conformational change in which the catalytic domain rotates ~50° and shifts ~10.1 Å (as measured at the position of the Zn atoms) relative to the dimerization domain. This heretofore unobserved closed conformation revealed significant movements within the catalytic domain compared to that of wild-type HiDapE, which results in effectively closing off access to the dinuclearmore » Zn(II) active site with the succinate carboxylate moiety bridging the dinculear Zn(II) cluster in a μ-1,3 fashion forming a bis(μ-carboxylato)dizinc(II) core with a Zn–Zn distance of 3.8 Å. Surprisingly, His194.B, which is located on the dimerization domain of the opposing chain ~10.1 Å from the dinuclear Zn(II) active site, forms a hydrogen bond (2.9 Å) with the oxygen atom of succinic acid bound to Zn2, forming an oxyanion hole. As the closed structure forms upon substrate binding, the movement of His194.B by more than ~10 Å is critical, based on site-directed mutagenesis data, for activation of the scissile carbonyl carbon of the substrate for nucleophilic attack by a hydroxide nucleophile. Employing the HiDapE product-bound structure as the starting point, a reverse engineering approach called product-based transition-state modeling provided structural models for each major catalytic step. Finally, these data provide insight into the catalytic reaction mechanism and also the future design of new, potent inhibitors of DapE enzymes.« less

  10. Structural Evidence of a Major Conformational Change Triggered by Substrate Binding in DapE Enzymes: Impact on the Catalytic Mechanism

    DOE PAGES

    Nocek, Boguslaw; Reidl, Cory; Starus, Anna; ...

    2017-12-22

    In this paper, the X-ray crystal structure of the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase from Haemophilus influenzae (HiDapE) bound by the products of hydrolysis, succinic acid and l,l-DAP, was determined at 1.95 Å. Surprisingly, the structure bound to the products revealed that HiDapE undergoes a significant conformational change in which the catalytic domain rotates ~50° and shifts ~10.1 Å (as measured at the position of the Zn atoms) relative to the dimerization domain. This heretofore unobserved closed conformation revealed significant movements within the catalytic domain compared to that of wild-type HiDapE, which results in effectively closing off access to the dinuclearmore » Zn(II) active site with the succinate carboxylate moiety bridging the dinculear Zn(II) cluster in a μ-1,3 fashion forming a bis(μ-carboxylato)dizinc(II) core with a Zn–Zn distance of 3.8 Å. Surprisingly, His194.B, which is located on the dimerization domain of the opposing chain ~10.1 Å from the dinuclear Zn(II) active site, forms a hydrogen bond (2.9 Å) with the oxygen atom of succinic acid bound to Zn2, forming an oxyanion hole. As the closed structure forms upon substrate binding, the movement of His194.B by more than ~10 Å is critical, based on site-directed mutagenesis data, for activation of the scissile carbonyl carbon of the substrate for nucleophilic attack by a hydroxide nucleophile. Employing the HiDapE product-bound structure as the starting point, a reverse engineering approach called product-based transition-state modeling provided structural models for each major catalytic step. Finally, these data provide insight into the catalytic reaction mechanism and also the future design of new, potent inhibitors of DapE enzymes.« less

  11. Structural Evidence of a Major Conformational Change Triggered by Substrate Binding in DapE Enzymes: Impact on the Catalytic Mechanism.

    PubMed

    Nocek, Boguslaw; Reidl, Cory; Starus, Anna; Heath, Tahirah; Bienvenue, David; Osipiuk, Jerzy; Jedrzejczak, Robert; Joachimiak, Andrzej; Becker, Daniel P; Holz, Richard C

    2018-02-06

    The X-ray crystal structure of the dapE-encoded N-succinyl-l,l-diaminopimelic acid desuccinylase from Haemophilus influenzae (HiDapE) bound by the products of hydrolysis, succinic acid and l,l-DAP, was determined at 1.95 Å. Surprisingly, the structure bound to the products revealed that HiDapE undergoes a significant conformational change in which the catalytic domain rotates ∼50° and shifts ∼10.1 Å (as measured at the position of the Zn atoms) relative to the dimerization domain. This heretofore unobserved closed conformation revealed significant movements within the catalytic domain compared to that of wild-type HiDapE, which results in effectively closing off access to the dinuclear Zn(II) active site with the succinate carboxylate moiety bridging the dinculear Zn(II) cluster in a μ-1,3 fashion forming a bis(μ-carboxylato)dizinc(II) core with a Zn-Zn distance of 3.8 Å. Surprisingly, His194.B, which is located on the dimerization domain of the opposing chain ∼10.1 Å from the dinuclear Zn(II) active site, forms a hydrogen bond (2.9 Å) with the oxygen atom of succinic acid bound to Zn2, forming an oxyanion hole. As the closed structure forms upon substrate binding, the movement of His194.B by more than ∼10 Å is critical, based on site-directed mutagenesis data, for activation of the scissile carbonyl carbon of the substrate for nucleophilic attack by a hydroxide nucleophile. Employing the HiDapE product-bound structure as the starting point, a reverse engineering approach called product-based transition-state modeling provided structural models for each major catalytic step. These data provide insight into the catalytic reaction mechanism and also the future design of new, potent inhibitors of DapE enzymes.

  12. Structural stability of Amandin, a major allergen from almond (Prunus dulcis), and its acidic and basic polypeptides.

    PubMed

    Albillos, Silvia M; Menhart, Nicholas; Fu, Tong-Jen

    2009-06-10

    Information relating to the resistance of food allergens to thermal and/or chemical denaturation is critical if a reduction in protein allergenicity is to be achieved through food-processing means. This study examined the changes in the secondary structure of an almond allergen, amandin, and its acidic and basic polypeptides as a result of thermal and chemical denaturation. Amandin ( approximately 370 kDa) was purified by cryoprecipitation followed by gel filtration chromatography and subjected to thermal (13-96 degrees C) and chemical (urea and dithiothreitol) treatments. Changes in the secondary structure of the protein were followed using circular dichroism spectroscopy. The secondary structure of the hexameric amandin did not undergo remarkable changes at temperatures up to 90 degrees C, although protein aggregation was observed. In the presence of a reducing agent, irreversible denaturation occurred with the following experimental values: T(m) = 72.53 degrees C (transition temperature), DeltaH = 87.40 kcal/mol (unfolding enthalpy), and C(p) = 2.48 kcal/(mol degrees C) (heat capacity). The concentration of urea needed to achieve 50% denaturation was 2.59 M, and the Gibbs free energy of chemical denaturation was calculated to be DeltaG = 3.82 kcal/mol. The basic and acidic polypeptides of amandin had lower thermal stabilities than the multimeric protein.

  13. Structural change and higher educated labour in Indonesia.

    PubMed

    Pasay, N H

    1990-12-01

    This paper describes an impending shortage of higher-educated labor in Indonesia. Dynamic change is occurring in both Indonesia's population and economy. Its rapidly growing population demands annual national economic growth of 2.2% to avoid declining per capita output. Accordingly, investments have surged in banking and manufacturing industries as Indonesia undergoes structural change from an agricultural to service-based economy. Plagued by a majority of low productivity, elementary-level educated workers, increased productivity is called for to ensure continued development. As the age structural shift progresses, many of these workers will be absorbed in the services sector. Jobs exist requiring workers of all skill levels. This paper is mainly concerned, however, with higher-educated labor's failure to be oriented to the research and development required for sustained economic growth and development, and their entry into clerical positions potentially filled by less educated and less skilled labor. The services sector, particularly public services, is responsible for absorbing much of this labor. As professional, technical, and managerial capabilities and qualifications become increasingly needed in the near future as sector investments take effect, a shortage of higher-educated labor will become apparent. Policy makers are advised to anticipate these shortages and contemplate investments in human capital to facilitate a more smooth adjustment to structural change.

  14. From SHAPE Signatures to 3-D Structures | Center for Cancer Research

    Cancer.gov

    RNAs undergo extensive folding to form sophisticated based-paired secondary structures that are, in part, indicators of more complex three-dimensional structures.  These 3-D shapes are an integral part of the cellular gene-expression machinery. Deconstructing these structures is no small matter, yet it is critical to understanding their function.

  15. Reusable fast opening switch

    DOEpatents

    Van Devender, J.P.; Emin, D.

    1983-12-21

    A reusable fast opening switch for transferring energy, in the form of a high power pulse, from an electromagnetic storage device such as an inductor into a load. The switch is efficient, compact, fast and reusable. The switch comprises a ferromagnetic semiconductor which undergoes a fast transition between conductive and metallic states at a critical temperature and which undergoes the transition without a phase change in its crystal structure. A semiconductor such as europium rich europhous oxide, which undergoes a conductor to insulator transition when it is joule heated from its conductor state, can be used to form the switch.

  16. Reusable fast opening switch

    DOEpatents

    Van Devender, John P.; Emin, David

    1986-01-01

    A reusable fast opening switch for transferring energy, in the form of a high power pulse, from an electromagnetic storage device such as an inductor into a load. The switch is efficient, compact, fast and reusable. The switch comprises a ferromagnetic semiconductor which undergoes a fast transition between conductive and insulating states at a critical temperature and which undergoes the transition without a phase change in its crystal structure. A semiconductor such as europium rich europhous oxide, which undergoes a conductor to insulator transition when it is joule heated from its conductor state, can be used to form the switch.

  17. Structural conversion of the transformer protein RfaH: new insights derived from protein structure prediction and molecular dynamics simulations.

    PubMed

    Balasco, Nicole; Barone, Daniela; Vitagliano, Luigi

    2015-01-01

    Recent structural investigations have shown that the C-terminal domain (CTD) of the transcription factor RfaH undergoes unique structural modifications that have a profound impact into its functional properties. These modifications cause a complete change in RfaH(CTD) topology that converts from an α-hairpin to a β-barrel fold. To gain insights into the determinants of this major structural conversion, we here performed computational studies (protein structure prediction and molecular dynamics simulations) on RfaH(CTD). Although these analyses, in line with literature data, suggest that the isolated RfaH(CTD) has a strong preference for the β-barrel fold, they also highlight that a specific region of the protein is endowed with a chameleon conformational behavior. In particular, the Leu-rich region (residues 141-145) has a good propensity to adopt both α-helical and β-structured states. Intriguingly, in the RfaH homolog NusG, whose CTD uniquely adopts the β-barrel fold, the corresponding region is rich in residues as Val or Ile that present a strong preference for the β-structure. On this basis, we suggest that the presence of this Leu-rich element in RfaH(CTD) may be responsible for the peculiar structural behavior of the domain. The analysis of the sequences of RfaH family (PfamA code PF02357) unraveled that other members potentially share the structural properties of RfaH(CTD). These observations suggest that the unusual conformational behavior of RfaH(CTD) may be rare but not unique.

  18. Composite Materials with Improved Properties in Compression: Synthesis of 3-Methylene-1,1-Dichlorosilacyclobutane and 1,1-Dichlorosilacyclopent-3-ene

    DTIC Science & Technology

    1990-05-09

    reagents may in fact be involved. Of synthetic interest, V undergoes intramolecular Grignard ring closure to yield III (10%). While the yield of III is low...VII) as the major product along with 1,4-bis(trichlorosilyl)- cis-2-butene (VIII). VII undergoes cyclization by an intramolec- ular Grignard ring...addition of methyl Grignard to III. The 1H 8 am NMR chemical shifts of I in diethyl ether are consistently about 0.4 ppm downfield from those previously

  19. Leaf-Litter Breakdown

    EPA Science Inventory

    Terrestrial leaves are a major energy source for forested stream ecosystems around the world. Leaves entering streams as litterfall undergo a series of physical and chemical transformations mediated by internal chemistry and the interaction of microbes and invertebrates resulting...

  20. Cognitive-Linguistic Functioning and Learning to Read in Preschoolers

    ERIC Educational Resources Information Center

    Goldstein, David M.

    1976-01-01

    The major results partially confirm the hypothesis of a reciprocal relationship between the experience of learning to read and the cognitive-linguistic skills which undergo development between the ages of five and seven. (RC)

  1. Changing technology in transportation : automated vehicles in freight.

    DOT National Transportation Integrated Search

    2017-06-27

    The world of transportation is on the verge of undergoing an impactful transformation. Over the past decade, automotive computing technology has progressed far more rapidly than anticipated. Most major auto manufacturers integrated automated features...

  2. The Changing Family Structure.

    ERIC Educational Resources Information Center

    Bernard van Leer Foundation Newsletter, 1993

    1993-01-01

    This newsletter issue contains feature articles and short reports on how and why family structures are undergoing substantial change in many parts of the world. These articles include: (1) "The Changing Family Structure," a review of how families are changing and why; (2) "Peru: Families in the Andes"; (3) "Thailand:…

  3. A human transcription factor in search mode.

    PubMed

    Hauser, Kevin; Essuman, Bernard; He, Yiqing; Coutsias, Evangelos; Garcia-Diaz, Miguel; Simmerling, Carlos

    2016-01-08

    Transcription factors (TF) can change shape to bind and recognize DNA, shifting the energy landscape from a weak binding, rapid search mode to a higher affinity recognition mode. However, the mechanism(s) driving this conformational change remains unresolved and in most cases high-resolution structures of the non-specific complexes are unavailable. Here, we investigate the conformational switch of the human mitochondrial transcription termination factor MTERF1, which has a modular, superhelical topology complementary to DNA. Our goal was to characterize the details of the non-specific search mode to complement the crystal structure of the specific binding complex, providing a basis for understanding the recognition mechanism. In the specific complex, MTERF1 binds a significantly distorted and unwound DNA structure, exhibiting a protein conformation incompatible with binding to B-form DNA. In contrast, our simulations of apo MTERF1 revealed significant flexibility, sampling structures with superhelical pitch and radius complementary to the major groove of B-DNA. Docking these structures to B-DNA followed by unrestrained MD simulations led to a stable complex in which MTERF1 was observed to undergo spontaneous diffusion on the DNA. Overall, the data support an MTERF1-DNA binding and recognition mechanism driven by intrinsic dynamics of the MTERF1 superhelical topology. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. A planning and marketing prototype for changing health care organizations.

    PubMed

    Boshard, N

    1986-11-01

    The U.S. health care industry is undergoing a radical transformation. The consolidation of excess hospital capacity, fierce competition within a shrinking medical marketplace and a growing number of competitive health plans (PPOs and HMOs) are causing a major structural realignment within most health care organizations (HCOs). This realignment has resulted in a much greater reliance upon strategic planning and marketing by HCOs to cope with market-driven competitive challenges. Health care organizations must identify a new cadre of health professionals to support strategic planning, market promotion, market research, market sales and product line management. This new cadre must hold the value that customers (physicians, patients, and employers) are the most valuable asset of the health care organizations. The planning and marketing prototype depicted herein is designed to help HCOs find, differentiate and keep customers.

  5. Severe coagulation factor VII deficiency caused by a novel homozygous mutation (p. Trp284Gly) in loop 140s.

    PubMed

    Hao, Xiuping; Cheng, XiaoLi; Ye, Jiajia; Wang, Yingyu; Yang, LiHong; Wang, Mingshan; Jin, Yanhui

    2016-06-01

    Congenital coagulation factor VII (FVII) deficiency is a rare disorder caused by mutation in F7 gene. Herein, we reported a patient who had unexplained hematuria and vertigo with consanguineous parents. He has been diagnosed as having FVII deficiency based on the results of reduced FVII activity (2.0%) and antigen (12.8%). The thrombin generation tests verified that the proband has obstacles in producing thrombin. Direct sequencing analysis revealed a novel homozygous missense mutation p.Trp284Gly. Also noteworthy is the fact that the mutational residue belongs to structurally conserved loop 140s, which majorly undergo rearrangement after FVII activation. Model analysis indicated that the substitution disrupts these native hydrophobic interactions, which are of great importance to the conformation in the activation domain of FVIIa.

  6. The Chandra X-ray Observatory removed from its container in the Vertical Processing Facility

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Inside the Vertical Processing Facility (VPF), the overhead crane lifts Chandra X-ray Observatory completely out of its protective container. While in the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe.

  7. The Chandra X-ray Observatory removed from its container in the Vertical Processing Facility

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Inside the Vertical Processing Facility (VPF), workers begin lifting the Chandra X-ray Observatory out of its protective container. While in the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe.

  8. KSC-99pc0175

    NASA Image and Video Library

    1999-02-08

    In the Vertical Processing Facility (VPF), workers check fittings and cables on the stand that will raise the Chandra X-ray Observatory to a vertical position. While in the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  9. KSC-99pc0168

    NASA Image and Video Library

    1999-02-08

    Inside the Vertical Processing Facility (VPF), the Chandra X-ray Observatory (top) lies in its protective container while workers on the floor prepare the overhead cable that will remove it. In the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  10. KSC-99pc0173

    NASA Image and Video Library

    1999-02-08

    In the Vertical Processing Facility (VPF), workers begin moving the overhead crane carrying the Chandra X-ray Observatory from its protective container to a stand on the floor. While in the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  11. Extracellular Matrix Degradation and Remodeling in Development and Disease

    PubMed Central

    Lu, Pengfei; Takai, Ken; Weaver, Valerie M.; Werb, Zena

    2011-01-01

    The extracellular matrix (ECM) serves diverse functions and is a major component of the cellular microenvironment. The ECM is a highly dynamic structure, constantly undergoing a remodeling process where ECM components are deposited, degraded, or otherwise modified. ECM dynamics are indispensible during restructuring of tissue architecture. ECM remodeling is an important mechanism whereby cell differentiation can be regulated, including processes such as the establishment and maintenance of stem cell niches, branching morphogenesis, angiogenesis, bone remodeling, and wound repair. In contrast, abnormal ECM dynamics lead to deregulated cell proliferation and invasion, failure of cell death, and loss of cell differentiation, resulting in congenital defects and pathological processes including tissue fibrosis and cancer. Understanding the mechanisms of ECM remodeling and its regulation, therefore, is essential for developing new therapeutic interventions for diseases and novel strategies for tissue engineering and regenerative medicine. PMID:21917992

  12. Benefits of Laparoscopy in Elderly Patients Requiring Major Liver Resection.

    PubMed

    Cauchy, François; Fuks, David; Nomi, Takeo; Dokmak, Safi; Scatton, Olivier; Schwarz, Lilian; Barbier, Louise; Belghiti, Jacques; Soubrane, Olivier; Gayet, Brice

    2016-02-01

    Although recent reports have suggested the potential advantages of laparoscopy in patients undergoing major hepatectomy, the benefits of this approach in elderly patients remain unclear. This study aimed to compare the short-term outcomes of laparoscopic major hepatectomy (LMH) and open major hepatectomy (OMH) in elderly patients. All patients aged 55 years and older undergoing laparoscopic LMH between 2000 and 2013 at 2 centers were retrospectively analyzed and divided into 3 groups (group 1: 55 to 64 years old; group 2: 65 to 74 years old; and group 3: 75 years and older). Risk factors for postoperative complications were determined on multivariable analysis in the overall LMH population and in each LMH group. Outcomes of LMH patients were compared with those of patients of similar age undergoing OMH at another center after propensity score matching. Laparoscopic major hepatectomy was performed in 174 patients, including 72 (41.4%) in group 1, 67 (38.5%) in group 2, and 35 (20.1%) in group 3. On multivariable analysis, diabetes (odds ratio [OR] = 2.349; 95% CI, 1.251-2.674; p = 0.047), American Society of Anesthesiologists status (OR = 2.881; 95% CI, 2.193-3.71; p = 0.017), cirrhosis (OR = 1.426; 95% CI, 1.092-2.025; p = 0.043), right-sided resection (OR = 2.001; 95% CI, 1.492-2.563; p = 0.037), conversion (OR = 1.950; 95% CI, 1.331-2.545; p = 0.024), and intraoperative transfusion (OR = 2.338, 95% CI, 1.738-2.701, p = 0.032) were associated with increased risk of postoperative complications in the whole LMH population. After propensity score matching, laparoscopy was associated with significantly decreased rates of pulmonary complications and shorter hospital stays in all groups, decreased rates of overall complications in group 2 and group 3, and decreased rates of postoperative confusion in group 3. The current study supports the benefits of laparoscopy in decreasing postoperative complications in elderly patients requiring major hepatectomy. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  13. Protein Interaction Profile Sequencing (PIP-seq).

    PubMed

    Foley, Shawn W; Gregory, Brian D

    2016-10-10

    Every eukaryotic RNA transcript undergoes extensive post-transcriptional processing from the moment of transcription up through degradation. This regulation is performed by a distinct cohort of RNA-binding proteins which recognize their target transcript by both its primary sequence and secondary structure. Here, we describe protein interaction profile sequencing (PIP-seq), a technique that uses ribonuclease-based footprinting followed by high-throughput sequencing to globally assess both protein-bound RNA sequences and RNA secondary structure. PIP-seq utilizes single- and double-stranded RNA-specific nucleases in the absence of proteins to infer RNA secondary structure. These libraries are also compared to samples that undergo nuclease digestion in the presence of proteins in order to find enriched protein-bound sequences. Combined, these four libraries provide a comprehensive, transcriptome-wide view of RNA secondary structure and RNA protein interaction sites from a single experimental technique. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  14. Design of Nanostructured Biological Materials Through Self-Assembly of Peptides and Proteins

    DTIC Science & Technology

    2002-01-01

    of applications, including scaffolding for tissue repair in regenerative medicine, drug delivery and biological surface engineering. Tirrell and...colleagues [2] designed artificial proteins that undergo self-assembly to form hydrogels responsive to pH and other environmental changes. Ghadiri and...showed that other β-sheet peptide systems can also undergo self-assembly into regular nanofiber structures. Although they share no sequence

  15. NASA Dryden's F-15B aircraft with the Gulfstream Quiet Spike sonic boom mitigator attached undergoes ground vibration testing in preparation for test flights

    NASA Image and Video Library

    2006-05-01

    NASA Dryden's F-15B testbed aircraft with the Gulfstream Quiet Spike sonic boom mitigator attached undergoes ground vibration testing in preparation for test flights. The project seeks to verify the structural integrity of the multi-segmented, articulating spike attachment designed to reduce and control a sonic boom.

  16. Photochemically Induced Transformations of Transition Complexes.

    DTIC Science & Technology

    1993-05-17

    simple Iron dinuclear species, the DPPM and DPPE phosphine bridged compounds undergo photolysis in CHCI3 to yield products containing formyl substitued...possible reaction pathway for the synthesis of these two monomers as byproducts In the ruthenium phosphine dimer preparation Is suggested. Full structural...DPPM dimer is also described. In contrast to the behavior of the simple iron dinuclear species, the DPPM and DPPE phosphine bridged compounds undergo

  17. Structure of Respiratory Syncytial Virus Fusion Glycoprotein in the Postfusion Conformation Reveals Preservation of Neutralizing Epitopes

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

    McLellan, Jason S.; Yang, Yongping; Graham, Barney S.

    2011-09-16

    Respiratory syncytial virus (RSV) invades host cells via a type I fusion (F) glycoprotein that undergoes dramatic structural rearrangements during the fusion process. Neutralizing monoclonal antibodies, such as 101F, palivizumab, and motavizumab, target two major antigenic sites on the RSV F glycoprotein. The structures of these sites as peptide complexes with motavizumab and 101F have been previously determined, but a structure for the trimeric RSV F glycoprotein ectodomain has remained elusive. To address this issue, we undertook structural and biophysical studies on stable ectodomain constructs. Here, we present the 2.8-{angstrom} crystal structure of the trimeric RSV F ectodomain in itsmore » postfusion conformation. The structure revealed that the 101F and motavizumab epitopes are present in the postfusion state and that their conformations are similar to those observed in the antibody-bound peptide structures. Both antibodies bound the postfusion F glycoprotein with high affinity in surface plasmon resonance experiments. Modeling of the antibodies bound to the F glycoprotein predicts that the 101F epitope is larger than the linear peptide and restricted to a single protomer in the trimer, whereas motavizumab likely contacts residues on two protomers, indicating a quaternary epitope. Mechanistically, these results suggest that 101F and motavizumab can bind to multiple conformations of the fusion glycoprotein and can neutralize late in the entry process. The structural preservation of neutralizing epitopes in the postfusion state suggests that this conformation can elicit neutralizing antibodies and serve as a useful vaccine antigen.« less

  18. Creating Reconfigurable Materials Using ``Colonies'' of Oscillating Polymer Gels

    NASA Astrophysics Data System (ADS)

    Deb, Debabrata; Dayal, Pratyush; Kuksenok, Olga; Balazs, Anna

    2013-03-01

    Species ranging from single-cell organisms to social insects can undergo auto-chemotaxis, where the entities move towards a chemo-attractant that they themselves emit. This mode of signaling allows the organisms to form large-scale structures. Using computational modeling, we show that millimeter-sized polymer gels can display similar auto-chemotaxis. In particular, we demonstrate that gels undergoing the self-oscillating Belousov-Zhabotinsky (BZ) reaction not only respond to a chemical signal from the surrounding solution, but also emit this signal and thus, multiple gel pieces can spontaneously self-aggregate. We focus on the collective behavior of ``colonies'' of BZ gels and show that communication between the individual pieces critically depends on all the neighboring gels. We isolate the conditions at which the BZ gels can undergo a type of self-recombining: if a larger gel is cut into distinct pieces that are moved relatively far apart, then their auto-chemotactic behavior drives them to move and autonomously recombine into a structure resembling the original, uncut sample. These findings reveal that the BZ gels can be used as autonomously moving building blocks to construct multiple structures and thus, provide a new route for creating dynamically reconfigurable materials.

  19. 28 CFR 100.11 - Allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) COST RECOVERY REGULATIONS, COMMUNICATIONS... reimbursement under section 109(e) CALEA are: (1) All reasonable plant costs directly associated with the... undergoes major modifications; (2) Additional reasonable plant costs directly associated with making the...

  20. The future for Canada-U.S. container port rivalries

    DOT National Transportation Integrated Search

    2003-06-01

    Canada's major container ports have competed successfully against their U.S. counterparts for overseas container traffic. However, the ocean container shipping industry is undergoing changes that will impact on their relationships with ports and comp...

  1. 28 CFR 100.11 - Allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) COST RECOVERY REGULATIONS, COMMUNICATIONS... reimbursement under section 109(e) CALEA are: (1) All reasonable plant costs directly associated with the... undergoes major modifications; (2) Additional reasonable plant costs directly associated with making the...

  2. 46 CFR 28.330 - Galley hood and other fire protection equipment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Stage of Construction on or After or Which Undergo a Major Conversion Completed on or After September 15... pre-engineered dry or wet chemical fire extinguishing system meeting the applicable sections of NFPA...

  3. Neurologic sequelae of cardiac surgery in children.

    PubMed

    Ferry, P C

    1987-03-01

    Major advances in surgical and cardiopulmonary bypass technology have occurred in the past 30 years. Total correction of previously inoperable congenital cardiac defects is being performed with increasing frequency and in children at progressively younger ages. While the majority of children undergoing cardiac surgery survive without incident, increasing concern is being raised about neurologic sequelae seen in some survivors. Complications such as embolization, hypoxia, inadequate cerebral perfusion, and biochemical disturbances may all lead to brain damage following cardiac surgery. Acute postoperative neurologic problems include seizures, impaired levels of consciousness, focal motor deficits, and movement disorders. Long-term sequelae include language and learning disorders, mental retardation, seizures, and cerebral palsy. Intraoperative cerebral monitoring techniques are as yet imperfect, but their use in combination with meticulous intraoperative and postoperative care currently provides the best means of reducing neurologic morbidity. Future studies should explore other methods of preserving neurologic integrity in children undergoing open heart surgery.

  4. Immediate outcomes of eptifibatide therapy during intracoronary stent implantation.

    PubMed

    Shariati, Hooman; Sanei, Hamid; Pourmoghadas, Ali; Salehizadeh, Leila; Amirpour, Afshin

    2016-01-01

    The objective of the present study was to assess the major immediate outcomes of eptifibatide therapy during intracoronary stent implantation. In an interventional study, patients undergoing percutaneous coronary intervention (PCI) were randomized into either the eptifibatide ( n = 100) or the control ( n = 107) group. In each group, demographic and clinical characteristics such as cardiac death, stent thrombosis (ST), myocardial infarction (MI), rates of target lesion and vessel revascularization, cerebral vascular accident (CVA), and emergency coronary artery bypass grafting (CABG) were recorded. The overall rates of major adverse events such as mortality, Stent thrombosis (ST), Myocardial Infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), CVA, and emergency CABG within 24 h after stent implantation were low and comparable between the two groups; P > 0.05 considered significant for all comparisons. There were no statistical differences between the clinical outcomes of groups administered with single-dose intracoronary eptifibatide and control groups among patients undergoing PCI during stent implantation.

  5. Activator Protein-1: redox switch controlling structure and DNA-binding

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

    Yin, Zhou; Machius, Mischa; Nestler, Eric J.

    The transcription factor, activator protein-1 (AP-1), binds to cognate DNA under redox control; yet, the underlying mechanism has remained enigmatic. A series of crystal structures of the AP-1 FosB/JunD bZIP domains reveal ordered DNA-binding regions in both FosB and JunD even in absence DNA. However, while JunD is competent to bind DNA, the FosB bZIP domain must undergo a large conformational rearrangement that is controlled by a ‘redox switch’ centered on an inter-molecular disulfide bond. Solution studies confirm that FosB/JunD cannot undergo structural transition and bind DNA when the redox-switch is in the ‘OFF’ state, and show that the mid-pointmore » redox potential of the redox switch affords it sensitivity to cellular redox homeostasis. The molecular and structural studies presented here thus reveal the mechanism underlying redox-regulation of AP-1 Fos/Jun transcription factors and provide structural insight for therapeutic interventions targeting AP-1 proteins.« less

  6. Preoperative anemia and postoperative outcomes after hepatectomy

    PubMed Central

    Tohme, Samer; Varley, Patrick R.; Landsittel, Douglas P.; Chidi, Alexis P.; Tsung, Allan

    2015-01-01

    Background Preoperative anaemia is associated with adverse outcomes after surgery but outcomes after liver surgery specifically are not well established. We aimed to analyze the incidence of and effects of preoperative anemia on morbidity and mortality in patients undergoing liver resection. Methods All elective hepatectomies performed for the period 2005–2012 recorded in the American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) database were evaluated. We obtained anonymized data for 30-day mortality and major morbidity (one or more major complication), demographics, and preoperative and perioperative risk factors. We used multivariable logistic regression models to assess the adjusted effect of anemia, which was defined as (hematocrit <39% in men, <36% in women), on postoperative outcomes. Results We obtained data for 12,987 patients, of whom 4260 (32.8%) had preoperative anemia. Patients with preoperative anemia experienced higher postoperative major morbidity and mortality rates compared to those without anemia. After adjustment for predefined variables, preoperative anemia was an independent risk factor for postoperative major morbidity (adjusted OR 1.21, 1.09–1.33). After adjustment, there was no significant difference in postoperative mortality for patients with or without preoperative anemia (adjusted OR 0.88, 0.66–1.16). Conclusion Preoperative anemia is independently associated with an increased risk of major morbidity in patients undergoing hepatectomy. Therefore, it is crucial to readdress preoperative blood management in anemic patients prior to hepatectomy. PMID:27017165

  7. Effects of baseline and early acquired thrombocytopaenia on long-term mortality in patients undergoing percutaneous coronary intervention with bivalirudin.

    PubMed

    Ali, Ziad A; Qureshi, Yasir H; Karimi Galougahi, Keyvan; Poludasu, Shyam; Roye, Swathi; Krishnan, Prakash; Zalewski, Adrian; Shah, Zainab Z; Bhatti, Navdeep; Kalapatapu, Kumar; Mehran, Roxana; Dangas, George; Kini, Annapoorna S; Sharma, Samin K

    2016-04-08

    Bivalirudin use as a procedural anticoagulant in patients undergoing percutaneous coronary intervention (PCI) is associated with a lower incidence of thrombocytopaenia compared to other antithrombotic agents. We aimed to evaluate the prognostic impact of baseline thrombocytopaenia and early changes in platelet counts among patients undergoing PCI with exclusive use of bivalirudin. We evaluated 7,505 patients who underwent PCI over a period of eight years. Patients who received unfractionated heparin and glycoprotein IIb/IIIa receptor inhibitors were specifically excluded. Eight hundred and fifty-eight (11.4%) patients had baseline thrombocytopaenia and 451 (6.0%) developed acquired thrombocytopaenia. After adjustment for potential covariates, moderate to severe acquired thrombocytopaenia was the strongest independent predictor (HR 4.34, 95% CI: 2.13-8.84; p<0.001) of in-hospital net adverse clinical events, which included major adverse cardiac events and major bleeding complications. Age, male gender, baseline platelet count and intra-aortic balloon pump (IABP) insertion were independent predictors of in-hospital acquired thrombocytopaenia. After a mean follow-up of 2.6±1.7 years, moderate to severe baseline thrombocytopaenia (HR 2.42, 95% CI: 1.79-3.29; p<0.001), moderate to severe acquired thrombocytopaenia (HR 2.37, 95% CI: 1.13-4.97; p=0.02) and severe changes in platelet count (>67 k) were significant predictors of mortality. In patients undergoing PCI with bivalirudin, moderate to severe baseline and acquired thrombocytopaenia along with severe changes in platelet count are associated with higher long-term mortality.

  8. Development and validation of a predictive score for perioperative transfusion in patients with hepatocellular carcinoma undergoing liver resection.

    PubMed

    Wang, Hai-Qing; Yang, Jian; Yang, Jia-Yin; Wang, Wen-Tao; Yan, Lu-Nan

    2015-08-01

    Liver resection is a major surgery requiring perioperative blood transfusion. Predicting the need for blood transfusion for patients undergoing liver resection is of great importance. The present study aimed to develop and validate a model for predicting transfusion requirement in HBV-related hepatocellular carcinoma patients undergoing liver resection. A total of 1543 consecutive liver resections were included in the study. Randomly selected sample set of 1080 cases (70% of the study cohort) were used to develop a predictive score for transfusion requirement and the remaining 30% (n=463) was used to validate the score. Based on the preoperative and predictable intraoperative parameters, logistic regression was used to identify risk factors and to create an integer score for the prediction of transfusion requirement. Extrahepatic procedure, major liver resection, hemoglobin level and platelets count were identified as independent predictors for transfusion requirement by logistic regression analysis. A score system integrating these 4 factors was stratified into three groups which could predict the risk of transfusion, with a rate of 11.4%, 24.7% and 57.4% for low, moderate and high risk, respectively. The prediction model appeared accurate with good discriminatory abilities, generating an area under the receiver operating characteristic curve of 0.736 in the development set and 0.709 in the validation set. We have developed and validated an integer-based risk score to predict perioperative transfusion for patients undergoing liver resection in a high-volume surgical center. This score allows identifying patients at a high risk and may alter transfusion practices.

  9. Adsorption of fibrinogen on a biomedical-grade stainless steel 316LVM surface: a PM-IRRAS study of the adsorption thermodynamics, kinetics and secondary structure changes.

    PubMed

    Desroches, Marie-Josee; Omanovic, Sasha

    2008-05-14

    Polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS) was employed to investigate the interaction of serum protein fibrinogen with a biomedical-grade 316LVM stainless steel surface, in terms of the adsorption thermodynamics, kinetics and secondary structure changes of the protein. Apparent Gibbs energy of adsorption values indicated a highly spontaneous and strong adsorption of fibrinogen onto the surface. The kinetics of fibrinogen adsorption were successfully modeled using a pseudo first-order kinetic model. Deconvolution of the amide I bands indicated that the adsorption of fibrinogen on 316LVM results in significant changes in the protein's secondary structure that occur predominantly within the first minute of adsorption. Among the investigated structures, the alpha-helix structure undergoes the smallest changes, while the beta-sheet and beta-turns structures undergo significant changes. It was shown that lateral interactions between the adsorbed molecules do not play a role in controlling the secondary structure changes. An increase in temperature induced changes in the secondary structure of the protein, characterized by a loss of the alpha-helical content and its transformation into the beta-turns structure.

  10. Counter effect of sucrose on ethanol-induced aggregation of protein.

    PubMed

    Yadav, Jay Kant; Chandani, N; Pande Prajakt, P R; Chauhan, Jyoti Bala

    2010-12-01

    The present paper is an attempt to study the mechanism of ethanol induced aggregation of chicken egg albumin and to stabilize the protein against ethanol induced aggregation. The protein aggregation was determined by monitoring the light scattering of protein aggregates spectrophotometrically. The protein undergoes certain structural changes in water-ethanol solution and the degree of aggregation was found to be linearly depending upon the concentration of alcohol used. The intrinsic fluorescence study showed a large blue shift in the λ(max) (16 nm) in the presence of 50% ethanol. The ANS fluorescence intensity was found to be gradually increasing with increasing concentration of ethanol. This indicates an increase in the hydrophobic cluster on the protein surface and as a result the hydrophobic interaction is the major driving force for the aggregate formation. Addition of sucrose significantly reduced the ethanol-induced protein aggregation. In presence of 50% sucrose the ethanol the aggregation was reduced to 5%. The study reveals that addition of sucrose brings out changes in the solvent distribution and prevents the structural changes in protein which lead the aggregation.

  11. Backbone ¹H, ¹³C, ¹⁵N NMR assignments of yeast OMP synthase in unliganded form and in complex with orotidine 5'-monophosphate.

    PubMed

    Hansen, Michael Riis; Harris, Richard; Barr, Eric W; Cheng, Hong; Girvin, Mark E; Grubmeyer, Charles

    2014-04-01

    The type I phosphoribosyltransferase OMP synthase (EC 2.4.2.10) is involved in de novo synthesis of pyrimidine nucleotides forming the UMP precursor orotidine 5'-monophosphate (OMP). The homodimeric enzyme has a Rossman α/β core topped by a base-enclosing "hood" domain and a flexible domain-swapped catalytic loop. High-resolution X-ray structures of the homologous Salmonella typhimurium and yeast enzymes show that a general compacting of the core as well as movement of the hood and a major disorder-to-order transition of the loop occur upon binding of ligands MgPRPP and orotate. Here we present backbone NMR assignments for the unliganded yeast enzyme (49 kDa) and its complex with product OMP. We were able to assign 212-213 of the 225 non-proline backbone (15)N and amide proton resonances. Significant difference in chemical shifts of the amide cross peaks occur in regions of the structure that undergo movement upon ligand occupancy in the S. typhimurium enzyme.

  12. LINCS: Livermore's network architecture. [Octopus computing network

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

    Fletcher, J.G.

    1982-01-01

    Octopus, a local computing network that has been evolving at the Lawrence Livermore National Laboratory for over fifteen years, is currently undergoing a major revision. The primary purpose of the revision is to consolidate and redefine the variety of conventions and formats, which have grown up over the years, into a single standard family of protocols, the Livermore Interactive Network Communication Standard (LINCS). This standard treats the entire network as a single distributed operating system such that access to a computing resource is obtained in a single way, whether that resource is local (on the same computer as the accessingmore » process) or remote (on another computer). LINCS encompasses not only communication but also such issues as the relationship of customer to server processes and the structure, naming, and protection of resources. The discussion includes: an overview of the Livermore user community and computing hardware, the functions and structure of each of the seven layers of LINCS protocol, the reasons why we have designed our own protocols and why we are dissatisfied by the directions that current protocol standards are taking.« less

  13. Alternative Conformations of Cytochrome c: Structure, Function, and Detection.

    PubMed

    Hannibal, Luciana; Tomasina, Florencia; Capdevila, Daiana A; Demicheli, Verónica; Tórtora, Verónica; Alvarez-Paggi, Damián; Jemmerson, Ronald; Murgida, Daniel H; Radi, Rafael

    2016-01-26

    Cytochrome c (cyt c) is a cationic hemoprotein of ∼100 amino acid residues that exhibits exceptional functional versatility. While its primary function is electron transfer in the respiratory chain, cyt c is also recognized as a key component of the intrinsic apoptotic pathway, the mitochondrial oxidative protein folding machinery, and presumably as a redox sensor in the cytosol, along with other reported functions. Transition to alternative conformations and gain-of-peroxidase activity are thought to further enable the multiple functions of cyt c and its translocation across cellular compartments. In vitro, direct interactions of cyt c with cardiolipin, post-translational modifications such as tyrosine nitration, phosphorylation, methionine sulfoxidation, mutations, and even fine changes in electrical fields lead to a variety of conformational states that may be of biological relevance. The identification of these alternative conformations and the elucidation of their functions in vivo continue to be a major challenge. Here, we unify the knowledge of the structural flexibility of cyt c that supports functional moonlighting and review biochemical and immunochemical evidence confirming that cyt c undergoes conformational changes during normal and altered cellular homeostasis.

  14. RNA versatility governs tRNA function: Why tRNA flexibility is essential beyond the translation cycle.

    PubMed

    Kuhn, Claus-D

    2016-05-01

    tRNAs undergo multiple conformational changes during the translation cycle that are required for tRNA translocation and proper communication between the ribosome and translation factors. Recent structural data on how destabilized tRNAs utilize the CCA-adding enzyme to proofread themselves put a spotlight on tRNA flexibility beyond the translation cycle. In analogy to tRNA surveillance, this review finds that other processes also exploit versatile tRNA folding to achieve, amongst others, specific aminoacylation, translational regulation by riboswitches or a block of bacterial translation. tRNA flexibility is thereby not restricted to the hinges utilized during translation. In contrast, the flexibility of tRNA is distributed all over its L-shape and is actively exploited by the tRNA-interacting partners to discriminate one tRNA from another. Since the majority of tRNA modifications also modulate tRNA flexibility it seems that cells devote enormous resources to tightly sense and regulate tRNA structure. This is likely required for error-free protein synthesis. © 2016 WILEY Periodicals, Inc.

  15. Septins - active GTPases or just GTP-binding proteins?

    PubMed

    Abbey, Megha; Gaestel, Matthias; Menon, Manoj B

    2018-05-10

    Septins are conserved cytoskeletal proteins with unique filament forming capabilities and roles in cytokinesis and cell morphogenesis. Septins undergo hetero-oligomerization and assemble into higher order structures including filaments, rings and cages. Hetero- and homotypic interactions of septin isoforms involve alternating GTPase (G)-domain interfaces and those mediated by N- and C-terminal extensions. While most septins bind GTP, display weak GTP-hydrolysis activity and incorporate guanine nucleotides in their interaction interfaces, studies using GTPase-inactivating mutations have failed to conclusively establish a crucial role for GTPase activity in mediating septin functions. In this mini-review, we will critically assess the role of GTP-binding and -hydrolysis on septin assembly and function. The relevance of G-domain activity will also be discussed in the context of human septin mutations as well as the development of specific small-molecules targeting septin polymerization. As structural determinants of septin oligomer interfaces, G-domains are attractive targets for ligand-based inhibition of septin assembly. Whether such an intervention can predictably alter septin function is a major question for future research. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  16. Association of the pr Peptides with Dengue Virus at Acidic pH Blocks Membrane Fusion

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

    Yu, I.-M.; Holdaway, H.A.; Chipman, P.R.

    Flavivirus assembles into an inert particle that requires proteolytic activation by furin to enable transmission to other hosts. We previously showed that immature virus undergoes a conformational change at low pH that renders it accessible to furin (I. M. Yu, W. Zhang, H. A. Holdaway, L. Li, V. A. Kostyuchenko, P. R. Chipman, R. J. Kuhn, M. G. Rossmann, and J. Chen, Science 319:1834-1837, 2008). Here we show, using cryoelectron microscopy, that the structure of immature dengue virus at pH 6.0 is essentially the same before and after the cleavage of prM. The structure shows that after cleavage, the proteolyticmore » product pr remains associated with the virion at acidic pH, and that furin cleavage by itself does not induce any major conformational changes. We also show by liposome cofloatation experiments that pr retention prevents membrane insertion, suggesting that pr is present on the virion in the trans-Golgi network to protect the progeny virus from fusion within the host cell.« less

  17. Enumeration of Ring–Chain Tautomers Based on SMIRKS Rules

    PubMed Central

    2015-01-01

    A compound exhibits (prototropic) tautomerism if it can be represented by two or more structures that are related by a formal intramolecular movement of a hydrogen atom from one heavy atom position to another. When the movement of the proton is accompanied by the opening or closing of a ring it is called ring–chain tautomerism. This type of tautomerism is well observed in carbohydrates, but it also occurs in other molecules such as warfarin. In this work, we present an approach that allows for the generation of all ring–chain tautomers of a given chemical structure. Based on Baldwin’s Rules estimating the likelihood of ring closure reactions to occur, we have defined a set of transform rules covering the majority of ring–chain tautomerism cases. The rules automatically detect substructures in a given compound that can undergo a ring–chain tautomeric transformation. Each transformation is encoded in SMIRKS line notation. All work was implemented in the chemoinformatics toolkit CACTVS. We report on the application of our ring–chain tautomerism rules to a large database of commercially available screening samples in order to identify ring–chain tautomers. PMID:25158156

  18. Observation of Nanoscale Morphological and Structural Degradation in Perovskite Solar Cells by In-Situ TEM

    DOE PAGES

    Yang, Bin; Dyck, Ondrej K.; Univ. of Tennessee, Knoxville, TN; ...

    2016-11-04

    The chemical stability of organometallic halide perovskites is a major barrier facing their application in the fast rising field of next generation photovoltaics. These materials were shown to undergo degradation due to the influence of heat or moisture, significantly limiting the lifetime of associated devices. To overcome this stability issue, a fundamental understanding of degradation mechanisms is of foremost importance. Here, high resolution in situ transmission electron microscopy and electron energy loss spectroscopy elemental mapping were applied to probe morphological and structural changes in perovskite films during controlled environmental exposure treatments. Both moisture and oxygen in ambient air are revealedmore » to facilitate degradation in CH 3NH 3PbI 3 perovskites through decomposition and oxidation pathways, respectively. In addition, even in moisture- and oxygen-free environment evident degradation could be induced by heating at the solar cell s real-field operating temperature and the degradation was found to originate from defect sites. These findings provide fundamental insight to prevent degradation of perovskite materials and associated devices for realistic applications.« less

  19. Observation of Nanoscale Morphological and Structural Degradation in Perovskite Solar Cells by In-Situ TEM

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

    Yang, Bin; Dyck, Ondrej K.; Univ. of Tennessee, Knoxville, TN

    The chemical stability of organometallic halide perovskites is a major barrier facing their application in the fast rising field of next generation photovoltaics. These materials were shown to undergo degradation due to the influence of heat or moisture, significantly limiting the lifetime of associated devices. To overcome this stability issue, a fundamental understanding of degradation mechanisms is of foremost importance. Here, high resolution in situ transmission electron microscopy and electron energy loss spectroscopy elemental mapping were applied to probe morphological and structural changes in perovskite films during controlled environmental exposure treatments. Both moisture and oxygen in ambient air are revealedmore » to facilitate degradation in CH 3NH 3PbI 3 perovskites through decomposition and oxidation pathways, respectively. In addition, even in moisture- and oxygen-free environment evident degradation could be induced by heating at the solar cell s real-field operating temperature and the degradation was found to originate from defect sites. These findings provide fundamental insight to prevent degradation of perovskite materials and associated devices for realistic applications.« less

  20. Safety and efficacy of hysteroscopic sterilization compared with laparoscopic sterilization: an observational cohort study.

    PubMed

    Mao, Jialin; Pfeifer, Samantha; Schlegel, Peter; Sedrakyan, Art

    2015-10-13

    To compare the safety and efficacy of hysteroscopic sterilization with the "Essure" device with laparoscopic sterilization in a large, all-inclusive, state cohort. Population based cohort study. Outpatient interventional setting in New York State. Women undergoing interval sterilization procedure, including hysteroscopic sterilization with Essure device and laparoscopic surgery, between 2005 and 2013. Safety events within 30 days of procedures; unintended pregnancies and reoperations within one year of procedures. Mixed model accounting for hospital clustering was used to compare 30 day and 1 year outcomes, adjusting for patient characteristics and other confounders. Time to reoperation was evaluated using frailty model for time to event analysis. We identified 8048 patients undergoing hysteroscopic sterilization and 44,278 undergoing laparoscopic sterilization between 2005 and 2013 in New York State. There was a significant increase in the use of hysteroscopic procedures during this period, while use of laparoscopic sterilization decreased. Patients undergoing hysteroscopic sterilization were older than those undergoing laparoscopic sterilization and were more likely to have a history of pelvic inflammatory disease (10.3% v 7.2%, P<0.01), major abdominal surgery (9.4% v 7.9%, P<0.01), and cesarean section (23.2% v 15.4%, P<0.01). At one year after surgery, hysteroscopic sterilization was not associated with a higher risk of unintended pregnancy (odds ratio 0.84 (95% CI 0.63 to 1.12)) but was associated with a substantially increased risk of reoperation (odds ratio 10.16 (7.47 to 13.81)) compared with laparoscopic sterilization. Patients undergoing hysteroscopic sterilization have a similar risk of unintended pregnancy but a more than 10-fold higher risk of undergoing reoperation compared with patients undergoing laparoscopic sterilization. Benefits and risks of both procedures should be discussed with patients for informed decisions making. © Mao et al 2015.

  1. Topics and structure in preoperative nursing consultations with patients undergoing colorectal cancer surgery.

    PubMed

    Pettersson, Monica E; Öhlén, Joakim; Friberg, Febe; Hydén, Lars-Christer; Carlsson, Eva

    2017-12-01

    The preoperative education, which occurs in preoperative patient consultations, is an important part of the surgical nurse's profession. These consultations may be the building blocks of a partnership that facilitates communication between patient and nurse. The aim of the study was to describe topics and structure and documentation in preoperative nursing consultations with patients undergoing surgery for colorectal cancer. The study was based on analysis of consultations between seven patients and nurses at a Swedish university hospital. The preplanned preoperative consultations were audio-recorded and transcribed verbatim. The structure of the consultations was described in terms of phases and the text was analysed according to a manifest content analysis RESULTS: The consultations were structured on an agenda that was used variously and communicating different topics in an equally varied manner. Seven main topics were found: Health status, Preparation before surgery, Discovery, Tumour, Operation, Symptoms and Recovery after surgery. The topic structure disclosed a high number of subtopics. The main topics 'Discovery', 'Tumour' and 'Symptoms' were only raised by patients and occupied only 11% of the discursive space. Documentation was sparse and included mainly task-oriented procedures rather than patients' worries and concerns. There was no clear structure regarding preoperative consultation purpose and content. Using closed questions instead of open is a hindrance of developing a dialogue and thus patient participation. Preoperative consultation practice needs to be strengthened to include explicit communication of the consultations' purpose and agenda, with nurses actively discussing and responding to patients' concerns and sensitive issues. The results of the study facilitate the development of methods and structure to support person-centred communication where the patient is given space to get help with the difficult issues he/she may have when undergoing surgery. © 2016 Nordic College of Caring Science.

  2. Regaining a sense of agency and shared self-reliance: the experience of advanced disease cancer patients participating in a multidimensional exercise intervention while undergoing chemotherapy--analysis of patient diaries.

    PubMed

    Midtgaard, Julie; Stelter, Reinhard; Rørth, Mikael; Adamsen, Lis

    2007-04-01

    Evidence is emerging that exercise can reduce psychological distress in cancer patients undergoing treatment. The present study aimed to (qualitatively) explore the experiences of advanced disease cancer patients participating in a 6-week, 9-hours weekly, structured, group-based multidimensional exercise intervention while undergoing chemotherapy. Unstructured diaries from a purposive sample of three females and two males (28-52 years old) who participated in the program served as the database. Data were analyzed using a phenomenological, narrative method. The analysis yielded three themes: shifting position, self-surveillance, and negotiated strength. The intervention highlighted situations making it possible for the participants to negate psychological and physical constraints. The concept of structured exercise contains viable psychotherapeutic potentials by allowing the development of alternative bodily and mental realities complying with cancer patients' demands and abilities to regain autonomy and commitment to discover and adopt a sense of agency and shared self-reliance.

  3. Functional Outcomes of Persons Undergoing Dysvascular Lower Extremity Amputations

    PubMed Central

    Sauter, Carley N.; Pezzin, Liliana E.; Dillingham, Timothy R.

    2012-01-01

    Objective To examine the effect of post-acute rehabilitation setting on functional outcomes among patients undergoing major lower extremity dysvascular amputations. Design A population-based, prospective cohort study conducted in Maryland and Wisconsin. Data collected from medical records and patient interviews conducted during acute hospitalization following amputation and at six-month following the acute care discharge were analyzed using multivariate models and instrumental variable techniques. Results A total of 297 patients were analyzed based on post-acute care rehabilitation setting: acute inpatient rehabilitation (IRF), skilled nursing facility (SNF) or home. The majority (43.4%) received care in IRF, 32% in SNF, and 24.6% at home. On SF-36 subscales, significantly improved outcomes were observed for patients receiving post-acute care at an IRF relative to those cared for at a SNF in physical function (PF), role physical (RF) and physical component score (PCS). Patients receiving post-acute care in IRFs also experienced better RF and PCS outcomes compared to those discharged directly home. In addition, patients receiving post-acute care at an IRF were significantly more likely to score in the top quartile for general health in IRF compared to SNF or home, and less likely to score in the lowest quartile for PF, RF and PCS in IRF compared to SNF. Lower ADL impairment was observed in IRF compared to SNF. Conclusions Among this large and diverse cohort of patients undergoing major dysvascular lower limb amputations, receipt of interdisciplinary rehabilitation services at an IRF yielded improved functional outcomes six months after amputation relative to care received at SNFs or home. PMID:23291599

  4. Diagnostic Accuracy of Computed Tomography Angiography as Compared to Conventional Angiography in Patients Undergoing Noncoronary Cardiac Surgery

    PubMed Central

    Joshi, Hasit; Shah, Ronak; Prajapati, Jayesh; Bhangdiya, Vipin; Shah, Jayal; Kandre, Yogini; Shah, Komal

    2016-01-01

    Objective: To compare the diagnostic accuracy of multi-slice computed tomography (MSCT) angiography with conventional angiography in patients undergoing major noncoronary cardiac surgeries. Materials and Methods: We studied fifty major noncoronary cardiac surgery patients scheduled for invasive coronary angiography, 29 (58%) female and 21 (42%) male. Inclusion criteria of the study were age of the patients ≥40 years, having low or intermediate probability of coronary artery disease (CAD), left ventricular ejection fraction (LVEF) >35%, and patient giving informed consent for undergoing MSCT and conventional coronary angiography. The patients with LVEF <35%, high pretest probability of CAD, and hemodynamically unstable were excluded from the study. Results: The diagnostic accuracy of CT coronary angiography was evaluated regarding true positive, true negative values. The overall sensitivity and specificity of CT angiography technique was 100% (95% confidence interval [CI]: 39.76%–100%) and 91.30% (95% CI: 79.21%–97.58%). The positive (50%; 95% CI: 15.70%–84.30%) and negative predictive values (100%; 95% CI: 91.59%–100%) of CT angiography were also fairly high in these patients. Conclusion: Our study suggests that this non-invasive technique may improve perioperative risk stratification in patients undegoing non-cardiac surgery. PMID:27867455

  5. Factors Associated With the Use of Postoperative Analgesics in Patients Undergoing Direct Microlaryngoscopy.

    PubMed

    Taliercio, Salvatore; Sanders, Brian; Achlatis, Stratos; Fang, Yixin; Branski, Ryan; Amin, Milan

    2017-05-01

    Morbidity associated with suspension laryngoscopy has been well documented. However, standard of care with regard to postoperative analgesia has not been described, and anecdotal evidence suggests wide variability with regard to postoperative narcotic and non-narcotic recommendations. We sought to quantify the postoperative course following suspension microlaryngoscopy by relating patient-based and intraoperative measures with analgesic use. Body mass index (BMI), Friedman tongue position (FTP), and Mallampati scores as well as laryngoscope type, number of attempts required for optimal visualization, and suspension time were documented in 50 consecutive patients undergoing routine suspension microlaryngoscopy. Postoperative symptoms and analgesic use was queried on postoperative days 1, 3, and 10. In this cohort, 62.5% employed postoperative analgesia. However, only 20% required narcotics. No difference in suspension time was identified in those taking analgesics (33.0 vs 37.3 minutes, P = .44). In addition, no relationship between procedure type and the need for analgesia was noted. The majority of patients (76%) described sore throat persisting for 3 postoperative days; 36% reported sore throat persisting beyond postoperative day 3. The majority of patients undergoing microlaryngoscopy reported discomfort, but symptoms were largely ameliorated with over-the-counter analgesics. Routine prescription of narcotics following routine suspension laryngoscopy may be unnecessary.

  6. Safety of intravenous tranexamic acid in patients undergoing majororthopaedic surgery: a meta-analysis of randomised controlled trials

    PubMed Central

    Franchini, Massimo; Mengoli, Carlo; Marietta, Marco; Marano, Giuseppe; Vaglio, Stefania; Pupella, Simonetta; Mannucci, Pier Mannuccio; Liumbruno, Giancarlo M.

    2018-01-01

    Among the various pharmacological options to decrease peri-operative bleeding, tranexamic acid appears to be one of the most interesting. Several trials have consistently documented the efficacy of this synthetic drug in reducing the risk of blood loss and the need for allogeneic blood transfusion in patients undergoing total hip and knee arthroplasty. The safety of intravenous tranexamic acid in major orthopaedic surgery, particularly regarding the risk of venous thromboembolism, was systematically analysed in this review. A systematic search of the literature identified 73 randomised controlled trials involving 4,174 patients and 2,779 controls. The raw overall incidence of venous thromboembolism was 2.1% in patients who received intravenous tranexamic acid and 2.0% in controls. A meta-analytic pooling showed that the risk of venous thromboembolism in tranexamic acid-treated patients was not significantly different from that of controls (risk difference: 0.01%, 95% confidence interval [CI]: −0.05%, 0.07%; risk ratio: 1.067, 95% CI: 0.760–1.496). Other severe drug-related adverse events occurred very rarely (0.1%). In conclusion, the results of this systematic review and meta-analysis show that intravenous tranexamic acid is a safe pharmacological treatment to reduce blood loss and transfusion requirements in patients undergoing major orthopaedic surgery. PMID:29337665

  7. Varicella-zoster virus induces the formation of dynamic nuclear capsid aggregates

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

    Lebrun, Marielle; Thelen, Nicolas; Thiry, Marc

    2014-04-15

    The first step of herpesviruses virion assembly occurs in the nucleus. However, the exact site where nucleocapsids are assembled, where the genome and the inner tegument are acquired, remains controversial. We created a recombinant VZV expressing ORF23 (homologous to HSV-1 VP26) fused to the eGFP and dually fluorescent viruses with a tegument protein additionally fused to a red tag (ORF9, ORF21 and ORF22 corresponding to HSV-1 UL49, UL37 and UL36). We identified nuclear dense structures containing the major capsid protein, the scaffold protein and maturing protease, as well as ORF21 and ORF22. Correlative microscopy demonstrated that the structures correspond tomore » capsid aggregates and time-lapse video imaging showed that they appear prior to the accumulation of cytoplasmic capsids, presumably undergoing the secondary egress, and are highly dynamic. Our observations suggest that these structures might represent a nuclear area important for capsid assembly and/or maturation before the budding at the inner nuclear membrane. - Highlights: • We created a recombinant VZV expressing the small capsid protein fused to the eGFP. • We identified nuclear dense structures containing capsid and procapsid proteins. • Correlative microscopy showed that the structures correspond to capsid aggregates. • Procapsids and partial capsids are found within the aggregates of WT and eGFP-23 VZV. • FRAP and FLIP experiments demonstrated that they are dynamic structures.« less

  8. The association between the transfusion of small volumes of leucocyte-depleted red blood cells and outcomes in patients undergoing open-heart valve surgery.

    PubMed

    Zittermann, Armin; Koster, Andreas; Faraoni, David; Börgermann, Jochen; Schirmer, Uwe; Gummert, Jan F

    2017-02-01

    The relationship between the transfusion of red blood cell (RBC) units and outcomes in patients undergoing cardiac surgery is the subject of intense debates. In this study, we investigated the relationship between the transfusion of 1-2 leucocyte-depleted (LD) RBC units and outcomes in patients undergoing open-heart valve surgery. The investigation encompassed consecutive patients undergoing open-heart valve surgery at our institution between July 2009 and March 2015 who received no (RBC- group) or 1-2 units of LD RBC (RBC+ group). End-points were 30-day mortality (primary), the incidence of in-hospital major organ dysfunctions and 1-year mortality (secondary). Propensity score (PS)-adjusted statistical analysis was used to assess the effect of RBC transfusion on end-points. Thirty-day mortality rate was 0.2% (3/1485) in the RBC- group and 0.4% (6/1672) in the RBC+ group, with a PS-adjusted odds ratio (OR) for 30-day mortality of 1.00 (95% CI: 0.21-4.83;P = 0.99). The two groups showed no significant differences in PS-adjusted ORs for major complications, such as stroke, low cardiac output syndrome, thoracic wound infection and prolonged mechanical ventilation (>24 h). The PS-adjusted ORs for prolonged intensive care unit stay (>48 h) were, however, significantly higher in the RBC+ group (OR = 1.34 [95%CI: 1.04-1.72; P = 0.02]) than in the RBC- group. One-year mortality was comparable between groups (PS-adjusted hazard ratio for the RBC+ group: 0.85 [95% CI: 0.42-1.72; P = 0.65]). Our data do not provide evidence that in patients undergoing valve surgery with cardiopulmonary bypass, transfusion of 1-2 units of LD RBC increases operative mortality, the incidence of postoperative complications or 1-year mortality. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  9. Blocking Glycolytic Metabolism Increases Memory T Cells and Antitumor Function | Center for Cancer Research

    Cancer.gov

    CD8+ T cells are a major component of the cellular immune response, which is necessary to control a variety of bacterial and viral infections. CD8+ T cells also play a major role in the cell-mediated antitumor immune response. After encountering antigen, naïve CD8+ T cells undergo an extensive period of proliferation and expansion, and differentiate into effector cells and

  10. Remote preconditioning and major clinical complications following adult cardiovascular surgery: systematic review and meta-analysis.

    PubMed

    Healy, D A; Khan, W A; Wong, C S; Moloney, M Clarke; Grace, P A; Coffey, J C; Dunne, C; Walsh, S R; Sadat, U; Gaunt, M E; Chen, S; Tehrani, S; Hausenloy, D J; Yellon, D M; Kramer, R S; Zimmerman, R F; Lomivorotov, V V; Shmyrev, V A; Ponomarev, D N; Rahman, I A; Mascaro, J G; Bonser, R S; Jeon, Y; Hong, D M; Wagner, R; Thielmann, M; Heusch, G; Zacharowski, K; Meybohm, P; Bein, B; Tang, T Y

    2014-09-01

    A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists. Clinical end-points were extracted from trial reports. In addition, trial principal investigators provided unpublished clinical outcome data. In total, 23 trials of RIPC in 2200 patients undergoing major adult cardiovascular surgery were identified. RIPC did not have a significant effect on clinical end-points (death, peri-operative myocardial infarction (MI), renal failure, stroke, mesenteric ischaemia, hospital or critical care length of stay). Pooled data from pilot trials cannot confirm that RIPC has any significant effect on clinically relevant end-points. Heterogeneity in study inclusion and exclusion criteria and in the type of preconditioning stimulus limits the potential for extrapolation at present. An effort must be made to clarify the optimal preconditioning stimulus. Following this, large-scale trials in a range of patient populations are required to ascertain the role of this simple, cost-effective intervention in routine practice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Stereoselective Borylative Ketone-Diene Coupling

    PubMed Central

    Cho, Hee Yeon; Yu, Zhiyong; Morken, James P.

    2011-01-01

    In the presence of catalytic Ni(cod)2 and P(t-Bu)3, ketones, dienes, and B2(pin)2 undergo a stereoselective multicomponent coupling reaction. Upon oxidation, the reaction furnishes 1,3-diols as the major reaction product. PMID:21905748

  12. Comparisons of Patient Demographics in Prospective Sports, Shoulder, and National Database Initiatives.

    PubMed

    Saltzman, Bryan M; Cvetanovich, Gregory L; Bohl, Daniel D; Cole, Brian J; Bach, Bernard R; Romeo, Anthony A

    2016-09-01

    There has been increased emphasis in orthopaedics on high-quality prospective research to provide evidence-based treatment guidelines, particularly in sports medicine/shoulder surgery. The external validity of these studies has not been established, and the generalizability of the results to clinical practice in the United States is unknown. Comparison of patient demographics in major prospective studies of arthroscopic sports and shoulder surgeries to patients undergoing the same procedures in the National Surgical Quality Improvement Program (NSQIP) database will show substantial differences to question the generalizability and external validity of those studies. Cross-sectional study; Level of evidence, 3. This study utilized patients undergoing arthroscopic anterior cruciate ligament reconstruction (ACLR), meniscectomy (MX), rotator cuff repair (RCR), and shoulder stabilization (SS) from the NSQIP database (2005-2013). Two prospective studies (either randomized controlled trials or, in 1 case, a major cohort study) were identified for each of the 4 procedures for comparison. Demographic variables available for comparison in both the identified prospective studies and the NSQIP included age, sex, and body mass index (BMI). From the NSQIP database, 5576 ACLR patients, 18,882 MX patients, 7282 RCR patients, and 993 SS patients were identified. The comparison clinical studies included cohort sizes as follows: ACLR, n = 121 and 2683; MX, n = 146 and 330; RCR, n = 90 and 103; SS, n = 88 and 196. Age differed significantly between the NSQIP and the patients in 6 of the 8 prospective clinical studies. Sex differed significantly between the NSQIP and the patients in 7 of the 8 prospective clinical studies. BMI differed significantly between the NSQIP and the patients of all 4 of the prospective clinical studies that reported this demographic variable. Significant differences exist for patient age, sex, and BMI between patients included in major sports medicine/shoulder prospective studies and corresponding patients undergoing the same procedures in a nationwide database of academic and community centers in the United States. Future work is needed to understand whether major prospective clinical studies-frequently performed in high-volume, specialized practices-are truly indicative of the types of patients treated and expected results in the general orthopaedic practice. This study additionally argues for the importance of initiating a national registry dedicated to patients undergoing orthopaedic procedures in the United States.

  13. Chromosomal instability in Streptomyces avermitilis: major deletion in the central region and stable circularized chromosome

    PubMed Central

    2010-01-01

    Background The chromosome of Streptomyces has been shown to be unstable, frequently undergoing gross chromosomal rearrangements. However, the mechanisms underlying this phenomenon remain unclear, with previous studies focused on two chromosomal ends as targets for rearrangements. Here we investigated chromosomal instability of Streptomyces avermitilis, an important producer of avermectins, and characterized four gross chromosomal rearrangement events, including a major deletion in the central region. The present findings provide a valuable contribution to the mechanistic study of genetic instability in Streptomyces. Results Thirty randomly-selected "bald" mutants derived from the wild-type strain all contained gross chromosomal rearrangements of various types. One of the bald mutants, SA1-8, had the same linear chromosomal structure as the high avermectin-producing mutant 76-9. Chromosomes of both strains displayed at least three independent chromosomal rearrangements, including chromosomal arm replacement to form new 88-kb terminal inverted repeats (TIRs), and two major deletions. One of the deletions eliminated the 36-kb central region of the chromosome, but surprisingly did not affect viability of the cells. The other deletion (74-kb) was internal to the right chromosomal arm. The chromosome of another bald mutant, SA1-6, was circularized with deletions at both ends. No obvious homology was found in all fusion sequences. Generational stability analysis showed that the chromosomal structure of SA1-8 and SA1-6 was stable. Conclusions Various chromosomal rearrangements, including chromosomal arm replacement, interstitial deletions and chromosomal circularization, occurred in S. avermitilis by non-homologous recombination. The finding of an inner deletion involving in the central region of S. avermitilis chromosome suggests that the entire Streptomyces chromosome may be the target for rearrangements, which are not limited, as previously reported, to the two chromosomal ends. PMID:20653985

  14. A Global Climatology of Extratropical Transition

    NASA Astrophysics Data System (ADS)

    Camargo, S. J.; Bieli, M.; Sobel, A. H.; Evans, J. L.; Hall, T. M.

    2017-12-01

    When moving into midlatitude regions, tropical cyclones often undergo a process called extratropical transition (ET), in which they radically change their physical structure and develop characteristics typical of extratropical cyclones. We present the first climatology of ET that encompasses all major global tropical cyclone basins and is based on a consistent set of data, time period, and method. Using best-track data from 1979-2015 to define the tracks of the storm centers, we identify storms that undergo ET by means of their paths in the cyclone phase space (CPS), calculated from geopotential height fields in reanalysis datasets. Two reanalyses are employed and compared for this purpose, the Japanese 55-year Reanalysis (JRA-55) and the ECMWF Interim Reanalysis (ERA-Interim). The results are used to study the seasonal and geographical distributions of storms undergoing ET, inter-basin differences in the statistics of ET occurrence, and the differences between the ETs defined by CPS and those defined by the 'extratropical' labels (determined subjectively by human forecasters using a wider range of data) in the best-track archives. About 50% of all storms in the North Atlantic and the Western North Pacific undergo ET. In the southern hemisphere, ET fractions range from about 20% in the South Indian Ocean and the Australian region to 40% in the South Pacific. The North Atlantic and Western North Pacific exhibit somewhat different seasonal cycles, with the probability of ET maximizing later in the North Atlantic, but having a local minimum in the earlier part of the peak season in both basins. Southern hemispheric basins have much less pronounced seasonal cycles. The classification of ET storms based on JRA-55 agrees better with the best-track data than the ERA-Interim classification. In the North Atlantic and the Western North Pacific, the differences are small and both reanalyses achieve F1 performance scores of at least 0.8, but JRA-55 has a higher classification skill in all other basins.Due to the global scope and consistent methodology, the results presented are well suited to serve as a benchmark for other studies including research on ET under climate change scenarios.

  15. 46 CFR 71.50-3 - Drydock examination, internal structural examination, underwater survey, and alternate hull exam...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., underwater survey, and alternate hull exam intervals. 71.50-3 Section 71.50-3 Shipping COAST GUARD...-3 Drydock examination, internal structural examination, underwater survey, and alternate hull exam... wooden hulls must undergo two drydock and two internal structural examinations within any five year...

  16. Which outcomes do women expect to achieve after undergoing induced abortion

    PubMed Central

    Nouhjah, Sedigheh; Zamani-Alavijeh, Fereshteh; Heydarabadi, Akbar Babaei; Hozaili, Maedeh

    2017-01-01

    Introduction Unsafe abortion is one of the most important health problems in many countries. Because of legal and moral issues, abortion is one of the most sensitive decisions. The aim of this study was to understand women’s expected gains from undergoing induced abortion. Methods To explain the factors leading to induced abortion, we collected the stories and experiences of a total of 21 people, including 18 women who underwent induced abortion in their most recent pregnancies, two women’s health providers, and a companion of a mother who died after an induced abortion. This qualitative study was conducted in Imam Khomeini and Razi hospital of Ahvaz and also a number of health centers, from February to September 2014. To collect the required data, we used open and semi-structured deep interviews. Content analysis method was used to analyze the data. Results Three major themes emerged from the analysis of the collected data, which included the following: 1) Expected favorable health-related outcomes, 2) Expected favorable economic outcomes, and 3. Expected favorable outcomes in social level and family relationships. Conclusion The results of this study showed that the studied women, to achieve to desirable outcomes in areas of health, economic and social, have undergone induced abortion. Hence, to develop programs for the prevention of induced abortion it is necessary to consider the motivations of women to intentionally terminate a pregnancy. PMID:28465801

  17. Which outcomes do women expect to achieve after undergoing induced abortion.

    PubMed

    Nouhjah, Sedigheh; Zamani-Alavijeh, Fereshteh; Heydarabadi, Akbar Babaei; Hozaili, Maedeh

    2017-02-01

    Unsafe abortion is one of the most important health problems in many countries. Because of legal and moral issues, abortion is one of the most sensitive decisions. The aim of this study was to understand women's expected gains from undergoing induced abortion. To explain the factors leading to induced abortion, we collected the stories and experiences of a total of 21 people, including 18 women who underwent induced abortion in their most recent pregnancies, two women's health providers, and a companion of a mother who died after an induced abortion. This qualitative study was conducted in Imam Khomeini and Razi hospital of Ahvaz and also a number of health centers, from February to September 2014. To collect the required data, we used open and semi-structured deep interviews. Content analysis method was used to analyze the data. Three major themes emerged from the analysis of the collected data, which included the following: 1) Expected favorable health-related outcomes, 2) Expected favorable economic outcomes, and 3. Expected favorable outcomes in social level and family relationships. The results of this study showed that the studied women, to achieve to desirable outcomes in areas of health, economic and social, have undergone induced abortion. Hence, to develop programs for the prevention of induced abortion it is necessary to consider the motivations of women to intentionally terminate a pregnancy.

  18. Eosinophilic Otitis Media: the Aftermath of Eosinophil Extracellular Trap Cell Death.

    PubMed

    Ueki, Shigeharu; Ohta, Nobuo; Takeda, Masahide; Konno, Yasunori; Hirokawa, Makoto

    2017-05-01

    Eosinophilic otitis media (EOM) is a refractory disease characterized by the accumulation of eosinophils in middle ear effusion and mucosa. We summarize current knowledge regarding the clinical characteristics and management of EOM. Although eosinophil activation in inflamed foci is involved in the pathogenesis of EOM, little is known about the fate of the eosinophils and aftermath of their cell death. We discuss the possibility that eosinophils undergo non-apoptotic cell death that worsens tissue damage and increases effusion viscosity. Unlike chronic otitis media, EOM is strongly associated with an allergic background. Corticosteroids are currently the only effective pharmacological treatment, and surgical intervention is often required. Mucosal eosinophils infiltrate extensively into the middle ear cavity where they are stimulated by locally produced activators including interleukin-5 and eotaxin. The eosinophils undergo cytolysis in the effusion, which represents a major fate of activated eosinophils in vivo. Recent data revealed cytolysis could be renamed as extracellular trap cell death (ETosis). ETosis represents suicidal cell death involving total cell degranulation and development of sticky chromatin structures (extracellular traps (ETs)). The characteristics of eosinophil- and neutrophil-derived ET polymers might contribute to the difference in viscosity of secretions between EOM and common chronic otitis media. The extracellular products remaining after eosinophil ETosis are an important aspect of EOM pathology. The concept of ETosis also has novel implications for potential therapeutic modalities in various eosinophilic disorders.

  19. The pattern of prognostic and risk indicators among women with breast cancer undergoing modified radical mastectomy in Dar es Salaam, Tanzania.

    PubMed

    Mwakigonja, Amos R; Rabiel, Happiness; Mbembati, Naboth A; Lema, Leonard E K

    2016-01-01

    Breast cancer is the commonest female malignancy globally and the second (after uterine cervix) in sub-Saharan Africa including Tanzania. Prognostic indicators reportedly influence post-mastectomy adjuvant therapy by predicting risks on survival and recurrence although in Tanzania this data is lacking. Here, we evaluate the pattern of prognostic and risk indicators among women with breast cancer undergoing modified-radical-mastectomy (MRM) at Muhimbili National Hospital (MNH) and Tumaini Hospital (TH), Dar es Salaam, Tanzania. This hospital-based prospective cross-sectional study included female patients undergoing MRM from April 2011 to January 2012. Clinical stage I-III patients were enrolled after being scheduled for mastectomy. Patients with evidence of distant metastasis (stage IV) were excluded. Mastectomy and axillary lymph nodes biopsies were submitted to the Histopathology laboratory for grade, type, nodal and margins status. Data was collected using a structured questionnaire and analyzed using SPSS. A total of 348 patients were admitted with breast cancer including 86 patients (with 16 from TH having similar demography and presentation) meeting inclusion criteria. Age-range at diagnosis was 28-79 years, mean 52.1 years. Most (89 %) attained menarche after 11 years. About 56 % were postmenopausal. The majority (78 %) were multiparous with positive family history in 14.1 and 37.6 % used hormonal contraceptives. About 27.1 % were social alcohol drinkers. The majority (61 %) had T4b disease, 75.6 % had positive axillary nodes including 42.7 % with 4-9 involved nodes (N2). The commonest (91.9 %) histological type was invasive ductal carcinoma. Lobular, medullary and mucinous carcinomas were rare. Most (83.7 %) of our patients presented with stage III and the rest stage II. Intermediate- and high-grade tumors accounted for 73.5 %. Following MRM, 25 % of our patients had positive surgical margins and similarly for the base. Most of our breast cancer patients present with frequent risks including younger age, multiparity, hormonal contraceptives use, alcohol use and family history. Unfavourable prognostic indicators including late stages, large primary tumor size, skin infiltration, positive surgical margins, positive axillary lymph nodes and a high histological grade were associated. A sustainable screening program by self-examination to allow early diagnosis is needed to reduce morbidity and mortality from this cancer.

  20. Thermal, spectroscopic and structural characterization of isostructural phase transition in 4-hydroxybenzaldehyde

    NASA Astrophysics Data System (ADS)

    Panicker, Lata

    2018-05-01

    Polycrystalline samples of 4-hydroxybenzaldehyde (4-HOBAL) were investigated using differential scanning calorimeter (DSC), Raman spectroscopy and X-ray powder diffraction. The DSC data indicated that 4-HOBAL on heating undergoes a polymorphic transformation from polymorph I to polymorph II. The polymorph II formed remains metastable at ambient condition and transforms to polymorph I when annealed at ambient temperature for more than seven days. The structural information of polymorphs I and II obtained using its X-ray powder diffraction patterns indicated that 4-HOBAL undergoes an isostructural phase transition from polymorph I (monoclinic, P21/c) to polymorph II (monoclinic, P21/c). Raman data suggest that this structural change is associated with some change in its molecular interactions. Thus, in 4-HOBAL the polymorphic phase transformation (II to I) even though energetically favoured is kinetically hindered.

  1. Stereoselective borylative ketone-diene coupling.

    PubMed

    Cho, Hee Yeon; Yu, Zhiyong; Morken, James P

    2011-10-07

    In the presence of catalytic Ni(cod)(2) and P(t-Bu)(3), ketones, dienes, and B(2)(pin)(2) undergo a stereoselective multicomponent coupling reaction. Upon oxidation, the reaction furnishes 1,3-diols as the major reaction product. © 2011 American Chemical Society

  2. Driving Decisions and Vehicle Crashes Among Older Drivers

    DOT National Transportation Integrated Search

    1995-07-01

    American society is undergoing a major demographic transformation. A larger proportion of the population is becoming older and an increasing number of older individuals are licensed to drive and they drive more than their age cohorts a decade ago. Th...

  3. Gateway Arch Circulator Conceptual Feasibility Study : Jefferson National Expansion Memorial

    DOT National Transportation Integrated Search

    2015-03-01

    The Jefferson National Expansion Memorial (JEFF) is undergoing major design changes as part of the City Arch River 2015 project (CAR) that will impact access for park visitors. The park and stakeholders are considering a circulator system to facilita...

  4. The Great Basin Research and Management Partnership

    USDA-ARS?s Scientific Manuscript database

    The Great Basin is undergoing major sociological and ecological change as a result of urbanization, changing technology and land use, climate change, limited water resources, altered fire regimes, and invasive species, insects, and disease. Sustaining ecosystems, resources, and human populations of...

  5. 75 FR 41206 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-15

    ... Prevention (CDC) works with states, territories, tribal organizations, and the District of Columbia... Federal agencies, nongovernmental organizations, local communities, public and private sector organizations, and major voluntary associations have been critical to the success of these efforts. CDC seeks...

  6. KSC-99pc0165

    NASA Image and Video Library

    1999-02-06

    Cradled in the cargo hold of a tractor-trailer rig called the Space Cargo Transportation System, the Chandra X-ray Observatory reaches the Vertical Processing Facility (VPF). Chandra arrived at the Shuttle Landing Facility on Thursday, Feb. 4, aboard an Air Force C-5 Galaxy aircraft. In the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  7. KSC-99pc0166

    NASA Image and Video Library

    1999-02-06

    Cradled in the cargo hold of a tractor-trailer rig called the Space Cargo Transportation System, the Chandra X-ray Observatory waits to be moved inside the Vertical Processing Facility (VPF). Chandra arrived at the Shuttle Landing Facility on Thursday, Feb. 4, aboard an Air Force C-5 Galaxy aircraft. In the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  8. Secondary migration and leakage of methane from a major tight-gas system

    NASA Astrophysics Data System (ADS)

    Wood, James M.; Sanei, Hamed

    2016-11-01

    Tight-gas and shale-gas systems can undergo significant depressurization during basin uplift and erosion of overburden due primarily to the natural leakage of hydrocarbon fluids. To date, geologic factors governing hydrocarbon leakage from such systems are poorly documented and understood. Here we show, in a study of produced natural gas from 1,907 petroleum wells drilled into a Triassic tight-gas system in western Canada, that hydrocarbon fluid loss is focused along distinct curvilinear pathways controlled by stratigraphic trends with superior matrix permeability and likely also structural trends with enhanced fracture permeability. Natural gas along these pathways is preferentially enriched in methane because of selective secondary migration and phase separation processes. The leakage and secondary migration of thermogenic methane to surficial strata is part of an ongoing carbon cycle in which organic carbon in the deep sedimentary basin transforms into methane, and ultimately reaches the near-surface groundwater and atmosphere.

  9. Secondary migration and leakage of methane from a major tight-gas system

    PubMed Central

    Wood, James M.; Sanei, Hamed

    2016-01-01

    Tight-gas and shale-gas systems can undergo significant depressurization during basin uplift and erosion of overburden due primarily to the natural leakage of hydrocarbon fluids. To date, geologic factors governing hydrocarbon leakage from such systems are poorly documented and understood. Here we show, in a study of produced natural gas from 1,907 petroleum wells drilled into a Triassic tight-gas system in western Canada, that hydrocarbon fluid loss is focused along distinct curvilinear pathways controlled by stratigraphic trends with superior matrix permeability and likely also structural trends with enhanced fracture permeability. Natural gas along these pathways is preferentially enriched in methane because of selective secondary migration and phase separation processes. The leakage and secondary migration of thermogenic methane to surficial strata is part of an ongoing carbon cycle in which organic carbon in the deep sedimentary basin transforms into methane, and ultimately reaches the near-surface groundwater and atmosphere. PMID:27874012

  10. Au/CdS Hybrid Nanoparticles in Block Copolymer Micellar Shells.

    PubMed

    Koh, Haeng-Deog; Changez, Mohammad; Lee, Jae-Suk

    2010-10-18

    A polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) micellar structure with a P2VP core containing 5 nm CdS nanoparticles (NPs) and a PS shell formed in toluene that is a good solvent for PS block undergoes the core-shell inversion by excess addition of methanol that is a good solvent for P2VP block. It leads to the formation of micellar shell-embedded CdS NPs in the methanol major phase. The spontaneous crystalline growth of Au NPs on the CdS surfaces positioned at micellar shells without a further reduction process is newly demonstrated. The nanostructure of Au/CdS/PS-b-P2VP hybrid NPs is confirmed by transmission electron microscopy, energy-dispersive X-ray, and UV-Vis absorption. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. The Chandra X-ray Observatory prepped for removal from its container in the Vertical Processing Faci

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Inside the Vertical Processing Facility (VPF), workers check the overhead cable that will lift the Chandra X-ray Observatory out of its protective container. While in the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe.

  12. The Chandra X-ray Observatory prepped for removal from its container in the Vertical Processing Faci

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Inside the Vertical Processing Facility (VPF), the Chandra X-ray Observatory (top) lies in its protective container while workers on the floor prepare the overhead cable that will remove it. In the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe.

  13. The Chandra X-ray Observatory prepped for removal from its container in the Vertical Processing Faci

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Inside the Vertical Processing Facility (VPF), workers attach the overhead cable to the Chandra X-ray Observatory to lift it out of its protective container. While in the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe.

  14. KSC-99pc0174

    NASA Image and Video Library

    1999-02-08

    In the Vertical Processing Facility (VPF), workers check the placement of the Chandra X-ray Observatory on the stand on the floor. The stand will be used to raise the observatory to a vertical position. While in the VPF, the telescope will undergo final installation of associated electronic components; it will also be tested, fueled and mated with the Inertial Upper Stage booster. A set of integrated tests will follow. Chandra is scheduled for launch July 9 aboard Space Shuttle Columbia, on mission STS-93 . Formerly called the Advanced X-ray Astrophysics Facility, Chandra comprises three major elements: the spacecraft, the science instrument module (SIM), and the world's most powerful X-ray telescope. Chandra will allow scientists from around the world to see previously invisible black holes and high-temperature gas clouds, giving the observatory the potential to rewrite the books on the structure and evolution of our universe

  15. Nuclear Proximity of Mtr4 with RNA exosome restricts DNA mutational asymmetry

    PubMed Central

    Lim, Junghyun; Giri, Pankaj Kumar; Kazadi, David; Laffleur, Brice; Zhang, Wanwei; Grinstein, Veronika; Pefanis, Evangelos; Brown, Lewis M.; Ladewig, Erik; Martin, Ophélie; Chen, Yuling; Rabadan, Raul; Boyer, François; Rothschild, Gerson; Cogné, Michel; Pinaud, Eric; Deng, Haiteng; Basu, Uttiya

    2017-01-01

    SUMMARY The distribution of sense and antisense strand DNA mutations on transcribed duplex DNA contributes to the development of immune and neural systems along with the progression of cancer. Because developmentally matured B cells undergo biologically programmed strand-specific DNA mutagenesis at focal DNA/RNA hybrid structures, they make a convenient system to investigate strand-specific mutagenesis mechanisms. We demonstrate that the sense and antisense strand DNA mutagenesis at the immunoglobulin heavy chain locus and some other regions of the B cell genome depends upon localized RNA processing protein complex formation in the nucleus. Both the physical proximity and coupled activities of RNA helicase Mtr4 (and Senataxin) with the noncoding RNA processing function of RNA exosome determine the strand specific distribution of DNA mutations. Our study suggests that strand-specific DNA mutagenesis-associated mechanisms will play major roles in other undiscovered aspects of organismic development. PMID:28431250

  16. Early impact of Medicare accountable care organizations on cancer surgery outcomes.

    PubMed

    Herrel, Lindsey A; Norton, Edward C; Hawken, Scott R; Ye, Zaojun; Hollenbeck, Brent K; Miller, David C

    2016-09-01

    Accountable care organizations (ACOs) were established to improve care and outcomes for beneficiaries requiring highly coordinated, complex care. The objective of this study was to evaluate the association between hospital ACO participation and the outcomes of major surgical oncology procedures. This was a retrospective cohort study of Medicare beneficiaries older than 65 years who were undergoing a major surgical resection for colorectal, bladder, esophageal, kidney, liver, ovarian, pancreatic, lung, or prostate cancer from 2011 through 2013. A difference-in-differences analysis was implemented to compare the postimplementation period (January 2013 through December 2013) with the baseline period (January 2011 through December 2012) to assess the impact of hospital ACO participation on 30-day mortality, complications, readmissions, and length of stay (LOS). Among 384,519 patients undergoing major cancer surgery at 106 ACO hospitals and 2561 control hospitals, this study found a 30-day mortality rate of 3.4%, a readmission rate of 12.5%, a complication rate of 43.8%, and a prolonged LOS rate of 10.0% in control hospitals and similar rates in ACO hospitals. Secular trends were noted, with reductions in perioperative adverse events in control hospitals between the baseline and postimplementation periods: mortality (percentage-point reduction, 0.1%; P = .19), readmissions (percentage-point reduction, 0.4%; P = .001), complications (percentage-point reduction, 1.0%; P < .001), and prolonged LOS (percentage-point reduction, 1.1%; P < .001). After accounting for these secular trends, this study identified no significant effect of hospital participation in an ACO on the frequency of perioperative outcomes (difference-in-differences estimator P values, .24-.72). Early hospital participation in the Medicare Shared Savings Program ACO program was not associated with greater reductions in adverse perioperative outcomes for patients undergoing major cancer surgery in comparison with control hospitals. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2739-2746. © 2016 American Cancer Society. © 2016 American Cancer Society.

  17. The influence of sarcopenia on survival and surgical complications in ovarian cancer patients undergoing primary debulking surgery.

    PubMed

    Rutten, I J G; Ubachs, J; Kruitwagen, R F P M; van Dijk, D P J; Beets-Tan, R G H; Massuger, L F A G; Olde Damink, S W M; Van Gorp, T

    2017-04-01

    Sarcopenia, severe skeletal muscle loss, has been identified as a prognostic factor in various malignancies. This study aims to investigate whether sarcopenia is associated with overall survival (OS) and surgical complications in patients with advanced ovarian cancer undergoing primary debulking surgery (PDS). Ovarian cancer patients (n = 216) treated with PDS were enrolled retrospectively. Total skeletal muscle surface area was measured on axial computed tomography at the level of the third lumbar vertebra. Optimum stratification was used to find the optimal skeletal muscle index cut-off to define sarcopenia (≤38.73 cm 2 /m 2 ). Cox-regression and Kaplan-Meier analysis were used to analyse the relationship between sarcopenia and OS. The effect of sarcopenia on the development of major surgical complications was studied with logistic regression. Kaplan-Meier analysis showed a significant survival disadvantage for patients with sarcopenia compared to patients without sarcopenia (p = 0.010). Sarcopenia univariably predicted OS (HR 1.536 (95% CI 1.105-2.134), p = 0.011) but was not significant in multivariable Cox-regression analysis (HR 1.362 (95% CI 0.968-1.916), p = 0.076). Significant predictors for OS in multivariable Cox-regression analysis were complete PDS, treatment in a specialised centre and the development of major complications. Sarcopenia was not predictive of major complications. Sarcopenia was not predictive of OS or major complications in ovarian cancer patients undergoing primary debulking surgery. However a strong trend towards a survival disadvantage for patients with sarcopenia was seen. Future prospective studies should focus on interventions to prevent or reverse sarcopenia and possibly increase ovarian cancer survival. Complete cytoreduction remains the strongest predictor of ovarian cancer survival. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  18. Onset of alveolar recirculation in the developing lungs and its consequence on nanoparticle deposition in the pulmonary acinus

    PubMed Central

    Henry, Frank S.

    2015-01-01

    The structure of the gas exchange region of the human lung (the pulmonary acinus) undergoes profound change in the first few years of life. In this paper, we investigate numerically how the change in alveolar shape with time affects the rate of nanoparticle deposition deep in the lung during postnatal development. As human infant data is unavailable, we use a rat model of lung development. The process of postnatal lung development in the rat is remarkably similar to that of the human, and the structure of the rat acinus is indistinguishable from that of the human acinus. The current numerical predictions support our group's recent in vivo findings, which were also obtained by using growing rat lung models, that nanoparticle deposition in infants is strongly affected by the change in the structure of the pulmonary acinus. In humans, this major structural change occurs over the first 2 yr of life. Our current predictions would suggest that human infants at the age of ∼2 yr might be most at risk to the harmful effects of air pollution. Our results also suggest that dose estimates for inhalation therapies using nanoparticles, based on fully developed adult lungs with simple body weight scaling, are likely to overestimate deposition by up to 55% for newborns and underestimate deposition by up to 17% for 2-yr-old infants. PMID:26494453

  19. Embedded micro-sensor for monitoring pH in concrete structures

    NASA Astrophysics Data System (ADS)

    Srinivasan, Rengaswamy; Phillips, Terry E.; Bargeron, C. Brent; Carlson, Micah A.; Schemm, Elizabeth R.; Saffarian, Hassan M.

    2000-04-01

    Three major causes of corrosion of steel in concrete are chloride ions (Cl-), temperature (T) and acidity (pH). Under normal operating temperatures and with pH above 13, steel does not undergo pitting corrosion. In presence of Cl-, if the pH decreases below 12, the probability of pitting increases. Acid rain and atmospheric carbon dioxide cause the pH to drop in concrete, often leading to corrosion of the structure with the concomitant cost of repair or replacement. Currently, the pH level in concrete is estimated through destructive testing of the structures. Glass ISFET, and other pH sensors that need maintenance and calibration cannot be embedded in concrete. In this paper, we describe an inexpensive solid state pH sensor that can be embedded in concrete, to detect pH changes at the early stages. It employs a chemical reagent, trinitrobenzenesulfonic acid (TNBS) that exhibits changes in optical properties in the 12 - 14 pH range, and is held in a film of a sol-gel/TNBS composite on an optically transparent surface. A simple LED/filter/photodiode transducer monitors pH-induced changes in TNBS. Such a device needs no periodic calibration or maintenance. The optical window, the light-source and sensor can be easily housed and encapsulated in a chemically inert structure, and embedded in concrete.

  20. Molecular architecture of human prion protein amyloid: a parallel, in-register beta-structure.

    PubMed

    Cobb, Nathan J; Sönnichsen, Frank D; McHaourab, Hassane; Surewicz, Witold K

    2007-11-27

    Transmissible spongiform encephalopathies (TSEs) represent a group of fatal neurodegenerative diseases that are associated with conformational conversion of the normally monomeric and alpha-helical prion protein, PrP(C), to the beta-sheet-rich PrP(Sc). This latter conformer is believed to constitute the main component of the infectious TSE agent. In contrast to high-resolution data for the PrP(C) monomer, structures of the pathogenic PrP(Sc) or synthetic PrP(Sc)-like aggregates remain elusive. Here we have used site-directed spin labeling and EPR spectroscopy to probe the molecular architecture of the recombinant PrP amyloid, a misfolded form recently reported to induce transmissible disease in mice overexpressing an N-terminally truncated form of PrP(C). Our data show that, in contrast to earlier, largely theoretical models, the con formational conversion of PrP(C) involves major refolding of the C-terminal alpha-helical region. The core of the amyloid maps to C-terminal residues from approximately 160-220, and these residues form single-molecule layers that stack on top of one another with parallel, in-register alignment of beta-strands. This structural insight has important implications for understanding the molecular basis of prion propagation, as well as hereditary prion diseases, most of which are associated with point mutations in the region found to undergo a refolding to beta-structure.

  1. Responses to Overdiagnosis in Thyroid Cancer Screening among Korean Women.

    PubMed

    Lee, Sangeun; Lee, Yoon Young; Yoon, Hyo Joong; Choi, Eunji; Suh, Mina; Park, Boyoung; Jun, Jae Kwan; Kim, Yeol; Choi, Kui Son

    2016-07-01

    Communicating the harms and benefits of thyroid screening is necessary to help individuals decide on whether or not to undergo thyroid cancer screening. This study was conducted to assess changes in thyroid cancer screening intention in response to receiving information about overdiagnosis and to determine factors with the greatest influence thereon. Data were acquired from subjects included in the 2013 Korean National Cancer Screening Survey (KNCSS), a nationwide, population-based, cross-sectional survey. Of the 4,100 respondents in the 2013 KNCSS, women were randomly subsampled and an additional face-to-face interview was conducted. Finally, a total of 586 female subjects were included in this study. Intention to undergo thyroid cancer screening was assessed before and after receiving information on overdiagnosis. Prior awareness of overdiagnosis in thyroid cancer screening was 27.8%. The majority of subjects intended to undergo thyroid cancer screening before and after receiving information on overdiagnosis (87% and 74%, respectively). Only a small number of subjects changed their intention to undergo thyroid cancer screening from positive to negative after receiving information on overdiagnosis. Women of higher education level and Medical Aid Program recipients reported being significantly more likely to change their intention to undergo thyroid cancer screening afterreceiving information on overdiagnosis,whilewomen with stronger beliefs on the efficacy of cancer screening were less likely to change their intention. Women in Korea appeared to be less concerned about overdiagnosis when deciding whether or not to undergo thyroid cancer screening.

  2. Environmental factors influencing the structural dynamics of soil microbial communities during assisted phytostabilization of acid-generating mine tailings: a mesocosm experiment.

    PubMed

    Valentín-Vargas, Alexis; Root, Robert A; Neilson, Julia W; Chorover, Jon; Maier, Raina M

    2014-12-01

    Compost-assisted phytostabilization has recently emerged as a robust alternative for reclamation of metalliferous mine tailings. Previous studies suggest that root-associated microbes may be important for facilitating plant establishment on the tailings, yet little is known about the long-term dynamics of microbial communities during reclamation. A mechanistic understanding of microbial community dynamics in tailings ecosystems undergoing remediation is critical because these dynamics profoundly influence both the biogeochemical weathering of tailings and the sustainability of a plant cover. Here we monitor the dynamics of soil microbial communities (i.e. bacteria, fungi, archaea) during a 12-month mesocosm study that included 4 treatments: 2 unplanted controls (unamended and compost-amended tailings) and 2 compost-amended seeded tailings treatments. Bacterial, fungal and archaeal communities responded distinctively to the revegetation process and concurrent changes in environmental conditions and pore water chemistry. Compost addition significantly increased microbial diversity and had an immediate and relatively long-lasting buffering-effect on pH, allowing plants to germinate and thrive during the early stages of the experiment. However, the compost buffering capacity diminished after six months and acidification took over as the major factor affecting plant survival and microbial community structure. Immediate changes in bacterial communities were observed following plant establishment, whereas fungal communities showed a delayed response that apparently correlated with the pH decline. Fluctuations in cobalt pore water concentrations, in particular, had a significant effect on the structure of all three microbial groups, which may be linked to the role of cobalt in metal detoxification pathways. The present study represents, to our knowledge, the first documentation of the dynamics of the three major microbial groups during revegetation of compost-amended, metalliferous mine tailings. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Environmental Factors Influencing the Structural Dynamics of Soil Microbial Communities During Assisted Phytostabilization of Acid-Generating Mine Tailings: a Mesocosm Experiment

    PubMed Central

    Valentín-Vargas, Alexis; Root, Robert A.; Neilson, Julia W; Chorover, Jon; Maier, Raina M.

    2014-01-01

    Compost-assisted phytostabilization has recently emerged as a robust alternative for reclamation of metalliferous mine tailings. Previous studies suggest that root-associated microbes may be important for facilitating plant establishment on the tailings, yet little is known about the long-term dynamics of microbial communities during reclamation. A mechanistic understanding of microbial community dynamics in tailings ecosystems undergoing remediation is critical because these dynamics profoundly influence both the biogeochemical weathering of tailings and the sustainability of a plant cover. Here we monitor the dynamics of soil microbial communities (i.e. bacteria, fungi, archaea) during a 12-month mesocosm study that included 4 treatments: 2 unplanted controls (unamended and compost-amended tailings) and 2 compost-amended seeded tailings treatments. Bacterial, fungal and archaeal communities responded distinctively to the revegetation process and concurrent changes in environmental conditions and pore water chemistry. Compost addition significantly increased microbial diversity and had an immediate and relatively long-lasting buffering-effect on pH, allowing plants to germinate and thrive during the early stages of the experiment. However, the compost buffering capacity diminished after six months and acidification took over as the major factor affecting plant survival and microbial community structure. Immediate changes in bacterial communities were observed following plant establishment, whereas fungal communities showed a delayed response that apparently correlated with the pH decline. Fluctuations in cobalt pore water concentrations, in particular, had a significant effect on the structure of all three microbial groups, which may be linked to the role of cobalt in metal detoxification pathways. The present study represents, to our knowledge, the first documentation of the dynamics of the three major microbial groups during revegetation of compost-amended, metalliferous mine tailings. PMID:25237788

  4. Impact of patients nutritional status on major surgery outcome.

    PubMed

    Mignini, E V; Scarpellini, E; Rinninella, E; Lattanzi, E; Valeri, M V; Clementi, N; Abenavoli, L; Gasbarrini, A; Rasetti, C; Santori, P

    2018-06-01

    Surgery is a major stress factor that activates several inflammatory and catabolic pathways in man. An appropriate nutritional status allows the body to react properly to this stressor and recover in a faster and more efficient manner. On the other hand, malnutrition is related to a worse surgery outcome and to a higher prevalence of comorbidities and mortality. The aims of this study were to evaluate the nutritional status of patients undergoing major surgery and investigate the potential correlation between malnutrition and surgical outcomes. Mini Nutritional Assessment (MNA) and global clinical examination (including biochemical parameters and comorbidities existence) were undertaken in 50 consecutive patients undergoing major surgery. Patients' clinical conditions were re-evaluated at 3 and 6 days after surgery, recording biochemical parameters and systemic and/or wound-related complications. A compromised nutritional status was present in more than half (54%) of patients (malnutrition in 10% and risk of malnutrition in 44% of patients, respectively). Females were slightly more at risk of malnutrition (48% vs. 41%, p=NS, females vs. males) and clearly malnourished (14% vs. 7%, p<0.05, females vs. males). Age was an independent risk factor for malnutrition and within the elders' group (> 80 years old) 16.70% of patients was diagnosed with malnutrition and 58.3% was at risk of malnutrition. Systemic complications were registered in all patients both at 3 and 6 days after surgery. However, well-nourished and at-risk of malnutrition patients had earlier complications that only partially resolved within six days after the operation. Malnourished patients showed fewer complications at the 3rd post-surgery follow-up day but had a worse outcome six days after surgery. Older age and but not female sex are independent risk factors for malnutrition development in patients undergoing major surgery. More interestingly, more than half of patients with an impaired nutritional status presented a less appropriated stress response to surgery. These data suggest that nutritional status assessment may be important to recognize patients at potential risk of surgical complications and that early nutritional interventions must be promptly arranged.

  5. Predictors of major complications after elective abdominal surgery in cancer patients.

    PubMed

    Simões, Claudia M; Carmona, Maria J C; Hajjar, Ludhmila A; Vincent, Jean-Louis; Landoni, Giovanni; Belletti, Alessandro; Vieira, Joaquim E; de Almeida, Juliano P; de Almeida, Elisangela P; Ribeiro, Ulysses; Kauling, Ana L; Tutyia, Celso; Tamaoki, Lie; Fukushima, Julia T; Auler, José O C

    2018-05-09

    Patients undergoing abdominal surgery for solid tumours frequently develop major postoperative complications, which negatively affect quality of life, costs of care and survival. Few studies have identified the determinants of perioperative complications in this group. We performed a prospective observational study including all patients (age > 18) undergoing abdominal surgery for cancer at a single institution between June 2011 and August 2013. Patients undergoing emergency surgery, palliative procedures, or participating in other studies were excluded. Primary outcome was a composite of 30-day all-cause mortality and infectious, cardiovascular, respiratory, neurologic, renal and surgical complications. Univariate and multiple logistic regression analyses were performed to identify predictive factors for major perioperative adverse events. Of a total 308 included patients, 106 (34.4%) developed a major complication during the 30-day follow-up period. Independent predictors of postoperative major complications were: age (odds ratio [OR] 1.03 [95% CI 1.01-1.06], p = 0.012 per year), ASA (American Society of Anesthesiologists) physical status greater than or equal to 3 (OR 2.61 [95% CI 1.33-5.17], p = 0.003), a preoperative haemoglobin level lower than 12 g/dL (OR 2.13 [95% CI 1.21-4.07], p = 0.014), intraoperative use of colloids (OR 1.89, [95% CI 1.03-4.07], p = 0.047), total amount of intravenous fluids (OR 1.22 [95% CI 0.98-1.59], p = 0.106 per litre), intraoperative blood losses greater than 500 mL (2.07 [95% CI 1.00-4.31], p = 0.043), and hypotension needing vasopressor support (OR 4.68 [95% CI 1.55-27.72], p = 0.004). The model had good discrimination with the area under the ROC curve being 0.80 (95% CI 0.75-0.84, p < 0.001). Our findings suggest that a perioperative strategy aimed at reducing perioperative complications in cancer surgery should include treatment of preoperative anaemia and an optimal fluid strategy, avoiding fluid overload and intraoperative use of colloids.

  6. Microsatellite Analysis of Museum Specimens Reveals Historical Differences in Genetic Diversity between Declining and More Stable Bombus Species.

    PubMed

    Maebe, Kevin; Meeus, Ivan; Ganne, Maarten; De Meulemeester, Thibaut; Biesmeijer, Koos; Smagghe, Guy

    2015-01-01

    Worldwide most pollinators, e.g. bumblebees, are undergoing global declines. Loss of genetic diversity can play an essential role in these observed declines. In this paper, we investigated the level of genetic diversity of seven declining Bombus species and four more stable species with the use of microsatellite loci. Hereto we genotyped a unique collection of museum specimens. Specimens were collected between 1918 and 1926, in 6 provinces of the Netherlands which allowed us to make interspecific comparisons of genetic diversity. For the stable species B. pascuorum, we also selected populations from two additional time periods: 1949-1955 and 1975-1990. The genetic diversity and population structure in B. pascuorum remained constant over the three time periods. However, populations of declining bumblebee species showed a significantly lower genetic diversity than co-occurring stable species before their major declines. This historical difference indicates that the repeatedly observed reduced genetic diversity in recent populations of declining bumblebee species is not caused solely by the decline itself. The historically low genetic diversity in the declined species may be due to the fact that these species were already rare, making them more vulnerable to the major drivers of bumblebee decline.

  7. Flexible Animation Computer Program

    NASA Technical Reports Server (NTRS)

    Stallcup, Scott S.

    1990-01-01

    FLEXAN (Flexible Animation), computer program animating structural dynamics on Evans and Sutherland PS300-series graphics workstation with VAX/VMS host computer. Typical application is animation of spacecraft undergoing structural stresses caused by thermal and vibrational effects. Displays distortions in shape of spacecraft. Program displays single natural mode of vibration, mode history, or any general deformation of flexible structure. Written in FORTRAN 77.

  8. The cell's nucleolus: an emerging target for chemotherapeutic intervention.

    PubMed

    Pickard, Amanda J; Bierbach, Ulrich

    2013-09-01

    The transient nucleolus plays a central role in the up-regulated synthesis of ribosomal RNA (rRNA) to sustain ribosome biogenesis, a hallmark of aberrant cell growth. This function, in conjunction with its unique pathohistological features in malignant cells and its ability to mediate apoptosis, renders this sub-nuclear structure a potential target for chemotherapeutic agents. In this Minireview, structurally and functionally diverse small molecules are discussed that have been reported to either interact with the nucleolus directly or perturb its function indirectly by acting on its dynamic components. These molecules include all major classes of nucleic-acid-targeted agents, antimetabolites, kinase inhibitors, anti-inflammatory drugs, natural product antibiotics, oligopeptides, as well as nanoparticles. Together, these molecules are invaluable probes of structure and function of the nucleolus. They also provide a unique opportunity to develop novel strategies for more selective and therefore better-tolerated chemotherapeutic intervention. In this regard, inhibition of RNA polymerase-I-mediated rRNA synthesis appears to be a promising mechanism for killing cancer cells. The recent development of molecules targeted at G-quadruplex-forming rRNA gene sequences, which are currently undergoing clinical trials, seems to attest to the success of this approach. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. DNA secondary structures are associated with recombination in major Plasmodium falciparum variable surface antigen gene families

    PubMed Central

    Sander, Adam F.; Lavstsen, Thomas; Rask, Thomas S.; Lisby, Michael; Salanti, Ali; Fordyce, Sarah L.; Jespersen, Jakob S.; Carter, Richard; Deitsch, Kirk W.; Theander, Thor G.; Pedersen, Anders Gorm; Arnot, David E.

    2014-01-01

    Many bacterial, viral and parasitic pathogens undergo antigenic variation to counter host immune defense mechanisms. In Plasmodium falciparum, the most lethal of human malaria parasites, switching of var gene expression results in alternating expression of the adhesion proteins of the Plasmodium falciparum-erythrocyte membrane protein 1 class on the infected erythrocyte surface. Recombination clearly generates var diversity, but the nature and control of the genetic exchanges involved remain unclear. By experimental and bioinformatic identification of recombination events and genome-wide recombination hotspots in var genes, we show that during the parasite’s sexual stages, ectopic recombination between isogenous var paralogs occurs near low folding free energy DNA 50-mers and that these sequences are heavily concentrated at the boundaries of regions encoding individual Plasmodium falciparum-erythrocyte membrane protein 1 structural domains. The recombinogenic potential of these 50-mers is not parasite-specific because these sequences also induce recombination when transferred to the yeast Saccharomyces cerevisiae. Genetic cross data suggest that DNA secondary structures (DSS) act as inducers of recombination during DNA replication in P. falciparum sexual stages, and that these DSS-regulated genetic exchanges generate functional and diverse P. falciparum adhesion antigens. DSS-induced recombination may represent a common mechanism for optimizing the evolvability of virulence gene families in pathogens. PMID:24253306

  10. Safety and feasibility of leadless pacemaker in patients undergoing atrioventricular node ablation for atrial fibrillation.

    PubMed

    Yarlagadda, Bharath; Turagam, Mohit K; Dar, Tawseef; Jangam, Pragna; Veerapaneni, Vaishnavi; Atkins, Donita; Bommana, Sudharani; Friedman, Paul; Deshmukh, Abhishek J; Doshi, Rahul; Reddy, Vivek Y; Dukkipati, Srinivas R; Natale, Andrea; Lakkireddy, Dhanunjaya

    2018-03-01

    Atrioventricular node (AVN) ablation and permanent pacing is an established strategy for rate control in the management of symptomatic atrial fibrillation (AF). Leadless pacemakers (LPs) can overcome some of the short-term and long-term limitations of conventional transvenous pacemakers (CTPs). The purpose of this study was to compare the feasibility and safety of LP with those of single-chamber CTP in patients with AF undergoing AVN ablation. We conducted a multicenter observational study of patients undergoing AVN ablation and pacemaker implantation (LP vs single-chamber CTP) between February 2014 and November 2016. The primary efficacy end points were acceptable sensing (R wave ≥5.0 mV) and pacing thresholds (≤2.0 V at 0.4 ms) at follow-up. Safety end points included device-related major and minor (early ≤1 month, late >1 month) adverse events. A total of 127 patients with LP (n = 60) and CTP (n = 67) were studied. The median follow-up was 12 months (interquartile range 12-18 months). Ninety-five percent of the LP group and 97% of the CTP group met the primary efficacy end point at follow-up (57 of 60 vs 65 of 67; P = .66). There was 1 major adverse event (loss of pacing and sensing) in the LP group and 2 (lead dislodgement) in the CTP group (1 of 60 vs 2 of 67; P = 1.00). There were 6 minor adverse events (5 early and 1 late) in the LP group and 3 (early) in the CTP group (6 of 60 vs 3 of 67; P = .30). Our results demonstrate the feasibility and safety of LP compared with CTP in patients undergoing AVN ablation for AF. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  11. Post-thyroidectomy complications. The role of the device: bipolar vs ultrasonic device: Collection of data from 1,846 consecutive patients undergoing thyroidectomy.

    PubMed

    De Palma, Maurizio; Rosato, Ludovico; Zingone, Fabiana; Orlando, Giulio; Antonino, Antonio; Vitale, Mario; Puzziello, Alessandro

    2016-07-01

    Specific complications after thyroid surgery, such as recurrent laryngeal nerve injury (RLN) or hypoparathyroidism, are feared because they may give rise to a lifelong disability for the patient. The aim of this study was to evaluate the possible association between the types of device used (bipolar vs ultrasound-based harmonic scalpel defined Harmonic Focus) and major postoperative complications. During a 1-year period, between October 2010 and October 2011, Italian Endocrine Surgery Units affiliated with the Italian Endocrine Surgery Units Association collected data on all consecutive patients older than 18 years who had undergone primary total thyroidectomy, near total thyroidectomy, and completion thyroidectomy. The data were included in a dataset, listing demographic variables, details on the surgical procedure, and 2 major complications of the thyroid surgery: postoperative RLN palsy/hypomobility and hypocalcemia. Our population comprised 1,846 subjects (78.6% women, median age 52 years). Six hundred four (32.7%) subjects underwent thyroidectomy by bipolar forceps and 1,242 (67.3%) by ultrasonic device. The risk of hypocalcemia in subjects undergoing thyroidectomy by ultrasonic device was similar to those undergoing thyroidectomy by bipolar after adjusting for sex, type of thyroidectomy, and central lymphadenectomy (odds ratio .94, 95% confidence interval .76 to 1.17). Subjects who underwent thyroidectomy by ultrasonic device had a lower risk of RLN paralysis compared with those undergoing thyroidectomy by bipolar forceps also after adjusting for central lymphadenectomy (odds ratio .39, 95% confidence interval .2 to .7). This multicenter study acknowledges the value of the ultrasonic device as a protective factor only for RLN palsy, confirming nodal dissection as a risk factor for postoperative hypocalcemia and vocal folds disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. The Value of the SYNTAX Score II in Predicting Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Implantation.

    PubMed

    Ryan, Nicola; Nombela-Franco, Luis; Jiménez-Quevedo, Pilar; Biagioni, Corina; Salinas, Pablo; Aldazábal, Andrés; Cerrato, Enrico; Gonzalo, Nieves; Del Trigo, María; Núñez-Gil, Iván; Fernández-Ortiz, Antonio; Macaya, Carlos; Escaned, Javier

    2017-11-27

    The predictive value of the SYNTAX score (SS) for clinical outcomes after transcatheter aortic valve implantation (TAVI) is very limited and could potentially be improved by the combination of anatomic and clinical variables, the SS-II. We aimed to evaluate the value of the SS-II in predicting outcomes in patients undergoing TAVI. A total of 402 patients with severe symptomatic aortic stenosis undergoing transfemoral TAVI were included. Preprocedural TAVI angiograms were reviewed and the SS-I and SS-II were calculated using the SS algorithms. Patients were stratified in 3 groups according to SS-II tertiles. The coprimary endpoints were all-cause death and major adverse cardiovascular events (MACE), a composite of all-cause death, cerebrovascular event, or myocardial infarction at 1 year. Increased SS-II was associated with higher 30-day mortality (P=.036) and major bleeding (P=.015). The 1-year risk of death and MACE was higher among patients in the 3rd SS-II tertile (HR, 2.60; P=.002 and HR, 2.66; P<.001) and was similar among patients in the 2nd tertile (HR, 1.27; P=.507 and HR, 1.05; P=.895) compared with patients in the 1st tertile. The highest SS-II tertile was an independent predictor of long-term mortality (P=.046) and MACE (P=.001). The SS-II seems more suited to predict clinical outcomes in patients undergoing TAVI than the SS-I. Increased SS-II was associated with poorer clinical outcomes at 1 and 4 years post-TAVI, independently of the presence of coronary artery disease. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  13. Postoperative hyperglycaemia of diabetic patients undergoing cardiac surgery - a clinical audit.

    PubMed

    Lehwaldt, Daniela; Kingston, Mary; O'Connor, Sheila

    2009-01-01

    Previous studies have shown that hyperglycaemia is associated with postoperative complications in cardiac surgical patients. Conversely, well-controlled glucose levels are said to reduce major infectious complications in diabetic patients. The purpose of this clinical audit was to evaluate the blood glucose levels of diabetic patients undergoing cardiac surgery and to determine the effectiveness of postoperative glycaemic control. A group of 150 patients from a large Irish cardiac surgery centre was selected by convenience sampling. An audit tool was designed to capture the patients' blood glucose levels, treatment regimes and postoperative complications. The findings showed major variations between 'high', 'good' and 'borderline' blood glucose levels in the pre- and postoperative phase. Although blood glucose testing practices seemed inconsistent, mean levels measured 'borderline'. Furthermore, the treatment regimes varied greatly and suggest a lack of consensus regarding the management of postoperative hyperglycaemia. A total of 52% (n = 78) patients developed 114 complications with a level of 21.4% (n = 32) postoperative wound infections. The findings from this audit highlight the importance of regular blood glucose testing to enable early detection of hyperglycaemia and timely initiation of appropriate treatments regimes for diabetic patients undergoing cardiac surgery. Findings also show that hyperglycaemia derangement may make a difference in the recovery phase. While patients will benefit from lesser wound infections, hospitals might save costs involved with treating postoperative complications. More consistent blood glucose testing might be achieved through the use of evidence-based protocols. However, the education of staff is as important as it develops knowledge on the complex metabolic interactions of diabetic patients undergoing cardiac surgery. While this means investing in staff education and policy development, costs for daily care and expensive treatments for complications will be saved as patient recovery will be speedier and less eventful.

  14. Role of Halides in the Ordered Structure Transitions of Heated Gold Nanocrystal Superlattices

    PubMed Central

    2015-01-01

    Dodecanethiol-capped gold (Au) nanocrystal superlattices can undergo a surprisingly diverse series of ordered structure transitions when heated (Goodfellow, B. W.; Rasch, M. R.; Hessel, C. M.; Patel, R. N.; Smilgies, D.-M.; Korgel, B. A. Nano Lett.2013, 13, 5710–5714). These are the result of highly uniform changes in nanocrystal size, which subsequently force a spontaneous rearrangement of superlattice structure. Here, we show that halide-containing surfactants play an essential role in these transitions. In the absence of any halide-containing surfactant, superlattices of dodecanethiol-capped (1.9-nm-diameter) Au nanocrystals do not change size until reaching about 190–205 °C, at which point the gold cores coalesce. In the presence of halide-containing surfactant, such as tetraoctylphosphonium bromide (TOPB) or tetraoctylammounium bromide (TOAB), the nanocrystals ripen at much lower temperature and superlattices undergo various ordered structure transitions upon heating. Chloride- and iodide-containing surfactants induce similar behavior, destabilizing the Au–thiol bond and reducing the thermal stability of the nanocrystals. PMID:26013597

  15. Crystal Structure and Proteomics Analysis of Empty Virus-like Particles of Cowpea Mosaic Virus

    PubMed Central

    Huynh, Nhung T.; Hesketh, Emma L.; Saxena, Pooja; Meshcheriakova, Yulia; Ku, You-Chan; Hoang, Linh T.; Johnson, John E.; Ranson, Neil A.; Lomonossoff, George P.; Reddy, Vijay S.

    2016-01-01

    SUMMARY Empty virus-like particles (eVLPs) of Cowpea mosaic virus (CPMV) are currently being utilized as reagents in various biomedical and nanotechnology applications. Here, we report the crystal structure of CPMV eVLPs determined using X-ray crystallography at 2.3 Å resolution and compare it with previously reported cryo-electron microscopy (cryo-EM) of eVLPs and virion crystal structures. Although the X-ray and cryo-EM structures of eVLPs are mostly similar, there exist significant differences at the C terminus of the small (S) subunit. The intact C terminus of the S subunit plays a critical role in enabling the efficient assembly of CPMV virions and eVLPs, but undergoes proteolysis after particle formation. In addition, we report the results of mass spectrometry-based proteomics analysis of coat protein subunits from CPMV eVLPs and virions that identify the C termini of S subunits undergo proteolytic cleavages at multiple sites instead of a single cleavage site as previously observed. PMID:27021160

  16. An origin of arc structures deeply embedded in dense molecular cloud cores

    NASA Astrophysics Data System (ADS)

    Matsumoto, Tomoaki; Onishi, Toshikazu; Tokuda, Kazuki; Inutsuka, Shu-ichiro

    2015-04-01

    We investigated the formation of arc-like structures in the infalling envelope around protostars, motivated by the recent Atacama Large Millimeter/Submillimeter Array (ALMA) observations of the high-density molecular cloud core, MC27/L1521F. We performed self-gravitational hydrodynamical numerical simulations with an adaptive mesh refinement code. A filamentary cloud with a 0.1 pc width fragments into cloud cores because of perturbations due to weak turbulence. The cloud core undergoes gravitational collapse to form multiple protostars, and gravitational torque from the orbiting protostars produces arc structures extending up to a 1000 au scale. As well as on a spatial extent, the velocity ranges of the arc structures, ˜0.5 km s-1, are in agreement with the ALMA observations. We also found that circumstellar discs are often misaligned in triple system. The misalignment is caused by the tidal interaction between the protostars when they undergo close encounters because of a highly eccentric orbit of the tight binary pair.

  17. The Great Basin Research and Management Partnership: Facilitating Collaborative Solutions

    USDA-ARS?s Scientific Manuscript database

    The Great Basin is undergoing major sociological and ecological change as a result of urbanization, changing technology and land use, climate change, limited water resources, altered fire regimes, and invasive species, insects, and disease. Sustaining ecosystems, resources, and human populations of...

  18. Atomic Structure of Salutaridine Reductase from the Opium Poppy (Papaver somniferum)

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

    Higashi, Yasuhiro; Kutchan, Toni M.; Smith, Thomas J.

    The opium poppy (Papaver somniferum L.) is one of the oldest known medicinal plants. In the biosynthetic pathway for morphine and codeine, salutaridine is reduced to salutaridinol by salutaridine reductase (SalR; EC 1.1.1.248) using NADPH as coenzyme. Here, we report the atomic structure of SalR to a resolution of {approx}1.9 {angstrom} in the presence of NADPH. The core structure is highly homologous to other members of the short chain dehydrogenase/reductase family. The major difference is that the nicotinamide moiety and the substrate-binding pocket are covered by a loop (residues 265-279), on top of which lies a large 'flap'-like domain (residuesmore » 105-140). This configuration appears to be a combination of the two common structural themes found in other members of the short chain dehydrogenase/reductase family. Previous modeling studies suggested that substrate inhibition is due to mutually exclusive productive and nonproductive modes of substrate binding in the active site. This model was tested via site-directed mutagenesis, and a number of these mutations abrogated substrate inhibition. However, the atomic structure of SalR shows that these mutated residues are instead distributed over a wide area of the enzyme, and many are not in the active site. To explain how residues distal to the active site might affect catalysis, a model is presented whereby SalR may undergo significant conformational changes during catalytic turnover.« less

  19. Chemotaxis in densely populated tissue determines germinal center anatomy and cell motility: a new paradigm for the development of complex tissues.

    PubMed

    Hawkins, Jared B; Jones, Mark T; Plassmann, Paul E; Thorley-Lawson, David A

    2011-01-01

    Germinal centers (GCs) are complex dynamic structures that form within lymph nodes as an essential process in the humoral immune response. They represent a paradigm for studying the regulation of cell movement in the development of complex anatomical structures. We have developed a simulation of a modified cyclic re-entry model of GC dynamics which successfully employs chemotaxis to recapitulate the anatomy of the primary follicle and the development of a mature GC, including correctly structured mantle, dark and light zones. We then show that correct single cell movement dynamics (including persistent random walk and inter-zonal crossing) arise from this simulation as purely emergent properties. The major insight of our study is that chemotaxis can only achieve this when constrained by the known biological properties that cells are incompressible, exist in a densely packed environment, and must therefore compete for space. It is this interplay of chemotaxis and competition for limited space that generates all the complex and biologically accurate behaviors described here. Thus, from a single simple mechanism that is well documented in the biological literature, we can explain both higher level structure and single cell movement behaviors. To our knowledge this is the first GC model that is able to recapitulate both correctly detailed anatomy and single cell movement. This mechanism may have wide application for modeling other biological systems where cells undergo complex patterns of movement to produce defined anatomical structures with sharp tissue boundaries.

  20. Activator Protein-1: redox switch controlling structure and DNA-binding.

    PubMed

    Yin, Zhou; Machius, Mischa; Nestler, Eric J; Rudenko, Gabby

    2017-11-02

    The transcription factor, activator protein-1 (AP-1), binds to cognate DNA under redox control; yet, the underlying mechanism has remained enigmatic. A series of crystal structures of the AP-1 FosB/JunD bZIP domains reveal ordered DNA-binding regions in both FosB and JunD even in absence DNA. However, while JunD is competent to bind DNA, the FosB bZIP domain must undergo a large conformational rearrangement that is controlled by a 'redox switch' centered on an inter-molecular disulfide bond. Solution studies confirm that FosB/JunD cannot undergo structural transition and bind DNA when the redox-switch is in the 'OFF' state, and show that the mid-point redox potential of the redox switch affords it sensitivity to cellular redox homeostasis. The molecular and structural studies presented here thus reveal the mechanism underlying redox-regulation of AP-1 Fos/Jun transcription factors and provide structural insight for therapeutic interventions targeting AP-1 proteins. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. Early relapse after single auto-SCT for multiple myeloma is a major predictor of survival in the era of novel agents.

    PubMed

    Jimenez-Zepeda, V H; Reece, D E; Trudel, S; Chen, C; Tiedemann, R; Kukreti, V

    2015-02-01

    The role of auto-SCT in the treatment of multiple myeloma (MM) in the era of novel agents continues to evolve. It is now clear that the depth of response and clinical outcomes have significantly improved as a result of the combination of these strategies. However, not all patients with MM who undergo auto-SCT are able to sustain a meaningful response and 20% of patients relapse shortly after auto-SCT. In this study, we aimed to assess the impact of early relapse (ER) after auto-SCT on OS for MM patients undergoing single auto-SCT who had received novel agent-based induction regimens. All consecutive patients with MM undergoing single auto-SCT from January 2002 to September 2012 who had novel induction therapy were evaluated. A total of 184 patients were identified. The median OS and PFS for the group of transplanted patients were 93 and 25.4 months, respectively. Median time to relapse was 17.2 months with 40% having relapsed at the time of analysis. ER (<12 months post auto-SCT) was seen in 27 (36%) out of 75 patients who had relapsed, and median OS was significantly shorter than in those with non-ER. Multivariate analysis showed ER as the major independent prognostic factor for OS. On the basis of these findings, we conclude that not only attainment of a good response, but sustainability of it, appears to be a major prognostic variable in MM in the era of novel therapy. Patients with ER post auto-SCT should biologically be characterized in prospective studies to better understand the mechanisms of resistance associated with this particular entity.

  2. A comparison of three antiemetic combinations for the prevention of postoperative nausea and vomiting.

    PubMed

    Sanchez-Ledesma, M J; López-Olaondo, L; Pueyo, F J; Carrascosa, F; Ortega, A

    2002-12-01

    In this study we compared the efficacy and safety of three antiemetic combinations in the prevention of postoperative nausea and vomiting (PONV). Ninety ASA status I-II women, aged 18-65 yr, undergoing general anesthesia for major gynecological surgery, were included in a prospective, randomized, double-blinded study. A standardized anesthetic technique and postoperative analgesia (intrathecal morphine plus IV patient-controlled analgesia (PCA) with morphine) were used in all patients. Patients were randomly assigned to receive ondansetron 4 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 1, n = 30), dexamethasone 8 mg plus droperidol 1.25 mg after the induction of anesthesia and droperidol 1.25 mg 12 h later (Group 2, n = 30), or ondansetron 4 mg plus dexamethasone 8 mg after the induction of anesthesia and placebo 12 h later (Group 3, n = 30). A complete response, defined as no PONV in 48 h, occurred in 80% of patients in Group 1, 70% in Group 3, and 40% in Group 2 (P = 0.004 versus Groups 1 and 3). The incidences of side effects and other variables that could modify the incidence of PONV were similar among groups. In conclusion, ondansetron, in combination with droperidol or dexamethasone, is more effective than dexamethasone in combination with droperidol in women undergoing general anesthesia for major gynecological surgery with intrathecal morphine plus IV PCA with morphine for postoperative analgesia. The combination of ondansetron plus dexamethasone or droperidol was significantly better than the combination of dexamethasone plus droperidol in the prophylaxis of postoperative nausea and vomiting in women undergoing general anesthesia for major gynecological surgery, with intrathecal and IV morphine (patient-controlled analgesia) for management of postoperative pain.

  3. Effect of Epsilon Aminocaproic Acid on Red-Cell Transfusion Requirements in Major Spinal Surgery

    PubMed Central

    Berenholtz, Sean M.; Pham, Julius Cuong; Garrett-Mayer, Elizabeth; Atchison, Christine W; Kostuik, John P.; Cohen, David B.; Nundy, Shantanu; Dorman, Todd; Ness, Paul M.; Klag, Michael J.; Pronovost, Peter J.; Kebaish, Khaled M.

    2009-01-01

    Study Design Randomized, placebo-controlled trial Objective To evaluate the efficacy of epsilon aminocaproic acid (EACA) to reduce the number of red-cell (RBC) transfusions in adult patients undergoing major spinal surgery. Summary of Background Data Reconstructive spinal surgery is associated with significant blood loss. The number of studies evaluating the efficacy of EACA in adult patients undergoing spinal surgery remains scarce and limited. Methods EACA (100 mg/kg) or placebo was administered to 182 adult patients after the induction of anesthesia followed by an infusion that was continued for 8 hours postoperatively. Primary end-points included total allogeneic RBC transfusions through postoperative day (POD) 8 and postoperative allogeneic plus autologus RBC transfusions through POD 8. Results Mean total allogeneic RBC transfusions were not statistically different between the groups (5.9 units EACA versus 6.9 units placebo; P=0.17). Mean postoperative RBC transfusions in the EACA group was less (2.0 units versus 2.8 units placebo; P=0.03). There was no significant difference in mean estimated intraoperative EBL (2938 cc EACA vs. 3273 cc placebo; P=0.32). Mean intensive care unit length of stay was decreased (EACA 1.8 days versus 2.8 days placebo; P=0.04). The incidence of thromboembolic complications was similar (2.2% EACA vs 6.6% placebo; P=0.15). Conclusions The difference in total allogeneic RBC transfusions between the groups was not statistically significant. EACA was associated with a 30% (0.8 units) reduction in postoperative RBC transfusions and a one-day reduction in ICU LOS, without an increased incidence of thromboembolic events. EACA may be considered for patients undergoing major spinal surgery. Larger studies are needed to evaluate the relationship between EACA and total RBC requirements. PMID:19730217

  4. Effect of epsilon aminocaproic acid on red-cell transfusion requirements in major spinal surgery.

    PubMed

    Berenholtz, Sean M; Pham, Julius Cuong; Garrett-Mayer, Elizabeth; Atchison, Christine W; Kostuik, John P; Cohen, David B; Nundy, Shantanu; Dorman, Todd; Ness, Paul M; Klag, Michael J; Pronovost, Peter J; Kebaish, Khaled M

    2009-09-01

    : Randomized, placebo-controlled trial. : To evaluate the efficacy of epsilon aminocaproic acid (EACA) to reduce the number of red-cell (RBC) transfusions in adult patients undergoing major spinal surgery. : Reconstructive spinal surgery is associated with significant blood loss. The number of studies evaluating the efficacy of EACA in adult patients undergoing spinal surgery remains scarce and limited. : EACA (100 mg/kg) or placebo was administered to 182 adult patients after the induction of anesthesia followed by an infusion that was continued for 8 hours after surgery. Primary end points included total allogeneic RBC transfusions through postoperative day 8 and postoperative allogeneic plus autologus RBC transfusions through postoperative day 8. : Mean total allogeneic RBC transfusions were not statistically different between the groups (5.9 units EACA vs. 6.9 units placebo; P = 0.17). Mean postoperative RBC transfusions in the EACA group was less (2.0 units vs. 2.8 units placebo; P = 0.03). There was no significantdifference in mean estimated intraoperative estimated-blood loss (2938 cc EACA vs. 3273 cc placebo; P = 0.32). Mean intensive care unit length of stay was decreased (EACA: 1.8 days vs. 2.8 days placebo; P = 0.04). The incidence of thromboembolic complications was similar (2.2% EACA vs. 6.6% placebo; P = 0.15). : The difference in total allogeneic RBC transfusions between the groups was not statistically significant. EACA was associated with a 30% (0.8 units) reduction in postoperative RBC transfusions and a 1-day reduction in ICU LOS, without an increased incidence of thromboembolic events. EACA may be considered for patients undergoing major spinal surgery. Larger studies are needed to evaluate the relationship between EACA and total RBC requirements.

  5. Safety and performance of a novel embolic deflection device in patients undergoing transcatheter aortic valve replacement: results from the DEFLECT I study.

    PubMed

    Baumbach, Andreas; Mullen, Michael; Brickman, Adam M; Aggarwal, Suneil K; Pietras, Cody G; Forrest, John K; Hildick-Smith, David; Meller, Stephanie M; Gambone, Louise; den Heijer, Peter; Margolis, Pauliina; Voros, Szilard; Lansky, Alexandra J

    2015-05-01

    This study aimed to evaluate the safety and performance of the TriGuard™ Embolic Deflection Device (EDD), a nitinol mesh filter positioned in the aortic arch across all three major cerebral artery take-offs to deflect emboli away from the cerebral circulation, in patients undergoing transcatheter aortic valve replacement (TAVR). The prospective, multicentre DEFLECT I study (NCT01448421) enrolled 37 consecutive subjects undergoing TAVR with the TriGuard EDD. Subjects underwent clinical and cognitive follow-up to 30 days; cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) was performed pre-procedure and at 4±2 days post procedure. The device performed as intended with successful cerebral coverage in 80% (28/35) of cases. The primary safety endpoint (in-hospital EDD device- or EDD procedure-related cardiovascular mortality, major stroke disability, life-threatening bleeding, distal embolisation, major vascular complications, or need for acute cardiac surgery) occurred in 8.1% of subjects (VARC-defined two life-threatening bleeds and one vascular complication). The presence of new cerebral ischaemic lesions on post-procedure DW-MRI (n=28) was similar to historical controls (82% vs. 76%, p=NS). However, an exploratory analysis found that per-patient total lesion volume was 34% lower than reported historical data (0.2 vs. 0.3 cm3), and 89% lower in patients with complete (n=17) versus incomplete (n=10) cerebral vessel coverage (0.05 vs. 0.45 cm3, p=0.016). Use of the first-generation TriGuard EDD during TAVR is safe, and device performance was successful in 80% of cases during the highest embolic-risk portions of the TAVR procedure. The potential of the TriGuard EDD to reduce total cerebral ischaemic burden merits further randomised investigation.

  6. Impact of remote ischaemic preconditioning on major clinical outcomes in patients undergoing cardiovascular surgery: A meta-analysis with trial sequential analysis of 32 randomised controlled trials.

    PubMed

    Wang, Shifei; Li, Hairui; He, Nvqin; Sun, Yili; Guo, Shengcun; Liao, Wangjun; Liao, Yulin; Chen, Yanmei; Bin, Jianping

    2017-01-15

    The impact of remote ischaemic preconditioning (RIPC) on major clinical outcomes in patients undergoing cardiovascular surgery remains controversial. We systematically reviewed the available evidence to evaluate the potential benefits of RIPC in such patients. PubMed, Embase, and Cochrane Library databases were searched for relevant randomised controlled trials (RCTs) conducted between January 2006 and March 2016. The pooled population of patients who underwent cardiovascular surgery was divided into the RIPC and control groups. Trial sequential analysis was applied to judge data reliability. The pooled relative risks (RRs) with 95% confidence intervals (CIs) between the groups were calculated for all-cause mortality, major adverse cardiovascular and cerebral events (MACCEs), myocardial infarction (MI), and renal failure. RIPC was not associated with improvement in all-cause mortality (RR, 1.04; 95%CI, 0.82-1.31; I 2 =26%; P>0.05) or MACCE incidence (RR, 0.90; 95%CI, 0.71-1.14; I 2 =40%; P>0.05) after cardiovascular surgery, and both results were assessed by trial sequential analysis as sufficient and conclusive. Nevertheless, RIPC was associated with a significantly lower incidence of MI (RR, 0.87; 95%CI, 0.76-1.00; I 2 =13%; P≤0.05). However, after excluding a study that had a high contribution to heterogeneity, RIPC was associated with increased rates of renal failure (RR, 1.53; 95%CI, 1.12-2.10; I 2 =5%; P≤0.05). In patients undergoing cardiovascular surgery, RIPC reduced the risk for postoperative MI, but not that for MACCEs or all-cause mortality, a discrepancy likely related to the higher rate of renal failure associated with RIPC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Thoracic Epidural analgesia versus Rectus Sheath Catheters for open midline incisions in major abdominal surgery within an enhanced recovery programme (TERSC): study protocol for a randomised controlled trial.

    PubMed

    Wilkinson, Kate M; Krige, Anton; Brearley, Sarah G; Lane, Steven; Scott, Michael; Gordon, Anthony C; Carlson, Gordon L

    2014-10-21

    Thoracic epidural analgesia (TEA) is recommended for post-operative pain relief in patients undergoing major abdominal surgery via a midline incision. However, the effectiveness of TEA is variable with high failure rates reported post-operatively. Common side effects such as low blood pressure and motor block can reduce mobility and hinder recovery, and a number of rare but serious complications can also occur following their use.Rectus sheath catheters (RSC) may provide a novel alternative approach to somatic analgesia without the associated adverse effects of TEA. The aim of this study is to compare the efficacy of both techniques in terms of pain relief, patient experience, post-operative functional recovery, safety and cost-effectiveness. This is a single-centre randomised controlled non-blinded trial, which also includes a nested qualitative study. Over a two-year period, 132 patients undergoing major abdominal surgery via a midline incision will be randomised to receive either TEA or RSC for post-operative analgesia. The primary outcome measures pain scores on moving from a supine to a sitting position at 24 hours post wound closure, and the patient experience between groups evaluated through in-depth interviews. Secondary outcomes include pain scores at rest and on movement at other time points, opiate consumption, functional recovery, morbidity and cost-effectiveness. This will be the first randomised controlled trial comparing thoracic epidurals to ultrasound-guided rectus sheath catheters in adults undergoing elective midline laparotomy. The standardised care provided by an Enhanced Recovery Programme makes this a comparison between two complex pain packages and not simply two analgesic techniques, in order to ascertain if RSC is a viable alternative to TEA. Current Controlled Trials ISRCTN81223298 (16 January 2014).

  8. Preoperative Cholangitis and Future Liver Remnant Volume Determine the Risk of Liver Failure in Patients Undergoing Resection for Hilar Cholangiocarcinoma

    PubMed Central

    Aloia, Thomas A; Shindoh, Junichi; Fabio, Forchino; Amisano, Marco; Passot, Guillaume; Ferrero, Alessandro; Vauthey, Jean-Nicolas

    2016-01-01

    Background The highest mortality rates after liver surgery are reported in patients who undergo resection for hilar cholangiocarcinoma (HCCA). In these patients, postoperative death usually follows the development of hepatic insufficiency. We sought to determine the factors associated with postoperative hepatic insufficiency and death due to liver failure in patients undergoing hepatectomy for HCCA. Study Design This study included all consecutive patients who underwent hepatectomy with curative intent for HCCA at two centers from 1996 through 2013. Preoperative clinical and operative data were analyzed to identify independent determinants of i) hepatic insufficiency and ii) liver failure–related death. Results The study included 133 patients with right or left major (n=67) or extended (n=66) hepatectomy. Preoperative biliary drainage was performed in 98 patients and was complicated by cholangitis in 40 cases. In all these patients, cholangitis was controlled before surgery. Major (Dindo III-IV) postoperative complications occurred in 73 patients (55%), with 29 suffering from hepatic insufficiency. Fifteen patients (11%) died within 90 days after surgery, 10 of them of liver failure. On multivariate analysis, predictors of postoperative hepatic insufficiency (all p<0.05) were preoperative cholangitis (odds ratio [OR]=3.2), future liver remnant (FLR) volume <30% (OR=3.5), preoperative total bilirubin level >3 mg/dl (OR=4), and albumin level <3.5 mg/dl (OR=3.3). Only preoperative cholangitis (OR=7.5, p=.016) and FLR volume <30% (OR=7.2, p=.019) predicted postoperative liver failure–related death. Conclusions Preoperative cholangitis and insufficient FLR volume are major determinants of hepatic insufficiency and postoperative liver failure–related death. Given the association between biliary drainage and cholangitis, the preoperative approach to patients with HCCA should be optimized to minimize the risk of cholangitis. PMID:27049784

  9. New Insight in Loss of Gut Barrier during Major Non-Abdominal Surgery

    PubMed Central

    Derikx, Joep P. M.; van Waardenburg, Dick A.; Thuijls, Geertje; Willigers, Henriëtte M.; Koenraads, Marianne; van Bijnen, Annemarie A.; Heineman, Erik; Poeze, Martijn; Ambergen, Ton; van Ooij, André; van Rhijn, Lodewijk W.; Buurman, Wim A.

    2008-01-01

    Background Gut barrier loss has been implicated as a critical event in the occurrence of postoperative complications. We aimed to study the development of gut barrier loss in patients undergoing major non-abdominal surgery. Methodology/Principal Findings Twenty consecutive children undergoing spinal fusion surgery were included. This kind of surgery is characterized by long operation time, significant blood loss, prolonged systemic hypotension, without directly leading to compromise of the intestines by intestinal manipulation or use of extracorporeal circulation. Blood was collected preoperatively, every two hours during surgery and 2, 4, 15 and 24 hours postoperatively. Gut mucosal barrier was assessed by plasma markers for enterocyte damage (I-FABP, I-BABP) and urinary presence of tight junction protein claudin-3. Intestinal mucosal perfusion was measured by gastric tonometry (PrCO2, Pr-aCO2-gap). Plasma concentration of I-FABP, I-BABP and urinary expression of claudin-3 increased rapidly and significantly after the onset of surgery in most children. Postoperatively, all markers decreased promptly towards baseline values together with normalisation of MAP. Plasma levels of I-FABP, I-BABP were significantly negatively correlated with MAP at ½ hour before blood sampling (−0.726 (p<0.001), −0.483 (P<0.001), respectively). Furthermore, circulating I-FABP correlated with gastric mucosal PrCO2, Pr-aCO2-gap measured at the same time points (0.553 (p = 0.040), 0.585 (p = 0.028), respectively). Conclusions/Significance This study shows the development of gut barrier loss in children undergoing major non-abdominal surgery, which is related to preceding hypotension and mesenterial hypoperfusion. These data shed new light on the potential role of peroperative circulatory perturbation and intestinal barrier loss. PMID:19088854

  10. Real-time monitoring system of composite aircraft wings utilizing Fibre Bragg Grating sensor

    NASA Astrophysics Data System (ADS)

    Vorathin, E.; Hafizi, Z. M.; Che Ghani, S. A.; Lim, K. S.

    2016-10-01

    Embedment of Fibre Bragg Grating (FBG) sensor in composite aircraft wings leads to the advancement of structural condition monitoring. The monitored aircraft wings have the capability to give real-time response under critical loading circumstances. The main objective of this paper is to develop a real-time FBG monitoring system for composite aircraft wings to view real-time changes when the structure undergoes some static loadings and dynamic impact. The implementation of matched edge filter FBG interrogation system to convert wavelength variations to strain readings shows that the structure is able to response instantly in real-time when undergoing few loadings and dynamic impact. This smart monitoring system is capable of updating the changes instantly in real-time and shows the weight induced on the composite aircraft wings instantly without any error. It also has a good agreement with acoustic emission (AE) sensor in the dynamic test.

  11. Population structuring of multi-copy, antigen-encoding genes in Plasmodium falciparum

    PubMed Central

    Artzy-Randrup, Yael; Rorick, Mary M; Day, Karen; Chen, Donald; Dobson, Andrew P; Pascual, Mercedes

    2012-01-01

    The coexistence of multiple independently circulating strains in pathogen populations that undergo sexual recombination is a central question of epidemiology with profound implications for control. An agent-based model is developed that extends earlier ‘strain theory’ by addressing the var gene family of Plasmodium falciparum. The model explicitly considers the extensive diversity of multi-copy genes that undergo antigenic variation via sequential, mutually exclusive expression. It tracks the dynamics of all unique var repertoires in a population of hosts, and shows that even under high levels of sexual recombination, strain competition mediated through cross-immunity structures the parasite population into a subset of coexisting dominant repertoires of var genes whose degree of antigenic overlap depends on transmission intensity. Empirical comparison of patterns of genetic variation at antigenic and neutral sites supports this role for immune selection in structuring parasite diversity. DOI: http://dx.doi.org/10.7554/eLife.00093.001 PMID:23251784

  12. LaRC-RP41: A Tough, High-Performance Composite Matrix

    NASA Technical Reports Server (NTRS)

    Pater, Ruth H.; Johnston, Norman J.; Smith, Ricky E.; Snoha, John J.; Gautreaux, Carol R.; Reddy, Rakasi M.

    1991-01-01

    New polymer exhibits increased toughness and resistance to microcracking. Cross-linking PMR-15 and linear LaRC-TPI combined to provide sequential semi-2-IPN designated as LaRC-RP41. Synthesized from PMR-15 imide prepolymer undergoing cross-linking in immediate presence of LaRC-TPI polyamic acid, also undergoing simultaneous imidization and linear chain extension. Potentially high-temperature matrix resin, adhesive, and molding resin. Applications include automobiles, electronics, aircraft, and aerospace structures.

  13. Endurance with partnership: a preliminary conceptual framework for couples undergoing in vitro fertilisation treatment.

    PubMed

    Ying, Liying; Wu, Lai Har; Wu, Xiangli; Shu, Jing; Loke, Alice Yuen

    2018-04-01

    Infertility affects both women and men in the physical, emotional, existential, and interpersonal realms. When couples seek in vitro fertilisation (IVF) treatment, they further suffer from the difficulties of the treatment and the uncertainty of its outcome. The aim of this study was to develop a preliminary conceptual framework for couples undergoing IVF treatment to give health professionals a better understanding of the experiences of such couples, and to guide the development of an intervention. The process of identifying frameworks adopted in intervention studies confirmed that there is no established framework for infertile couples undergoing IVF treatment. A skeletal framework identified from previous studies provides an internal structure for the proposed framework for couples undergoing IVF treatment, filled out with concepts drawn from a concept analysis and a qualitative study, knitting the structure together. This preliminary framework is the Endurance with Partnership Conceptual Framework (P-EPCF). It consists of four domains: the impacts of infertility and stressors, dyadic mediators, dyadic moderators and dyadic outcomes. According to the P-EPCF, the impacts of infertility and IVF treatment can be mediated by the couples' partnership and dyadic coping. Improvements in the psychological well-being and marital functioning of IVF couples can then be expected. The P-EPCF would be potentially valuable in guiding the development of a complex, couple-based intervention, which could focus on enhancing the partnership of couples and their coping strategies.

  14. 77 FR 57197 - Proposed Collection; Comment Request for Form 1099-CAP

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-17

    ... 1099-CAP AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Form 1099-CAP, Changes in Corporate Control and Capital Structure. DATES: Written comments should be... Structure. OMB Number: 1545-1814. Form Number: 1099-CAP. Abstract: Any corporation that undergoes...

  15. Spine tumor resection among patients who refuse blood product transfusion: a retrospective case series.

    PubMed

    Kisilevsky, Alexandra E; Stobart, Liam; Roland, Kristine; Flexman, Alana M

    2016-12-01

    To describe the perioperative blood conservation strategies and postoperative outcomes in patients who undergo complex spinal surgery for tumor resection and who also refuse blood product transfusion. A retrospective case series. A single-center, tertiary care and academic teaching hospital in Canada. All adult patients undergoing elective major spine tumor resection and refusing blood product transfusion who were referred to our institutional Blood Utilization Program between June 1, 2004, and May 9, 2014. Data on the use of iron, erythropoietin, preoperative autologous blood donation, acute normovolemic hemodilution, antifibrinolytic therapy, cell salvage, intraoperative hypotension, and active warming techniques were collected. Data on perioperative hemoglobin nadir, adverse outcomes, and hospital length of stay were also collected. Four patients who refused blood transfusion (self-identified as Jehovah's Witnesses) underwent non-emergent complex spine surgery for recurrent chondrosarcoma, meningioma, metastatic adenocarcinoma, and metastatic malignant melanoma. All patients received 1 or more perioperative blood conservation strategy including preoperative iron and/or erythropoietin, intraoperative antifibrinolytic therapy, and cell salvage. No patients experienced severe perioperative anemia (average hemoglobin nadir, 124 g/L) or anemia-related postoperative complications. Patients who decline blood product transfusion can successfully undergo major spine tumor resection. Careful patient selection and timely referral for perioperative optimization such that the risk of severe anemia is minimized are important for success. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Postoperative infections after major heart surgery and prevention of ventilator-associated pneumonia: a one-day European prevalence study (ESGNI-008).

    PubMed

    Bouza, E; Hortal, J; Muñoz, P; Pascau, J; Pérez, M J; Hiesmayr, M

    2006-11-01

    Few data have been published on the prevalence of postoperative infection in patients undergoing major heart surgery (MHS). The degree of compliance with standard measures used to prevent them is unknown. This study assessed the prevalence of infections, particularly ventilator-associated pneumonia (VAP), in patients undergoing MHS in 42 institutions from 13 European countries. On the study day, there were 321 postoperative MHS patients, of whom 164 (51%) were mechanically ventilated. The overall prevalence of infection was 26.8%. Lower respiratory tract infections represented 57% of all the infections present on the study day. Other infections included intravenous-catheter-related bloodstream infections (2.8%), surgical site infections (2.2%), urinary tract infections (0.9%) and postoperative mediastinitis (0.9%). Of the mechanically ventilated patients, 55 (33.5%) were not being nursed in a semi-recumbent position, 36 (22%) had heat-moisture exchangers with no antibacterial filters, and intracuff pressure was not monitored in 78 patients (47.6%). Only 13 patients (8%) were given continuous subglottic suctioning, 64 patients (39%) did not receive postural oscillation, and gastric overdistension was not actively prevented in 23 patients (14%). In conclusion, these data from intensive care units across Europe provide information on postoperative infections in an important subset of the patient population, and stress the need for active interventions to prevent VAP in patients undergoing MHS.

  17. Mechanisms of CTC Biomarkers in Breast Cancer Brain Metastasis

    DTIC Science & Technology

    2015-10-01

    3. ACCOMPLISHMENTS What were the major goals of the project? Dr. David Hong at MD Anderson was the partnering PI of this protocol . The major...blood (CTC analyses). Peripheral blood samples and tumor tissues will be collected and provided by Dr. David Hong under a MDACC IRB- protocol which has...per IRB-approved protocol ) will be drawn and immediately undergo CTC analyses. Blood may be drawn from the same individual on more than one occasion

  18. All sorts of options for food product sorting

    USDA-ARS?s Scientific Manuscript database

    Most food products undergo significant processing before arrival at the grocery store or local market. A major component of this processing includes sorting the product according to quality attributes such as size, color, sweetness, and ripeness. In addition, removal of defects or contaminants is a ...

  19. KENNEDY SPACE CENTER, FLA. - During power-up of the orbiter Discovery in the Orbiter Processing Facility, a technician moves a switch. Discovery has been undergoing Orbiter Major Modifications in the past year, ranging from wiring, control panels and black boxes to gaseous and fluid systems tubing and components. These systems were deserviced, disassembled, inspected, modified, reassembled, checked out and reserviced, as were most other systems onboard. The work includes the installation of the Multifunction Electronic Display Subsystem (MEDS) - a state-of-the-art “glass cockpit.”

    NASA Image and Video Library

    2003-08-27

    KENNEDY SPACE CENTER, FLA. - During power-up of the orbiter Discovery in the Orbiter Processing Facility, a technician moves a switch. Discovery has been undergoing Orbiter Major Modifications in the past year, ranging from wiring, control panels and black boxes to gaseous and fluid systems tubing and components. These systems were deserviced, disassembled, inspected, modified, reassembled, checked out and reserviced, as were most other systems onboard. The work includes the installation of the Multifunction Electronic Display Subsystem (MEDS) - a state-of-the-art “glass cockpit.”

  20. KENNEDY SPACE CENTER, FLA. - During power-up of the orbiter Discovery in the Orbiter Processing Facility, a technician turns on a switch. Discovery has been undergoing Orbiter Major Modifications in the past year, ranging from wiring, control panels and black boxes to gaseous and fluid systems tubing and components. These systems were deserviced, disassembled, inspected, modified, reassembled, checked out and reserviced, as were most other systems onboard. The work includes the installation of the Multifunction Electronic Display Subsystem (MEDS) - a state-of-the-art “glass cockpit.”

    NASA Image and Video Library

    2003-08-27

    KENNEDY SPACE CENTER, FLA. - During power-up of the orbiter Discovery in the Orbiter Processing Facility, a technician turns on a switch. Discovery has been undergoing Orbiter Major Modifications in the past year, ranging from wiring, control panels and black boxes to gaseous and fluid systems tubing and components. These systems were deserviced, disassembled, inspected, modified, reassembled, checked out and reserviced, as were most other systems onboard. The work includes the installation of the Multifunction Electronic Display Subsystem (MEDS) - a state-of-the-art “glass cockpit.”

  1. Prospective comparison of two management strategies of central venous catheters in burn patients.

    PubMed

    Kealey, G P; Chang, P; Heinle, J; Rosenquist, M D; Lewis, R W

    1995-03-01

    Central venous catheters (CVCs) are associated with sepsis in burn patients. This study was undertaken to compare two strategies of CVC management in patients with major burn injuries. Forty-two burn patients with major burn injuries were randomly assigned to undergo site change every 48 hours of the CVC or to undergo wire guide exchange of the CVC every 48 hours at the same site. Catheter insertion site, distance from the burn wound, cultures of catheter tips, and blood cultures were obtained from all patients in a prospective manner. There was no difference in the incidence of CVC sepsis between the two groups studied. CVCs inserted less than 5 cm from the burn wound developed bacterial contamination at an earlier time than CVCs inserted more than 5 cm from the burn wound. There was no advantage to changing the CVC insertion site every 48 hours. Changing the CVC using the wire guide technique did not prevent, nor predict, CVC bacterial contamination.

  2. Acetylation of pregnane X receptor protein determines selective function independent of ligand activation

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

    Biswas, Arunima; Pasquel, Danielle; Tyagi, Rakesh Kumar

    2011-03-18

    Research highlights: {yields} Pregnane X receptor (PXR), a major regulatory protein, is modified by acetylation. {yields} PXR undergoes dynamic deacetylation upon ligand-mediated activation. {yields} SIRT1 partially mediates PXR deacetylation. {yields} PXR deacetylation per se induces lipogenesis mimicking ligand-mediated activation. -- Abstract: Pregnane X receptor (PXR), like other members of its class of nuclear receptors, undergoes post-translational modification [PTM] (e.g., phosphorylation). However, it is unknown if acetylation (a major and common form of protein PTM) is observed on PXR and, if it is, whether it is of functional consequence. PXR has recently emerged as an important regulatory protein with multiple ligand-dependentmore » functions. In the present work we show that PXR is indeed acetylated in vivo. SIRT1 (Sirtuin 1), a NAD-dependent class III histone deacetylase and a member of the sirtuin family of proteins, partially mediates deacetylation of PXR. Most importantly, the acetylation status of PXR regulates its selective function independent of ligand activation.« less

  3. Successful use of nitrous oxide during lumbar punctures: A call for nitrous oxide in pediatric oncology clinics.

    PubMed

    Livingston, Mylynda; Lawell, Miranda; McAllister, Nancy

    2017-11-01

    Numerous reports describe the successful use of nitrous oxide for analgesia in children undergoing painful procedures. Although shown to be safe, effective, and economical, nitrous oxide use is not yet common in pediatric oncology clinics and few reports detail its effectiveness for children undergoing repeated lumbar punctures. We developed a nitrous oxide clinic, and undertook a review of pediatric oncology lumbar puncture records for those patients receiving nitrous oxide in 2011. No major complications were noted. Minor complications were noted in 2% of the procedures. We offer guidelines for establishing such a clinic. © 2017 Wiley Periodicals, Inc.

  4. Arc is a flexible modular protein capable of reversible self-oligomerization

    PubMed Central

    Myrum, Craig; Baumann, Anne; Bustad, Helene J.; Flydal, Marte Innselset; Mariaule, Vincent; Alvira, Sara; Cuéllar, Jorge; Haavik, Jan; Soulé, Jonathan; Valpuesta, José Maria; Márquez, José Antonio; Martinez, Aurora; Bramham, Clive R.

    2015-01-01

    The immediate early gene product Arc (activity-regulated cytoskeleton-associated protein) is posited as a master regulator of long-term synaptic plasticity and memory. However, the physicochemical and structural properties of Arc have not been elucidated. In the present study, we expressed and purified recombinant human Arc (hArc) and performed the first biochemical and biophysical analysis of hArc's structure and stability. Limited proteolysis assays and MS analysis indicate that hArc has two major domains on either side of a central more disordered linker region, consistent with in silico structure predictions. hArc's secondary structure was estimated using CD, and stability was analysed by CD-monitored thermal denaturation and differential scanning fluorimetry (DSF). Oligomerization states under different conditions were studied by dynamic light scattering (DLS) and visualized by AFM and EM. Biophysical analyses show that hArc is a modular protein with defined secondary structure and loose tertiary structure. hArc appears to be pyramid-shaped as a monomer and is capable of reversible self-association, forming large soluble oligomers. The N-terminal domain of hArc is highly basic, which may promote interaction with cytoskeletal structures or other polyanionic surfaces, whereas the C-terminal domain is acidic and stabilized by ionic conditions that promote oligomerization. Upon binding of presenilin-1 (PS1) peptide, hArc undergoes a large structural change. A non-synonymous genetic variant of hArc (V231G) showed properties similar to the wild-type (WT) protein. We conclude that hArc is a flexible multi-domain protein that exists in monomeric and oligomeric forms, compatible with a diverse, hub-like role in plasticity-related processes. PMID:25748042

  5. Safety and efficacy of hysteroscopic sterilization compared with laparoscopic sterilization: an observational cohort study

    PubMed Central

    Mao, Jialin; Pfeifer, Samantha; Schlegel, Peter

    2015-01-01

    Objective To compare the safety and efficacy of hysteroscopic sterilization with the “Essure” device with laparoscopic sterilization in a large, all-inclusive, state cohort. Design Population based cohort study. Settings Outpatient interventional setting in New York State. Participants Women undergoing interval sterilization procedure, including hysteroscopic sterilization with Essure device and laparoscopic surgery, between 2005 and 2013. Main outcomes measures Safety events within 30 days of procedures; unintended pregnancies and reoperations within one year of procedures. Mixed model accounting for hospital clustering was used to compare 30 day and 1 year outcomes, adjusting for patient characteristics and other confounders. Time to reoperation was evaluated using frailty model for time to event analysis. Results We identified 8048 patients undergoing hysteroscopic sterilization and 44 278 undergoing laparoscopic sterilization between 2005 and 2013 in New York State. There was a significant increase in the use of hysteroscopic procedures during this period, while use of laparoscopic sterilization decreased. Patients undergoing hysteroscopic sterilization were older than those undergoing laparoscopic sterilization and were more likely to have a history of pelvic inflammatory disease (10.3% v 7.2%, P<0.01), major abdominal surgery (9.4% v 7.9%, P<0.01), and cesarean section (23.2% v 15.4%, P<0.01). At one year after surgery, hysteroscopic sterilization was not associated with a higher risk of unintended pregnancy (odds ratio 0.84 (95% CI 0.63 to 1.12)) but was associated with a substantially increased risk of reoperation (odds ratio 10.16 (7.47 to 13.81)) compared with laparoscopic sterilization. Conclusions Patients undergoing hysteroscopic sterilization have a similar risk of unintended pregnancy but a more than 10-fold higher risk of undergoing reoperation compared with patients undergoing laparoscopic sterilization. Benefits and risks of both procedures should be discussed with patients for informed decisions making. PMID:26462857

  6. T cells' immunological synapses induce polarization of brain astrocytes in vivo and in vitro: a novel astrocyte response mechanism to cellular injury.

    PubMed

    Barcia, Carlos; Sanderson, Nicholas S R; Barrett, Robert J; Wawrowsky, Kolja; Kroeger, Kurt M; Puntel, Mariana; Liu, Chunyan; Castro, Maria G; Lowenstein, Pedro R

    2008-08-20

    Astrocytes usually respond to trauma, stroke, or neurodegeneration by undergoing cellular hypertrophy, yet, their response to a specific immune attack by T cells is poorly understood. Effector T cells establish specific contacts with target cells, known as immunological synapses, during clearance of virally infected cells from the brain. Immunological synapses mediate intercellular communication between T cells and target cells, both in vitro and in vivo. How target virally infected astrocytes respond to the formation of immunological synapses established by effector T cells is unknown. Herein we demonstrate that, as a consequence of T cell attack, infected astrocytes undergo dramatic morphological changes. From normally multipolar cells, they become unipolar, extending a major protrusion towards the immunological synapse formed by the effector T cells, and withdrawing most of their finer processes. Thus, target astrocytes become polarized towards the contacting T cells. The MTOC, the organizer of cell polarity, is localized to the base of the protrusion, and Golgi stacks are distributed throughout the protrusion, reaching distally towards the immunological synapse. Thus, rather than causing astrocyte hypertrophy, antiviral T cells cause a major structural reorganization of target virally infected astrocytes. Astrocyte polarization, as opposed to hypertrophy, in response to T cell attack may be due to T cells providing a very focused attack, and thus, astrocytes responding in a polarized manner. A similar polarization of Golgi stacks towards contacting T cells was also detected using an in vitro allogeneic model. Thus, different T cells are able to induce polarization of target astrocytes. Polarization of target astrocytes in response to immunological synapses may play an important role in regulating the outcome of the response of astrocytes to attacking effector T cells, whether during antiviral (e.g. infected during HIV, HTLV-1, HSV-1 or LCMV infection), anti-transplant, autoimmune, or anti-tumor immune responses in vivo and in vitro.

  7. Investigation of the Enzymes Involved in Lantibiotic Biosynthesis: Lacticin 481 and Haloduracin

    ERIC Educational Resources Information Center

    Ihnken, Leigh Anne Furgerson

    2009-01-01

    Lantibiotics are cyclic peptides that exhibit a range of biological properties, including antimicrobial activity. They are ribosomally-synthesized as linear precursor peptides that consist of two regions, an N-terminal leader peptide and a C-terminal propeptide (or structural) region. The structural region undergoes extensive enzyme-catalyzed…

  8. Centrifugation of Cultured Osteoblasts And Macrophages as a Model To Study How Gravity Regulates The Function of Skeletal Cells

    NASA Technical Reports Server (NTRS)

    Globus, Ruth K.; Searby, Nancy D.; Almeida, Eduardo A. C.; Sutijono, Darrell; Yu, Joon-Ho; Malouvier, Alexander; Doty, Steven B.; Morey-Holton, Emily; Weinstein, Steven L.; Dalton, Bonnie P. (Technical Monitor)

    2000-01-01

    Mechanical loading helps define the architecture of weight-bearing bone via the tightly regulated process of skeletal turnover. Turnover occurs by the concerted activity of osteoblasts, responsible for bone formation. and osteoclasts, responsible for bone resorption. Osteoclasts are specialized megakaryon macrophages, which differentiate from monocytes in response to resorption stimuli, such as reduced weight-bearing. Habitation in space dramatically alters musculoskeletal loading, which modulates both cell function and bone structure. Our long-term objective is to define the molecular and cellular mechanisms that mediate skeletal adaptations to altered gravity environments. Our experimental approach is to apply hypergravity loads by centrifugation to rodents and cultured cells. As a first step, we examined the influence of centrifugation on the structure of cancellous bone in rats to test the ability of hypergravity to change skeletal architecture. Since cancellous bone undergoes rapid turnover we expected the most dramatic structural changes to occur in the shape of trabeculae of weight-bearing, cancellous bone. To define the cellular responses to hypergravity loads, we exposed cultured osteoblasts and macrophages to centrifugation. The intraosseous and intramedullary pressures within long bones in vivo reportedly range from 12-40 mm Hg, which would correspond to 18-59 gravity (g) in our cultures. We assumed that hydrostatic pressure from the medium above the cell layer is at least one major component of the mechanical load generated by centrifuging cultured cells. and therefore we exposed the cells to 10-50g. In osteoblasts, we examined the structure of their actin and microtubule networks, production of prostaglandin E2 (PGE2), and cell survival. Analysis of the shape of the cytoskeletal networks provides evidence for the ability of centrifugation to affect cell structure, while the production of PGE2 serves as a convenient marker for mechanical stimulation. We examined cell survival, reasoning that osteoblasts might mold skeletal structure in a hypergravity environment in part by regulating apoptosis and thus the duration of osteoblast productivity. Finally, we tested the influence of centrifugation on microbial activation of a macrophage cell line (RAW264.7). In response to the appropriate hormonal stimulation, this cell line is reportedly capable of undergoing differentiation to express osteoclast markers. In addition, a component of the cell wall of gram-negative bacteria, lipopolysaccaride (LPS), stimulates the formation of osteoclasts in vivo. Thus we tested the influence on centrifugation on RAW264.7 cells stimulated with LPS to provide an index of the function of osteoclast precursors.

  9. Shape Complementarity of Protein-Protein Complexes at Multiple Resolutions

    PubMed Central

    Zhang, Qing; Sanner, Michel; Olson, Arthur J.

    2010-01-01

    Biological complexes typically exhibit intermolecular interfaces of high shape complementarity. Many computational docking approaches use this surface complementarity as a guide in the search for predicting the structures of protein-protein complexes. Proteins often undergo conformational changes in order to create a highly complementary interface when associating. These conformational changes are a major cause of failure for automated docking procedures when predicting binding modes between proteins using their unbound conformations. Low resolution surfaces in which high frequency geometric details are omitted have been used to address this problem. These smoothed, or blurred, surfaces are expected to minimize the differences between free and bound structures, especially those that are due to side chain conformations or small backbone deviations. In spite of the fact that this approach has been used in many docking protocols, there has yet to be a systematic study of the effects of such surface smoothing on the shape complementarity of the resulting interfaces. Here we investigate this question by computing shape complementarity of a set of 66 protein-protein complexes represented by multi-resolution blurred surfaces. Complexed and unbound structures are available for these protein-protein complexes. They are a subset of complexes from a non-redundant docking benchmark selected for rigidity (i.e. the proteins undergo limited conformational changes between their bound and unbound states). In this work we construct the surfaces by isocontouring a density map obtained by accumulating the densities of Gaussian functions placed at all atom centers of the molecule. The smoothness or resolution is specified by a Gaussian fall-off coefficient, termed “blobbyness”. Shape complementarity is quantified using a histogram of the shortest distances between two proteins' surface mesh vertices for both the crystallographic complexes and the complexes built using the protein structures in their unbound conformation. The histograms calculated for the bound complex structures demonstrate that medium resolution smoothing (blobbyness=−0.9) can reproduce about 88% of the shape complementarity of atomic resolution surfaces. Complexes formed from the free component structures show a partial loss of shape complementarity (more overlaps and gaps) with the atomic resolution surfaces. For surfaces smoothed to low resolution (blobbyness=−0.3), we find more consistency of shape complementarity between the complexed and free cases. To further reduce bad contacts without significantly impacting the good contacts we introduce another blurred surface, in which the Gaussian densities of flexible atoms are reduced. From these results we discuss the use of shape complementarity in protein-protein docking. PMID:18837463

  10. Creating Conventional Soybeans with the High Oleic Acid Seed Oil Trait

    USDA-ARS?s Scientific Manuscript database

    Commodity soybeans are poised to undergo a revolutionary change. Major shifts in market expectations for the nutritional quality of the oil, brought about in part through food labeling requirements and the suitability for biodiesel, are driving the commodity soybean to embrace new seed compositiona...

  11. 75 FR 80506 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-22

    .... Proposed Project Persistence of Viable Influenza Virus in Aerosols--New--National Institute for... Safety and Health Act. Influenza continues to be a major public health concern because of the substantial health burden from seasonal influenza and the potential for a severe pandemic. Although influenza is...

  12. The Advanced Study of Gymnastics.

    ERIC Educational Resources Information Center

    Salmela, John H., Ed.

    The sport of artistic gymnastics is viewed from a multidisciplinary point of view. The training, performance, and judgment of the sport undergo specialized study of interest to sport scientists, teachers, coaches, and athletes. Organized into five major sections, the book presents such themes as the psychological, physiological, biomechanical,…

  13. The Grasshopper Neuroblast Culture Technique and its Value in Radiobiological Studies

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

    Carlson, J. Gordon

    1961-11-01

    A technique is described for the culture of grasshopper neuroblasts in which the neuroblast undergoes successive divisions at a relatively uniform rate through a total of 6 mitotic cycles over a period of 5 to 6 days at 26 deg C. Even after mitosis ceases, most of the embryonic cells live and undergo differentiation. Results are summarized from studies on the effects of different kinds of radiation on mitosis and on structure and behavior of various parts of the dividing cell. (C.H.)

  14. Impact of frailty on approach to colonic resection: Laparoscopy vs open surgery.

    PubMed

    Mosquera, Catalina; Spaniolas, Konstantinos; Fitzgerald, Timothy L

    2016-11-21

    To understand the influence of frailty on postoperative outcomes for laparoscopic and open colectomy. Data were obtained from the National Surgical Quality Improvement Program (2005-2012) for patients undergoing colon resection [open colectomy (OC) and laparoscopic colectomy (LC)]. Patients were classified as non-frail (0 points), low frailty (1 point), moderate frailty (2 points), and severe frailty (≥ 3) using the Modified Frailty Index. 30-d mortality and complications were used as the primary end point and analyzed for the overall population. Complications were grouped into major and minor. Subset analysis was performed for patients undergoing colectomy (total colectomy, partial colectomy and sigmoid colectomy) and separately for patients undergoing rectal surgery (abdominoperineal resection, low anterior resection, and proctocolectomy). We analyzed the data using SAS Platform JMP Pro version 10.0.0 (SAS Institute Inc., Cary, NC, United States). A total of 94811 patients were identified; the majority underwent OC (58.7%), were white (76.9%), and non-frail (44.8%). The median age was 61.3 years. Prolonged length of stay (LOS) occurred in 4.7%, and 30-d mortality was 2.28%. Patients undergoing OC were older (61.89 ± 15.31 vs 60.55 ± 14.93) and had a higher ASA score (48.3% ASA3 vs 57.7% ASA2 in the LC group) ( P < 0.0001). Most patients were non-frail (42.5% OC vs 48% LC, P < 0.0001). Complications, prolonged LOS, and mortality were significantly more common in patients undergoing OC ( P < 0.0001). OC had a higher risk of death and complications compared to LC for all frailty scores (non-frail: OR = 4.7, and OR = 4.67; mildly frail: OR = 2.51, and OR = 2.47; moderately frail: OR = 2.94, and OR = 2.02, severely frail: OR = 2.37, and OR = 2.34, P < 0.05) and an increase in absolute mortality with increasing frailty (non-frail 0.68% OC, mildly frail 1.39%, moderately frail 3.44%, and severely frail 5.83%, P < 0.0001). LC is associated with improved outcomes. Although the odds of mortality are higher in non-frail, there is a progressive increase in mortality with increasing frailty.

  15. The American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator Does Not Accurately Predict Risk of 30-Day Complications Among Patients Undergoing Microvascular Head and Neck Reconstruction.

    PubMed

    Arce, Kevin; Moore, Eric J; Lohse, Christine M; Reiland, Matthew D; Yetzer, Jacob G; Ettinger, Kyle S

    2016-09-01

    The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Surgical Risk Calculator (SRC) is a novel universal risk calculator designed to aid in risk stratification of patients undergoing various types of major surgery. The purpose of this study was to assess the validity of the ACS NSQIP SRC in predicting postoperative complications in patients undergoing microvascular head and neck reconstruction. A retrospective cohort study of patients undergoing head and neck microvascular reconstruction with fibular free flaps at a single institution was completed. The NSQIP SRC was used to compute complication risk estimates and length of stay (LOS) estimates for all patients under study. Associations between complication risk estimates generated by the SRC and actual rates of observed complications were evaluated using logistic regression models. Logistic regression models also were used to evaluate the SRC estimates for LOS duration compared with the actual observed LOS after surgery. Of 153 patients under study, 46 (30%) developed a postoperative complication corresponding to those defined by NSQIP SRC. Thirty-eight patients (25%) developed a postoperative complication categorized as severe in the parameters of the NSQIP SRC. None of the SRC complication estimates showed a statistically relevant association with the corresponding observed rates of complications. The mean LOS predicted by the SRC was 8.0 days (median, 7.5 days; interquartile range [IQR], 6.5 to 9; range, 5.0 to 18.5 days). The mean observed LOS for the study group was 9.6 days (median, 7.0 days; IQR, 6 to 9; range, 5 to 67 days). Lin's (Biometrics 45:255, 1989) concordance correlation coefficient to measure agreement between observed and predicted LOS was 0.10, indicating only slight agreement between the 2 values. The ACS NSQIP SRC is not a useful risk-stratifying metric for patients undergoing major head and neck reconstruction with microvascular fibular free flaps. The SRC also does not accurately predict hospital LOS for this same patient cohort. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  16. Marginal Hospital Cost of Surgery-related Hospital-acquired Pressure Ulcers.

    PubMed

    Spector, William D; Limcangco, Rhona; Owens, Pamela L; Steiner, Claudia A

    2016-09-01

    Patients who develop hospital-acquired pressure ulcers (HAPUs) are more likely to die, have longer hospital stays, and are at greater risk of infections. Patients undergoing surgery are prone to developing pressure ulcers (PUs). To estimate the hospital marginal cost of a HAPU for adults patients who were hospitalized for major surgeries, adjusted for patient characteristics, comorbidities, procedures, and hospital characteristics. Data are from the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases and the Medicare Patient Safety Monitoring System for 2011 and 2012. PU information was obtained using retrospective structured record review from trained MPMS data abstractors. Costs are derived using HCUP hospital-specific cost-to-charge ratios. Marginal cost estimates were made using Extended Estimating Equations. We estimated the marginal cost at the 25th, 50th, and 75th percentiles of the cost distribution using Simultaneous Quantile Regression. We find that 3.5% of major surgical patients developed HAPUs and that the HAPUs added ∼$8200 to the cost of a surgical stay after adjusting for comorbidities, patient characteristics, procedures, and hospital characteristics. This is an ∼44% addition to the cost of a major surgical stay but less than half of the unadjusted cost difference. In addition, we find that for high-cost stays (75th percentile) HAPUs added ∼$12,100, whereas for low-cost stays (25th percentile) HAPUs added ∼$3900. This paper suggests that HAPUs add ∼44% to the cost of major surgical hospital stays, but the amount varies depending on the total cost of the visit.

  17. Nursing Diagnosis of "Spiritual Distress" in Women With Breast Cancer: Prevalence and Major Defining Characteristics.

    PubMed

    Caldeira, Sílvia; Timmins, Fiona; de Carvalho, Emília C; Vieira, Margarida

    2016-01-01

    Spirituality and spiritual needs of cancer patients are frequently mentioned in the nursing literature, but the most significant defining characteristics of spiritual distress in the context of clinical reasoning and nursing diagnosis are rarely explored. Understanding of these is important for effective spiritual intervention. The aim of this study was to identify the prevalence and the defining characteristics of the nursing diagnosis "spiritual distress," as classified according to NANDA International, among women with breast cancer. This was a quantitative and cross-sectional study, comprising the third phase of a larger study investigating the clinical validation of spiritual distress in cancer patients undergoing chemotherapy. Fehring's clinical diagnostic validation model was used to identify the prevalence and the major defining characteristics of the diagnosis. A convenience sample was used, and data were collected by structured interview. A total of 70 women participated; most were married (62.9%) and had a mean age of 54 years, and 55.7% reported having at least 1 person depending on them. The average length of time since the cancer diagnosis was 30.9 months. Twenty-seven participants were experiencing spiritual distress (38.6%). Eleven defining characteristics were classified as major. The prevalence of spiritual distress and the major defining characteristics give clinical evidence about the nurse's role in providing spiritual care. The results are useful for the improved use of the NANDA International diagnoses within this domain. The findings highlight the importance of assessing the defining characteristics of the diagnosis as an objective strategy to improve clinical reasoning related to spirituality and to facilitate more effective interventions.

  18. pH-Controlled Two-Step Uncoating of Influenza Virus

    PubMed Central

    Li, Sai; Sieben, Christian; Ludwig, Kai; Höfer, Chris T.; Chiantia, Salvatore; Herrmann, Andreas; Eghiaian, Frederic; Schaap, Iwan A.T.

    2014-01-01

    Upon endocytosis in its cellular host, influenza A virus transits via early to late endosomes. To efficiently release its genome, the composite viral shell must undergo significant structural rearrangement, but the exact sequence of events leading to viral uncoating remains largely speculative. In addition, no change in viral structure has ever been identified at the level of early endosomes, raising a question about their role. We performed AFM indentation on single viruses in conjunction with cellular assays under conditions that mimicked gradual acidification from early to late endosomes. We found that the release of the influenza genome requires sequential exposure to the pH of both early and late endosomes, with each step corresponding to changes in the virus mechanical response. Step 1 (pH 7.5–6) involves a modification of both hemagglutinin and the viral lumen and is reversible, whereas Step 2 (pH <6.0) involves M1 dissociation and major hemagglutinin conformational changes and is irreversible. Bypassing the early-endosomal pH step or blocking the envelope proton channel M2 precludes proper genome release and efficient infection, illustrating the importance of viral lumen acidification during the early endosomal residence for influenza virus infection. PMID:24703306

  19. Hyperbiofilm Formation by Bordetella pertussis Strains Correlates with Enhanced Virulence Traits

    PubMed Central

    Cattelan, Natalia; Jennings-Gee, Jamie; Dubey, Purnima

    2017-01-01

    ABSTRACT Pertussis, or whooping cough, caused by the obligate human pathogen Bordetella pertussis is undergoing a worldwide resurgence. The majority of studies of this pathogen are conducted with laboratory-adapted strains which may not be representative of the species as a whole. Biofilm formation by B. pertussis plays an important role in pathogenesis. We conducted a side-by-side comparison of the biofilm-forming abilities of the prototype laboratory strains and the currently circulating isolates from two countries with different vaccination programs. Compared to the reference strain, all strains examined herein formed biofilms at high levels. Biofilm structural analyses revealed country-specific differences, with strains from the United States forming more structured biofilms. Bacterial hyperaggregation and reciprocal expression of biofilm-promoting and -inhibitory factors were observed in clinical isolates. An association of increased biofilm formation with augmented epithelial cell adhesion and higher levels of bacterial colonization in the mouse nose and trachea was detected. To our knowledge, this work links for the first time increased biofilm formation in bacteria with a colonization advantage in an animal model. We propose that the enhanced biofilm-forming capacity of currently circulating strains contributes to their persistence, transmission, and continued circulation. PMID:28893915

  20. Polyimine and its potential significance for prebiotic chemistry on Titan

    NASA Astrophysics Data System (ADS)

    Rahm, Martin; Lunine, Jonathan I.; Usher, David; Shalloway, David

    2016-10-01

    Hydrogen cyanide (HCN), a key reagent in prebiotic chemistry, is being generated in large amounts in the atmosphere of Titan. Contradictions between Cassini-Huygens measurements of the atmosphere and the surface of Titan, suggest that HCN is undergoing reaction chemistry, despite the frigid temperatures of 90-94 K. We will discuss computational results [1] investigating polyimine as one potential explanation for this observation. Polyimine is a polymer identified as the major component of polymerized HCN in laboratory experiments. It is flexible, which aids low temperature mobility, and it is able to form intermolecular and intramolecular =N-H...N hydrogen bonds, allowing for different polymorphs. Polymorphs have been predicted and explored by density functional theory coupled with a structure-searching algorithm. We have calculated the thermodynamics of polymerization, and show that polyimine is capable of absorbing light in a window of relative transparency in Titan's atmosphere. Light absorption and the possible catalytic functions of polyimine are suggestive of it driving photochemistry on the surface, with potential prebiotic implications.References:[1] M. Rahm, J. I. Lunine, D. Usher, D. Shalloway, "Polymorphism and electronic structure of polyimine and its potential significance for prebiotic chemistry on Titan", PNAS, early view. doi: 10.1073/pnas.1606634113

  1. Coupling Damage-Sensing Particles to the Digitial Twin Concept

    NASA Technical Reports Server (NTRS)

    Hochhalter, Jacob; Leser, William P.; Newman, John A.; Gupta, Vipul K.; Yamakov, Vesselin; Cornell, Stephen R.; Willard, Scott A.; Heber, Gerd

    2014-01-01

    The research presented herein is a first step toward integrating two emerging structural health management paradigms: digital twin and sensory materials. Digital twin is an emerging life management and certification paradigm whereby models and simulations consist of as-built vehicle state, as-experienced loads and environments, and other vehicle-specific history to enable high-fidelity modeling of individual aerospace vehicles throughout their service lives. The digital twin concept spans many disciplines, and an extensive study on the full domain is out of the scope of this study. Therefore, as it pertains to the digital twin, this research focused on one major concept: modeling specifically the as-manufactured geometry of a component and its microstructure (to the degree possible). The second aspect of this research was to develop the concept of sensory materials such that they can be employed within the digital twin framework. Sensory materials are shape-memory alloys that undergo an audible phase transformation while experiencing sufficient strain. Upon embedding sensory materials with a structural alloy, this audible transformation helps improve the reliability of crack detection especially at the early stages of crack growth. By combining these two early-stage technologies, an automated approach to evidence-based inspection and maintenance of aerospace vehicles is sought.

  2. Membrane fusion activity of vesicular stomatitis virus glycoprotein G is induced by low pH but not by heat or denaturant.

    PubMed

    Yao, Yi; Ghosh, Kakoli; Epand, Raquel F; Epand, Richard M; Ghosh, Hara P

    2003-06-05

    The fusogenic envelope glycoprotein G of the rhabdovirus vesicular stomatitis virus (VSV) induces membrane fusion at acidic pH. At acidic pH the G protein undergoes a major structural reorganization leading to the fusogenic conformation. However, unlike other viral fusion proteins, the low-pH-induced conformational change of VSV G is completely reversible. As well, the presence of an alpha-helical coiled-coil motif required for fusion by a number of viral and cellular fusion proteins was not predicted in VSV G protein by using a number of algorithms. Results of pH dependence of the thermal stability of G protein as determined by intrinsic Trp fluorescence and circular dichroism (CD) spectroscopy show that the G protein is equally stable at neutral or acidic pH. Destabilization of G structure at neutral pH with either heat or urea did not induce membrane fusion or conformational change(s) leading to membrane fusion. Taken together, these data suggest that the mechanism of VSV G-induced fusion is distinct from the fusion mechanism of fusion proteins that involve a coiled-coil motif.

  3. Isotopic analysis for degradation diagnosis of calcite matrix in mortar.

    PubMed

    Dotsika, E; Psomiadis, D; Poutoukis, D; Raco, B; Gamaletsos, P

    2009-12-01

    Mortar that was used in building as well as in conservation and restoration works of wall paintings have been analysed isotopically (delta(13)C and delta(18)O) in order to evaluate the setting environments and secondary processes, to distinguish the structural components used and to determine the exact causes that incurred the degradation phenomena. The material undergoes weathering and decay on a large proportion of its surface and in depth, due to the infiltration of water through the structural blocks. Mineralogical analysis indicated signs of sulphation and dissolution/recrystallisation processes taking place on the material, whereas stable isotopes provided information relative to the origin of the CO(2) and water during calcite formation and degradation processes. Isotopic change of the initial delta(13)C and delta(18)O in carbonate matrix was caused by alteration of the primary source of CO(2) and H(2)O in mortar over time, particularly by recrystallisation of calcite with porewater, evaporated or re-condensed water, and CO(2) from various sources of atmospheric and biogenic origin. Human influence (surface treatment) and biological growth (e.g. fungus) are major exogenic processes which may alter delta(18)O and delta(13)C in lime mortar.

  4. Prognosis of venous thromboembolism in orthopaedic surgery or trauma patients and use of thromboprophylaxis.

    PubMed

    Gutiérrez Guisado, J; Trujillo-Santos, J; Arcelus, J I; Bertoletti, L; Fernandez-Capitán, C; Valle, R; Hernandez-Hermoso, J A; Erice Calvo-Sotelo, A; Nieto, J A; Monreal, M

    2018-06-18

    There is scarce evidence about the prognosis of venous thromboembolism in patients undergoing orthopedic surgery and in patients suffering non-surgical trauma. We used the RIETE database (Registro Informatizado de pacientes con Enfermedad Trombo Embólica) to compare the prognosis of venous thromboembolism and the use of thromboprophylaxis in patients undergoing different orthopedic procedures and in trauma patients not requiring surgery. From March 2001 to March 2015, a total of 61,789 patients were enrolled in RIETE database. Of these, 943 (1.52%) developed venous thromboembolism after elective arthroplasty, 445 (0.72%) after hip fracture, 1,045 (1.69%) after non-major orthopedic surgery and 2,136 (3.46%) after non-surgical trauma. Overall, 2,283 patients (50%) initially presented with pulmonary embolism. Within the first 90 days of therapy, 30 patients (0.66%; 95% CI 0.45-0.93) died from pulmonary embolism. The rate of fatal pulmonary embolism was significantly higher after hip fracture surgery (n = 9 [2.02%]) than after elective arthroplasty (n = 5 [0.53%]), non-major orthopedic surgery (n = 5 [0.48%]) or non surgical trauma (n = 11 [0.48%]). Thromboprophylaxis was more commonly used for hip fracture (93%) or elective arthroplasty (94%) than for non-major orthopedic surgery (71%) or non-surgical trauma (32%). Major bleeding was significantly higher after hip fracture surgery (4%) than that observed after elective arthroplasty (1.6%), non-major orthopedic surgery (1.5%) or non-surgical trauma (1.4%). Thromboprophylaxis was less frequently used in lower risk procedures despite the absolute number of fatal pulmonary embolism after non-major orthopedic surgery or non-surgical trauma, exceeded that observed after high risk procedures. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  5. Role of clinical and laboratory parameters for treatment choice in patients with inherited FVII deficiency undergoing surgical procedures: evidence from the STER registry.

    PubMed

    Di Minno, Matteo N D; Napolitano, Mariasanta; Dolce, Alberto; Mariani, Guglielmo

    2018-02-01

    Perioperative bleeding is a major concern in patients with factor VII (FVII) deficiency. Evaluating data of 95 FVII-deficient patients undergoing 110 surgical procedures (61 major, 49 minor), we assessed the impact of type of surgery, bleeding phenotype and FVII coagulant activity (FVII:C) levels on perioperative replacement therapy (RT). Compared to those with higher FVII:C levels, patients with <3% FVII:C received a higher number of RT doses (8 vs. 2, P = 0·003) for a longer RT duration (3 days vs. 1 day, P = 0·001), with no difference in RT dose. Similarly, patients with a history of major bleeds received a higher number of RT doses (8·5 vs. 2-3, P = 0·013) for a longer RT duration (2 days vs. 1 day, P = 0·005) as compared to those with a history of minor bleeds or to asymptomatic patients. No difference in RT was found among major and minor surgical procedures. Overall, multivariate analysis showed that history of major bleeding was the only independent predictor of number of RT doses (β = 0·352, P = 0·001) and RT duration (β = 0·405, P = 0·018). Overall, a ≈20 μg/kg perioperative RT was efficacious in 95·5% of cases. The infusion should be repeated ≈8 times in high-risk subsets (i.e. patients with a history of major bleeding). © 2017 John Wiley & Sons Ltd.

  6. Discovery Orbiter Major Modifications

    NASA Image and Video Library

    2003-08-27

    During power-up of the orbiter Discovery in the Orbiter Processing Facility, a technician moves a circuit reset on the cockpit console. Discovery has been undergoing Orbiter Major Modifications in the past year, ranging from wiring, control panels and black boxes to gaseous and fluid systems tubing and components. These systems were deserviced, disassembled, inspected, modified, reassembled, checked out and reserviced, as were most other systems onboard. The work includes the installation of the Multifunction Electronic Display Subsystem (MEDS) - a state-of-the-art “glass cockpit.”

  7. The psychological impact of genetic testing on parents.

    PubMed

    Dinc, Leyla; Terzioglu, Fusun

    2006-01-01

    The aim of this descriptive study was to explore the psychological impact of genetic testing on parents whose children have been referred for genetic testing. Genetic tests enable individuals to be informed about their health status and to have the opportunity of early diagnosis and treatment of their diseases. However undergoing genetic testing and receiving a positive test result may also cause stress and anxiety. This descriptive study was carried out at the genetic departments of two university hospitals in Ankara. The sample of this study consisted of 128 individuals whose children have been referred for chromosomal analysis. Data were collected through using a semi-structured interview method with a data collection form and the anxiety inventory and analysed using the percentages and independent samples t-test. The majority of our participants experienced distress before genetic testing. Their general trait anxiety score before receiving the test results was 47.38, and following the test results the state anxiety score was 50.65. Having a previous child with an abnormality, a positive test result, and being a mother elevated the anxiety of individuals. This paper supports the findings of previous studies, which indicated that genetic test results might lead to anxiety in individuals and reveals the importance of genetic counselling. As the results of this study indicated, genetic testing causes distress and anxiety in individuals. Nurses can play an important role in minimizing anxiety of parents whose children undergo genetic testing by providing information about genetic testing and by taking part in the counselling process.

  8. Responsive measures to prehabilitation in patients undergoing bowel resection surgery.

    PubMed

    Kim, Do Jun; Mayo, Nancy E; Carli, Franco; Montgomery, David L; Zavorsky, Gerald S

    2009-02-01

    Surgical patients often show physiological and metabolic distress, muscle weakness, and long hospital stays. Physical conditioning might help recovery. We attempted to identify the most responsive measure of aerobic fitness from a four-week pre-surgical aerobic exercise program (prehabilitation) in patients undergoing major bowel resection. Twenty-one subjects randomized two to one (exercise: control) scheduled for colorectal surgery. Fourteen subjects [Body Mass Index (BMI) = 27 +/- 6 kg/m(2); maximal oxygen uptake (VO(2max)) = 22 +/- 10 ml/kg/min] underwent 3.8 +/- 1.2 weeks (27 +/- 8 sessions) of progressive, structured pre-surgical aerobic exercise training at 40 to 65% of heart rate reserve (%HRR). Peak power output was the only maximal measure that was responsive to training [26 +/- 27%, Effects Size (ES) = 0.24; Standardized Response Mean (SRM) = 1.05; p < 0.05]. For the submaximal measures, heart rate and oxygen uptake during submaximal exercise was most responsive to training (decrease by 13% +/- 15%, ES = -0.24; SRM = -0.57; and 7% +/- 6%, ES = -0.40; SRM -0.97; p < 0.05) at an exercise intensity of 76 +/- 47 W. There was no change to maximal or submaximal measures in the control group. The distance walked over six minutes improved in both groups (by approximately 30 m), but the effect size and t-statistic were higher in the exercise group. Heart rate and oxygen uptake during submaximal exercise, and peak power output are the most responsive measures to four weeks of prehabilitation in subjects with low initial fitness.

  9. Assessment of Physical Therapy Strategies for Recovery of Urinary Continence after Prostatectomy

    PubMed Central

    Santos, Nivea Adriano de Santana e; Saintrain, Maria Vieira de Lima; Regadas, Rommel Prata; da Silveira, Romulo Augusto; de Menezes, Francisco Julimar Correia

    2017-01-01

    Introduction: Urinary incontinence is a complication of radical prostatectomy. Pelvic floor exercises can facilitate recovery of continence after surgery; however, there is not sufficient evidence that physical therapy with biofeedback training is effective, particularly with respect to providing a faster recovery. Objective: To analyze the application of physical therapy techniques in the recovery of urinary incontinence after prostatectomy. Methodology: A randomized clinical trial was conducted from April to October 2015 with patients undergoing radical prostatectomy up to three months after surgery at the Santa Casa de Misericordia in Northeastern Brazil. The physical therapy intervention consisted of up to eight individual sessions. Patients were randomized into the intervention group, which performed exercises and received biofeedback training, and the control group, which performed exercises alone. Participants were assessed before, during and after treatment. The initial assessment included a structured instrument addressing sociodemographic and urological data. Frequencies were calculated for all variables and comparisons were checked by the Mann-Whitney test and for correlation significance. Results: The study included 13 patients aged 54-74 years, the majority undergoing retropubic surgery with mild urinary incontinence [11 (84.6%)]. There was a significant difference in the outcome of the pad test before (p=0.070) and after (p=0.015) treatment between the groups, but the reduction of urinary loss and the time to recovery of continence were equivalent for both groups. Conclusion: Both interventions provided improvement in the degree of incontinence within two months of treatment. PMID:28240013

  10. Completed Gravity Probe B Undergoes Thermal Vacuum Testing

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The Gravity Probe B (GP-B) is the relativity experiment developed at Stanford University to test two extraordinary predictions of Albert Einstein's general theory of relativity. The experiment will measure, very precisely, the expected tiny changes in the direction of the spin axes of four gyroscopes contained in an Earth-orbiting satellite at a 400-mile altitude. So free are the gyroscopes from disturbance that they will provide an almost perfect space-time reference system. They will measure how space and time are very slightly warped by the presence of the Earth, and, more profoundly, how the Earth's rotation very slightly drags space-time around with it. These effects, though small for the Earth, have far-reaching implications for the nature of matter and the structure of the Universe. In this photograph, the completed space vehicle is undergoing thermal vacuum environment testing. GP-B is among the most thoroughly researched programs ever undertaken by NASA. This is the story of a scientific quest in which physicists and engineers have collaborated closely over many years. Inspired by their quest, they have invented a whole range of technologies that are already enlivening other branches of science and engineering. Launched April 20, 2004 , the GP-B program was managed for NASA by the Marshall Space Flight Center. Development of the GP-B is the responsibility of Stanford University along with major subcontractor Lockheed Martin Corporation. (Image credit to Russ Underwood, Lockheed Martin Corporation.)

  11. Surgical apgar score in patients undergoing lumbar fusion for degenerative spine diseases.

    PubMed

    Ou, Chien-Yu; Hsu, Shih-Yuan; Huang, Jian-Hao; Huang, Yu-Hua

    2017-01-01

    Lumbar fusion is a procedure broadly performed for degenerative diseases of spines, but it is not without significant morbidities. Surgical Apgar Score (SAS), based on intraoperative blood loss, blood pressure, and heart rate, was developed for prognostic prediction in general and vascular operations. We aimed to examine whether the application of SAS in patients undergoing fusion procedures for degeneration of lumbar spines predicts in-hospital major complications. One hundred and ninety-nine patients that underwent lumbar fusion operation for spine degeneration were enrolled in this retrospective study. Based on whether major complications were present (N=16) or not (N=183), the patients were subdivided. We identified the intergroup differences in SAS and clinical parameters. The incidence of in-hospital major complications was 8%. The duration of hospital stay for the morbid patents was significantly prolonged (p=0.04). In the analysis of multivariable logistic regression, SAS was an independent predicting factor of the complications after lumbar fusion for degenerative spine diseases [p=0.001; odds ratio (95% confidence interval)=0.35 (0.19-0.64)]. Lower scores were accompanied with higher rates of major complications, and the area was 0.872 under the receiver operating characteristic curve. SAS is an independent predicting factor of major complications in patients after fusion surgery for degenerative diseases of lumbar spines, and provides good risk discrimination. Since the scoring system is relatively simple, objective, and practical, we suggest that SAS be included as an indicator in the guidance for level of care after lumbar fusion surgery. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Harmonic dissection versus electrocautery in breast surgery in regional Victoria.

    PubMed

    Kiyingi, Andrew K; Macdonald, Leigh J; Shugg, Sarah A; Bollard, Ruth C

    2015-05-01

    Harmonic instruments are an alternative tool for surgical dissection. The aim of this study is to evaluate differences in clinical outcomes relating to harmonic dissection when compared with electrocautery in patients undergoing major breast surgery in a regional centre over a 3-year period. Retrospective chart analysis was conducted of 52 patients undergoing major breast surgery for carcinoma or ductal carcinoma in situ by a single surgeon in a regional centre from May 2008 to January 2011. Analysis involved the extraction of qualitative data relating to patient demographics, surgery type and specimen histopathology. Quantitative data were extracted relating to duration of surgery, duration of patient-controlled analgesia (PCA) use, length of hospital admission, drainage output and presence of infection, haematoma or seroma. Fifty-two patients underwent major breast surgery; harmonic dissection n = 32 and electrocautery n = 20. The two groups were comparable. There was no significant difference identified relating the outcome measures. The median operative duration was shorter in the harmonic dissection group, however, was not of statistical significance. No significant difference was identified between groups relating to length of inpatient stay, duration of PCA use and total volume wound drainage and total days of drainage. Incidence of seroma and infection in the groups was not significantly different. The harmonic dissection is safe and effective in major breast surgery. The study did not demonstrate any clinical advantage from the use of harmonic dissection in major breast surgery compared with electrocautery, nor was there any difference in the complication rates measured. © 2014 Royal Australasian College of Surgeons.

  13. Perioperative Management of Patients on Clopidogrel (Plavix) Undergoing Major Lung Resection

    PubMed Central

    Ceppa, DuyKhanh P.; Welsby, Ian J.; Wang, Tracy Y.; Onaitis, Mark W.; Tong, Betty C.; Harpole, David H.; D’Amico, Thomas A.; Berry, Mark F.

    2014-01-01

    BACKGROUND Management of patients requiring antiplatelet therapy with clopidogrel (Plavix) and major lung resection must balance the risks of bleeding and cardiovascular events. We reviewed our experience with patients treated with clopidogrel perioperatively to examine outcomes, including results of a new strategy for high-risk patients. METHODS Patients who underwent major lung resection and received perioperative clopidogrel between January 2005 and September 2010 were reviewed. Initially, clopidogrel management consisted of discontinuation approximately 5 days before surgery and resumption immediately after surgery. Following July 2010, high-risk patients (drug-eluting coronary stent placement within prior year or previous coronary event after clopidogrel discontinuation) were admitted 2–3 days preoperatively and bridged with the intravenous GP IIb/IIIa receptor inhibitor eptifibatide (Integrilin) according to a multidisciplinary cardiology/anesthesiology/thoracic surgery protocol. Outcomes were compared to control patients (matched for preoperative risk factors and extent of pulmonary resection) who did not receive perioperative clopidogrel. RESULTS Fifty-four patients who had major lung resection between January 2005 and September 2010 and received clopidogrel perioperatively were matched with 108 controls. Both groups had similar mortality, postoperative length of stay, and no differences in the rates of perioperative transfusions, reoperations for bleeding, myocardial infarctions, and strokes. Seven of the 54 clopidogrel patients were admitted preoperatively for an eptifibatide bridge. Two of these patients received perioperative transfusions, but there were no mortalities, reoperations, myocardial infarctions, or stroke. CONCLUSIONS Patients taking clopidogrel can safely undergo major lung resection. Treatment with an eptifibatide bridge may minimize the risk of cardiovascular events in higher risk patients. PMID:21978871

  14. Intense pumping and time- and frequency-resolved CARS for driving and tracking structural deformation and recovery of liquid nitromethane molecules

    NASA Astrophysics Data System (ADS)

    Wang, Chang; Wu, Hong-lin; Song, Yun-fei; He, Xing; Yang, Yan-qiang; Tan, Duo-wang

    2015-11-01

    A modified CARS technique with an intense nonresonant femtosecond laser is presented to drive the structural deformation of liquid nitromethane molecules and track their structural relaxation process. The CARS spectra reveal that the internal rotation of the molecule can couple with the CN symmetric stretching vibration and the molecules undergo ultrafast structural deformation of the CH3 groups from 'opened umbrella' to 'closed umbrella' shape, and then experience a structural recovery process within 720 fs.

  15. The utility of FRAX® in predicting bone fractures in patients with chronic kidney disease on hemodialysis: a two-year prospective multicenter cohort study.

    PubMed

    Przedlacki, J; Buczyńska-Chyl, J; Koźmiński, P; Niemczyk, E; Wojtaszek, E; Gieglis, E; Żebrowski, P; Podgórzak, A; Wściślak, J; Wieliczko, M; Matuszkiewicz-Rowińska, J

    2018-05-01

    We assessed the FRAX® method in 718 hemodialyzed patients in estimating increased risk of bone major and hip fractures. Over two prospective years, statistical analysis showed that FRAX® enables a better assessment of bone major fracture risk in these patients than any of its components and other risk factors considered in the analysis. Despite the generally increased risk of bone fractures among patients with end-stage renal disease, no prediction models for identifying individuals at particular risk have been developed to date. The goal of this prospective, multicenter observational study was to assess the usefulness of the FRAX® method in comparison to all its elements considered separately, selected factors associated with renal disease and the history of falls, in estimating increased risk of low-energy major bone and hip fractures in patients undergoing chronic hemodialysis. The study included a total of 1068 hemodialysis patients, who were followed for 2 years, and finally, 718 of them were analyzed. The risk analysis included the Polish version of the FRAX® calculator (without bone mineral density), dialysis vintage, mineral metabolism disorders (serum calcium, phosphate, and parathyroid hormone), and the number of falls during the last year before the study. Over 2 years, low-energy 30 major bone fractures were diagnosed and 13 of hip fractures among them. Area under the curve for FRAX® was 0.76 (95% CI 0.69-0.84) for major fractures and 0.70 (95% CI 0.563-0.832) for hip fractures. The AUC for major bone fractures was significantly higher than for all elements of the FRAX® calculator. In logistic regression analysis FRAX® was the strongest independent risk factor of assessment of the major bone fracture risk. FRAX® enables a better assessment of major bone fracture risk in ESRD patients undergoing hemodialysis than any of its components and other risk factors considered in the analysis.

  16. Free energy landscapes of RNA/RNA complexes: with applications to snRNA complexes in spliceosomes.

    PubMed

    Cao, Song; Chen, Shi-Jie

    2006-03-17

    We develop a statistical mechanical model for RNA/RNA complexes with both intramolecular and intermolecular interactions. As an application of the model, we compute the free energy landscapes, which give the full distribution for all the possible conformations, for U4/U6 and U2/U6 in major spliceosome and U4atac/U6atac and U12/U6atac in minor spliceosome. Different snRNA experiments found contrasting structures, our free energy landscape theory shows why these structures emerge and how they compete with each other. For yeast U2/U6, the model predicts that the two distinct experimental structures, the four-helix junction structure and the helix Ib-containing structure, can actually coexist and specifically compete with each other. In addition, the energy landscapes suggest possible mechanisms for the conformational switches in splicing. For instance, our calculation shows that coaxial stacking is essential for stabilizing the four-helix junction in yeast U2/U6. Therefore, inhibition of the coaxial stacking possibly by protein-binding may activate the conformational switch from the four-helix junction to the helix Ib-containing structure. Moreover, the change of the energy landscape shape gives information about the conformational changes. We find multiple (native-like and misfolded) intermediates formed through base-pairing rearrangements in snRNA complexes. For example, the unfolding of the U2/U6 undergoes a transition to a misfolded state which is functional, while in the unfolding of U12/U6atac, the functional helix Ib is found to be the last one to unfold and is thus the most stable structural component. Furthermore, the energy landscape gives the stabilities of all the possible (functional) intermediates and such information is directly related to splicing efficiency.

  17. Toward Developmental Connectomics of the Human Brain

    PubMed Central

    Cao, Miao; Huang, Hao; Peng, Yun; Dong, Qi; He, Yong

    2016-01-01

    Imaging connectomics based on graph theory has become an effective and unique methodological framework for studying structural and functional connectivity patterns of the developing brain. Normal brain development is characterized by continuous and significant network evolution throughout infancy, childhood, and adolescence, following specific maturational patterns. Disruption of these normal changes is associated with neuropsychiatric developmental disorders, such as autism spectrum disorders or attention-deficit hyperactivity disorder. In this review, we focused on the recent progresses regarding typical and atypical development of human brain networks from birth to early adulthood, using a connectomic approach. Specifically, by the time of birth, structural networks already exhibit adult-like organization, with global efficient small-world and modular structures, as well as hub regions and rich-clubs acting as communication backbones. During development, the structure networks are fine-tuned, with increased global integration and robustness and decreased local segregation, as well as the strengthening of the hubs. In parallel, functional networks undergo more dramatic changes during maturation, with both increased integration and segregation during development, as brain hubs shift from primary regions to high order functioning regions, and the organization of modules transitions from a local anatomical emphasis to a more distributed architecture. These findings suggest that structural networks develop earlier than functional networks; meanwhile functional networks demonstrate more dramatic maturational changes with the evolution of structural networks serving as the anatomical backbone. In this review, we also highlighted topologically disorganized characteristics in structural and functional brain networks in several major developmental neuropsychiatric disorders (e.g., autism spectrum disorders, attention-deficit hyperactivity disorder and developmental dyslexia). Collectively, we showed that delineation of the brain network from a connectomics perspective offers a unique and refreshing view of both normal development and neuropsychiatric disorders. PMID:27064378

  18. Civil Rights and Organized Labor.

    ERIC Educational Resources Information Center

    Hill, Herbert

    1984-01-01

    The refusal of union leadership to accept the perspective of interracial unionism has meant the failure to organize the South. If unions are to implement the principle of democracy in the workplace, they must undergo a major transformation, becoming the voice of the unemployed, the working poor, and of women and racial minorities. (Author)

  19. Microbial minimalism: genome reduction in bacterial pathogens.

    PubMed

    Moran, Nancy A

    2002-03-08

    When bacterial lineages make the transition from free-living or facultatively parasitic life cycles to permanent associations with hosts, they undergo a major loss of genes and DNA. Complete genome sequences are providing an understanding of how extreme genome reduction affects evolutionary directions and metabolic capabilities of obligate pathogens and symbionts.

  20. Lipid droplet meets a mitochondrial protein to regulate adipocyte lipolysis

    USDA-ARS?s Scientific Manuscript database

    In response to adrenergic stimulation, adipocytes undergo protein kinase A (PKA)-stimulated lipolysis. A key PKA target in this context is perilipin 1, a major regulator of lipolysis on lipid droplets (LDs). A study published in this issue of The EMBO Journal (Pidoux et al, 2011) identifies optic at...

  1. Glacier National Park : Going-to-the-Sun Road Corridor management plan - existing conditions of the transportation system

    DOT National Transportation Integrated Search

    2014-06-27

    The Going-to-the-Sun Road (GTSR) Corridor has been undergoing major shifts in use due to ongoing construction, implementation of a shuttle system, and changes in visitor use patterns. Glacier National Park (GLAC) is developing the GTSR Transportation...

  2. Distress Behavior in Children With Leukemia Undergoing Medical Procedures.

    ERIC Educational Resources Information Center

    Katz, Ernest R.

    Improving prognosis for many forms of childhood cancer has resulted in increased attention on the quality-of-life experience. Conditioned anxiety and pain associated with recurrent diagnostic and treatment procedures have been identified as major sources of distress in children with malignant disease. To evaluate the efficacy of various…

  3. 75 FR 16128 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ... Project Evaluation of Childhood Obesity Prevention and Control Initiative: New York City Health Bucks... Disease Control and Prevention (CDC). Background and Brief Description Childhood obesity is a major public health concern. One out of every five children is affected by overweight or obesity in the United States...

  4. Effect of Professional Development on Teaching Behaviors and Efficacy in Qatari Educational Reforms

    ERIC Educational Resources Information Center

    Zimmerman, Whitney Alicia; Knight, Stephanie L.; Favre, David E.; Ikhlef, Atman

    2017-01-01

    Qatar is undergoing major educational reform that is shifting its educational policy toward an instructional orientation grounded in constructivism and student-centered instruction. Differences in cultural conceptions of knowledge acquisition and the purpose of education are examined to highlight challenges to Qatar's reform implementation…

  5. Amyloid Beta Mediates Memory Formation

    ERIC Educational Resources Information Center

    Garcia-Osta, Ana; Alberini, Cristina M.

    2009-01-01

    The amyloid precursor protein (APP) undergoes sequential cleavages to generate various polypeptides, including the amyloid [beta] (1-42) peptide (A[beta][1-42]), which is believed to play a major role in amyloid plaque formation in Alzheimer's disease (AD). Here we provide evidence that, in contrast with its pathological role when accumulated,…

  6. Improving School Accountability in California

    ERIC Educational Resources Information Center

    Larsen, S. Eric; Lipscomb, Stephen; Jaquet, Karina

    2011-01-01

    Federal education policy will soon undergo a major revision, with significant consequences for the state's own policy and practices. This report seeks to help federal and state policymakers consider this restructuring and one of its core questions: How should schools and school districts be held accountable for the academic progress of their…

  7. Bidirectional Signaling of Mammary Epithelium and Stroma: Implications for Breast Cancer—Preventive Actions of Dietary Factors

    USDA-ARS?s Scientific Manuscript database

    The mammary gland is composed of two major cellular compartments: a highly dynamic epithelium that undergoes cycles of proliferation, differentiation, and apoptosis in response to local and endocrine signals and the underlying stroma comprised of fibroblasts, endothelial cells, and adipocytes that c...

  8. 78 FR 75920 - Agency Forms Undergoing Paperwork Reduction Act Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-13

    ... mail interviews. Questions related to federal and state health insurance marketplaces will be included... should be received within 30 days of this notice. Proposed Project The National Health Interview Survey... National Health Interview Survey is a major source of general statistics on the health of the U.S...

  9. Childbearing and Schooling: New Evidence from South Africa

    ERIC Educational Resources Information Center

    Madhavan, Sangeetha; Thomas, Kevin J. A.

    2005-01-01

    The importance of the authors' research can be summarized in several ways. First, it contributes to an ongoing discussion about the relative importance of childbearing in determining a girl's life chances, particularly in societies undergoing major transitions. Second, the twin issues of adolescent fertility and educational attainment feature…

  10. School Attendance and the District Budget

    ERIC Educational Resources Information Center

    Joubert-Guillory, Julie

    2009-01-01

    House Bill 1 became a major piece of legislation in Texas a few years ago. It was designed primarily to address public school finance, property tax relief, public school accountability, and education-related matters. This piece of legislation has forced districts to manage their finances very differently, undergo budget reductions, and continue…

  11. Dynamic structure of confined shocks undergoing sudden expansion

    NASA Astrophysics Data System (ADS)

    Abate, G.; Shyy, W.

    2002-01-01

    The gas dynamic phenomenon associated with a normal shock wave within a tube undergoing a sudden area expansion consists of highly transient flow and diffraction that give rise to turbulent, compressible, vortical flows. These interactions can occur at time scales typically ranging from micro- to milliseconds. In this article, we review recent experimental and numerical results to highlight the flow phenomena and main physical mechanisms associated with this geometry. The topics addressed include time-accurate shock and vortex locations, flowfield evolution and structure, wall-shock Mach number, two- vs. three-dimensional sudden expansions, and the effect of viscous dissipation on planar shock-front expansions. Between axisymmetric and planar geometries, the flow structure evolves very similarly early on in the sudden expansion process (i.e., within the first two shock tube diameters). Both numerical and experimental studies confirm that the trajectory of the vortex formed at the expansion corner is convected into the flowfield faster in the axisymmetric case than the planar case. The lateral propagation of the vortices correlates very well between axisymmetric and planar geometries. In regard to the rate of dissipation of turbulent kinetic energy (TKE) for a two-dimensional planar shock undergoing a sudden expansion within a confined chamber, calculations show that the solenoidal dissipation is confined to the region of high strain rates arising from the expansion corner. Furthermore, the dilatational dissipation is concentrated mainly at the curvature of the incident, reflected, and barrel shock fronts. The multiple physical mechanisms identified, including shock-strain rate interaction, baroclinic effect, vorticity generation, and different aspects of viscous dissipation, have produced individual and collective flow structures observed experimentally.

  12. Evaluation of a transient, simultaneous, arbitrary Lagrange-Euler based multi-physics method for simulating the mitral heart valve.

    PubMed

    Espino, Daniel M; Shepherd, Duncan E T; Hukins, David W L

    2014-01-01

    A transient multi-physics model of the mitral heart valve has been developed, which allows simultaneous calculation of fluid flow and structural deformation. A recently developed contact method has been applied to enable simulation of systole (the stage when blood pressure is elevated within the heart to pump blood to the body). The geometry was simplified to represent the mitral valve within the heart walls in two dimensions. Only the mitral valve undergoes deformation. A moving arbitrary Lagrange-Euler mesh is used to allow true fluid-structure interaction (FSI). The FSI model requires blood flow to induce valve closure by inducing strains in the region of 10-20%. Model predictions were found to be consistent with existing literature and will undergo further development.

  13. 46 CFR 115.600 - Drydock examination, internal structural examination, and underwater survey intervals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... a United States port, it must undergo the required examination before sailing. (c) If your vessel is... hull exams and two internal structural exams within any five-year period. If a vessel completes a satisfactory alternate hull exam, with the underwater survey portion conducted predominantly by an approved...

  14. Reforms in German Higher Education: Implementing and Adapting Anglo-American Organizational and Management Structures at German Universities

    ERIC Educational Resources Information Center

    Liefner, Ingo; Schatzl, Ludwig; Schroder, Thomas

    2004-01-01

    Currently, the German higher education system is undergoing drastic reform. Competitive structures and funding mechanisms are being introduced that are already successfully used in other countries. However, critics state that cultural differences prevent the effective application, in German universities, of funding mechanisms and incentives…

  15. Rules and Construction Effects in Learning the Argument Structure of Verbs

    ERIC Educational Resources Information Center

    Demuth, Katherine; Machobane, 'Malillo; Moloi, Francina

    2003-01-01

    Theorists of language acquisition have long debated the means by which children learn the argument structure of verbs (e.g. Bowerman, 1974, 1990; Pinker, 1984, 1989; Tomasello, 1992). Central to this controversy has been the possible role of verb semantics, especially in learning which verbs undergo dative-shift alternation in languages like…

  16. 46 CFR 169.229 - Drydock examination, internal structural examination, and underwater survey intervals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., and underwater survey intervals. 169.229 Section 169.229 Shipping COAST GUARD, DEPARTMENT OF HOMELAND... Hauling Out § 169.229 Drydock examination, internal structural examination, and underwater survey... period unless it has been approved to undergo an underwater survey (UWILD) under § 169.230 of this part...

  17. Crystal Structure and Proteomics Analysis of Empty Virus-like Particles of Cowpea Mosaic Virus.

    PubMed

    Huynh, Nhung T; Hesketh, Emma L; Saxena, Pooja; Meshcheriakova, Yulia; Ku, You-Chan; Hoang, Linh T; Johnson, John E; Ranson, Neil A; Lomonossoff, George P; Reddy, Vijay S

    2016-04-05

    Empty virus-like particles (eVLPs) of Cowpea mosaic virus (CPMV) are currently being utilized as reagents in various biomedical and nanotechnology applications. Here, we report the crystal structure of CPMV eVLPs determined using X-ray crystallography at 2.3 Å resolution and compare it with previously reported cryo-electron microscopy (cryo-EM) of eVLPs and virion crystal structures. Although the X-ray and cryo-EM structures of eVLPs are mostly similar, there exist significant differences at the C terminus of the small (S) subunit. The intact C terminus of the S subunit plays a critical role in enabling the efficient assembly of CPMV virions and eVLPs, but undergoes proteolysis after particle formation. In addition, we report the results of mass spectrometry-based proteomics analysis of coat protein subunits from CPMV eVLPs and virions that identify the C termini of S subunits undergo proteolytic cleavages at multiple sites instead of a single cleavage site as previously observed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Adopted Individuals' Views on the Utility and Value of Expanded Carrier Screening.

    PubMed

    Spencer, Sara; Ewing, Sarah; Calcagno, Kathryn; O'Neill, Suzanne

    2018-03-30

    Adoptees may not have family medical history and ethnicity information. Carrier screening assesses reproductive risk. Expanded carrier screening (ECS) screens for many genetic conditions regardless of a patient's knowledge of family history and ethnicity. This study aimed to better understand the opinions and attitudes of adopted individuals on the use of ECS in determining a patient's reproductive genetic risks. Specifically, the study assessed how adopted individuals feel that results of ECS may be useful to them and whether adoptees feel that meeting with a genetics professional in the process of undergoing ECS would be useful. Adult adoptees (N = 124) were recruited online. Their opinions on ECS were explored. The majority reported they had never been offered carrier screening (92%). The majority of adoptees wanted ECS (76%). Neither the amount of contact with biological relatives nor having medical knowledge about biological relatives was significantly associated with adoptees' desire to pursue ECS. There was a significant positive correlation between adoptees of higher education levels and the amount they would pay for ECS (p = 0.004). The majority of participants (95%) indicated a genetics professional would be helpful when undergoing ECS. The findings suggest this population may want ECS and support from genetics healthcare professionals. Advocacy for genetic counseling and testing for adoptees appears justifiable.

  19. High-pressure protein crystallography of hen egg-white lysozyme

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

    Yamada, Hiroyuki; Nagae, Takayuki; Watanabe, Nobuhisa, E-mail: nobuhisa@nagoya-u.jp

    The crystal structure of hen egg-white lysozyme (HEWL) was analyzed under pressures of up to 950 MPa. The high pressure modified the conformation of the molecule and induced a novel phase transition in the tetragonal crystal of HEWL. Crystal structures of hen egg-white lysozyme (HEWL) determined under pressures ranging from ambient pressure to 950 MPa are presented. From 0.1 to 710 MPa, the molecular and internal cavity volumes are monotonically compressed. However, from 710 to 890 MPa the internal cavity volume remains almost constant. Moreover, as the pressure increases to 950 MPa, the tetragonal crystal of HEWL undergoes a phasemore » transition from P4{sub 3}2{sub 1}2 to P4{sub 3}. Under high pressure, the crystal structure of the enzyme undergoes several local and global changes accompanied by changes in hydration structure. For example, water molecules penetrate into an internal cavity neighbouring the active site and induce an alternate conformation of one of the catalytic residues, Glu35. These phenomena have not been detected by conventional X-ray crystal structure analysis and might play an important role in the catalytic activity of HEWL.« less

  20. Vibration energy harvesting based monitoring of an operational bridge undergoing forced vibration and train passage

    NASA Astrophysics Data System (ADS)

    Cahill, Paul; Hazra, Budhaditya; Karoumi, Raid; Mathewson, Alan; Pakrashi, Vikram

    2018-06-01

    The application of energy harvesting technology for monitoring civil infrastructure is a bourgeoning topic of interest. The ability of kinetic energy harvesters to scavenge ambient vibration energy can be useful for large civil infrastructure under operational conditions, particularly for bridge structures. The experimental integration of such harvesters with full scale structures and the subsequent use of the harvested energy directly for the purposes of structural health monitoring shows promise. This paper presents the first experimental deployment of piezoelectric vibration energy harvesting devices for monitoring a full-scale bridge undergoing forced dynamic vibrations under operational conditions using energy harvesting signatures against time. The calibration of the harvesters is presented, along with details of the host bridge structure and the dynamic assessment procedures. The measured responses of the harvesters from the tests are presented and the use the harvesters for the purposes of structural health monitoring (SHM) is investigated using empirical mode decomposition analysis, following a bespoke data cleaning approach. Finally, the use of sequential Karhunen Loeve transforms to detect train passages during the dynamic assessment is presented. This study is expected to further develop interest in energy-harvesting based monitoring of large infrastructure for both research and commercial purposes.

  1. Study of Three-dimensional Magnetic Structure and the Successive Eruptive Nature of Active Region 12371

    NASA Astrophysics Data System (ADS)

    Vemareddy, P.; Demóulin, P.

    2018-04-01

    We study the magnetic structure of a successively erupting sigmoid in active region 12371 by modeling the quasi-static coronal field evolution with nonlinear force-free field (NLFFF) equilibria. Helioseismic and Magnetic Imager/Solar Dynamic Observatory vector magnetograms are used as input to the NLFFF model. In all eruption events, the modeled structure resembles the observed pre-eruptive coronal sigmoid and the NLFFF core field is a combination of double inverse-J-shaped and inverse-S field lines with dips touching the photosphere. Such field lines are formed by the flux cancellation reconnection of opposite-J field lines at bald-patch locations, which in turn implies the formation of a weakly twisted flux-rope (FR) from large-scale sheared arcade field lines. Later on, this FR undergoes coronal tether-cutting reconnection until a coronal mass ejection is triggered. The modeled structure captured these major features of sigmoid-to-arcade-to-sigmoid transformation, which is reoccuring under continuous photospheric flux motions. Calculations of the field line twist reveal a fractional increase followed by a decrease of the number of pixels having a range of twist. This traces the buildup process of a twisted core field by slow photospheric motions and the relaxation after eruption, respectively. Our study infers that the large eruptivity of this AR is due to a steep decrease of the background coronal field meeting the torus instability criteria at a low height (≈40 Mm) in contrast to noneruptive ARs.

  2. Time- and Space-Resolved SAXS Experiments Inform on Phase Transition Kinetics in Hydrated, Liquid-Crystalline Films of Polyion-Surfactant Ion "Complex Salts".

    PubMed

    Li, Joaquim; Gustavsson, Charlotte; Piculell, Lennart

    2016-05-24

    Detailed time- and space-resolved SAXS experiments show the variation with hydration of liquid crystalline structures in ethanol-cast 5-80 μm thick films of polyion-surfactant ion "complex salts" (CS). The CS were dodecyl- (C12) or hexadecyl- (C16) trimethylammonium surfactants with polyacrylate (DP 25 or 6000) counter-polyions. The experiments were carried out on vertical films in humid air above a movable water bath, so that gradients of hydration were generated, which could rapidly be altered. Scans over different positions along a film, kept fixed relative to the bath, showed that the surfactant aggregates of the various liquid-crystalline CS structures grow in cross-sectional area with decreasing hydration. This behavior is attributed to the low water content. Studies of films undergoing rapid dehydration, made possible by the original experimental setup, gave strong evidence that some of the investigated systems remain kinetically trapped for minutes in a nonequilibrium Pm3n micellar cubic phase before switching to the equilibrium P6mm 2D hexagonal phase. Both the length of the polyion and the length of the surfactant hydrocarbon "tail" affect the kinetics of the phase transition. The slowness of the cubic-to-hexagonal structural transition is attributed to the fact that it requires major rearrangements of the polyions and surfactant ions relative to each other. By contrast, other structure changes, such as between the hexagonal and rectangular phases, were observed to occur much more rapidly.

  3. Ontogeny of a surgical technique: Robotic kidney transplantation with regional hypothermia.

    PubMed

    Sood, Akshay; McCulloch, Peter; Dahm, Philipp; Ahlawat, Rajesh; Jeong, Wooju; Bhandari, Mahendra; Menon, Mani

    2016-01-01

    Innovation is a hallmark of surgical practice. It is generally accepted that a new procedure will undergo technical changes during its evolution; however, quantitative accounts of the process are limited. Multiple groups, including our own, have recently described a minimally-invasive approach to conventional kidney transplantation (KT) operation. Unique to our experience is a structured development of the technique within the confines of a safe surgical innovation framework - the IDEAL framework (idea, development, exploration, assessment, long-term monitoring; stages 0-4). We here provide a first-hand narrative of the progress of robotic KT operation from preclinical trial to clinical application. Overall, 54 patients underwent robotic KT with regional hypothermia successfully. Major technical changes including selection of optimal patient position (flank vs. lithotomy), robotic instrumentation, vascular occlusion method (bulldog vs. tourniquet) and suture material (prolene vs. GoreTex) occurred early during the procedure development (IDEAL stage 0, preclinical). Minor technical changes such as utilization of the aortic punch for arteriotomy (case 3), use of barbed suture during ureteroneocystostomy (case 6) and extraperitonealization of the graft kidney (case 6) that increased the efficiency and safety of the procedure continued throughout procedure development (IDEAL stages 1-2, clinical stages). We demonstrate that a surgical technique evolves continually; although, the majority of technical alterations occur early in the life-cycle of the procedure. Development of a new technique within the confines a structured surgical innovation framework allows for evidence based progression of the technique and may minimize the risk of harm to the patient. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  4. Injury to the Lumbar Plexus and its Branches After Lateral Fusion Procedures: A Cadaver Study.

    PubMed

    Grunert, Peter; Drazin, Doniel; Iwanaga, Joe; Schmidt, Cameron; Alonso, Fernando; Moisi, Marc; Chapman, Jens R; Oskouian, Rod J; Tubbs, Richard Shane

    2017-09-01

    Neurologic deficits from lumbar plexus nerve injuries commonly occur in patients undergoing lateral approaches. However, it is not yet clear what types of injury occur, where anatomically they are located, or what mechanism causes them. We aimed to study 1) the topographic anatomy of lumbar plexus nerves and their injuries in human cadavers after lateral transpsoas approaches to the lumbar spine, 2) the structural morphology of those injuries, and 3) the topographic anatomy of the lumbar plexus throughout the mediolateral approach corridor. Fifteen adult fresh frozen cadaveric torsos (26 sides) underwent lateral approaches (L1-L5) by experienced lateral spine surgeons. The cadavers were subsequently opened and the entire plexus dissected and examined for nerve injuries. The topographic anatomy of the lumbar plexus and its branches, their injuries, and the morphology of these injuries were documented. Fifteen injuries were found with complete or partial nerve transections (Sunderland IV and V). Injuries were found throughout the mediolateral approach corridor. At L1/2, the iliohypogastric, ilioinguinal, and subcostal nerves were injured within the psoas major muscle, the retroperitoneal space, or the outer abdominal muscles and subcutaneous tissues. Genitofemoral nerve injuries were found in the retroperitoneal space. Nerve root injuries occurred within the retroperitoneal space and psoas muscle. Femoral nerve injuries were found only within the psoas major muscle. No obturator nerve injuries occurred. Lateral approaches can lead to structural nerve damage. Knowledge of the complex plexus anatomy, specifically its mediolateral course, is critical to avoid approach-related injuries. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Suicidal behavior in obsessive-compulsive disorder.

    PubMed

    Kamath, Prakash; Reddy, Y C Janardhan; Kandavel, Thennarasu

    2007-11-01

    There are limited data on suicidal behavior in obsessive-compulsive disorder (OCD). This study examines suicidal behavior and its clinical correlates in OCD subjects. One hundred consecutive DSM-IV OCD subjects attending the specialty OCD clinic and the inpatient services of a major psychiatric hospital in India from November 1, 2003, to October 31, 2004, formed the sample of this study. Subjects were assessed systematically by using structured interviews and various rating scales. The Scale for Suicide Ideation-worst ever (lifetime) and -current measured suicidal ideation. The 24-item Hamilton Rating Scale for Depression (HAM-D) measured severity of depression, and the Beck Hopelessness Scale (BHS) measured hopelessness. We performed assessments at study entry. We employed binary logistic regression (Wald) forward stepwise analysis for prediction of suicidal ideation and suicide attempt, and we used structural equation modeling for identifying the potential factors contributing to suicidal ideation. The rates of suicidal ideation, worst ever and current, were 59% and 28%, respectively. History of suicide attempt was reported in 27% of the subjects. For past suicide attempt, worst ever suicidal ideation (p < .001) was the only significant predictor, with an overall prediction of 89%, and accounted for 60% of the variance. For worst ever suicidal ideation, major depression (p = .043), HAM-D score (p = .013), BHS score (p = .011), and history of attempt (p = .009) were significant predictors, with an overall prediction of 82% and variance of 56%. Somewhat similar predictors emerged as significant for current suicidal ideators, with an overall prediction of 85% and variance of 50%. In the structural equation model, too, presence of depression and high BHS score contributed to suicidal ideation. OCD is associated with a high risk for suicidal behavior. Depression and hopelessness are the major correlates of suicidal behavior. It is vital that patients with OCD undergo detailed assessment for suicide risk and associated depression. Aggressive treatment of depression may be warranted to modify the risk for suicide. Future studies should examine suicidal behavior in a prospective design in larger samples to examine if severity of OCD and treatment nonresponse contribute to suicide risk.

  6. Antithrombotic therapy in anticoagulated patients with atrial fibrillation presenting with acute coronary syndromes and/or undergoing percutaneous coronary intervention/stenting.

    PubMed

    Wrigley, Benjamin J; Tapp, Luke D; Shantsila, Eduard; Lip, Gregory Yh

    2010-07-01

    The management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary inter vention/stenting cannot be done according to a regimented common protocol, and stroke and bleeding risk stratification schema should be employed to individualize treatment options. A delicate balance is needed between the prevention of thromboembolism, against recurrent cardiac ischemia or stent thrombosis, and bleeding risk. New guidance from a consensus document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association and the European Association of Percutaneous Cardiovascular Interventions on the management of Antithrombotic Therapy in Atrial Fibrillation Patients Presenting with Acute Coronary Syndrome and/or Undergoing Percutaneous Coronary Intervention/Stenting has sought to clarify some of the major issues and problems surrounding this practice, and will allow clinicians to make much more informed decisions when faced with treating such patients.

  7. Smoking, drinking, and depression: comorbidity in head and neck cancer patients undergoing radiotherapy.

    PubMed

    McCarter, Kristen; Baker, Amanda L; Britton, Benjamin; Wolfenden, Luke; Wratten, Chris; Bauer, Judith; Halpin, Sean A; Carter, Gregory; Beck, Alison K; Leigh, Lucy; Oldmeadow, Christopher

    2018-04-19

    We aimed to determine the prevalence and co-occurrence of tobacco smoking, alcohol consumption, and depressive symptoms among a sample of head and neck cancer (HNC) patients undergoing radiotherapy. A total of 307 HNC patients participated in a multi-site stepped-wedge randomized controlled trial (RCT) evaluating the effectiveness of a dietitian-delivered health behavior intervention in patients with HNC undergoing radiotherapy. During week one of radiotherapy patients completed measures of smoking, alcohol consumption, and level of depression. Approximately one-fifth (21%) of patients had two or more co-occurring problems: current smoking, hazardous alcohol use, and/or likely presence of a major depressive episode (MDE). Approximately one-third (34%) of the sample were current smokers, one-third (31%) were drinking hazardously and almost one-fifth (19%) had likely cases of depression. Comorbidity of smoking, hazardous alcohol use, and MDE is high in HNC patients, and interventions need to address this cluster of cancer risk factors. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  8. Third-space fluid shift in elderly patients undergoing gastrointestinal surgery: Part 1: Pathophysiological mechanisms.

    PubMed

    Redden, Maurine; Wotton, Karen

    2002-06-01

    Third-space fluid shift, the movement of body fluid to a non-functional space, is a frequently occurring and potentially fatal clinical phenomenon. Little published research exists however in medical or nursing journals concerning its incidence, significance and ramifications in elderly patients undergoing major gastrointestinal surgery. This initial article, part I, explores fluid movement between fluid compartments and uses these principles to discuss the pathophysiology of the two distinct phases of third-space fluid shift. Part II will examine the criteria nurses could use in the clinical assessment of patients in both first and second phases third-space fluid shift and discuss the clinical reliability of these criteria.

  9. Using Landsat digital data to detect moisture stress in corn-soybean growing regions

    NASA Technical Reports Server (NTRS)

    Thompson, D. R.; Wehmanen, O. A.

    1980-01-01

    As a part of a follow-on study to the moisture stress detection effort conducted in the Large Area Crop Inventory Experiment (LACIE), a technique utilizing transformed Landsat digital data was evaluated for detecting moisture stress in humid growing regions using sample segments from Iowa, Illinois, and Indiana. At known growth stages of corn and soybeans, segments were classified as undergoing moisture stress or not undergoing stress. The remote-sensing-based information was compared to a weekly ground-based index (Crop Moisture Index). This comparison demonstrated that the remote sensing technique could be used to monitor the growing conditions within a region where corn and soybeans are the major crop.

  10. View south of sail loft mid loft area. Note ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    View south of sail loft - mid- loft area. Note inflatable boats undergoing pressure testing. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structure Shop, League Island, Philadelphia, Philadelphia County, PA

  11. Prospective dynamic functional evaluation of gait and spinal balance following spinal fusion in adolescent idiopathic scoliosis.

    PubMed

    Lenke, L G; Engsberg, J R; Ross, S A; Reitenbach, A; Blanke, K; Bridwell, K H

    2001-07-15

    Prospective evaluation of gait and spinal-pelvic balance parameters in patients with adolescent idiopathic scoliosis undergoing a spinal fusion. To evaluate changes in gait and three-dimensional alignment and balance of the spine relative to the pelvis as a consequence of spinal fusion. Preoperative and postoperative spinal radiographs have been the major forms of outcome analysis of adolescent idiopathic scoliosis fusions. The use of optoelectronic analysis for posture and gait has gained acceptance recently. However, there is a paucity of data quantifying, comparing, and correlating structural and functional changes in patients undergoing scoliosis fusion surgery including upright posture and gait. Thirty patients with adolescent idiopathic scoliosis undergoing an instrumented spinal fusion were prospectively evaluated. Coronal and sagittal vertical alignment was evaluated on radiographs (CVA-R, SVA-R), during upright posture (CVA-P and SVA-P), and during gait (CVA-G, SVA-G). Transverse plane alignment was evaluated by the acromion-pelvis angle during gait. Gait speed was significantly decreased (P < 0.05) between preoperative (129 +/- 16 cm/sec) and 2-year postoperative (119 +/- 16 cm/sec) testing sessions. Decreasing gait speed was the result of significantly reduced cadence and decreased stride length. There were no significant differences for lower extremity kinematics over the entire gait cycle. Spinal-pelvic balance parameters showed significant improvement in mean CVA-R, CVA-G (P < 0.05), then unchanged CVA-P at 2 years postoperation. CVA-P was relatively unchanged while the mean CVA-G also showed significant improvement from preoperation (2.2 +/- 2.4 cm) to 2 years postoperation (1.3 +/- 1.3 cm)(P < 0.05). The mean SVA-R, SVA-P, and SVA-G were unchanged at 2 years postoperation (P > 0.05). The acromion-pelvis angle during gait at maximum shoulder rotation was statistically improved at 1 year (P = 0.002) and 2 years (P = 0.001) after surgery. Importantly, CVA-P correlated with CVA-G, and SVA-P correlated with SVA-G to the P < 0.05 level. Patients with adolescent idiopathic scoliosis undergoing spinal fusion show slightly decreased gait speed at 2 years postoperation without any change in lower extremity kinematics. Spinal-pelvic balance parameters are improved in the coronal plane and unchanged in the sagittal plane radiographically and during standing posture and gait. Transverse plane parameters also are improved at maximum shoulder rotation during gait.

  12. A meta-analysis of randomised controlled trials on preoperative oral carbohydrate treatment in elective surgery.

    PubMed

    Awad, Sherif; Varadhan, Krishna K; Ljungqvist, Olle; Lobo, Dileep N

    2013-02-01

    Whilst preoperative carbohydrate treatment (PCT) results in beneficial physiological effects, the effects on postoperative clinical outcomes remain unclear and were studied in this meta-analysis. Prospective studies that randomised adult non-diabetic patients to either PCT (≥50 g oral carbohydrates 2-4 h pre-anaesthesia) or control (fasted/placebo) were included. The primary outcome was length of hospital stay. Secondary outcomes included development of postoperative insulin resistance, complications, nausea and vomiting. Methodological quality was assessed using GRADEpro® software. Twenty-one randomised studies of 1685 patients (733 PCT: 952 control) were included. No overall difference in length of stay was noted for analysis of all studies or subgroups of patients undergoing surgery with an expected hospital stay ≤2 days or orthopaedic procedures. However, patients undergoing major abdominal surgery following PCT had reduced length of stay [mean difference, 95% confidence interval: -1.08 (-1.87 to -0.29); I² = 60%, p = 0.007]. PCT reduced postoperative insulin resistance with no effects on in-hospital complications over control (risk ratio, 95% confidence interval, 0.88 (0.50-1.53), I² = 41%; p = 0.640). There was significant heterogeneity amongst studies and, therefore, quality of evidence was low to moderate. PCT may be associated with reduced length of stay in patients undergoing major abdominal surgery, however, the included studies were of low to moderate quality. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  13. Length of Barrett's segment predicts failure of eradication in radiofrequency ablation for Barrett's esophagus: a retrospective cohort study.

    PubMed

    Luckett, Tyler; Allamneni, Chaitanya; Cowley, Kevin; Eick, John; Gullick, Allison; Peter, Shajan

    2018-05-21

    We aim to investigate factors that may contribute to failure of eradication of dysplastic Barrett's Esophagus among patients undergoing radiofrequency ablation treatment. A retrospective review of patients undergoing radiofrequency ablation for treatment of Barrett's Esophagus was performed. Data analyzed included patient demographics, medical history, length of Barrett's Esophagus, number of radiofrequency ablation sessions, and histopathology. Subsets of patients achieving complete eradication were compared with those not achieving complete eradication. A total of 107 patients underwent radiofrequency ablation for Barrett's Esophagus, the majority white, overweight, and male. Before treatment, 63 patients had low-grade dysplasia, and 44 patients had high-grade dysplasia or carcinoma. Complete eradication was achieved in a majority of patients (57% for metaplasia, and 76.6% for dysplasia). Failure of eradication occurred in 15.7% of patients. The median number of radiofrequency ablation treatments in patients achieving complete eradication was 3 sessions, compared to 4 sessions for failure of eradication (p = 0.06). Barrett's esophagus length of more than 5 cm was predictive of failure of eradication (p < 0.001). Radiofrequency ablation for dysplastic Barrett's Esophagus is a proven and effective treatment modality, associated with a high rate of complete eradication. Our rates of eradication from a center starting an ablation program are comparable to previously published studies. Length of Barrett's segment > 5 cm was found to be predictive of failure of eradication in patients undergoing radiofrequency ablation.

  14. Responses of advanced directives by Jehovah’s Witnesses on a gynecologic oncology service

    PubMed Central

    Nagarsheth, Nimesh P; Gupta, Nikhil; Gupta, Arpeta; Moshier, Erin; Gretz, Herbert; Shander, Aryeh

    2015-01-01

    Objectives To review the responses of advance directives signed by Jehovah’s Witness patients prior to undergoing surgery at a gynecologic oncology service. Study design A retrospective chart review of gynecologic oncology patients undergoing surgery at a bloodless surgery center from 1998–2007 was conducted. Demographic, pathologic, and clinical data were recorded. The proportion of patients who accepted and refused various blood-derived products was determined and was compared to previously published results from a similar study of labor and delivery unit patients. Results No gynecologic oncology patients agreed to accept transfusions of whole blood, red cells, white cells, platelets, or plasma under any circumstance, whereas 9.8% of pregnant patients accepted transfusion (P=0.0385). However, 98% of gynecologic oncology patients agreed to accept some blood products, including fractions such as albumin, immunoglobulins, and clotting factors, while only 39% of pregnant patients agreed (P<0.0001). In addition, all gynecologic oncology patients (100%) accepted intraoperative hemodilution, compared to 55% of pregnant patients (P<0.0001). Conclusion Our results confirm the commonly held belief that the majority of Jehovah’s Witness patients refuse to accept major blood components. However, Jehovah’s Witness patients at a gynecologic oncology service will accept a variety of blood-derived products (minor fractions) and interventions designed to optimize outcomes when undergoing transfusion-free surgery. Patients presenting to a gynecologic oncology service respond differently to advanced directives related to bloodless surgery, as compared to patients from an obstetrical service. PMID:25565911

  15. Epidemiological profile and postoperative complications of women undergoing gynecological surgery in a reference center in the northern Brazilian legal Amazon.

    PubMed

    Coelho, Sônia Maria; Perez, Elizabeth de La Trinidad Castro; Lins, Cynthia Dantas de Macedo; Gomes, Mariano Tamura Vieira; Bella, Zsuzsanna Illona Katalin de Jármy Di; Andres, Marina de Paula; Podgaec, Sergio

    2015-01-01

    To evaluate the epidemiological profile and the operative complications of patients undergoing gynecological operations for benign diseases in a tertiary public hospital in the state of Roraima, Brazil. We conducted a retrospective survey through the analysis of 518 records of patients submitted to gynecological operations between January and June 2012. We included the three major operations during this period (n = 175): hysterectomy, colpoperineoplasty and suburethral sling placement. We excluded 236 cases of tubal ligation and 25 cases where it was not possible to access to medical records. The mean age was 47.6 years; the education level of most patients was completed junior high (36.6%); 77% were from the State capital, 47.4% were in stable relationships and 26.3% were housewives. The majority of patients had given birth three or more times (86.6%), with previous vaginal delivery in 50.2%, and cesarean delivery, 21%. The main diagnostic indications for surgical treatment were uterine myoma (46.3%), urinary incontinence (27.4%) and genital dystopias (17.7%). We found three cases (1.7%) of high-grade intraepithelial lesions on Pap smear. The most common procedure was total hysterectomy (19.8%), 15.5% vaginally. The most common complication was wound infection (2.2%). Women undergoing gynecological operations due to benign disease had a mean age of 47 years, most had levels of basic education, came from the capital, were in stable relationships, predominantly housewives, multiparous and showed low operative complication rates.

  16. An environmental scan of advance care planning decision AIDS for patients undergoing major surgery: a study protocol.

    PubMed

    Aslakson, Rebecca A; Schuster, Anne L R; Miller, Judith; Weiss, Matthew; Volandes, Angelo E; Bridges, John F P

    2014-01-01

    Patients who undergo major surgery are at risk for perioperative morbidity and mortality. It would be appropriate to initiate advance care planning with patients prior to surgery, but surgeons may experience difficulty initiating such conversations. Rather than focus on changing clinician behavior, advance care planning decision aids can be an innovative vehicle to motivate advance care planning among surgical patients and their families. The purpose of this paper is to describe a study protocol for conducting an environmental scan concerning advance care planning decision aids that may be relevant to patients undergoing high-risk surgery. This study will gather information from written or verbal data sources that incorporate professional and lay perspectives: a systematic review, a grey literature review, key informant interviews, and patient and family engagement. It is envisioned that this study will generate three outcomes: a synthesis of current evidence, a summary of gaps in knowledge, and a taxonomy of existing advance care planning decision aids. This environmental scan will demonstrate principles of patient-centered outcomes research, and it will exemplify a pioneering approach for reviewing complex interventions. Anticipated limitations are that information will be gathered from a small sample of patients and families, and that potentially relevant information could also be missing from the environmental scan due to the inclusion/exclusion criteria. Outcomes from the environmental scan will inform future patient-centered research to develop and evaluate a new decision aid.

  17. High salt solution structure of a left-handed RNA double helix

    PubMed Central

    Popenda, Mariusz; Milecki, Jan; Adamiak, Ryszard W.

    2004-01-01

    Right-handed RNA duplexes of (CG)n sequence undergo salt-induced helicity reversal, forming left-handed RNA double helices (Z-RNA). In contrast to the thoroughly studied Z-DNA, no Z-RNA structure of natural origin is known. Here we report the NMR structure of a half-turn, left-handed RNA helix (CGCGCG)2 determined in 6 M NaClO4. This is the first nucleic acid motif determined at such high salt. Sequential assignments of non-exchangeable proton resonances of the Z-form were based on the hitherto unreported NOE connectivity path [H6(n)-H5′/H5″(n)-H8(n+1)-H1′(n+1)-H6(n+2)] found for left-handed helices. Z-RNA structure shows several conformational features significantly different from Z-DNA. Intra-strand but no inter-strand base stacking was observed for both CpG and GpC steps. Helical twist angles for CpG steps have small positive values (4–7°), whereas GpC steps have large negative values (−61°). In the full-turn model of Z-RNA (12.4 bp per turn), base pairs are much closer to the helix axis than in Z-DNA, thus both the very deep, narrow minor groove with buried cytidine 2′-OH groups, and the major groove are well defined. The 2′-OH group of cytidines plays a crucial role in the Z-RNA structure and its formation; 2′-O-methylation of cytidine, but not of guanosine residues prohibits A to Z helicity reversal. PMID:15292450

  18. Diabetes mellitus is associated with increased acute kidney injury and 1-year mortality after transcatheter aortic valve replacement: A meta-analysis.

    PubMed

    Mina, George S; Gill, Priyanka; Soliman, Demiana; Reddy, Pratap; Dominic, Paari

    2017-09-01

    Diabetes mellitus (DM) is associated with adverse outcomes after surgical aortic valve replacement. However, there are conflicting data on the impact of DM on outcomes of transcatheter aortic valve replacement (TAVR). DM is associated with poor outcomes after different cardiac procedures. Therefore, DM can also be associated with poor outcomes after TAVR. We searched PubMed and Cochrane Central Register of Controlled Trials for studies that evaluated outcomes after TAVR and stratified at least 1 of the studied endpoints by DM status. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints were early (up to 30 days) mortality, acute kidney injury (AKI), cerebrovascular accident (CVA), major bleeding, and major vascular complications. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random effects models. We included 64 studies with a total of 38 686 patients. DM was associated with significantly higher 1-year mortality (OR: 1.14, 95% CI: 1.04-1.26, P = 0.008) and periprocedural AKI (OR: 1.28, 95% CI: 1.08-1.52, P = 0.004). On the other hand, there were no significant differences between diabetics and nondiabetics in early mortality, CVAs, major bleeding, or major vascular complications. DM is associated with increased 1-year mortality and periprocedural AKI in patients undergoing TAVR. The results of this study suggest that DM is a predictor of adverse outcomes in patients undergoing TAVR. © 2017 Wiley Periodicals, Inc.

  19. Ultratrace Detection of Nitroaromatics: Picric Acid Responsive Aggregation/Disaggregation of Self-Assembled p-Terphenylbenzimidazolium-Based Molecular Baskets.

    PubMed

    Sandhu, Sana; Kumar, Rahul; Singh, Prabhpreet; Mahajan, Aman; Kaur, Manmeet; Kumar, Subodh

    2015-05-20

    1-(p-Terphenyl)-benzimidazolium (TRIPOD-TP) molecules undergo self-assembly to form rodlike structures in aqueous medium, as shown by field-emission scanning electron microscopy, transmission electron microscopy, and dynamic light scattering studies. Upon gradual addition of picric acid (PA), these aggregates undergo an aggregation/disaggregation process to complex morphological structures (10(-12)-10(-10) M PA) and spherical aggregates (10(-9)-10(-8) M PA). These spherical aggregates undergo further dissolution to well-dispersed spheres between 10(-7)-10(-6) M PA. During fluorescence studies, these aggregates demonstrate superamplified fluorescence quenching (>97%) in the presence of 10(-5) to 0.2 equiv of the probe concentration, an unprecedented process with PA. The lowest detection limits by solution of TRIPOD-TP are 5 × 10(-13) PA, 50 × 10(-12) M 2,4-dinitrophenol, 200 × 10(-12) M 2,4,6-trinitrotoluene, and 1 nM 1-chloro-2,4-dinitrobenzene. Paper strips dipped in the solution of TRIPOD-TP demonstrate quantitative fluorescence quenching between 10(-17) and 10(-6) M PA using front-surface steady state studies and can measure as low as 2.29 × 10(-20) g/cm(2) PA.

  20. Mycobacterium tuberculosis acyl carrier protein synthase adopts two different pH-dependent structural conformations

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

    Gokulan, Kuppan; Aggarwal, Anup; Shipman, Lance

    2011-09-20

    The crystal structures of acyl carrier protein synthase (AcpS) from Mycobacterium tuberculosis (Mtb) and Corynebacterium ammoniagenes determined at pH 5.3 and pH 6.5, respectively, are reported. Comparison of the Mtb apo-AcpS structure with the recently reported structure of the Mtb AcpS-ADP complex revealed that AcpS adopts two different conformations: the orthorhombic and trigonal space-group structures show structural differences in the {alpha}2 helix and in the conformation of the {alpha}3-{alpha}4 connecting loop, which is in a closed conformation. The apo-AcpS structure shows electron density for the entire model and was obtained at lower pH values (4.4-6.0). In contrast, at a highermore » pH value (6.5) AcpS undergoes significant conformational changes, resulting in disordered regions that show no electron density in the AcpS model. The solved structures also reveal that C. ammoniagenes AcpS undergoes structural rearrangement in two regions, similar to the recently reported Mtb AcpS-ADP complex structure. In vitro reconstitution experiments show that AcpS has a higher post-translational modification activity between pH 4.4 and 6.0 than at pH values above 6.5, where the activity drops owing to the change in conformation. The results show that apo-AcpS and AcpS-ADP adopt different conformations depending upon the pH conditions of the crystallization solution.« less

  1. Structure, phase transitions, and isotope effects in [(CH3)4N]2PuCl6

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

    Wilson, Richard E.

    2015-11-02

    The single crystal X-ray diffraction structure of [(CH3)4N]2PuCl6 is presented for the first time, resolving long standing confusion and speculation regarding the structure of this compound in the literature. A temperature dependent study of this compound shows that the structure of [(CH3)4N]2PuCl6 undergoes no fewer than two phase transitions between 100 and 360 K. The phase of [(CH3)4N]2PuCl6 at room temperature is Fd-3c a = 26.012(3) Å. At 360 K, the structure is in space group Fm-3m with a = 13.088(1) Å. The plutonium octahedra and tetramethylammonium cations undergo a rotative displacement and the degree of rotation varies with temperature,more » giving rise to the phase transition from Fm-3m to Fd-3c as the crystal is cooled. Synthesis and structural studies of the deuterated salt [(CD3)4N]2PuCl6 suggest that there is an isotopic effect associated with this phase transition as revealed by a changing transition temperature in the deuterated versus protonated compound indicating that the donor-acceptor interactions between the tetramethylammonium cations and the hexachloroplutonate anions are driving the phase transformation.« less

  2. The effect of aprotinin, tranexamic acid, and aminocaproic acid on blood loss and use of blood products in major pediatric surgery: a meta-analysis.

    PubMed

    Schouten, Esther S; van de Pol, Alma C; Schouten, Anton N J; Turner, Nigel M; Jansen, Nicolaas J G; Bollen, Casper W

    2009-03-01

    Aprotinin reduces the blood loss and transfusion of blood products in children undergoing major surgery. Aprotinin has been associated with severe side effects in adults, and tranexamic acid and aminocaproic acid have been found to be safer alternatives in adults. This systematic review addresses the question of whether tranexamic acid and aminocaproic acid are equally effective as aprotinin for reducing blood loss and transfusion in children undergoing major surgery. A systematic review of the literature was conducted to identify all randomized controlled trials of aprotinin, tranexamic acid, and aminocaproic acid involving children undergoing cardiac or scoliosis surgery. Twenty-three cardiac studies, totaling 1893 patients, met the inclusion criteria. None of the studies directly compared aprotinin to an alternative antifibrinolytic. Five scoliosis studies, totaling 207 patients, met the inclusion criteria. Data on blood loss and use of blood products in the first 24 postoperative hours were extracted. Only homogenously distributed outcomes were pooled. Tranexamic acid showed a homogeneously distributed reduction of blood loss by 11 mL/kg (95% confidence interval [CI] 9-13 mL/kg). Outcomes of blood loss reduction by aprotinin and aminocaproic acid were too heterogeneously distributed to be pooled, so the effect on blood loss could not be evaluated. Both aprotinin and tranexamic acid significantly reduced packed red cell transfusion (4 mL/kg, 95% CI 2-7 mL/kg and 7 mL/kg, 95% CI 5-10 mL/kg, respectively). Type of antifibrinolytic was not a determining factor that explained differences in outcome among trials in a meta-regression analysis. In the scoliosis studies, aprotinin and tranexamic acid significantly reduced blood loss compared with placebo (385 mL, 95% CI 727-42 mL and 682 mL, 95% CI 1149-214 mL, respectively). There is no evidence that suggests that, compared with aprotinin, alternative antifibrinolytics such as tranexamic acid were less effective in reducing blood loss in major pediatric surgery.

  3. Risks of Cardiovascular Adverse Events and Death in Patients with Previous Stroke Undergoing Emergency Noncardiac, Nonintracranial Surgery: The Importance of Operative Timing.

    PubMed

    Christiansen, Mia N; Andersson, Charlotte; Gislason, Gunnar H; Torp-Pedersen, Christian; Sanders, Robert D; Føge Jensen, Per; Jørgensen, Mads E

    2017-07-01

    The outcomes of emergent noncardiac, nonintracranial surgery in patients with previous stroke remain unknown. All emergency surgeries performed in Denmark (2005 to 2011) were analyzed according to time elapsed between previous ischemic stroke and surgery. The risks of 30-day mortality and major adverse cardiovascular events were estimated as odds ratios (ORs) and 95% CIs using adjusted logistic regression models in a priori defined groups (reference was no previous stroke). In patients undergoing surgery immediately (within 1 to 3 days) or early after stroke (within 4 to 14 days), propensity-score matching was performed. Of 146,694 nonvascular surgeries (composing 98% of all emergency surgeries), 5.3% had previous stroke (mean age, 75 yr [SD = 13]; 53% women, 50% major orthopedic surgery). Antithrombotic treatment and atrial fibrillation were more frequent and general anesthesia less frequent in patients with previous stroke (all P < 0.001). Risks of major adverse cardiovascular events and mortality were high for patients with stroke less than 3 months (20.7 and 16.4% events; OR = 4.71 [95% CI, 4.18 to 5.32] and 1.65 [95% CI, 1.45 to 1.88]), and remained increased for stroke within 3 to 9 months (10.3 and 12.3%; OR = 1.93 [95% CI, 1.55 to 2.40] and 1.20 [95% CI, 0.98 to 1.47]) and stroke more than 9 months (8.8 and 11.7%; OR = 1.62 [95% CI, 1.43 to 1.84] and 1.20 [95% CI, 1.08 to 1.34]) compared with no previous stroke (2.3 and 4.8% events). Major adverse cardiovascular events were significantly lower in 323 patients undergoing immediate surgery (21%) compared with 323 successfully propensity-matched early surgery patients (29%; P = 0.029). Adverse cardiovascular outcomes and mortality were greatly increased among patients with recent stroke. However, events were higher 4 to 14 days after stroke compared with 1 to 3 days after stroke.

  4. Burden of Geriatric Events Among Older Adults Undergoing Major Cancer Surgery

    PubMed Central

    Saliba, Debra; Kwan, Lorna; Moore, Alison A.; Litwin, Mark S.

    2016-01-01

    Purpose Most malignancies are diagnosed in older adults who are potentially susceptible to aging-related health conditions; however, the manifestation of geriatric syndromes during surgical cancer treatment is not well quantified. Accordingly, we sought to assess the prevalence and ramifications of geriatric events during major surgery for cancer. Patients and Methods Using Nationwide Inpatient Sample data from 2009 to 2011, we examined hospital admissions for major cancer surgery among elderly patients (ie, age ≥ 65 years) and a referent group age 55 to 64 years. From these observations, we identified geriatric events that included delirium, dehydration, falls and fractures, failure to thrive, and pressure ulcers. We then estimated the collective prevalence of these events according to age, comorbidity, and cancer site and further explored their relationship with other hospital-based outcomes. Results Within a weighted sample of 939,150 patients, we identified at least one event in 9.2% of patients. Geriatric events were most common among patients age ≥ 75 years, with a Charlson comorbidity score ≥ 2, and who were undergoing surgery for cancer of the bladder, ovary, colon and/or rectum, pancreas, or stomach (P < .001). Adjusting for patient and hospital characteristics, those patients who experienced a geriatric event had a greater likelihood of concurrent complications (odds ratio [OR], 3.73; 95% CI, 3.55 to 3.92), prolonged hospitalization (OR, 5.47; 95% CI, 5.16 to 5.80), incurring high cost (OR, 4.97; 95% CI, 4.58 to 5.39), inpatient mortality (OR, 3.22; 95% CI, 2.94 to 3.53), and a discharge disposition other than home (OR, 3.64; 95% CI, 3.46 to 3.84). Conclusion Many older patients who receive cancer-directed surgery experience a geriatric event, particularly those who undergo major abdominal surgery. These events are linked to operative morbidity, prolonged hospitalization, and more expensive health care. As our population ages, efforts focused on addressing conditions and complications that are more common in older adults will be essential to delivering high-quality cancer care. PMID:26884578

  5. Burden of Geriatric Events Among Older Adults Undergoing Major Cancer Surgery.

    PubMed

    Tan, Hung-Jui; Saliba, Debra; Kwan, Lorna; Moore, Alison A; Litwin, Mark S

    2016-04-10

    Most malignancies are diagnosed in older adults who are potentially susceptible to aging-related health conditions; however, the manifestation of geriatric syndromes during surgical cancer treatment is not well quantified. Accordingly, we sought to assess the prevalence and ramifications of geriatric events during major surgery for cancer. Using Nationwide Inpatient Sample data from 2009 to 2011, we examined hospital admissions for major cancer surgery among elderly patients (ie, age ≥ 65 years) and a referent group age 55 to 64 years. From these observations, we identified geriatric events that included delirium, dehydration, falls and fractures, failure to thrive, and pressure ulcers. We then estimated the collective prevalence of these events according to age, comorbidity, and cancer site and further explored their relationship with other hospital-based outcomes. Within a weighted sample of 939,150 patients, we identified at least one event in 9.2% of patients. Geriatric events were most common among patients age ≥ 75 years, with a Charlson comorbidity score ≥ 2, and who were undergoing surgery for cancer of the bladder, ovary, colon and/or rectum, pancreas, or stomach (P < .001). Adjusting for patient and hospital characteristics, those patients who experienced a geriatric event had a greater likelihood of concurrent complications (odds ratio [OR], 3.73; 95% CI, 3.55 to 3.92), prolonged hospitalization (OR, 5.47; 95% CI, 5.16 to 5.80), incurring high cost (OR, 4.97; 95% CI, 4.58 to 5.39), inpatient mortality (OR, 3.22; 95% CI, 2.94 to 3.53), and a discharge disposition other than home (OR, 3.64; 95% CI, 3.46 to 3.84). Many older patients who receive cancer-directed surgery experience a geriatric event, particularly those who undergo major abdominal surgery. These events are linked to operative morbidity, prolonged hospitalization, and more expensive health care. As our population ages, efforts focused on addressing conditions and complications that are more common in older adults will be essential to delivering high-quality cancer care. © 2016 by American Society of Clinical Oncology.

  6. Probing the structural dependency of photoinduced properties of colloidal quantum dots using metal-oxide photo-active substrates.

    PubMed

    Patty, Kira; Sadeghi, Seyed M; Campbell, Quinn; Hamilton, Nathan; West, Robert G; Mao, Chuanbin

    2014-09-21

    We used photoactive substrates consisting of about 1 nm coating of a metal oxide on glass substrates to investigate the impact of the structures of colloidal quantum dots on their photophysical and photochemical properties. We showed during irradiation these substrates can interact uniquely with such quantum dots, inducing distinct forms of photo-induced processes when they have different cores, shells, or ligands. In particular, our results showed that for certain types of core-shell quantum dot structures an ultrathin layer of a metal oxide can reduce suppression of quantum efficiency of the quantum dots happening when they undergo extensive photo-oxidation. This suggests the possibility of shrinking the sizes of quantum dots without significant enhancement of their non-radiative decay rates. We show that such quantum dots are not influenced significantly by Coulomb blockade or photoionization, while those without a shell can undergo a large amount of photo-induced fluorescence enhancement via such blockade when they are in touch with the metal oxide.

  7. Probing the structural dependency of photoinduced properties of colloidal quantum dots using metal-oxide photo-active substrates

    PubMed Central

    Patty, Kira; Sadeghi, Seyed M.; Campbell, Quinn; Hamilton, Nathan; West, Robert G.; Mao, Chuanbin

    2014-01-01

    We used photoactive substrates consisting of about 1 nm coating of a metal oxide on glass substrates to investigate the impact of the structures of colloidal quantum dots on their photophysical and photochemical properties. We showed during irradiation these substrates can interact uniquely with such quantum dots, inducing distinct forms of photo-induced processes when they have different cores, shells, or ligands. In particular, our results showed that for certain types of core-shell quantum dot structures an ultrathin layer of a metal oxide can reduce suppression of quantum efficiency of the quantum dots happening when they undergo extensive photo-oxidation. This suggests the possibility of shrinking the sizes of quantum dots without significant enhancement of their non-radiative decay rates. We show that such quantum dots are not influenced significantly by Coulomb blockade or photoionization, while those without a shell can undergo a large amount of photo-induced fluorescence enhancement via such blockade when they are in touch with the metal oxide. PMID:25316953

  8. Real-time observation of fluctuations in a driven-dissipative quantum many-body system undergoing a phase transition

    NASA Astrophysics Data System (ADS)

    Donner, Tobias

    2015-03-01

    A Bose-Einstein condensate whose motional degrees of freedom are coupled to a high-finesse optical cavity via a transverse pump beam constitutes a dissipative quantum many-body system with long range interactions. These interactions can induce a structural phase transition from a flat to a density-modulated state. The transverse pump field simultaneously represents a probe of the atomic density via cavity- enhanced Bragg scattering. By spectrally analyzing the light field leaking out of the cavity, we measure non-destructively the dynamic structure factor of the fluctuating atomic density while the system undergoes the phase transition. An observed asymmetry in the dynamic structure factor is attributed to the coupling to dissipative baths. Critical exponents for both sides of the phase transition can be extracted from the data. We further discuss our progress in adding strong short-range interactions to this system, in order to explore Bose-Hubbard physics with cavity-mediated long-range interactions and self-organization in lower dimensions.

  9. Structural violence and the state: HIV and labour migration from Pakistan to the Persian Gulf.

    PubMed

    Qureshi, Ayaz

    2013-01-01

    This paper examines the biopolitics of HIV and labour migration from Pakistan (a country classified by UNAIDS as at 'high risk' of a generalised epidemic) to the countries of the Gulf Cooperation Council (GCC). The remittances by the labour migrants in the Gulf are an invaluable source of foreign exchange for Pakistan and a large number of households are entirely dependent upon them. At the same time, the National AIDS Control Programme regards Gulf migrants as a key risk factor for an HIV epidemic. The majority of HIV positive people in clinics comprise Gulf returnee migrants and their family members. This paper suggests that in the process of migrating, prospective migrants are subjected to structural violence that increases their HIV vulnerabilities. In this process, they are subjected to regimes of medical inspection, reduced to their certifiable labour power, inscribed with nationalist ideologies identifying HIV as a disease that strikes 'the other', and exposed to exploitation that increases their vulnerabilities. After migration, they are made to undergo compulsory periodic medical examinations in the GCC and, if found to be HIV positive, they are forcibly deported without papers, proper diagnosis or healthcare - only to return as 'failed subjects'. Taking a disaggregated view of the state, the paper argues that, in order to be effective, debates on structural violence and the HIV epidemic must make explicit the role of the state in producing migrants' vulnerabilities.

  10. Structural brain imaging correlates of ASD and ADHD across the lifespan: a hypothesis-generating review on developmental ASD-ADHD subtypes.

    PubMed

    Rommelse, Nanda; Buitelaar, Jan K; Hartman, Catharina A

    2017-02-01

    We hypothesize that it is plausible that biologically distinct developmental ASD-ADHD subtypes are present, each characterized by a distinct time of onset of symptoms, progression and combination of symptoms. The aim of the present narrative review was to explore if structural brain imaging studies may shed light on key brain areas that are linked to both ASD and ADHD symptoms and undergo significant changes during development. These findings may possibly pinpoint to brain mechanisms underlying differential developmental ASD-ADHD subtypes. To this end we brought together the literature on ASD and ADHD structural brain imaging symptoms and particularly highlight the adolescent years and beyond. Findings indicate that the vast majority of existing MRI studies has been cross-sectional and conducted in children, and sometimes did include adolescents as well, but without explicitly documenting on this age group. MRI studies documenting on age effects in adults with ASD and/or ADHD are rare, and if age is taken into account, only linear effects are examined. Data from various studies suggest that a crucial distinctive feature underlying different developmental ASD-ADHD subtypes may be the differential developmental thinning patterns of the anterior cingulate cortex and related connections towards other prefrontal regions. These regions are crucial for the development of cognitive/effortful control and socio-emotional functioning, with impairments in these features as key to both ASD and ADHD.

  11. Embrittlement and Flow Localization in Reactor Structural Materials

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

    Xianglin Wu; Xiao Pan; James Stubbins

    2006-10-06

    Many reactor components and structural members are made from metal alloys due, in large part, to their strength and ability to resist brittle fracture by plastic deformation. However, brittle fracture can occur when structural material cannot undergo extensive, or even limited, plastic deformation due to irradiation exposure. Certain irradiation conditions lead to the development of a damage microstructure where plastic flow is limited to very small volumes or regions of material, as opposed to the general plastic flow in unexposed materials. This process is referred to as flow localization or plastic instability. The true stress at the onset of neckingmore » is a constant regardless of the irradiation level. It is called 'critical stress' and this critical stress has strong temperature dependence. Interrupted tensile testes of 316L SS have been performed to investigate the microstructure evolution and competing mechanism between mechanic twinning and planar slip which are believed to be the controlling mechanism for flow localization. Deformation twinning is the major contribution of strain hardening and good ductility for low temperatures, and the activation of twinning system is determined by the critical twinning stress. Phases transform and texture analyses are also discussed in this study. Finite element analysis is carried out to complement the microstructural analysis and for the prediction of materaials performance with and without stress concentration and irradiation.« less

  12. Preoperative Status and Risk of Complications in Patients with Hip Fracture

    PubMed Central

    McLaughlin, Mary Ann; Orosz, Gretchen M; Magaziner, Jay; Hannan, Edward L; McGinn, Thomas; Morrison, R Sean; Hochman, Tsivia; Koval, Kenneth; Gilbert, Marvin; Siu, Albert L

    2006-01-01

    BACKGROUND Limited information is available on preoperative status and risks for complications for older patients having surgery for hip fracture. Our objective was to identify potentially modifiable clinical findings that should be considered in decisions about the timing of surgery. METHODS We conducted a prospective cohort study with data obtained from medical records and through structured interviews with patients. A total of 571 adults with hip fracture who were admitted to 4 metropolitan hospitals were included. RESULTS Multiple logistic regression was used to identify risk factors (including 11 categories of physical and laboratory findings, classified as mild and severe abnormalities) for in-hospital complications. The presence of more than 1 (odds ratiol [OR] 9.7, 95% confidence interval [CI] 2.8 to 33.0) major abnormality before surgery or the presence of major abnormalities on admission that were not corrected prior to surgery (OR 2.8, 95% CI 1.2 to 6.4) was independently associated with the development of postoperative complications. We also found that minor abnormalities, while warranting correction, did not increase risk (OR 0.70, 95% CI 0.28 to 1.73). CONCLUSIONS In this study of older adults undergoing urgent surgery, potentially reversible abnormalities in laboratory and physical examination occurred frequently and significantly increased the risk of postoperative complications. Major clinical abnormalities should be corrected prior to surgery, but patients with minor abnormalities may proceed to surgery with attention to these medical problems perioperatively. PMID:16390507

  13. Gut microbiota and bacterial translocation in digestive surgery: the impact of probiotics.

    PubMed

    Komatsu, Shunichiro; Yokoyama, Yukihiro; Nagino, Masato

    2017-05-01

    It is conceivable that manipulation of the gut microbiota could reduce the incidence or magnitude of surgical complications in digestive surgery. However, the evidence remains inconclusive, although much effort has been devoted to randomized controlled trials (RCTs) and meta-analyses on probiotics. Furthermore, the mechanism behind the protective effects of probiotics appears elusive, our understanding of probiotic actions being fragmentary. The objective of this review is to assess the clinical relevance of the perioperative use of probiotics in major digestive surgery, based on a comprehensive view of the gut microbiota, bacterial translocation (BT), and host defense system. The first part of this article describes the pathophysiological events associated with the gut microbiota. Results of RCTs for the perioperative use of probiotics in major digestive surgery are reviewed in the latter part. The development of the structural and functional barrier to protect against BT primarily results from the generally cooperative interactions between the host and resident microbiota. There is a large body of evidence indicating that probiotics, by enhancing beneficial interactions, reinforce the host defense system to limit BT. The perioperative use of probiotics in patients undergoing hepatobiliary and pancreatic surgery is a promising approach for the prevention of postoperative infectious complications, while the effectiveness in colorectal surgery remains controversial due to substantial heterogeneity among the RCTs with small sample populations. Further studies, such as multi-center RCTs with a larger sample size, are necessary to confirm the clinical relevance of probiotic agents in major digestive surgery.

  14. Rate Kinetics and Molecular Dynamics of the Structural Transitions in Amyloidogenic Proteins

    NASA Astrophysics Data System (ADS)

    Steckmann, Timothy M.

    Amyloid fibril aggregation is associated with several horrific diseases such as Alzheimer's, Creutzfeld-Jacob, diabetes, Parkinson's and others. The process of amyloid aggregation involves forming myriad different metastable intermediate aggregates. Amyloid fibrils are composed of proteins that originate in an innocuous alpha-helix or random-coil structure. The alpha-helices convert their structure to beta-strands that aggregate into beta-sheets, and then into protofibrils, and ultimately into fully formed amyloid fibrils. On the basis of experimental data, I have developed a mathematical model for the kinetics of the reaction pathways and determined rate parameters for peptide secondary structural conversion and aggregation during the entire fibrillogenesis process from random coil to fibrils, including the molecular species that accelerate the conversions. The specific steps of the model and the rate constants that are determined by fitting to experimental data provide insight on the molecular species involved in the fibril formation process. To better understand the molecular basis of the protein structural transitions and aggregation, I report on molecular dynamics (MD) computational studies on the formation of amyloid protofibrillar structures in the small model protein ccbeta, which undergoes many of the structural transitions of the larger, naturally occurring amyloid forming proteins. Two different structural transition processes involving hydrogen bonds are observed for aggregation into fibrils: the breaking of intrachain hydrogen bonds to allow beta-hairpin proteins to straighten, and the subsequent formation of interchain hydrogen bonds during aggregation into amyloid fibrils. For my MD simulations, I found that the temperature dependence of these two different structural transition processes results in the existence of a temperature window that the ccbeta protein experiences during the process of forming protofibrillar structures. Both the mathematical modeling of the kinetics and the MD simulations show that molecular structural heterogeneity is a major factor in the process. The MD simulations also show that intrachain and interchain hydrogen bonds breaking and forming is strongly correlated to the process of amyloid formation.

  15. Effect of marital status on the outcome of patients undergoing elective or urgent coronary revascularization.

    PubMed

    Barbash, Israel M; Gaglia, Michael A; Torguson, Rebecca; Minha, Sa'ar; Satler, Lowell F; Pichard, Augusto D; Waksman, Ron

    2013-10-01

    Marriage confers various health advantages in the general population. However, the added value of marriage among patients who undergo percutaneous coronary intervention (PCI) beyond the standard cardiovascular risk factors is not clear. This study aimed to assess the effects of marital status on outcomes of patients undergoing elective or urgent PCI. Clinical observational analysis of consecutive patients undergoing elective or urgent PCI from 1993 to 2011 was performed. Patients were stratified by marital status, comparing married to unmarried patients. Clinical outcome up to 12 months was obtained by telephone contact or office visit. A total of 11,216 patients were included in the present analysis; 55% were married and 45% unmarried. Significant differences in baseline characteristics were noted, including a lower prevalence of hypertension (86% vs 88%), diabetes (34% vs 38%), and smoking (19% vs 25%) among married vs unmarried patients, respectively (P < .001). However, married patients had a higher prevalence of hypercholesterolemia and family history of coronary artery disease. Early and late major adverse cardiac event rates were significantly lower for married vs unmarried patients up to 1 year (13.3% vs 8.2%, P < .001). Married status was independently associated with improved outcome in multivariable analysis (hazard ratio 0.7, 95% CI 0.6-0.9). Married patients who undergo urgent or elective PCI have superior short- and long-term outcomes up to 1 year when compared with unmarried patients. These benefits persist after adjustment for multiple traditional cardiovascular risk factors. © 2013.

  16. Measurement of serum amyloid A1 (SAA1), a major isotype of acute phase SAA.

    PubMed

    Xu, Yuanyuan; Yamada, Toshiyuki; Satoh, Takahiko; Okuda, Yasuaki

    2006-01-01

    Serum amyloid A (SAA), a plasma precursor of reactive amyloid deposits, is a multigene product. SAA1 and SAA2, with primary structures that are 93% identical (98 of 104 amino acids), behave as acute phase proteins, as demonstrated by their increasing levels in plasma. Heretofore, it has been understood that SAA1 predominates and functions as an isotype in plasma. However, accurate measurements differentiating the two isotypes have not been reported. In this study, using monoclonal antibodies specific for SAA1, we developed an enzyme-linked immunosorbent assay (ELISA) for SAA1. The levels and ratios of SAA1 in total SAA (TSAA) were investigated in healthy subjects and patients with rheumatoid arthritis (RA). The SAA1/TSAA ratio was 74 +/- 12% and 77 +/- 12% in healthy subjects and RA patients, respectively. In RA patients, the ratios were not influenced by SAA1 genotype, which has been proposed to affect plasma SAA values. The kinetics of SAA1 in inflamed patients undergoing hemodialysis was found to be parallel with total SAA and C-reactive protein. Finally, this study confirmed that SAA1 is a major isotype of acute phase SAA and may determine total SAA values. This specific assay could be used in the evaluation of SAA behavior in several clinical conditions.

  17. Microsatellite Analysis of Museum Specimens Reveals Historical Differences in Genetic Diversity between Declining and More Stable Bombus Species

    PubMed Central

    Maebe, Kevin; Meeus, Ivan; Ganne, Maarten; De Meulemeester, Thibaut; Biesmeijer, Koos; Smagghe, Guy

    2015-01-01

    Worldwide most pollinators, e.g. bumblebees, are undergoing global declines. Loss of genetic diversity can play an essential role in these observed declines. In this paper, we investigated the level of genetic diversity of seven declining Bombus species and four more stable species with the use of microsatellite loci. Hereto we genotyped a unique collection of museum specimens. Specimens were collected between 1918 and 1926, in 6 provinces of the Netherlands which allowed us to make interspecific comparisons of genetic diversity. For the stable species B. pascuorum, we also selected populations from two additional time periods: 1949–1955 and 1975–1990. The genetic diversity and population structure in B. pascuorum remained constant over the three time periods. However, populations of declining bumblebee species showed a significantly lower genetic diversity than co-occurring stable species before their major declines. This historical difference indicates that the repeatedly observed reduced genetic diversity in recent populations of declining bumblebee species is not caused solely by the decline itself. The historically low genetic diversity in the declined species may be due to the fact that these species were already rare, making them more vulnerable to the major drivers of bumblebee decline. PMID:26061732

  18. Rib Diced Cartilage-Fascia Grafting in Dorsal Nasal Reconstruction: A Randomized Clinical Trial of Wrapping With Rectus Muscle Fascia vs Deep Temporal Fascia.

    PubMed

    As'adi, Kamran; Salehi, Seyed Hamid; Shoar, Saeed

    2014-08-01

    Rib cartilage is an abundant source for cartilage grafts when significant dorsal nasal augmentation or structural support is indicated. Diced cartilage wrapped in fascia was developed to counteract warping, visibility, and displacement of rib cartilage as a dorsal solid graft. The technique for wrapping diced cartilage has evolved during the past several years. The authors compared 2 distinct fascial sleeves for wrapping rib diced cartilage in the treatment of patients who required major dorsal nasal augmentation. Thirty-six patients who planned to undergo major dorsal nasal reconstruction with diced costal rib cartilage were assigned randomly to 1 of 2 groups: the intervention group, which received grafts wrapped with rectus muscle fascia from the rib cartilage harvesting site, or the control group, which received deep temporal fascia harvested separately. Outcomes were compared between the groups. Patients in the intervention group had significantly shorter operating times, significantly higher average satisfaction scores, and significantly shorter postoperative hospital stays than did patients in the control group. Harvesting rectus muscle fascia for wrapping diced rib cartilage is a feasible and reliable technique in dorsal nasal reconstruction surgery. It is associated with favorable outcomes and a high level of patient satisfaction. 4. © 2014 The American Society for Aesthetic Plastic Surgery, Inc.

  19. AUTEN-67, an autophagy-enhancing drug candidate with potent antiaging and neuroprotective effects.

    PubMed

    Papp, Diána; Kovács, Tibor; Billes, Viktor; Varga, Máté; Tarnóci, Anna; Hackler, László; Puskás, László G; Liliom, Hanna; Tárnok, Krisztián; Schlett, Katalin; Borsy, Adrienn; Pádár, Zsolt; Kovács, Attila L; Hegedűs, Krisztina; Juhász, Gábor; Komlós, Marcell; Erdős, Attila; Gulyás, Balázs; Vellai, Tibor

    2016-01-01

    Autophagy is a major molecular mechanism that eliminates cellular damage in eukaryotic organisms. Basal levels of autophagy are required for maintaining cellular homeostasis and functioning. Defects in the autophagic process are implicated in the development of various age-dependent pathologies including cancer and neurodegenerative diseases, as well as in accelerated aging. Genetic activation of autophagy has been shown to retard the accumulation of damaged cytoplasmic constituents, delay the incidence of age-dependent diseases, and extend life span in genetic models. This implies that autophagy serves as a therapeutic target in treating such pathologies. Although several autophagy-inducing chemical agents have been identified, the majority of them operate upstream of the core autophagic process, thereby exerting undesired side effects. Here, we screened a small-molecule library for specific inhibitors of MTMR14, a myotubularin-related phosphatase antagonizing the formation of autophagic membrane structures, and isolated AUTEN-67 (autophagy enhancer-67) that significantly increases autophagic flux in cell lines and in vivo models. AUTEN-67 promotes longevity and protects neurons from undergoing stress-induced cell death. It also restores nesting behavior in a murine model of Alzheimer disease, without apparent side effects. Thus, AUTEN-67 is a potent drug candidate for treating autophagy-related diseases.

  20. Bivalirudin Versus Heparin Anticoagulation in Transcatheter Aortic Valve Replacement: The Randomized BRAVO-3 Trial.

    PubMed

    Dangas, George D; Lefèvre, Thierry; Kupatt, Christian; Tchetche, Didier; Schäfer, Ulrich; Dumonteil, Nicolas; Webb, John G; Colombo, Antonio; Windecker, Stephan; Ten Berg, Jurriën M; Hildick-Smith, David; Mehran, Roxana; Boekstegers, Peter; Linke, Axel; Tron, Christophe; Van Belle, Eric; Asgar, Anita W; Fach, Andreas; Jeger, Raban; Sardella, Gennaro; Hink, Hans Ulrich; Husser, Oliver; Grube, Eberhard; Deliargyris, Efthymios N; Lechthaler, Ilknur; Bernstein, Debra; Wijngaard, Peter; Anthopoulos, Prodromos; Hengstenberg, Christian

    2015-12-29

    Anticoagulation is required during transcatheter aortic valve replacement (TAVR) procedures. Although an optimal regimen has not been determined, heparin is mainly used. Direct thrombin inhibition with bivalirudin may be an effective alternative to heparin as the procedural anticoagulant agent in this setting. The goal of this study was to determine whether bivalirudin offers an alternative to heparin as the procedural anticoagulant agent in patients undergoing TAVR. A total of 802 patients with aortic stenosis were randomized to undergo transfemoral TAVR with bivalirudin versus unfractionated heparin during the procedure. The 2 primary endpoints were major bleeding within 48 h or before hospital discharge (whichever occurred first) and 30-day net adverse clinical events, defined as the combination of major adverse cardiovascular events (all-cause mortality, myocardial infarction, or stroke) and major bleeding. Anticoagulation with bivalirudin versus heparin did not meet superiority because it did not result in significantly lower rates of major bleeding at 48 h (6.9% vs. 9.0%; relative risk: 0.77; 95% confidence interval [CI]: 0.48 to 1.23; p = 0.27) or net adverse cardiovascular events at 30 days (14.4% vs. 16.1%; relative risk: 0.89; 95% CI: 0.64 to 1.24; risk difference: -1.72; 95% CI: -6.70 to 3.25; p = 0.50); regarding the latter, the prespecified noninferiority hypothesis was met (pnoninferiority < 0.01). Rates of major adverse cardiovascular events at 48 h were not significantly different (3.5% vs. 4.8%; relative risk: 0.73; 95% CI: 0.37 to 1.43; p = 0.35). At 48 h, the bivalirudin group had significantly fewer myocardial infarctions but more acute kidney injury events than the heparin group; at 30 days, these differences were no longer significant. In this randomized trial of TAVR procedural pharmacotherapy, bivalirudin did not reduce rates of major bleeding at 48 h or net adverse cardiovascular events within 30 days compared with heparin. Although superiority was not shown, the noninferiority hypothesis was met with respect to the latter factor. Given the lower cost, heparin should remain the standard of care, and bivalirudin can be an alternative anticoagulant option in patients unable to receive heparin in TAVR. (International, Multi-center, Open-label, Randomized Controlled Trial in Patients Undergoing TAVR to Determine the Treatment Effect [Both Safety and Efficacy] of Using Bivalirudin Instead of UFH [BRAVO-2/3]; NCT01651780). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  1. Outcomes of lower extremity bypass performed for acute limb ischemia

    PubMed Central

    Baril, Donald T.; Patel, Virendra I.; Judelson, Dejah R.; Goodney, Philip P.; McPhee, James T.; Hevelone, Nathanael D.; Cronenwett, Jack L.; Schanzer, Andres

    2013-01-01

    Objective Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia. Methods All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year. Results Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation, deterioration in renal function, and respiratory complications. Patients who underwent lower extremity bypass for acute limb ischemia had no difference in rates of graft occlusion (18.1% vs 18.5%; P = .77), but did have significantly higher rates of limb loss (22.4% vs 9.7%; P < .0001) and mortality (20.9% vs 13.1%; P < .0001) at 1 year. On multivariable analysis, acute limb ischemia was an independent predictor of both major amputation (hazard ratio, 2.16; confidence interval, 1.38–3.40; P = .001) and mortality (hazard ratio, 1.41; confidence interval, 1.09–1.83; P = .009) at 1 year. Conclusions Patients who present with acute limb ischemia represent a less medically optimized subgroup within the population of patients undergoing lower extremity bypass. These patients may be expected to have more complex operations followed by increased rates of perioperative adverse events. Additionally, despite equivalent graft patency rates, patients undergoing lower extremity bypass for acute ischemia have significantly higher rates of major amputation and mortality at 1 year. PMID:23714364

  2. Outcomes of lower extremity bypass performed for acute limb ischemia.

    PubMed

    Baril, Donald T; Patel, Virendra I; Judelson, Dejah R; Goodney, Philip P; McPhee, James T; Hevelone, Nathanael D; Cronenwett, Jack L; Schanzer, Andres

    2013-10-01

    Acute limb ischemia remains one of the most challenging emergencies in vascular surgery. Historically, outcomes following interventions for acute limb ischemia have been associated with high rates of morbidity and mortality. The purpose of this study was to determine contemporary outcomes following lower extremity bypass performed for acute limb ischemia. All patients undergoing infrainguinal lower extremity bypass between 2003 and 2011 within hospitals comprising the Vascular Study Group of New England were identified. Patients were stratified according to whether or not the indication for lower extremity bypass was acute limb ischemia. Primary end points included bypass graft occlusion, major amputation, and mortality at 1 year postoperatively as determined by Kaplan-Meier life table analysis. Multivariable Cox proportional hazards models were constructed to evaluate independent predictors of mortality and major amputation at 1 year. Of 5712 lower extremity bypass procedures, 323 (5.7%) were performed for acute limb ischemia. Patients undergoing lower extremity bypass for acute limb ischemia were similar in age (66 vs 67; P = .084) and sex (68% male vs 69% male; P = .617) compared with chronic ischemia patients, but were less likely to be on aspirin (63% vs 75%; P < .0001) or a statin (55% vs 68%; P < .0001). Patients with acute limb ischemia were more likely to be current smokers (49% vs 39%; P < .0001), to have had a prior ipsilateral bypass (33% vs 24%; P = .004) or a prior ipsilateral percutaneous intervention (41% vs 29%; P = .001). Bypasses performed for acute limb ischemia were longer in duration (270 vs 244 minutes; P = .007), had greater blood loss (363 vs 272 mL; P < .0001), and more commonly utilized prosthetic conduits (41% vs 33%; P = .003). Acute limb ischemia patients experienced increased in-hospital major adverse events (20% vs 12%; P < .0001) including myocardial infarction, congestive heart failure exacerbation, deterioration in renal function, and respiratory complications. Patients who underwent lower extremity bypass for acute limb ischemia had no difference in rates of graft occlusion (18.1% vs 18.5%; P = .77), but did have significantly higher rates of limb loss (22.4% vs 9.7%; P < .0001) and mortality (20.9% vs 13.1%; P < .0001) at 1 year. On multivariable analysis, acute limb ischemia was an independent predictor of both major amputation (hazard ratio, 2.16; confidence interval, 1.38-3.40; P = .001) and mortality (hazard ratio, 1.41; confidence interval, 1.09-1.83; P = .009) at 1 year. Patients who present with acute limb ischemia represent a less medically optimized subgroup within the population of patients undergoing lower extremity bypass. These patients may be expected to have more complex operations followed by increased rates of perioperative adverse events. Additionally, despite equivalent graft patency rates, patients undergoing lower extremity bypass for acute ischemia have significantly higher rates of major amputation and mortality at 1 year. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  3. Dynamical transitions of a driven Ising interface

    NASA Astrophysics Data System (ADS)

    Sahai, Manish K.; Sengupta, Surajit

    2008-03-01

    We study the structure of an interface in a three-dimensional Ising system created by an external nonuniform field H(r,t) . H changes sign over a two-dimensional plane of arbitrary orientation. When the field is pulled with velocity ve , [i.e., H(r,t)=H(r-vet) ], the interface undergoes several dynamical transitions. For low velocities it is pinned by the field profile and moves along with it, the distribution of local slopes undergoing a series of commensurate-incommensurate transitions. For large ve the interface depins and grows with Kardar-Parisi-Zhang exponents.

  4. Effects of preoperative aspirin on cardiocerebral and renal complications in non-emergent cardiac surgery patients: a sub-group and cohort study.

    PubMed

    Cao, Longhui; Silvestry, Scott; Zhao, Ning; Diehl, James; Sun, Jianzhong

    2012-01-01

    Postoperative cardiocerebral and renal complications are a major threat for patients undergoing cardiac surgery. This study was aimed to examine the effect of preoperative aspirin use on patients undergoing cardiac surgery. An observational cohort study was performed on consecutive patients (n = 1879) receiving cardiac surgery at this institution. The patients excluded from the study were those with preoperative anticoagulants, unknown aspirin use, or underwent emergent cardiac surgery. Outcome events included were 30-day mortality, renal failure, readmission and a composite outcome--major adverse cardiocerebral events (MACE) that include permanent or transient stroke, coma, perioperative myocardial infarction (MI), heart block and cardiac arrest. Of all patients, 1145 patients met the inclusion criteria and were divided into two groups: those taking (n = 858) or not taking (n = 287) aspirin within 5 days preceding surgery. Patients with aspirin presented significantly more with history of hypertension, diabetes, peripheral arterial disease, previous MI, angina and older age. With propensity scores adjusted and multivariate logistic regression, however, this study showed that preoperative aspirin therapy (vs. no aspirin) significantly reduced the risk of MACE (8.4% vs. 12.5%, odds ratio [OR] 0.585, 95% CI 0.355-0.964, P = 0.035), postoperative renal failure (2.6% vs. 5.2%, OR 0.438, CI 0.203-0.945, P = 0.035) and dialysis required (0.8% vs. 3.1%, OR 0.230, CI 0.071-0.742, P = 0.014), but did not significantly reduce 30-day mortality (4.1% vs. 5.8%, OR 0.744, CI 0.376-1.472, P = 0.396) nor it increased readmissions in the patients undergoing cardiac surgery. Preoperative aspirin therapy is associated with a significant decrease in the risk of MACE and renal failure and did not increase readmissions in patients undergoing non-emergent cardiac surgery.

  5. Alternative splicing and nonsense-mediated decay of circadian clock genes under environmental stress conditions in Arabidopsis

    PubMed Central

    2014-01-01

    Background The circadian clock enables living organisms to anticipate recurring daily and seasonal fluctuations in their growth habitats and synchronize their biology to the environmental cycle. The plant circadian clock consists of multiple transcription-translation feedback loops that are entrained by environmental signals, such as light and temperature. In recent years, alternative splicing emerges as an important molecular mechanism that modulates the clock function in plants. Several clock genes are known to undergo alternative splicing in response to changes in environmental conditions, suggesting that the clock function is intimately associated with environmental responses via the alternative splicing of the clock genes. However, the alternative splicing events of the clock genes have not been studied at the molecular level. Results We systematically examined whether major clock genes undergo alternative splicing under various environmental conditions in Arabidopsis. We also investigated the fates of the RNA splice variants of the clock genes. It was found that the clock genes, including EARLY FLOWERING 3 (ELF3) and ZEITLUPE (ZTL) that have not been studied in terms of alternative splicing, undergo extensive alternative splicing through diverse modes of splicing events, such as intron retention, exon skipping, and selection of alternative 5′ splice site. Their alternative splicing patterns were differentially influenced by changes in photoperiod, temperature extremes, and salt stress. Notably, the RNA splice variants of TIMING OF CAB EXPRESSION 1 (TOC1) and ELF3 were degraded through the nonsense-mediated decay (NMD) pathway, whereas those of other clock genes were insensitive to NMD. Conclusion Taken together, our observations demonstrate that the major clock genes examined undergo extensive alternative splicing under various environmental conditions, suggesting that alternative splicing is a molecular scheme that underlies the linkage between the clock and environmental stress adaptation in plants. It is also envisioned that alternative splicing of the clock genes plays more complex roles than previously expected. PMID:24885185

  6. Health Care Needs and Support for Patients Undergoing Treatment for Prosthetic Joint Infection following Hip or Knee Arthroplasty: A Systematic Review.

    PubMed

    Kunutsor, Setor K; Beswick, Andrew D; Peters, Tim J; Gooberman-Hill, Rachael; Whitehouse, Michael R; Blom, Ashley W; Moore, Andrew J

    2017-01-01

    Hip and knee arthroplasty are common interventions for the treatment of joint conditions, most notably osteoarthritis. Although many patients benefit from surgery, approximately 1% of patients develop infection afterwards known as deep prosthetic joint infection (PJI), which often requires further major surgery. To assess support needs of patients undergoing treatment for PJI following hip or knee arthroplasty and to identify and evaluate what interventions are routinely offered to support such patients. Systematic review. MEDLINE, EMBASE, Web of Science, PsycINFO, Cinahl, Social Science Citation Index, The Cochrane Library, and reference lists of relevant studies from January 01, 1980 to October 05, 2016. Observational (prospective or retrospective cohort, nested case-control or case-control) studies, qualitative studies, or clinical trials conducted in patients treated for PJI and/or other major adverse occurrences following hip or knee arthroplasty. Data were extracted by two independent investigators and consensus was reached with involvement of a third. Given the heterogeneous nature of study designs, methods, and limited number of studies, a narrative synthesis is presented. Of 4,213 potentially relevant citations, we identified one case-control, one prospective cohort and two qualitative studies for inclusion in the synthesis. Patients report that PJI and treatment had a profoundly negative impact affecting physical, emotional, social and economic aspects of their lives. No study evaluated support interventions. The findings demonstrate that patients undergoing treatment for PJI have extensive physical, psychological, social and economic support needs. The interpretation of study results is limited by variation in study design, outcome measures and the small number of relevant eligible studies. However, our review highlights a lack of evidence about support strategies for patients undergoing treatment for PJI and other adverse occurrences following hip or knee arthroplasty. There is a need to design, implement and evaluate interventions to support these patients. PROSPERO 2015: CRD42015027175.

  7. Patients' perception of noise in the operating room--a descriptive and analytic cross-sectional study.

    PubMed

    Hasfeldt, Dorthe; Maindal, Helle Terkildsen; Toft, Palle; Birkelund, Regner

    2014-10-01

    Noise is a general stressor that affects the cardiovascular system, resulting in increased blood pressure and heart rate, both of which can be problematic for the patient preparing for anesthesia and surgery. The purpose of this study was to investigate the patient's perception of noise in the OR before anesthesia, the correlation between the actual noise levels and the patient's perception of noise, and if there are particular patient subgroups that are especially vulnerable to noise. This cross-sectional study was performed within a mixed descriptive and analytical design, including 120 patients (60 acute/60 elective) undergoing general anesthesia for orthopaedic surgery. Data collection consisted of registration of demographic variables and measurements of noise levels in the OR combined with a questionnaire. Results showed that 10% of the patients perceived noise levels in the OR as very high and experienced the noise as annoying, disruptive, and stressful. There was no correlation between the actual noise levels to which patients were exposed and their perception of noise. Acute patients perceived significantly more noise than elective patients (P<.01), although they were actually exposed to less noise. Of the acute patients, those undergoing major surgery perceived more noise than patients undergoing minor surgery (P<.01), although actually exposed to less noise. There was a significant correlation between patients' sense of coherence (SOC) and their perception of noise (P<.01). Most patients who perceived noise levels as very high had a SOC below 50 (scale: 13-91). Perianesthesia nurses need to maintain their focus on keeping noise levels in the OR as low as possible. When caring for acute patients, patients undergoing major surgery and patients with a low SOC perianesthesia nurses should be particularly aware, as these patients might be more vulnerable to noise. Copyright © 2014 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

  8. Major cardiac surgery induces an increase in sex steroids in prepubertal children.

    PubMed

    Heckmann, Matthias; d'Uscio, Claudia H; de Laffolie, Jan; Neuhaeuser, Christoph; Bödeker, Rolf-Hasso; Thul, Josef; Schranz, Dietmar; Frey, Brigitte M

    2014-03-01

    While the neuroprotective benefits of estrogen and progesterone in critical illness are well established, the data regarding the effects of androgens are conflicting. Surgical repair of congenital heart disease is associated with significant morbidity and mortality, but there are scant data regarding the postoperative metabolism of sex steroids in this setting. The objective of this prospective observational study was to compare the postoperative sex steroid patterns in pediatric patients undergoing major cardiac surgery (MCS) versus those undergoing less intensive non-cardiac surgery. Urinary excretion rates of estrogen, progesterone, and androgen metabolites (μg/mmol creatinine/m(2) body surface area) were determined in 24-h urine samples before and after surgery using gas chromatography-mass spectrometry in 29 children undergoing scheduled MCS and in 17 control children undergoing conventional non-cardiac surgery. Eight of the MCS patients had Down's syndrome. There were no significant differences in age, weight, or sex between the groups. Seven patients from the MCS group showed multi-organ dysfunction after surgery. Before surgery, the median concentrations of 17β-estradiol, pregnanediol, 5α-dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA) were (control/MCS) 0.1/0.1 (NS), 12.4/11.3 (NS), 4.7/4.4 (NS), and 2.9/1.1 (p=0.02). Postoperatively, the median delta 17β-estradiol, delta pregnanediol, delta DHT, and delta DHEA were (control/MCS) 0.2/6.4 (p=0.0002), -3.2/23.4 (p=0.013), -0.6/3.7 (p=0.0004), and 0.5/4.2 (p=0.004). Postoperative changes did not differ according to sex. We conclude that MCS, but not less intensive non-cardiac surgery, induced a distinct postoperative increase in sex steroid levels. These findings suggest that sex steroids have a role in postoperative metabolism following MCS in prepubertal children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Ventilator-associated pneumonia in patients undergoing major heart surgery: an incidence study in Europe.

    PubMed

    Hortal, Javier; Muñoz, Patricia; Cuerpo, Gregorio; Litvan, Hector; Rosseel, Peter M; Bouza, Emilio

    2009-01-01

    Patients undergoing major heart surgery (MHS) represent a special subpopulation at risk for nosocomial infections. Postoperative infection is the main non-cardiac complication after MHS and has been clearly related to increased morbidity, use of hospital resources and mortality. Our aim was to determine the incidence, aetiology, risk factors and outcome of ventilator-associated pneumonia (VAP) in patients who have undergone MHS in Europe. Our study was a prospective study of patients undergoing MHS in Europe who developed suspicion of VAP. During a one-month period, participating units submitted a protocol of all patients admitted to their units who had undergone MHS. Overall, 25 hospitals in eight different European countries participated in the study. The number of patients intervened for MHS was 986. Fifteen patients were excluded because of protocol violations. One or more nosocomial infections were detected in 43 (4.4%) patients. VAP was the most frequent nosocomial infection (2.1%; 13.9 episodes per 1000 days of mechanical ventilation). The microorganisms responsible for VAP in this study were: Enterobacteriaceae (45%), Pseudomonas aeruginosa (20%), methicillin-resistant Staphylococcus aureus (10%) and a range of other microorganisms. We identified the following significant independent risk factors for VAP: ascending aorta surgery (odds ratio (OR) = 6.22; 95% confidence interval (CI) = 1.69 to 22.89), number of blood units transfused (OR = 1.08 per unit transfused; 95% CI = 1.04 to 1.13) and need for re-intervention (OR = 6.65; 95% CI = 2.10 to 21.01). The median length of stay in the intensive care unit was significantly longer (P < 0.001) in patients with VAP than in patients without VAP (23 days versus 2 days). Death was significantly more frequent (P < 0.001) in patients with VAP (35% versus 2.3%). Patients undergoing aortic surgery and those with complicated post-intervention courses, requiring multiple transfusions or re-intervention, constitute a high-risk group probably requiring more active preventive measures.

  10. New Challenges in Distance Education. Occasional Papers 7.

    ERIC Educational Resources Information Center

    Roberts, David, Ed.

    Three challenges that face distance educators at the national, institute, and individual subject level in Australia are discussed in a set of Occasional Papers by the Riverina-Murray Institute of Higher Education (RMIHE). Australia is undergoing a period of major change. The binary system of universities and colleges of advanced education is…

  11. Exploring the Social Benefits of Agri-Environment Schemes in England

    ERIC Educational Resources Information Center

    Mills, Jane

    2012-01-01

    Recent decades have seen sustainable development emerging as a core concern of European Union (EU) policy. In order to consider how policies can contribute more positively to the goals of sustainable development, major EU policies must undergo an assessment of their potential economic, environmental and social impacts. Within the agri-environment…

  12. Mentoring in the Clinical Setting to Improve Student Decision-Making Competence

    ERIC Educational Resources Information Center

    Stick-Mueller, Misty; Boesch, Ron; Silverman, Steven; Carpenter, Scott; Illingworth, Robert; Countryman, James

    2010-01-01

    Introduction: The physician-intern relationship can be difficult to develop. A new chiropractic intern in a teaching clinic undergoes a major transition from classroom to clinical practice and must learn to turn classroom knowledge into clinical application. The ability to start formulating clinical techniques and apply them on a patient is…

  13. Stress Management Techniques for Graduate Students: Cognitive Coping, Problem-Solving and Time Management.

    ERIC Educational Resources Information Center

    Kolko, David J.

    The application of stress management techniques to highly specialized populations and disorders has become an increasingly important clinical endeavor in recent years. Curiously, however, individuals undergoing one of the most stress-laden experiences, graduate school, have rarely been the focus of such efforts. There are three major forms of…

  14. The Language of Coping: Understanding Filipino Geriatric Patients' Hemodialysis Lived Experiences

    ERIC Educational Resources Information Center

    de Guzman, Allan B.; Chy, Mark Anthony S.; Concepcion, April Faye P.; Conferido, Alvin John C.; Coretico, Kristine I.

    2009-01-01

    The majority of patients with chronic kidney disease (CKD) are undergoing maintenance hemodialysis. Hemodialysis is a process of removing metabolic waste, other poisons, and excess fluids from the blood and replacing essential blood constituents through a dialysis machine. With hemodialysis causing stress not only to physical status but also to…

  15. Pine straw production: from forest to front yard

    Treesearch

    Janice F. Dyer; Rebecca J. Barlow; John S. Kush; John C. Gilbert

    2012-01-01

    Southern forestry may be undergoing a paradigm shift in which timber production is not necessarily the major reason for owning forested land. However, there remains interest in generating income from the land and landowners are exploring alternatives, including agroforestry practices and production of non-timber forest products (NTFPs). One such alternative more recent...

  16. 77 FR 18248 - Agency for Toxic Substances and Disease Registry; Agency Forms Undergoing Paperwork Reduction Act...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-27

    ... Survey, Ages and Stages Questionnaire (ASQ-I), Mullen Stages of Early Development (MSEL), Postpartum...% of all US mothers. Early and regular prenatal care is a major predicator of positive birth outcomes... endpoints. Biological sample analysis, surveys, and developmental screenings will be performed during this...

  17. 75 FR 63404 - Fossil Fuel-Generated Energy Consumption Reduction for New Federal Buildings and Major...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-15

    ... [Docket No. EERE-2010-BT-STD-0031] RIN 1904-AB96 Fossil Fuel-Generated Energy Consumption Reduction for... of fossil fuel-generated energy consumption in new Federal buildings and Federal buildings undergoing... full fossil fuel-generated energy consumption reduction level is technically impracticable in light of...

  18. Retroactive maintains cuticle integrity by promoting the trafficking of Knickkopf into the procuticle of Tribolium castaneum

    USDA-ARS?s Scientific Manuscript database

    Molting, or the replacement of the old exoskeleton with a new cuticle, is a complex developmental process that all insects must undergo to maintain growth. Our work has uncovered a major pathway involved in cuticular chitin maintenance wherein accumulation of the Tribolium castaneum knickkopf protei...

  19. Young Adolescents and Middle Level Education: A Review of Current Issues, Concerns, and Recommendations.

    ERIC Educational Resources Information Center

    Whisler, Jo Sue

    The ages between 10 and 14 years represent a period of transition between childhood and adolescence when feelings of confusion, anxiety, excitement, and frustration are widely experienced. During this period, early adolescents undergo major developmental changes. Educators working with these young people need accurate knowledge of early…

  20. Children Home Alone Unsupervised: Modeling Parental Decisions and Associated Factors in Botswana, Mexico, and Vietnam

    ERIC Educational Resources Information Center

    Ruiz-Casares, Monica; Heymann, Jody

    2009-01-01

    Objective: This paper examines different child care arrangements utilized by working families in countries undergoing major socio-economic transitions, with a focus on modeling parental decisions to leave children home alone. Method: The study interviewed 537 working caregivers attending government health clinics in Botswana, Mexico, and Vietnam.…

  1. Genomic science provides new insights into the biology of forest trees

    Treesearch

    Andrew Groover

    2015-01-01

    Forest biology is undergoing a fundamental change fostered by the application of genomic science to longstanding questions surrounding the evolution, adaptive traits, development, and environmental interactions of tree species. Genomic science has made major technical leaps in recent years, most notably with the advent of 'next generation sequencing' but...

  2. Sixth Form Colleges: Isomorphism, Adaptation and the New Education Market

    ERIC Educational Resources Information Center

    Stoten, David William

    2014-01-01

    The English education sector is undergoing major restructuring with the coalition government placing great emphasis on two key principles of policy: deregulation and marketisation. This development follows on two decades in which the British state has sought to raise performance levels and reduce costs through a variety of policies that are drawn…

  3. Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework

    EPA Science Inventory

    Driven by major scientific advances in analytical methods, biomonitoring, computation, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deploy...

  4. Design and Validation of a Questionnaire to Measure Research Skills: Experience with Engineering Students

    ERIC Educational Resources Information Center

    Cobos Alvarado, Fabián; Peñaherrera León, Mónica; Ortiz Colon, Ana María

    2016-01-01

    Universities in Latin American countries are undergoing major changes in its institutional and academic settings. One strategy for continuous improvement of teaching and learning process is the incorporation of methods and teaching aids seeking to develop scientific research skills in students from their undergraduate studies. The aim of this…

  5. Case management and quality: have we reached a tipping point?

    PubMed

    Dulworth, Sherrie

    2006-01-01

    In The Tipping Point, Malcolm Gladwell describes a phenomenon in which a niche market or fad undergoes transformation into mainstream acceptability, resulting in widespread social change. He concludes that a "tipping point" occurs when a series of small events results in a critical mass of acceptance that produces sudden major changes.

  6. The Reform Process of Portuguese Higher Education Institutions: From Collegial to Managerial Governance

    ERIC Educational Resources Information Center

    Bruckmann, Sofia; Carvalho, Teresa

    2014-01-01

    Portuguese public higher education institutions have been undergoing a major reform process since 2007. The most noticeable changes were introduced by Law 62/2007, which gave higher education institutions the option to choose between two different institutional models (foundational and public institute), and allowed the implementation of new…

  7. The minute virus of mice (MVM) nonstructural protein NS1 induces nicking of MVM DNA at a unique site of the right-end telomere in both hairpin and duplex conformations in vitro.

    PubMed

    Willwand, K; Baldauf, A Q; Deleu, L; Mumtsidu, E; Costello, E; Beard, P; Rommelaere, J

    1997-10-01

    The right-end telomere of replicative form (RF) DNA of the autonomous parvovirus minute virus of mice (MVM) consists of a sequence that is self-complementary except for a three nucleotide loop around the axis of symmetry and an interior bulge of three unpaired nucleotides on one strand (designated the right-end 'bubble'). This right-end inverted repeat can exist in the form of a folded-back strand (hairpin conformation) or in an extended form, base-paired to a copy strand (duplex conformation). We recently reported that the right-end telomere is processed in an A9 cell extract supplemented with the MVM nonstructural protein NS1. This processing is shown here to result from the NS1-dependent nicking of the complementary strand at a unique position 21 nt inboard of the folded-back genomic 5' end. DNA species terminating in duplex or hairpin configurations, or in a mutated structure that has lost the right-end bulge, are all cleaved in the presence of NS1, indicating that features distinguishing these structures are not prerequisites for nicking under the in vitro conditions tested. Cleavage of the hairpin structure is followed by strand-displacement synthesis, generating the right-end duplex conformation, while processing of the duplex structure leads to the release of free right-end telomeres. In the majority of molecules, displacement synthesis at the right terminus stops a few nucleotides before reaching the end of the template strand, possibly due to NS1 which is covalently bound to this end. A fraction of the right-end duplex product undergoes melting and re-folding into hairpin structures (formation of a 'rabbit-ear' structure).

  8. KENNEDY SPACE CENTER, FLA. - During power-up of the orbiter Discovery in the Orbiter Processing Facility, a technician (left) looks at the circuit breaker lights in the cabin. Discovery has been undergoing Orbiter Major Modifications in the past year, ranging from wiring, control panels and black boxes to gaseous and fluid systems tubing and components. These systems were deserviced, disassembled, inspected, modified, reassembled, checked out and reserviced, as were most other systems onboard. The work includes the installation of the Multifunction Electronic Display Subsystem (MEDS) - a state-of-the-art “glass cockpit.”

    NASA Image and Video Library

    2003-08-27

    KENNEDY SPACE CENTER, FLA. - During power-up of the orbiter Discovery in the Orbiter Processing Facility, a technician (left) looks at the circuit breaker lights in the cabin. Discovery has been undergoing Orbiter Major Modifications in the past year, ranging from wiring, control panels and black boxes to gaseous and fluid systems tubing and components. These systems were deserviced, disassembled, inspected, modified, reassembled, checked out and reserviced, as were most other systems onboard. The work includes the installation of the Multifunction Electronic Display Subsystem (MEDS) - a state-of-the-art “glass cockpit.”

  9. Orion Crew Module Adapter-Structural Test Article and European S

    NASA Image and Video Library

    2017-05-09

    Inside the Neil Armstrong Operations and Checkout Building high bay at NASA's Kennedy Space Center in Florida, operations are underway to lower the Orion crew module adapter structural test article onto the European Space Agency's service module structural test article. After the hardware is attached, the structure will be packed and shipped to Lockheed Martin's Denver facility to undergo testing. The Orion spacecraft will launch atop the agency's Space Launch System rocket on Exploration Mission-1 in 2019.

  10. Cooperative structural transitions in amyloid-like aggregation

    NASA Astrophysics Data System (ADS)

    Steckmann, Timothy; Bhandari, Yuba R.; Chapagain, Prem P.; Gerstman, Bernard S.

    2017-04-01

    Amyloid fibril aggregation is associated with several horrific diseases such as Alzheimer's, Creutzfeld-Jacob, diabetes, Parkinson's, and others. Although proteins that undergo aggregation vary widely in their primary structure, they all produce a cross-β motif with the proteins in β-strand conformations perpendicular to the fibril axis. The process of amyloid aggregation involves forming myriad different metastable intermediate aggregates. To better understand the molecular basis of the protein structural transitions and aggregation, we report on molecular dynamics (MD) computational studies on the formation of amyloid protofibrillar structures in the small model protein ccβ, which undergoes many of the structural transitions of the larger, naturally occurring amyloid forming proteins. Two different structural transition processes involving hydrogen bonds are observed for aggregation into fibrils: the breaking of intrachain hydrogen bonds to allow β-hairpin proteins to straighten, and the subsequent formation of interchain H-bonds during aggregation into amyloid fibrils. For our MD simulations, we found that the temperature dependence of these two different structural transition processes results in the existence of a temperature window that the ccβ protein experiences during the process of forming protofibrillar structures. This temperature dependence allows us to investigate the dynamics on a molecular level. We report on the thermodynamics and cooperativity of the transformations. The structural transitions that occurred in a specific temperature window for ccβ in our investigations may also occur in other amyloid forming proteins but with biochemical parameters controlling the dynamics rather than temperature.

  11. Expression of inactive glutathione peroxidase 4 leads to embryonic lethality, and inactivation of the Alox15 gene does not rescue such knock-in mice.

    PubMed

    Brütsch, Simone Hanna; Wang, Chi Chiu; Li, Lu; Stender, Hannelore; Neziroglu, Nilgün; Richter, Constanze; Kuhn, Hartmut; Borchert, Astrid

    2015-02-01

    Glutathione peroxidases (Gpx) and lipoxygenases (Alox) are functional counterplayers in the metabolism of hydroperoxy lipids that regulate cellular redox homeostasis. Gpx4 is a moonlighting protein that has been implicated not only as an enzyme in anti-oxidative defense, gene expression regulation, and programmed cell death, but also as a structural protein in spermatogenesis. Homozygous Gpx4 knock-out mice are not viable, but molecular reasons for intrauterine lethality are not completely understood. This study was aimed at investigating whether the lack of catalytic activity or the impaired function as structural protein is the dominant reason for embryonic lethality. We further explored whether the pro-oxidative enzyme mouse 12/15 lipoxygenase (Alox15) plays a major role in embryonic lethality of Gpx4-deficient mice. To achieve these goals, we first created knock-in mice, which express a catalytically inactive Gpx4 mutant (Sec46Ala). As homozygous Gpx4-knock-out mice Sec46Ala-Gpx4(+/+) knock-in animals are not viable but undergo intrauterine resorption between embryonic day 6 and 7 (E6-7). In contrast, heterozygous knock-in mice (Sec46Ala-Gpx4(-/+)) are viable, fertile and do not show major phenotypic alterations. Interestingly, homozygous Alox15 deficiency did not rescue the U46A-Gpx4(+/+) mice from embryonic lethality. In fact, when heterozygous U46A-Gpx4(-/+) mice were stepwise crossed into an Alox15-deficent background, no viable U46A-Gpx4(+/+)+Alox15(-/-) individuals were obtained. However, we were able to identify U46A-Gpx4(+/+)+Alox15(-/-) embryos in the state of resorption around E7. These data suggest that the lack of catalytic activity is the major reason for the embryonic lethality of Gpx4(-/-) mice and that systemic inactivation of the Alox15 gene does not rescue homozygous knock-in mice expressing catalytically silent Gpx4.

  12. Genetic analysis of the major homology region of the Rous sarcoma virus Gag protein.

    PubMed Central

    Craven, R C; Leure-duPree, A E; Weldon, R A; Wills, J W

    1995-01-01

    The mature cores of all retroviruses contain a major structural protein known as the CA (capsid) protein. Although it appears to form a shell around the ribonucleoprotein complex that contains the viral RNA, its function in viral replication is largely unknown. Little sequence similarity exists between the CA proteins of different retroviruses, except for a region of about 20 amino acids termed the major homology region (MHR). To examine the role of the CA protein in particle assembly and release, mutants of Rous sarcoma virus were created in which segments of CA were deleted or single conserved residues in the MHR were altered. The ability of the deletion mutants to release particles at rates similar to the wild-type protein demonstrated that the CA domain of Gag is not an essential component of the minimal budding machinery. Certain point mutations in the MHR region did block assembly and release in certain cell types, presumably by perturbing the global structure of the Gag precursor. Another group of MHR substitutions produced noninfectious or poorly infectious particles that were normal in their content of gag and pol gene products and viral RNA. The mutants were capable of initiating reverse transcription in vitro; however, the association of CA protein with the core was compromised, as indicated by its sensitivity to extraction with nonionic detergent. Prominent blebs on the virion envelope also indicated a disturbance at the membrane. Finally, an anti-peptide serum directed against MHR was found to react with the uncleaved Gag protein but not with mature CA, suggesting that MHR undergoes a dynamic rearrangement upon liberation from the polyprotein. We conclude that the MHR is involved in the very late steps in maturation of the virion (i.e., ones that occur after budding is initiated) and is essential for proper function of the core upon entry into a new host cell. PMID:7769681

  13. [The preparation of a new hydroxyapatite and the study on its cytocompatibility].

    PubMed

    Tao, Kai; Mao, Tianqiu; Chen, Fulin; Liu, Xiaoyan

    2006-08-01

    The cuttlebones, harvested from cuttles, undergo the chemical reaction in high temperature and high pressure for a certain time. The products are qualitatively analysed, and spacial structure observation and cytocompatibility are tested. The results show that the chemical component of the cuttlebone is CaCO3 and the crystal type is aragonite. Cuttlebones undergo a hydro-thermal reaction, and thus transform into hydroxyapatite-that is, the cuttlebone-transformed hydroxyapatite(CBHA). The CBHA materials have the interconnected microporous network structures. Under the high magnification, CBHAs appear to have many micro-spheres, thus construct a new self-assembled nano-material system. The marrow stromal osteoblasts can adhere to and proliferate well on the surface of the CBHAs. These results show that CBHAs have good biocompatibility. Therefore, it can be a potential candidate scaffold for bone tissue engineering.

  14. Shock Initiation of Thermally Expanded TATB

    NASA Astrophysics Data System (ADS)

    Mulford, Roberta; Swift, Damian

    2011-06-01

    The plastic-bonded explosive PBX-9502 undergoes unusual hysteretic thermal expansion, or ``ratchet growth'' as a consequence of the uniaxial thermal expansion of the graphitic structure of the major component, TATB explosive. Upon thermal cycling, the density of the material can be reduced by as much as 9%, resulting in a distinct increase in the shock sensitivity of the solid. Run distances to detonation have been measured in thermally expanded samples of PBX-9502, using embedded particle velocity gauges and shock tracker gauges. Uniaxial shocks were generated using a light gas gun, to provide a repeatable stimulus for initiation of detonation. We have applied a porosity model to adjust standard Pop plot data to the reduced density of our samples, to investigate whether the sensitivity of the PBX 9502 increases ideally with the decreasing density, or whether the microscopically non-uniform expansion that occurs during ``ratchet growth'' leads to abnormal sensitivity, possibly as a result of cracking or debonding from the binder, as observed in micrographs of the sample.

  15. Direct Force Measurements on Neurofilaments: Gel Expanded to Gel Condensed Transition

    NASA Astrophysics Data System (ADS)

    Beck, R.; Deek, J.; Jones, J. B.; Safinya, C. R.

    2010-03-01

    Neurofilaments (NFs)--the major cytoskeletal constituent of axons in vertebrates, consist of three subunit proteins assembled to form filaments with protruding unstructured C-terminus sidearms. Liquid crystal gel networks of sidearm-mediated NF assemblies play a key role in the mechanical while disruptions of this network, due to over-accumulation or incorrect sidearm interactions, are a hallmark of motor neuron diseases. Using synchrotron SAXS [1,2] and microscopy techniques [1,3] we report a direct force measurement of reconstituted NF-gels under osmotic pressure (P), which revealed the role of subunit sidearms on structure and interaction of NFs. With increasing P, near physiological condition, the gels undergo an abrupt nonreversible gel expanded to gel condensed transition that indicates sidearm-mediated attractions between NFs. This attraction is consistent with an electrostatic model of interpenetrating chains.[4pt] [1] J.B. Jones, C.R. Safinya, Biophys. J. 95, 823 (2008);[0pt] [2] R. Beck et al., Nature Mat. (2009) in press;[0pt] [3] H. Hess et al. Langmuir 24, 8397 (2008)

  16. Directional selection effects on patterns of phenotypic (co)variation in wild populations

    PubMed Central

    Patton, J. L.; Hubbe, A.; Marroig, G.

    2016-01-01

    Phenotypic (co)variation is a prerequisite for evolutionary change, and understanding how (co)variation evolves is of crucial importance to the biological sciences. Theoretical models predict that under directional selection, phenotypic (co)variation should evolve in step with the underlying adaptive landscape, increasing the degree of correlation among co-selected traits as well as the amount of genetic variance in the direction of selection. Whether either of these outcomes occurs in natural populations is an open question and thus an important gap in evolutionary theory. Here, we documented changes in the phenotypic (co)variation structure in two separate natural populations in each of two chipmunk species (Tamias alpinus and T. speciosus) undergoing directional selection. In populations where selection was strongest (those of T. alpinus), we observed changes, at least for one population, in phenotypic (co)variation that matched theoretical expectations, namely an increase of both phenotypic integration and (co)variance in the direction of selection and a re-alignment of the major axis of variation with the selection gradient. PMID:27881744

  17. Metallic corrosion processes reactivation sustained by iron-reducing bacteria: Implication on long-term stability of protective layers

    NASA Astrophysics Data System (ADS)

    Esnault, L.; Jullien, M.; Mustin, C.; Bildstein, O.; Libert, M.

    In deep geological environments foreseen for the disposal of radioactive waste, metallic containers will undergo anaerobic corrosion. In this context, the formation of corrosion products such as magnetite may reduce the rate of corrosion processes through the formation of a protective layer. This study aims at determining the direct impact of iron-reducing bacteria (IRB) activity on the stability of corrosion protective layers. Batch experiments investigating iron corrosion processes including the formation of secondary magnetite and its subsequent alteration in the presence of IRB show the bacteria ability to use structural Fe(III) for respiration which leads to the sustainment of a high corrosion rate. With the bio-reduction of corrosion products such as magnetite, and H 2 as electron donor, IRB promote the reactivation of corrosion processes in corrosive environments by altering the protective layer. This phenomenon could have a major impact on the long-term stability of metallic compounds involved in multi-barrier system for high-level radioactive waste containment.

  18. Transcriptomic and macroevolutionary evidence for phenotypic uncoupling between frog life history phases

    PubMed Central

    Wollenberg Valero, Katharina C.; Garcia-Porta, Joan; Rodríguez, Ariel; Arias, Mónica; Shah, Abhijeet; Randrianiaina, Roger Daniel; Brown, Jason L.; Glaw, Frank; Amat, Felix; Künzel, Sven; Metzler, Dirk; Isokpehi, Raphael D.; Vences, Miguel

    2017-01-01

    Anuran amphibians undergo major morphological transitions during development, but the contribution of their markedly different life-history phases to macroevolution has rarely been analysed. Here we generate testable predictions for coupling versus uncoupling of phenotypic evolution of tadpole and adult life-history phases, and for the underlying expression of genes related to morphological feature formation. We test these predictions by combining evidence from gene expression in two distantly related frogs, Xenopus laevis and Mantidactylus betsileanus, with patterns of morphological evolution in the entire radiation of Madagascan mantellid frogs. Genes linked to morphological structure formation are expressed in a highly phase-specific pattern, suggesting uncoupling of phenotypic evolution across life-history phases. This gene expression pattern agrees with uncoupled rates of trait evolution among life-history phases in the mantellids, which we show to have undergone an adaptive radiation. Our results validate a prevalence of uncoupling in the evolution of tadpole and adult phenotypes of frogs. PMID:28504275

  19. Phase equilibria in the Bi 2TeO 5Bi 2SeO 5 system and a high temperature neutron powder diffraction study of Bi 2SeO 5

    NASA Astrophysics Data System (ADS)

    Dityatyev, Oleg A.; Smidt, Peer; Stefanovich, Sergey Yu; Lightfoot, Philip; Dolgikh, Valery A.; Opperman, Heinrich

    2004-09-01

    Phase equilibria in the Bi 2TeO 5Bi 2SeO 5 system were studied by X-ray, DTA and second harmonic generation (SHG). The samples were synthesized by solid state reactions of the Bi, Te and Se oxides. The phase diagram is interpreted as a quasibinary peritectic one with wide ranges of solid solutions on the basis of both compounds. The SHG study showed Bi 2SeO 5 to undergo a phase transition at about 250 °C. Neutron diffraction (25-650 °C) showed no major changes in the structure of Bi 2SeO 5 at high temperatures. However, the analysis of the oxygen atom thermal factors and site occupancies suggested that the mechanism of the phase transformation is an order-disorder transition involving reorientation of the SeO 3 group.

  20. Single-shot diffraction data from the Mimivirus particle using an X-ray free-electron laser.

    PubMed

    Ekeberg, Tomas; Svenda, Martin; Seibert, M Marvin; Abergel, Chantal; Maia, Filipe R N C; Seltzer, Virginie; DePonte, Daniel P; Aquila, Andrew; Andreasson, Jakob; Iwan, Bianca; Jönsson, Olof; Westphal, Daniel; Odić, Duško; Andersson, Inger; Barty, Anton; Liang, Meng; Martin, Andrew V; Gumprecht, Lars; Fleckenstein, Holger; Bajt, Saša; Barthelmess, Miriam; Coppola, Nicola; Claverie, Jean-Michel; Loh, N Duane; Bostedt, Christoph; Bozek, John D; Krzywinski, Jacek; Messerschmidt, Marc; Bogan, Michael J; Hampton, Christina Y; Sierra, Raymond G; Frank, Matthias; Shoeman, Robert L; Lomb, Lukas; Foucar, Lutz; Epp, Sascha W; Rolles, Daniel; Rudenko, Artem; Hartmann, Robert; Hartmann, Andreas; Kimmel, Nils; Holl, Peter; Weidenspointner, Georg; Rudek, Benedikt; Erk, Benjamin; Kassemeyer, Stephan; Schlichting, Ilme; Strüder, Lothar; Ullrich, Joachim; Schmidt, Carlo; Krasniqi, Faton; Hauser, Günter; Reich, Christian; Soltau, Heike; Schorb, Sebastian; Hirsemann, Helmut; Wunderer, Cornelia; Graafsma, Heinz; Chapman, Henry; Hajdu, Janos

    2016-08-01

    Free-electron lasers (FEL) hold the potential to revolutionize structural biology by producing X-ray pules short enough to outrun radiation damage, thus allowing imaging of biological samples without the limitation from radiation damage. Thus, a major part of the scientific case for the first FELs was three-dimensional (3D) reconstruction of non-crystalline biological objects. In a recent publication we demonstrated the first 3D reconstruction of a biological object from an X-ray FEL using this technique. The sample was the giant Mimivirus, which is one of the largest known viruses with a diameter of 450 nm. Here we present the dataset used for this successful reconstruction. Data-analysis methods for single-particle imaging at FELs are undergoing heavy development but data collection relies on very limited time available through a highly competitive proposal process. This dataset provides experimental data to the entire community and could boost algorithm development and provide a benchmark dataset for new algorithms.

Top