WorldWideScience

Sample records for hamlet treatment delays

  1. HAMLET treatment delays bladder cancer development.

    Science.gov (United States)

    Mossberg, Ann-Kristin; Hou, Yuchuan; Svensson, Majlis; Holmqvist, Bo; Svanborg, Catharina

    2010-04-01

    HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Why must Hamlet Delay in the Revenge?

    Institute of Scientific and Technical Information of China (English)

    贾艳平; 金梅

    2013-01-01

    Hamlet is the greatest tragedy play of William Shakespeare. Hamlet is centred on the hesitation and the options of the heroic Hamlet's action. The purpose of the paper is to give an analysis of the essential reason of Hamlet ’s delay in his revenge. The thesis is arranged as following:firstly, it focuses on the analysis of the complicated characteristics of Hamlet;then, it will anal-yse the options that Hamlet has. Hamlet is great with absolute no doubt.

  3. Depressive illness delayed Hamlet's revenge.

    Science.gov (United States)

    Shaw, A B; Pickering, Neil

    2002-12-01

    If Hamlet had not delayed his revenge there would have been no play. Many explanations of the delay have been offered in the last four centuries. None is convincing. The interpretation which best fits the evidence best is that Hamlet was suffering from an acute depressive illness, with some obsessional features. He could not make a firm resolve to act. In Shakespeare's time there was no concept of acute depressive illness, although melancholy was well known. Melancholy, however, would have been seen as a character defect. In the tragic model the hero brings himself and others to ruin because of a character defect. Thus, at the time, the play conformed to the tragic model. With today's knowledge, it does not. This analysis adds to, but does not replace, other insights into the play.

  4. Prevention and treatment of colon cancer by peroral administration of HAMLET (human α-lactalbumin made lethal to tumour cells).

    Science.gov (United States)

    Puthia, Manoj; Storm, Petter; Nadeem, Aftab; Hsiung, Sabrina; Svanborg, Catharina

    2014-01-01

    Most colon cancers start with dysregulated Wnt/β-catenin signalling and remain a major therapeutic challenge. Examining whether HAMLET (human α-lactalbumin made lethal to tumour cells) may be used for colon cancer treatment is logical, based on the properties of the complex and its biological context. To investigate if HAMLET can be used for colon cancer treatment and prevention. Apc(Min)(/+) mice, which carry mutations relevant to hereditary and sporadic human colorectal tumours, were used as a model for human disease. HAMLET was given perorally in therapeutic and prophylactic regimens. Tumour burden and animal survival of HAMLET-treated and sham-fed mice were compared. Tissue analysis focused on Wnt/β-catenin signalling, proliferation markers and gene expression, using microarrays, immunoblotting, immunohistochemistry and ELISA. Confocal microscopy, reporter assay, immunoprecipitation, immunoblotting, ion flux assays and holographic imaging were used to determine effects on colon cancer cells. Peroral HAMLET administration reduced tumour progression and mortality in Apc(Min)(/+) mice. HAMLET accumulated specifically in tumour tissue, reduced β-catenin and related tumour markers. Gene expression analysis detected inhibition of Wnt signalling and a shift to a more differentiated phenotype. In colon cancer cells with APC mutations, HAMLET altered β-catenin integrity and localisation through an ion channel-dependent pathway, defining a new mechanism for controlling β-catenin signalling. Remarkably, supplying HAMLET to the drinking water from the time of weaning also significantly prevented tumour development. These data identify HAMLET as a new, peroral agent for colon cancer prevention and treatment, especially needed in people carrying APC mutations, where colon cancer remains a leading cause of death.

  5. Hamlet's Transformation.

    Science.gov (United States)

    Usher, P. D.

    1997-12-01

    William Shakespeare's Hamlet has much evidence to suggest that the Bard was aware of the cosmological models of his time, specifically the geocentric bounded Ptolemaic and Tychonic models, and the infinite Diggesian. Moreover, Shakespeare describes how the Ptolemaic model is to be transformed to the Diggesian. Hamlet's "transformation" is the reason that Claudius, who personifies the Ptolemaic model, summons Rosencrantz and Guildenstern, who personify the Tychonic. Pantometria, written by Leonard Digges and his son Thomas in 1571, contains the first technical use of the word "transformation." At age thirty, Thomas Digges went on to propose his Perfit Description, as alluded to in Act Five where Hamlet's age is given as thirty. In Act Five as well, the words "bore" and "arms" refer to Thomas' vocation as muster-master and his scientific interest in ballistics. England's leading astronomer was also the father of the poet whose encomium introduced the First Folio of 1623. His oldest child Dudley became a member of the Virginia Company and facilitated the writing of The Tempest. Taken as a whole, such manifold connections to Thomas Digges support Hotson's contention that Shakespeare knew the Digges family. Rosencrantz and Guildenstern in Hamlet bear Danish names because they personify the Danish model, while the king's name is latinized like that of Claudius Ptolemaeus. The reason Shakespeare anglicized "Amleth" to "Hamlet" was because he saw a parallel between Book Three of Saxo Grammaticus and the eventual triumph of the Diggesian model. But Shakespeare eschewed Book Four, creating this particular ending from an infinity of other possibilities because it "suited his purpose," viz. to celebrate the concept of a boundless universe of stars like the Sun.

  6. Hamlet the Humanist

    Institute of Scientific and Technical Information of China (English)

    刘恒

    2014-01-01

    William Shakespeare has left us the remarkable tragedy Hamlet, a typical novel in which the readers are deeply im-pressed by Hamlet, a special hero of his kind and also a humanist in the Renaissance Period.

  7. Hamlet and psychiatry intertwined.

    Science.gov (United States)

    Rotstein, Sarah

    2018-05-01

    This article considers selected landmarks in the history of psychiatry and their impact on Hamlet productions, including Burton's Anatomy of Melancholia, Emil Kraepelin's manic-depression, Freud's oedipal complex and R.D. Laing's 'divided self'. Additionally, this article considers the way Shakespeare's Hamlet has influenced the course of psychiatry. The linkages between psychiatry and Hamlet have existed since the 17th century, and perhaps Shakespeare's Hamlet should have a place on every psychiatrist's shelf.

  8. Human alpha-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival.

    Science.gov (United States)

    Fischer, Walter; Gustafsson, Lotta; Mossberg, Ann-Kristin; Gronli, Janne; Mork, Sverre; Bjerkvig, Rolf; Svanborg, Catharina

    2004-03-15

    Malignant brain tumors present a major therapeutic challenge because no selective or efficient treatment is available. Here, we demonstrate that intratumoral administration of human alpha-lactalbumin made lethal to tumor cells (HAMLET) prolongs survival in a human glioblastoma (GBM) xenograft model, by selective induction of tumor cell apoptosis. HAMLET is a protein-lipid complex that is formed from alpha-lactalbumin when the protein changes its tertiary conformation and binds oleic acid as a cofactor. HAMLET induces apoptosis in a wide range of tumor cells in vitro, but the therapeutic effect in vivo has not been examined. In this study, invasively growing human GBM tumors were established in nude rats (Han:rnu/rnu Rowett, n = 20) by transplantation of human GBM biopsy spheroids. After 7 days, HAMLET was administered by intracerebral convection-enhanced delivery for 24 h into the tumor area; and alpha-lactalbumin, the native, folded variant of the same protein, was used as a control. HAMLET reduced the intracranial tumor volume and delayed the onset of pressure symptoms in the tumor-bearing rats. After 8 weeks, all alpha-lactalbumin-treated rats had developed pressure symptoms, but the HAMLET-treated rats remained asymptomatic. Magnetic resonance imaging scans revealed large differences in tumor volume (456 versus 63 mm(3)). HAMLET caused apoptosis in vivo in the tumor but not in adjacent intact brain tissue or in nontransformed human astrocytes, and no toxic side effects were observed. The results identify HAMLET as a new candidate in cancer therapy and suggest that HAMLET should be additionally explored as a novel approach to controlling GBM progression.

  9. Histone deacetylase inhibitors promote the tumoricidal effect of HAMLET.

    Science.gov (United States)

    Brest, Patrick; Gustafsson, Mattias; Mossberg, Ann-Kristin; Gustafsson, Lotta; Duringer, Caroline; Hamiche, Ali; Svanborg, Catharina

    2007-12-01

    Histone deacetylase inhibitors (HDIs) and HAMLET (human alpha-lactalbumin made lethal to tumor cells) interact with histones, modify the structure of chromatin, and trigger tumor cell death. This study investigated how the combination of HDIs and HAMLET influences cell viability, histone acetylation, and DNA integrity. The pretreatment of tumor cells with HDIs was shown to enhance the lethal effect of HAMLET and the histone hyperacetylation response to HDIs increased even further after HAMLET treatment. HDIs and HAMLET were shown to target different histone domains as HAMLET bound tailless core histones, whereas HDIs modify the acetylation of the histone tail. DNA damage in response to HAMLET was increased by HDIs. The DNA repair response (p21WAFI expression) was induced by both agonists but abolished when the two agonists were combined. The results suggest that the synergy of HDIs and HAMLET is based on different but converging death pathways, both involving chromatin alterations. We speculate that HAMLET and HDIs might be combined to promote tumor cell death in vivo.

  10. Shaw on Hamlet

    Science.gov (United States)

    Dukore, Bernard F.

    1971-01-01

    Shaw's preoccupation with Hamlet resonates in his creative writing. Article documents this statement not only by examining his novels and plays but by searching through prefaces, postscripts, reviews, letters, speeches, etc. that span Shaw's lifetime. (Author/RB)

  11. Theatrum Mundi: Ur-Hamlet

    DEFF Research Database (Denmark)

    Christoffersen, Erik Exe

    2009-01-01

    Om Odin Teatrets dramaturgier og om Barbas dramaturgi-begreb relateret til forestillingen Ur-Hamlet (2006)......Om Odin Teatrets dramaturgier og om Barbas dramaturgi-begreb relateret til forestillingen Ur-Hamlet (2006)...

  12. Astronomy and Shakespeare's Hamlet.

    Science.gov (United States)

    Usher, P. D.

    1996-05-01

    Payne-Gaposchkin and others have suggested that Hamlet shows evidence of the Bard's awareness of the astronomical revolutions of the sixteenth century. I summarize major arguments and note that the play's themes recur in modern astronomy teaching and research: (1) The play amounts to a redefinition of universal order and humankind's position in it. (2) There is interplay between appearance and reality. Such a contrast is commonplace wherever superficial celestial appearances obscure underlying physical realities, the nature of which emerge as the tale unfolds. (3) The outermost sphere of the Ptolemaic and Copernican models seems to encase humanity, who are liberated by the reality of Digges' model and the implications advanced by Bruno. Similarly the oppressiveness of the castle interior is relieved by the observing platform which enables the heavens to be viewed in their true light. (4) Hamlet could be bounded in a nut-shell and count himself a king of infinite space, were it not that he has bad dreams. These concern the subversiveness of the new doctrine, for Hamlet refers to the infinite universe only hypothetically and in the presence of Rosencrantz and Guildenstern, who are named for relatives of the Danish astronomer Brahe. (5) Hamlet, and Brahe and Bruno, have connections to the university at Wittenberg, as does the Copernican champion Rheticus. (6) Ways are needed to reveal both the truths of nature, and the true nature of Danish royalty. Those unaccustomed to science think that there is madness in Hamlet's method. In particular, `doubt' is advanced as a methodological principle of inquiry. (7) The impression of normalcy and propriety in the upper reaches of society is like the false impression of an encapsulating universe. In Hamlet this duality is dramatized tragically, whereas in King John (cf. BAAS 27, 1325, 1995) it is not; for by 1601 when the writing of Hamlet was probably completed, Shakespeare would have known of the martyrdom of Bruno the previous

  13. The Hamlet Project.

    Science.gov (United States)

    Dynak, Dave

    1998-01-01

    Describes a three-week summer theater program for middle and high school students. Discusses the reconstructing of Shakespeare's play "Hamlet" by students in the class from prior viewings of movie versions of the play and from students' past experiences with the play. Includes the play script as rewritten by the students. (CR)

  14. Don Quijote y Hamlet

    Directory of Open Access Journals (Sweden)

    Lúdovik B. Osterc

    2002-12-01

    Hamlet está loco, es un alucinado que duda de sus propios sentidos. Para él existe sólo un lado negro de la existencia, su único objeto es llegar más pronto al descubrimiento del crimen. Es egocentrico, ne cree en nada, eternamente mira en su interior, se alimenta en su desprecio de sí mismo y su sufrimiento es mucho más doloroso.que aquel de Don Quijote. Don Quijote, al contrario, cree en el hombre y su futuro. Su ideal es implantar por la fuerza, la verdad, el bien y la justicia en la tierra. Para servir a su ideal, está dispuesto a sufrir todas las posibles privaciones. Representa la fe en la verdad. Es ridículo y quizás el más cómico tipo disenado jamás por un literato. Hamlet es el hijo del rey muerte, mientras que Don Quijote está pobre. Se hace los enemigos imaginarios y lucha contra ellos, mientras que Hamlet no cree en las ilusiones (siempre duda, y tampoco no combatiría si supiera que son sinónimos de opresores. Continua con la examinación de la actitud del pueblo o sus representantes hacia Don Quijote y Hamlet y viceversa. Polonia es el representante de las multitudes populares ante Hamlet, Sancho lo es ante su senor. El primero es de sano pensamiento y al mismo tiempo un viejo charalatán. Para él Hamlet no es tanto un loco como un nino y le parece inútil para la sociedad. Sancho Pansa está persuadido de que su senor está loco, pero le está leal hasta la muerte. Don Quijote simpatiza profundamente con el pueblo, pero la única persona con la que se entiende verdaderamente es Sancho Pansa (uno no puede vivir sin otro. La actitud de Hamlet es completamente diferente, él desprecia las multitudes populares, porque también desprecia a sí mismo. social: el tedio, el hastío, el descontento de la vida, desorientación espiritual y la eclipse de la fe, miéntras que Don Quijote encarna el mundo libre, bien estar y la felicidad de los seres humanos. Por eso y porque es un ideal el más humano, generoso, noble y elevado, el autor del

  15. HAMLET binding to α-actinin facilitates tumor cell detachment.

    Science.gov (United States)

    Trulsson, Maria; Yu, Hao; Gisselsson, Lennart; Chao, Yinxia; Urbano, Alexander; Aits, Sonja; Mossberg, Ann-Kristin; Svanborg, Catharina

    2011-03-08

    Cell adhesion is tightly regulated by specific molecular interactions and detachment from the extracellular matrix modifies proliferation and survival. HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a protein-lipid complex with tumoricidal activity that also triggers tumor cell detachment in vitro and in vivo, suggesting that molecular interactions defining detachment are perturbed in cancer cells. To identify such interactions, cell membrane extracts were used in Far-western blots and HAMLET was shown to bind α-actinins; major F-actin cross-linking proteins and focal adhesion constituents. Synthetic peptide mapping revealed that HAMLET binds to the N-terminal actin-binding domain as well as the integrin-binding domain of α-actinin-4. By co-immunoprecipitation of extracts from HAMLET-treated cancer cells, an interaction with α-actinin-1 and -4 was observed. Inhibition of α-actinin-1 and α-actinin-4 expression by siRNA transfection increased detachment, while α-actinin-4-GFP over-expression significantly delayed rounding up and detachment of tumor cells in response to HAMLET. In response to HAMLET, adherent tumor cells rounded up and detached, suggesting a loss of the actin cytoskeletal organization. These changes were accompanied by a reduction in β1 integrin staining and a decrease in FAK and ERK1/2 phosphorylation, consistent with a disruption of integrin-dependent cell adhesion signaling. Detachment per se did not increase cell death during the 22 hour experimental period, regardless of α-actinin-4 and α-actinin-1 expression levels but adherent cells with low α-actinin levels showed increased death in response to HAMLET. The results suggest that the interaction between HAMLET and α-actinins promotes tumor cell detachment. As α-actinins also associate with signaling molecules, cytoplasmic domains of transmembrane receptors and ion channels, additional α-actinin-dependent mechanisms are discussed.

  16. A unifying mechanism for cancer cell death through ion channel activation by HAMLET.

    Science.gov (United States)

    Storm, Petter; Klausen, Thomas Kjaer; Trulsson, Maria; Ho C S, James; Dosnon, Marion; Westergren, Tomas; Chao, Yinxia; Rydström, Anna; Yang, Henry; Pedersen, Stine Falsig; Svanborg, Catharina

    2013-01-01

    Ion channels and ion fluxes control many aspects of tissue homeostasis. During oncogenic transformation, critical ion channel functions may be perturbed but conserved tumor specific ion fluxes remain to be defined. Here we used the tumoricidal protein-lipid complex HAMLET as a probe to identify ion fluxes involved in tumor cell death. We show that HAMLET activates a non-selective cation current, which reached a magnitude of 2.74±0.88 nA within 1.43±0.13 min from HAMLET application. Rapid ion fluxes were essential for HAMLET-induced carcinoma cell death as inhibitors (amiloride, BaCl2), preventing the changes in free cellular Na(+) and K(+) concentrations also prevented essential steps accompanying carcinoma cell death, including changes in morphology, uptake, global transcription, and MAP kinase activation. Through global transcriptional analysis and phosphorylation arrays, a strong ion flux dependent p38 MAPK response was detected and inhibition of p38 signaling delayed HAMLET-induced death. Healthy, differentiated cells were resistant to HAMLET challenge, which was accompanied by innate immunity rather than p38-activation. The results suggest, for the first time, a unifying mechanism for the initiation of HAMLET's broad and rapid lethal effect on tumor cells. These findings are particularly significant in view of HAMLET's documented therapeutic efficacy in human studies and animal models. The results also suggest that HAMLET offers a two-tiered therapeutic approach, killing cancer cells while stimulating an innate immune response in surrounding healthy tissues.

  17. Hamlet and psychoanalytic experience.

    Science.gov (United States)

    Schwaber, Paul

    2007-01-01

    Hamlet draws us into its rendered world, enabling us to experience it with depth, awareness, and resonance, in a mode we recognize as aesthetic. By way of Shakespeare's play--primarily the first act--and a detailed case study, aesthetic and psychoanalytic experience are compared, to suggest that, for our own analytic discourse, we revalue Freud's unease that his case studies read like short stories.

  18. Olivier's 'Essay on Hamlet'

    Directory of Open Access Journals (Sweden)

    Koprivica Zoran

    2017-01-01

    Full Text Available Laurence Olivier's Hamlet is more a renaissance character, a melancholic and a daydreamer, than a man of action, unlike his Henry V and Richard III film adaptations. However, it seems that Olivier showed outstanding courage not in his extremely liberal approach to interpreting this Shakespeare's tragedy, but in literal application of Freud's model on his inner problems, seen through the prism of the professor Ernest Johnson. Transposing Shakespeare's original text, starting with its global features, he abstracts numerous and diversified eventful and associative moments which might burden the polyphonic structure of his own - film story. Moreover, Olivier wants to avoid its dramatic deconstruction and focuses the viewer's attention to the climactic moments. However, dramatically the strongest and most effective scenes in his film adaptation of Hamlet are the ones related to the use of camera, that is to say, its movement and analyticity. The intention was to point not only to the ostentatious difference between cinematographic and theatrical stylisation, but, to a certain extent, he defines the viewer's standpoint. In his 'essay on Hamlet', Olivier does not consider chronology, that is to say, the problem of temporal relations. The visual structure of the film and its dynamics are determined a priori by the rhythmic parameters of the Elsinore's labyrinthic space.

  19. HAMLET kills tumor cells by apoptosis: structure, cellular mechanisms, and therapy.

    Science.gov (United States)

    Gustafsson, Lotta; Hallgren, Oskar; Mossberg, Ann-Kristin; Pettersson, Jenny; Fischer, Walter; Aronsson, Annika; Svanborg, Catharina

    2005-05-01

    New cancer treatments should aim to destroy tumor cells without disturbing normal tissue. HAMLET (human alpha-lactalbumin made lethal to tumor cells) offers a new molecular approach to solving this problem, because it induces apoptosis in tumor cells but leaves normal differentiated cells unaffected. After partial unfolding and binding to oleic acid, alpha-lactalbumin forms the HAMLET complex, which enters tumor cells and freezes their metabolic machinery. The cells proceed to fragment their DNA, and they disintegrate with apoptosis-like characteristics. HAMLET kills a wide range of malignant cells in vitro and maintains this activity in vivo in patients with skin papillomas. In addition, HAMLET has striking effects on human glioblastomas in a rat xenograft model. After convection-enhanced delivery, HAMLET diffuses throughout the brain, selectively killing tumor cells and controlling tumor progression without apparent tissue toxicity. HAMLET thus shows great promise as a new therapeutic with the advantage of selectivity for tumor cells and lack of toxicity.

  20. Mason & Dixon and Hamlet

    Directory of Open Access Journals (Sweden)

    Celia Wallhead

    2014-08-01

    Full Text Available Although there is no explicit comparison in 'Mason & Dixon' of the astronomer protagonist Charles Mason to the eponymous hero of Shakespeare's masterpiece, indisputable references to the play are to be found in the novel. Mason is endowed with qualities which mirror Hamlet's virtues and vices: he is a leader and a man of education and wit, though his metaphysical longings entice him towards madness and suicide. He is emburdened with a  deep melancholy stemming from bereavement, loss of love, the hauntings of a ghost, indecision, even cowardice and frustrated ambition.

  1. Hamlet: virtù man

    OpenAIRE

    Roio, Marcos Del [UNESP; Martinez, Vinício C. [UNESP

    2008-01-01

    O artigo traz algumas relações/semelhanças entre Hamlet, de Shakespeare, e O Príncipe de Maquiavel. Portanto, pela “perspectiva” da Razão de Estado e não pela versão reducionista do “maquiavelismo” (maniqueísmo político), também podemos observar uma teoria política em Shakespeare. Palavras-chave: Maquiavel. Príncipe. Virtù. Hamlet. Astúcia. The article reports some relations/similarities between Shakespeare’s Hamlet and Machiavelli’s Prince. Therefore, by the Sta...

  2. Irony in Tennyson's "Little Hamlet".

    Science.gov (United States)

    Harrison, Antony H.

    1981-01-01

    Points out similarities between the events and characters of Tennyson's "Maud" and Shakespeare's "Hamlet." Identifies traits which "Maud" shares with Spasmodic poetry. Argues that Tennyson consciously employed these similarities to expose the deficiencies of the Spasmodic school. (DMM)

  3. Compact oleic acid in HAMLET.

    Science.gov (United States)

    Fast, Jonas; Mossberg, Ann-Kristin; Nilsson, Hanna; Svanborg, Catharina; Akke, Mikael; Linse, Sara

    2005-11-07

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a complex between alpha-lactalbumin and oleic acid that induces apoptosis in tumor cells, but not in healthy cells. Heteronuclear nuclear magnetic resonance (NMR) spectroscopy was used to determine the structure of 13C-oleic acid in HAMLET, and to study the 15N-labeled protein. Nuclear Overhauser enhancement spectroscopy shows that the two ends of the fatty acid are in close proximity and close to the double bond, indicating that the oleic acid is bound to HAMLET in a compact conformation. The data further show that HAMLET is a partly unfolded/molten globule-like complex under physiological conditions.

  4. HAMLET E O PODER

    OpenAIRE

    Gomes, Analice Franco; Parente Rebouças, Marcus Vinícius

    2017-01-01

    Este artigo científico analisa a tragédia shakespeariana de Hamlet sob o prisma específico das relações de poder, estabelecendo uma interface entre a Ciência Política e a Arte Teatral, com o propósito de produzir aportes teóricos que permitam melhor compreender o fenômeno político. Além de considerações acerca de dados biográficos de Shakespeare e de aspectos gerais a respeito da peça “Hamlet”, delineou-se um conceito de poder enquanto relação humana, adotando-se Michel Foucault como referenc...

  5. alpha-Lactalbumin species variation, HAMLET formation, and tumor cell death.

    Science.gov (United States)

    Pettersson, Jenny; Mossberg, Ann-Kristin; Svanborg, Catharina

    2006-06-23

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal complex of apo alpha-lactalbumin and oleic acid, formed in casein after low pH treatment of human milk. This study examined if HAMLET-like complexes are present in casein from different species and if isolated alpha-lactalbumin from those species can form such complexes with oleic acid. Casein from human, bovine, equine, and porcine milk was separated by ion exchange chromatography and active complexes were only found in human casein. This was not explained by alpha-lactalbumin sequence variation, as purified bovine, equine, porcine, and caprine alpha-lactalbumins formed complexes with oleic acid with biological activity similar to HAMLET. We conclude that structural variation of alpha-lactalbumins does not preclude the formation of HAMLET-like complexes and that natural HAMLET formation in casein was unique to human milk, which also showed the highest oleic acid content.

  6. The human milk protein-lipid complex HAMLET sensitizes bacterial pathogens to traditional antimicrobial agents.

    Science.gov (United States)

    Marks, Laura R; Clementi, Emily A; Hakansson, Anders P

    2012-01-01

    The fight against antibiotic resistance is one of the most significant challenges to public health of our time. The inevitable development of resistance following the introduction of novel antibiotics has led to an urgent need for the development of new antibacterial drugs with new mechanisms of action that are not susceptible to existing resistance mechanisms. One such compound is HAMLET, a natural complex from human milk that kills Streptococcus pneumoniae (the pneumococcus) using a mechanism different from common antibiotics and is immune to resistance-development. In this study we show that sublethal concentrations of HAMLET potentiate the effect of common antibiotics (penicillins, macrolides, and aminoglycosides) against pneumococci. Using MIC assays and short-time killing assays we dramatically reduced the concentrations of antibiotics needed to kill pneumococci, especially for antibiotic-resistant strains that in the presence of HAMLET fell into the clinically sensitive range. Using a biofilm model in vitro and nasopharyngeal colonization in vivo, a combination of HAMLET and antibiotics completely eradicated both biofilms and colonization in mice of both antibiotic-sensitive and resistant strains, something each agent alone was unable to do. HAMLET-potentiation of antibiotics was partially due to increased accessibility of antibiotics to the bacteria, but relied more on calcium import and kinase activation, the same activation pathway HAMLET uses when killing pneumococci by itself. Finally, the sensitizing effect was not confined to species sensitive to HAMLET. The HAMLET-resistant respiratory species Acinetobacter baumanii and Moraxella catarrhalis were all sensitized to various classes of antibiotics in the presence of HAMLET, activating the same mechanism as in pneumococci. Combined these results suggest the presence of a conserved HAMLET-activated pathway that circumvents antibiotic resistance in bacteria. The ability to activate this pathway may extend

  7. Hamlet: virtù man

    OpenAIRE

    Roio, Marcos Del; UNESP - Universidade Estadual Paulista / Marília - SP; Martinez, Vinício C.; UNESP - Universidade Estadual Paulista / Marília - SP

    2008-01-01

    The article reports some relations/similarities between Shakespeare’s Hamlet and Machiavelli’s Prince. Therefore, by the State Reasoning “perspective” and not by the reductionism version of “machiavellism” (political maniqueism), we can also observe a political theory in Shakespeare. O artigo traz algumas relações/semelhanças entre Hamlet, de Shakespeare, e O Príncipe de Maquiavel. Portanto, pela “perspectiva” da Razão de Estado e não pela versão reducionista do “maquiavelismo” (maniqueísm...

  8. Conserved features of cancer cells define their sensitivity to HAMLET-induced death; c-Myc and glycolysis.

    Science.gov (United States)

    Storm, P; Aits, S; Puthia, M K; Urbano, A; Northen, T; Powers, S; Bowen, B; Chao, Y; Reindl, W; Lee, D Y; Sullivan, N L; Zhang, J; Trulsson, M; Yang, H; Watson, J D; Svanborg, C

    2011-12-01

    HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here, we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small-hairpin RNA (shRNA) inhibition, proteomic and metabolomic technology, we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, HAMLET sensitivity was modified by the glycolytic state of tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen, hexokinase 1 (HK1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 and hypoxia-inducible factor 1α modified HAMLET sensitivity. HK1 was shown to bind HAMLET in a protein array containing ∼8000 targets, and HK activity decreased within 15 min of HAMLET treatment, before morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 min. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene addiction or the Warburg effect.

  9. Conserved features of cancer cells define their sensitivity of HAMLET-induced death; c-Myc and glycolysis

    Science.gov (United States)

    Storm, Petter; Puthia, Manoj Kumar; Aits, Sonja; Urbano, Alexander; Northen, Trent; Powers, Scott; Bowen, Ben; Chao, Yinxia; Reindl, Wolfgang; Lee, Do Yup; Sullivan, Nancy Liu; Zhang, Jianping; Trulsson, Maria; Yang, Henry; Watson, James; Svanborg, Catharina

    2014-01-01

    HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small hairpin RNA inhibition, proteomic and metabolomic technology we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted the sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, the HAMLET sensitivity was modified by the glycolytic state of the tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen Hexokinase 1, PFKFB1 and HIF1α modified HAMLET sensitivity. Hexokinase 1 was shown to bind HAMLET in a protein array containing approximately 8000 targets and Hexokinase activity decreased within 15 minutes of HAMLET treatment, prior to morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. The glycolytic machinery was modified and glycolysis was shifted towards the pentose phosphate pathway. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 minutes. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene-addiction or the Warburg effect. PMID:21643007

  10. Translational Implications of Tamil "Hamlets."

    Science.gov (United States)

    Kanakaraj, S.

    1994-01-01

    Discusses the use of translation when teaching English as a Second Language in a Tamil context. Singles out the fencing episode in Shakespeare's "Hamlet" to illustrate the difficulties of translating cultural aspects. Concludes that successful translations of Shakespeare into Indian languages should involve collaboration between…

  11. Ruin and Revolution in ``Hamlet."

    Science.gov (United States)

    Usher, P. D.

    1999-05-01

    In the cosmic allegorical interpretation of Shakespeare's "Hamlet" (BAAS 28, 859 & 1305, 1996; Mercury 26:1, 20, 1997; RPS 18:3, 6, 1997; Giornale di Astronomia 24:3, 27, 1998), the usurper King Claudius, namesake of Ptolemy, personifies geocentricity. Textual support for this reading is found in 1.2 where Hamlet is associated with the Sun, as befits a rightful heir, while Claudius is associated with the Earth. In 3.3 Claudius fears Hamlet's antics. Rosencrantz states that the lives of many depend on the well-being of the King. He warns that if the King were to be imperiled, his subjects, those "ten thousand lesser things", would fall in a "boisterous ruin" along with "each small annexment" and "petty consequence." These 10,000 lesser lights are the naked eye stars (mv ~ 6.5) which would collapse with the demise of the pre-Diggesian firmament, along with ancient planets and their geometrical contrivances. In 5.1 Shakespeare puns on "De revolutionibus" when he refers to "fine revolution." The double meaning of "revolution" (alteration, orbital motion) was in use long before 1600. Since "revolution" is used in the context of digging, it may refer as much to the Diggesian as the Copernican Revolution. Shakespeare's prescience is revealed by his anticipation of change, as encapsulated geocentricity is transformed to stellar boundlessness, while his presence is suggested by fatherly concerns and ghost-like direction.

  12. The Influence of Hamlet' s Humanistic Views on His Delay%哈姆雷特的人文主义思想对他犹豫不决性格的影响

    Institute of Scientific and Technical Information of China (English)

    石钧元

    2012-01-01

    数不胜数的评论家,学者以及热爱文学的人们在研究莎士比亚的悲剧《哈姆雷特》。这部戏剧的各个方面都几乎被分析研究过了,特别是关于哈姆雷特的犹豫不决。他的犹豫不决是由他的性格所决定的。关于他犹豫不决这种性格形成的原因有不同的解释。本文从他的教育背景这个角度本文分析了哈姆雷特犹豫的原因。%William Shakespeare' s Hamlet is studied by numerous critics, scholars and people who love hterature. Probably every aspect of the drama has been analyzed, especially Hamlet' s hesitation. It is decided by his character. But how does he have the hesitation in his character? This paper sets out to analyze why he hesitate from the angle of his educa- tion background.

  13. Reading Hamlet. The NCTE Chalkface Series.

    Science.gov (United States)

    Mellor, Bronwyn

    This book, for grades 9-12, contains a wealth of ideas and practical activities for studying Shakespeare's "Hamlet." The first section, "Revenge Tragedy," provides background materials to help prepare students to read "Hamlet," including a discussion of revenge tragedies, comparisons to other plays from the period,…

  14. HAMLET: functional properties and therapeutic potential.

    Science.gov (United States)

    Ho C S, James; Rydström, Anna; Trulsson, Maria; Bålfors, Johannes; Storm, Petter; Puthia, Manoj; Nadeem, Aftab; Svanborg, Catharina

    2012-10-01

    Human α-lactalbumin made lethal to tumor cells (HAMLET) is the first member in a new family of protein-lipid complexes that kills tumor cells with high selectivity. The protein component of HAMLET is α-lactalbumin, which in its native state acts as a substrate specifier in the lactose synthase complex, thereby defining a function essential for the survival of lactating mammals. In addition, α-lactalbumin acquires tumoricidal activity after partial unfolding and binding to oleic acid. The lipid cofactor serves the dual role as a stabilizer of the altered fold of the protein and a coactivator of specific steps in tumor cell death. HAMLET is broadly tumoricidal, suggesting that the complex identifies conserved death pathways suitable for targeting by novel therapies. Sensitivity to HAMLET is defined by oncogene expression including Ras and c-Myc and by glycolytic enzymes. Cellular targets are located in the cytoplasmic membrane, cytoskeleton, mitochondria, proteasomes, lysosomes and nuclei, and specific signaling pathways are rapidly activated, first by interactions of HAMLET with the cell membrane and subsequently after HAMLET internalization. Therapeutic effects of HAMLET have been demonstrated in human skin papillomas and bladder cancers, and HAMLET limits the progression of human glioblastomas, with no evidence of toxicity for normal brain or bladder tissue. These findings open up new avenues for cancer therapy and the understanding of conserved death responses in tumor cells.

  15. Theatrum Mundi: Odin Teatret's Ur-Hamlet

    DEFF Research Database (Denmark)

    Christoffersen, Erik Exe

    2008-01-01

    Analyse af Odin Teatrets forestilling Ur-Hamlet opført på Kronborg 2006 med 100 medvirkende fra hele verden.......Analyse af Odin Teatrets forestilling Ur-Hamlet opført på Kronborg 2006 med 100 medvirkende fra hele verden....

  16. No Hamlet, two Hamlets: The Shakespearean Tragedy Directed by Carmelo Bene and Celestino Coronado

    Directory of Open Access Journals (Sweden)

    Armando Rotondi

    2014-12-01

    Full Text Available The Italian artist Carmelo Bene and the British director Celestino Coronado have worked intensively on Shakespeare and in particular on Hamlet, but giving opposing interpretations of the work. In his Un Amleto di Meno (1973, Carmelo Bene, taking as starting point Jules Laforgue’s Hamlet, ou les suites de le pitié filiale (1877, redefines the drama of Hamlet,refusing to see him as a man who wants to escape his destiny. In Bene’s adaptation, Hamlet disappears from the stage. By contrast, Celestino Coronado, in his film version in 1976, underlines the presence of Hamlet on the screen, casting twins, Anthony and David Meyer, in the role and working on the idea of a Shakespearean Doppelgänger. This paper aims to analyze the specific elements of the two adaptations of Hamlet, in which there is the common presence of the Lacanian psychoanalysis.

  17. Delays in presentation and treatment of breast cancer in Enugu ...

    African Journals Online (AJOL)

    To assess the delays and define the causes of delay in presentation and treatment of breast cancer patients inEnugu,Nigeria. Across-sectional survey of breast cancer patients using a semi structured questionnaire. SurgicalOncology unit,University ofNigeriaTeachingHospitalEnugu, (UNTH-E),Nigeria. 164 consecutively ...

  18. Determinants of patient delay in seeking treatment among ...

    African Journals Online (AJOL)

    Patients delay in seeking care increases the transmission of pulmonary tuberculosis and hence the burden of the disease. This study investigates the pattern and determinants of patients delay in seeking treatment among pulmonary tuberculosis cases attending a Government Chest Clinic in Ibadan, Nigeria. A descriptive ...

  19. Treatment delay and radiological errors in patients with bone metastases

    International Nuclear Information System (INIS)

    Ichinohe, K.; Takahashi, M.; Tooyama, N.

    2003-01-01

    During routine investigations, we are surprised to find that therapy for bone metastases is sometimes delayed for a considerable period of time. To determine the extent of this delay and its causes, we reviewed the medical records of symptomatic patients seen at our hospital who had been recently diagnosed as having bone metastases for the last four years. The treatment delay was defined as the interval between presentation with symptoms and definitive treatment for bone metastases. The diagnostic delay was defined as the interval between presentation with symptoms and diagnosis of bone metastases. The results of diagnostic radiological examinations were also reviewed for errors. The study population included 76 males and 34 females with a median age of 66 years. Most bone metastases were diagnosed radiologically. Over 75% of patients were treated with radiotherapy. The treatment delay ranged from 2 to 307 days, with a mean of 53.3 days. In 490 radiological studies reviewed, we identified 166 (33.9%) errors concerning 62 (56.4%) patients. The diagnostic delay was significantly longer for patients with radiological errors than for patients without radiological errors (P < 0.001), and much of it was due to radiological errors. In conclusion, the treatment delay in patients with symptomatic bone metastases was much longer than expected, and much of it was caused by radiological errors. Considerable efforts should therefore be made to more carefully examine the radiological studies in order to ensure prompt treatment of bone metastases. (author)

  20. Do health systems delay the treatment of poor children?

    DEFF Research Database (Denmark)

    Samuelsen, Helle; Tersbøl, Britt Pinkowski; Mbuyita, Selemani Said

    2013-01-01

    Child mortality remains one of the major public-health problems in Tanzania. Delays in receiving and accessing adequate care contribute to these high rates. The literature on public health often focuses on the role of mothers in delaying treatment, suggesting that they contact the health system too...... late and that they prefer to treat their children at home, a perspective often echoed by health workers. Using the three-delay methodology, this study focus on the third phase of the model, exploring the delays experienced in receiving adequate care when mothers with a sick child contact a health......-care facility. The overall objective is to analyse specific structural factors embedded in everyday practices at health facilities in a district in Tanzania which cause delays in the treatment of poor children and to discuss possible changes to institutions and social technologies....

  1. Bladder cancers respond to intravesical instillation of HAMLET (human alpha-lactalbumin made lethal to tumor cells).

    Science.gov (United States)

    Mossberg, Ann-Kristin; Wullt, Björn; Gustafsson, Lotta; Månsson, Wiking; Ljunggren, Eva; Svanborg, Catharina

    2007-09-15

    We studied if bladder cancers respond to HAMLET (human alpha-lactalbumin made lethal to tumor cells) to establish if intravesical HAMLET application might be used to selectively remove cancer cells in vivo. Patients with nonmuscle invasive transitional cell carcinomas were included. Nine patients received 5 daily intravesical instillations of HAMLET (25 mg/ml) during the week before scheduled surgery. HAMLET stimulated a rapid increase in the shedding of tumor cells into the urine, daily, during the 5 days of instillation. The effect was specific for HAMLET, as intravesical instillation of NaCl, PBS or native alpha-lactalbumin did not increase cell shedding. Most of the shed cells were dead and an apoptotic response was detected in 6 of 9 patients, using the TUNEL assay. At surgery, morphological changes in the exophytic tumors were documented by endoscopic photography and a reduction in tumor size or change in tumor character was detected in 8 of 9 patients. TUNEL staining was positive in biopsies from the remaining tumor in 4 patients but adjacent healthy tissue showed no evidence of apoptosis and no toxic response. The results suggest that HAMLET exerts a direct and selective effect on bladder cancer tissue in vivo and that local HAMLET administration might be of value in the future treatment of bladder cancers. (c) 2007 Wiley-Liss, Inc.

  2. "Hamlet" rändab Gdanskisse

    Index Scriptorium Estoniae

    2004-01-01

    Theatrum mängib 2. ja 3. aug. Gdanskis rahvusvahelise Shakespeare'i - festivali raames oma lavastust "Hamlet". Theatrumi kunstiline juht L. Peterson annab Poola teatrikoolide üliõpilastele ka meistriklassi

  3. Hamlet and Japanese Men of Letters

    Directory of Open Access Journals (Sweden)

    Kawachi Yoshiko

    2016-12-01

    Full Text Available Shakespeare has exerted a powerful influence on Japanese literature since he was accepted in the second half of the nineteenth century. Particularly Hamlet has had a strong impact on Japanese men of letters and provided them with the impetus to revive the play in contemporary literature. In this paper I discuss how they have utilized Hamlet for their creative activity and enriched Japanese literature.

  4. Hamlet er manden i mit liv

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2009-01-01

    Hamlet er manden i mit liv. Min elskede. Jeg har en drøm om at frelse ham. At redde ham ud af sin mors soveværelse og ind i mit. Væk fra det ødipale Helvede han befinder sig i, fastlåst mellem et svin af en faderskikkelse (Claudius) og en alt for idealiseret far (gamle Hamlet), vågende over sin m...

  5. Lifetime treatment contact and delay in treatment seeking after first onset of a mental disorder

    NARCIS (Netherlands)

    ten Have, M.; de Graaf, R.; van Dorsselaer, S.; Beekman, A.T.F.

    2013-01-01

    Objective: This study examined lifetime treatment contact and delays in treatment seeking, including rates for receipt of helpful treatment, after the onset of specific mental disorders and evaluated factors that predicted treatment seeking and delays in treatment seeking. Methods: Data were from

  6. Delayed bracket placement in orthodontic treatment

    Directory of Open Access Journals (Sweden)

    Chandra Wigati

    2008-12-01

    Full Text Available Background: Beside bracket position, the timing of bracket placement is one of the most essential in orthodontic treatment with fixed appliances. Even it seems simple the timing of bracket placement can be crucial and significantly influence the result of orthodontic treatment. However it is often found brackets are placed without complete understanding of its purpose and effects, which could be useless and even detrimental for the case. Purpose: The aim of this case report is to show that the timing of bracket placement could be different depending on the cases. Case: Five different cases are presented here with different timing of bracket placement. Case management: On these cases, brackets were placed on the upper arch first, on the lower arch first, or even only on some teeth first. Good and efficient orthodontic treatment results were achieved. Conclusion: For every orthodontic case, from the very beginning of treatment, bracket should be placed with the end result in mind. If brackets are correctly placed at a correct time, better treatment result could be achieved without unnecessary round tripping tooth movement.

  7. Autophagy protein p62/SQSTM1 is involved in HAMLET-induced cell death by modulating apotosis in U87MG cells.

    Science.gov (United States)

    Zhang, Y-B; Gong, J-L; Xing, T-Y; Zheng, S-P; Ding, W

    2013-03-21

    HAMLET is a complex of oleic acids and decalcified α-lactalbumin that was discovered to selectively kill tumor cells both in vitro and in vivo. Autophagy is an important cellular process involved in drug-induced cell death of glioma cells. We treated U87MG human glioma cells with HAMLET and found that the cell viability was significantly decreased and accompanied with the activation of autophagy. Interestingly, we observed an increase in p62/SQSTM1, an important substrate of autophagosome enzymes, at the protein level upon HAMLET treatment for short periods. To better understand the functionality of autophagy and p62/SQSTM1 in HAMLET-induced cell death, we modulated the level of autophagy or p62/SQSTM1 with biochemical or genetic methods. The results showed that inhibition of autophagy aggravated HAMLET-induced cell death, whereas activation of authophagy attenuated this process. Meanwhile, we found that overexpression of wild-type p62/SQSTM1 was able to activate caspase-8, and then promote HAMLET-induced apoptosis, whereas knockdown of p62/SQSTM1 manifested the opposite effect. We further demonstrated that the function of p62/SQSTM1 following HAMLET treatment required its C-terminus UBA domain. Our results indicated that in addition to being a marker of autophagy activation in HAMLET-treated glioma cells, p62/SQSTM1 could also function as an important mediator for the activation of caspase-8-dependent cell death.

  8. HAMLET interacts with histones and chromatin in tumor cell nuclei.

    Science.gov (United States)

    Düringer, Caroline; Hamiche, Ali; Gustafsson, Lotta; Kimura, Hiroshi; Svanborg, Catharina

    2003-10-24

    HAMLET is a folding variant of human alpha-lactalbumin in an active complex with oleic acid. HAMLET selectively enters tumor cells, accumulates in their nuclei and induces apoptosis-like cell death. This study examined the interactions of HAMLET with nuclear constituents and identified histones as targets. HAMLET was found to bind histone H3 strongly and to lesser extent histones H4 and H2B. The specificity of these interactions was confirmed using BIAcore technology and chromatin assembly assays. In vivo in tumor cells, HAMLET co-localized with histones and perturbed the chromatin structure; HAMLET was found associated with chromatin in an insoluble nuclear fraction resistant to salt extraction. In vitro, HAMLET bound strongly to histones and impaired their deposition on DNA. We conclude that HAMLET interacts with histones and chromatin in tumor cell nuclei and propose that this interaction locks the cells into the death pathway by irreversibly disrupting chromatin organization.

  9. Accounting for treatment delays when treating highly proliferative tumours

    International Nuclear Information System (INIS)

    Jones, L.; Metcalfe, P.; Hoban, P.

    1999-01-01

    This study was undertaken to investigate the possibility of increasing the dose per fraction or increasing the number of fractions to account for treatment delays occurring during radiotherapy treatments for highly proliferative tumours. The linear quadratic model with time was used to determine the difference in biological effective dose (BED) for the original schedule and the schedule including a treatment delay. Tables of extra fractions and extra dose per fraction required to account for a number of possible delays have been determined. It has been shown that for tumours with very short potential doubling times it is best to deliver the extra dose as an increase in dose per fraction rather than an increase in the number of fractions, while for tumours with moderately short potential doubling times (above 7 days) the reverse is true. The equivalent uninterrupted schedules, which would have delivered the same effects to the tumour, have also been determined. (author)

  10. HAMLET. LITERATURE CURRICULUM VI, TEACHER AND STUDENT VERSIONS.

    Science.gov (United States)

    KITZHABER, ALBERT R.

    THIS CULMINATING UNIT OF THE 12TH-GRADE OREGON LITERATURE CURRICULUM IS BASED UPON ONE WORK, "HAMLET." THE TEACHER VERSION INCLUDES DISCUSSIONS OF (1) THE RELEVANCE OF HAMLET'S CHARACTER TO MODERN TIMES, (2) THE PROBLEMS IN THE CHARACTERIZATIONS OF THE GHOST, CLAUDIUS, AND HAMLET, (3) THE PLAY'S THREE-PHASE STRUCTURE, (4) THE PLAY'S…

  11. Delay to first treatment contact for alcohol use disorder.

    Science.gov (United States)

    Chapman, Cath; Slade, Tim; Hunt, Caroline; Teesson, Maree

    2015-02-01

    This study explored the patterns and correlates of time to first treatment contact among people with alcohol use disorder (AUD) in Australia. Specifically it examined the relationship between sex, birth cohort, onset of AUD symptoms, severity, comorbidity, symptom type and time to first treatment contact (treatment delay) among those with alcohol abuse and dependence in a large population sample. Data came from the 2007 Australian National Survey of Mental Health and Wellbeing (N=8841). A modified version of the World Health Organization's Composite International Diagnostic Interview was used to determine the presence and age of onset of DSM-IV AUD and other mental disorders and the age at which respondents first sought treatment for alcohol or other drug-related problems. Median time to first treatment contact for an AUD was 18 years (14 years dependence, 23 years abuse). Projected lifetime treatment rates were 78.1% for alcohol dependence and 27.5% for abuse. Those with earlier onset and from older cohorts reported longer delay and were less likely to ever seek treatment compared to those with later onset or from more recent cohorts. Those with comorbid anxiety but not mood disorder, or who reported alcohol-related role disruption or recurrent interpersonal problems were more likely to ever seek treatment and reported shorter delay compared to those who did not report these symptoms. Treatment delay for alcohol use disorder in Australia is substantial. Those with earlier onset and those with comorbid mood disorder should be a target for earlier treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Determinants of patient delay in seeking treatment among ...

    African Journals Online (AJOL)

    lmboera

    A descriptive cross sectional study was employed. A face to .... Face validation of the instrument was done through peer review and pretesting. In this ..... patient delay for Christians was about 3.3 fold higher compared with Muslims. ... Grover, A., Kumar, R. & Jindal, K. (2006) Socio-demographic determinants of treatment.

  13. Delays in switching patients onto second-line antiretroviral treatment ...

    African Journals Online (AJOL)

    Background: South Africa has one of the largest antiretroviral treatment (ART) programmes globally. In addition to increasing access to ART, it is important that the health system also focuses on the appropriate management of patients who fail first-line ART. Delays in switching patients onto second-line ART can adversely ...

  14. Hamlet — An Imperfect Humanist%Hamlet—An Imperfect Humanist

    Institute of Scientific and Technical Information of China (English)

    闫莹莹

    2017-01-01

    Hamlet is an eternal classic written by William Shakespeare. It drew much attention from the first edition and got a mixed reception. People argued about the characteristic of Hamlet during more than 400 years. Many western critics concerned Hamlet was hesitated, cowardly, oedipal and was not a humanist. However, investigators in China regarded Hamlet as a perfect humanist. It argues that the characteristic of Hamlet is so complicated, it can't be summarized in one sentence. It is sensible to make a comprehensive study on the limitation of Hamlet as a pure person in a world which the god withdraws. Began with cow-ardice and ended with peaceful death, Hamlet shows the soul of an imperfect humanist.

  15. Hamlet: homem de virtú Hamlet: virtù man

    Directory of Open Access Journals (Sweden)

    Marcos Del Roio

    2008-12-01

    Full Text Available O artigo traz algumas relações/semelhanças entre Hamlet, de Shakespeare, e O Príncipe de Maquiavel. Portanto, pela “perspectiva” da Razão de Estado e não pela versão reducionista do “maquiavelismo” (maniqueísmo político, também podemos observar uma teoria política em Shakespeare. Palavras-chave: Maquiavel. Príncipe. Virtù. Hamlet. Astúcia. The article reports some relations/similarities between Shakespeare’s Hamlet and Machiavelli’s Prince. Therefore, by the State Reasoning “perspective” and not by the reductionism version of “machiavellism” (political maniqueism, we can also observe a political theory in Shakespeare. Keywords:Machiavelli. Prince. Virtù. Hamlet. Cunning.

  16. Factors that influence treatment delay in patients with colorectal cancer

    Science.gov (United States)

    Zarcos-Pedrinaci, Irene; Fernández-López, Alberto; Téllez, Teresa; Rivas-Ruiz, Francisco; Rueda A, Antonio; Suarez-Varela, María Manuela Morales; Briones, Eduardo; Baré, Marisa; Escobar, Antonio; Sarasqueta, Cristina; de Larrea, Nerea Fernández; Aguirre, Urko; Quintana, José María; Redondo, Maximino

    2017-01-01

    A prospective study was performed of patients diagnosed with colorectal cancer (CRC), distinguishing between colonic and rectal location, to determine the factors that may provoke a delay in the first treatment (DFT) provided. 2749 patients diagnosed with CRC were studied. The study population was recruited between June 2010 and December 2012. DFT is defined as time elapsed between diagnosis and first treatment exceeding 30 days. Excessive treatment delay was recorded in 65.5% of the cases, and was more prevalent among rectal cancer patients. Independent predictor variables of DFT in colon cancer patients were a low level of education, small tumour, ex-smoker, asymptomatic at diagnosis and following the application of screening. Among rectal cancer patients, the corresponding factors were primary school education and being asymptomatic. We conclude that treatment delay in CRC patients is affected not only by clinicopathological factors, but also by sociocultural ones. Greater attention should be paid by the healthcare provider to social groups with less formal education, in order to optimise treatment attention. PMID:27888636

  17. Patient Delay, Diagnosis Delay and Treatment Delay for Breast Cancer: Comparison of the Pattern between Patients in Public and Private Health Sectors

    Directory of Open Access Journals (Sweden)

    Iraj Harirchi

    2015-05-01

    Full Text Available Background: The purpose of this study was to compare patient delay, diagnosis delay and treatment delay in breast cancer patients of selected public and private health centers in Tehran, Iran.Methods: In this cross-sectional study, female patients with newly diagnosed breast cancer in a public medical complex and a private breast clinic within one year were included. Patient delay was considered positive, if the interval between the detection of the first symptom by the patient and the first visit to a health care provider took longer than one month. Delay in diagnosis was defined as the period of more than one week between the first medical visit for the symptoms and the diagnosis of breast cancer. Following the confirmed diagnosis of breast malignancy, if the medical treatment was initiated later than one week, treatment delay had occurred. The potential reasons for patient, diagnosis and treatment delay according to the patients’ reports were also recorded.Results: Overall, 385 patients were included of whom 52.7% were recruited from the public hospitals and 47.3% from a private clinic. The prevalence of patient delay, diagnosis delay and treatment delay were 31.7%, 17.9% and 28.3%, respectively. Patient delay was significantly more common among patients with lower socio-economic status and those recruited from the public hospitals. All the patients with diagnosis delay were in the group recruited from the public hospitals.Conclusions: Gaps between women of different socio-economic levels of the society need to be addressed in order to decrease patient, diagnosis and treatment delay.

  18. Kuressaare Hamlet on inglane / Andres Laasik

    Index Scriptorium Estoniae

    Laasik, Andres, 1960-2016

    2000-01-01

    29.oktoobril esilinastub Eesti Televisioonis Hamleti-teemaline ingliskeelne lühimängufilm "Miski on mäda ehk Kogu vale Hamletist" ("Something is Rotten or All the Lie About Hamlet") : režissöör, stsenarist ja produtsent Ilmar Raag : OÜ Kinomees 2000

  19. Kuressaare Hamlet ahistab Opheliat / Andres Laasik

    Index Scriptorium Estoniae

    Laasik, Andres, 1960-2016

    2000-01-01

    Ilmar Raag väntab Saaremaal Hamleti-teemalist ingliskeelset mängufilmi inglise näitlejatega esialgse pealkirjaga "Miski on riigis mäda ehk Kogu vale Hamletist" ("Something is Rotten or All the Lie About Hamlet". Filmi operaator on Madis Mihkelsoo ja kunstnik Liina Unt

  20. The Thing's the Play: Doing "Hamlet."

    Science.gov (United States)

    Sowder, Wilbur H., Jr.

    1993-01-01

    Argues for the use of film in the teaching of William Shakespeare's "Hamlet" because the play was meant to be seen and heard and not just read. Outlines a method of teaching the play by which students select a scene and perform it. Gives an example of a successful student performance. (HB)

  1. "Remember Me": Memory and Action in "Hamlet".

    Science.gov (United States)

    Andrews, Michael Cameron

    1981-01-01

    Examines the relationship between Hamlet's commitments to the past and his failure to translate these commitments into action, as he permits himself to be deflected by preoccupation with the future consequences of his action. Cites supportive evidence from the text. (DMM)

  2. HAMLET - A protein-lipid complex with broad tumoricidal activity.

    Science.gov (United States)

    Ho, James C S; Nadeem, Aftab; Svanborg, Catharina

    2017-01-15

    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a tumoricidal protein-lipid complex with broad effects against cancer cells of different origin. The therapeutic potential is emphasized by a high degree of specificity for tumor tissue. Here we review early studies of HAMLET, in collaboration with the Orrenius laboratory, and some key features of the subsequent development of the HAMLET project. The early studies focused on the apoptotic response that accompanies death in HAMLET treated tumor cells and the role of mitochondria in this process. In subsequent studies, we have identified a sequence of interactions that starts with the membrane integration of HAMLET and the activation of ion fluxes followed by HAMLET internalization, progressive inhibition of MAPK kinases and GTPases and sorting of HAMLET to different cellular compartments, including the nuclei. Therapeutic efficacy of HAMLET has been demonstrated in animal models of glioblastoma, bladder cancer and intestinal cancer. In clinical studies, HAMLET has been shown to target skin papillomas and bladder cancers. The findings identify HAMLET as a new drug candidate with promising selectivity for cancer cells and a strong therapeutic potential. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Delayed complications of radiotherapy treatment for nasopharyngeal carcinoma: imaging findings

    International Nuclear Information System (INIS)

    King, A.D.; Ahuja, A.T.; Yeung, D.K.; Wong, J.K.T.; Lee, Y.Y.P.; Lam, W.W.M.; Ho, S.S.M.; Yu, S.C.H.; Leung, S.-F.

    2007-01-01

    Radiotherapy is used to treat a wide variety of head and neck tumours that arise in and around the skull base. The delayed effects of radiation damages a range of structures, including the nervous system, bone, major vessels, mucus membranes, pituitary and salivary glands, as well as increasing the risk of radiation-induced neoplasms. In this review the complications resulting from radiation treatment for nasopharyngeal carcinoma (NPC), a cancer treated with a high dose of radiation to a fairly large region, are illustrated. Many patients with NPC have a long-term survival, so are at risk of developing delayed radiation effects, and hence may demonstrate a wide range of complications on imaging. Other tumours around the skull base treated with radiotherapy include meningiomas, chordomas, chondrosarcomas, pituitary adenomas, paranasal sinus and nasal cavity tumours. In these cases similar complications may be encountered on imaging, although the severity, incidence and location will vary

  4. Patient delay is the main cause of treatment delay in acute limb ischemia: an investigation of pre- and in-hospital time delay

    DEFF Research Database (Denmark)

    Londero, Louise Skovgaard; Nørgaard, Birgitte; Houlind, Kim Christian

    2014-01-01

    Abstract BACKGROUND: The prognosis of acute limb ischemia is severe, with amputation rates of up to 25% and in-hospital mortality of 9-15%. Delay in treatment increases the risk of major amputation and may be present at different stages, including patient delay, doctors´ delay and waiting time...... in the emergency department. It is important to identify existing problems in order to reduce time delay. The aim of this study was to collect data for patients with acute limb ischemia and to evaluate the time delay between the different events from onset of symptoms to specialist evaluation and further treatment...... (median (range)) was identified. From onset of symptoms to first contact with a doctor the time for all patients were 24 (0-1200) hours. Thirty patients needed immediate intervention. In the group of fourteen patients who had immediate operation, the median time from vascular evaluation...

  5. Hamlet, Performance and Chaotic Cultural Networks

    Directory of Open Access Journals (Sweden)

    Emil Rybczak

    2015-10-01

    Full Text Available Since the 1960s, chaos theory has become an important but controversial tool used by scientists and mathematicians to describe physical or theoretical systems or networks. It explains how the simple can generate the complex. Its central tenets can also provide an alternative language and means of literary interpretation. This article will explore how the principles of chaos theory can be used to close read and systematise various aspects of the language and performance of Shakespeare. The argument is built upon an analysis of Hamlet, in an effort to understand the play and its reproduction as the evolution of interconnected complex networks. Various aspects of the text will be discussed, including its language, structural and character patterning, and its reproduction through performance and cinematic adaptation. Each of these topics, and the characters, devices or ideas they discuss, constitute nodes of the complex network of Hamlet as both text and idea. Responding to the cultural analysis of other scholars, this article uses Hamlet as an ideal example of how the appropriation of scientific language can defamiliarise a particular literary or dramatic artefact. This allows fresh interpretation and understanding of its location within the broader networks of theatre and culture. I suggest the possibilities of close reading literary works through the lens of chaos and suggest how they might be applied and developed in conjunction with other texts, media or performances.

  6. Delayed access to treatments for rare diseases: who's to blame?

    Science.gov (United States)

    Feltmate, Karen; Janiszewski, Peter M; Gingerich, Sheena; Cloutier, Michael

    2015-04-01

    The development and commercialization of drugs for rare diseases, termed 'orphan drugs', has historically been economically unattractive. However, because of the introduction of legislation that provides financial and regulatory incentives for the development of orphan drugs, new developments are making their way through the regulatory approval processes. Unfortunately, delays in availability of new drugs for treating rare disease continue to persist. This paper reviews the approach of several regulatory jurisdictions to orphan drugs in an effort to determine their relative effectiveness in providing patient access. Generally speaking, regulatory authorities across jurisdictions have recognized the need to enhance timely access to safe, effective treatment for patients with rare diseases and have been able to shift the approval timelines for access to new care. The greater impediment to orphan drug access appears to be funding, particularly in publicly sponsored health-care systems. Redundancies in federal and provincial reviews of orphan drugs can result in significant delays in access to new drugs. Clearly, more must be done to accelerate access to the treatments so desperately needed by patients. Public payers must be held accountable for their process and decisions--especially for rare disease therapies. © 2015 Asian Pacific Society of Respirology.

  7. "By Indirections Find Directions Out": The Soliloquies in Hamlet

    Science.gov (United States)

    Champion, Larry S.

    1976-01-01

    Article analyzed the soliloquies in Hamlet and showed that Shakespeare used the device of the soliloquy not for clarification (as he did elsewhere) but for complication instead, so that the audience is made to see Hamlet's character as consisting of diverse ingredients, a personality fragmented rather than whole. (Editor/RK)

  8. Hamlet, iscenesættelse Roger Vontobel, Staatsschauspiel Dresden

    DEFF Research Database (Denmark)

    Kuhlmann, Annelis

    2015-01-01

    Hamlet iscenesat af Roger Vontobel, Staatsschauspiel Dresden. Gæstespil på Kronborg Slot under Hamletscenens Shakespearefestival 1.-4. august 2015......Hamlet iscenesat af Roger Vontobel, Staatsschauspiel Dresden. Gæstespil på Kronborg Slot under Hamletscenens Shakespearefestival 1.-4. august 2015...

  9. Noble Gases in the Hamlet Meteorite (LL4)

    Science.gov (United States)

    Amari, S.; Sabe, Y.; Shiraishi, T.; Matsuda, J.

    2014-09-01

    We analyzed noble gases in a bulk sample and an HF-HCl residue of Hamlet (LL4). The Xe composition of the residue shows that no diamond is contained in the residue. The 20Ne/22Ne ratio of Hamlet Ne-Q has been determined to be 11.0 ± 0.5.

  10. Spaghetti Shakespeare: Johnny Hamlet and the Italian Western

    Directory of Open Access Journals (Sweden)

    Ciraulo Darlena

    2017-09-01

    Full Text Available The Italian Western, Johnny Hamlet (1968, directed by Enzo G. Castellari, draws on the revenge story of Shakespeare’s tragedy Hamlet for plot and characterization. While international distributors of the film downplayed its connection to highbrow Shakespeare, they emphasized the movie’s violent content and action-packed revenge narrative, which was typical of the western all’italiana. Johnny Hamlet shares similarities with the brutally violent Django (1966, directed by Sergio Corbucci, whose avenging angel protagonist epitomizes the Spaghetti Western antihero. Although the filmmakers of Johnny Hamlet characterized Johnny as a vindicator, they also sought to develop the “broody” aspect of this gunfighter, one based on Shakespeare’s famously ruminating hero. Using innovative film techniques, Johnny Hamlet shows Johnny as a contemplative pistolero.

  11. Treatment for delayed brain injury after pituitary irradiation

    International Nuclear Information System (INIS)

    Fujii, Takashi; Misumi, Shuzoh; Shibasaki, Takashi; Tamura, Masaru; Kunimine, Hideo; Hayakawa, Kazushige; Niibe, Hideo; Miyazaki, Mizuho; Miyagi, Osamu.

    1988-01-01

    Treatment for delayed brain injury after pituitary irradiation is discussed. Six cases with delayed brain injury were treated with a combination of dexamethasone or betamethasone, with heparin, glycerol, dextran 40 and some vasodilators. Two cases with temporal lobe syndrome were treated in the early stages of brain injury for a period of over 12 months were almost completely cured, another two cases with chiasma syndrome were treated in the relatively late stages, showed a partial improvement. One case which was irradiated 120 GY during 13 years did not improve. The final case treated with steroids for a short period also resulted in failure and the patient underwent an operation for the removal of the necrotic mass three years after the radiotherapy. Steroid therapy started in the early stages of brain injury after irradiation for over the 12 months is thought to be effective. Heparin therapy was also effective in one out of three cases, but in one of the cases subarachnoid hemorrhage from a traumatic aneurysm occurred during the therapy. In an acute phase, showing edematous change of the injured brain, the administration of glycerol is also thought to be useful. But the effectiveness of the other medicines containing some vasodilators was obscure or doubtful. We propose the following : (1) A meticulous observation is essential for the patients who received high doses of irradiation to diagnose brain injury in the early reversible stage. (2) Steroids should be given immediately in this reversible stage of brain injury before the irreversible ''necrosis'' occurs. (3) Steroids should be maintained for a long period over 12 months. (4) Heparin therapy is also thought to be effective, but careful precautions to avoid hemorrhagic complications before the therapy should be scheduled. This recommended plan may also be used for the treatment of brain injuries after cranial irradiation for other intracranial tumors. (author)

  12. Delays in diagnosis and treatment of extrapulmonary tuberculosis in Guatemala.

    Science.gov (United States)

    Shah, Pooja Ajay; Coj, Merida; Rohloff, Peter

    2017-10-09

    A 23-year-old indigenous Guatemalan man presented in 2016 to our clinic in Sololá, Guatemala, with 10 months of recurrent neck swelling, fevers, night sweats and weight loss. Previously, he had sought care in three different medical settings, including a private physician-run clinic, a tertiary private cancer treatment centre and, finally, a rural government health post. With assistance from our institution's accompaniment staff, the patient was admitted to a public tertiary care hospital for work-up. Rifampin-susceptible tuberculosis was diagnosed, and appropriate treatment was begun. The case illustrates how low tuberculosis recognition among community health workers and health system segmentation creates obstacles to appropriate care, especially for patients with limited means. As a result, significant diagnostic and treatment delays can occur, increasing the public health burden of tuberculosis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. A New Reading of Shakespeare's Hamlet.

    Science.gov (United States)

    Usher, P. D.

    1996-12-01

    I argue that Hamlet is an allegory for the competition between the cosmological models of the contemporaries Thomas Digges (1546-1595) of England and Tycho Brahe (1546-1601) of Denmark. Through his acquaintance with the Digges' family, Shakespeare would have known of the essential elements of the revolutionary model of Nicholas Copernicus (1473-1543) as well as Digges' extension of it. Prior to 1601 when the writing of Hamlet was completed, Shakespeare knew also of Tycho and his relatives Rosencrantz and Guildenstern, and would have seen that Tycho's hybrid geocentric model was a substantial regression to the well-known geocentricism of Ptolemy (fl. 140 A.D.). It has been suggested that Polonius is named for a fictional character Pollinio, an Aristotelian pedant. I suggest that Claudius is named for Claudius Ptolemy for whom Polonius would have been a suitable attendant. I suggest further that the slaying of Rosencrantz and Guildenstern is the Bard's way of killing the Tychonic model. The slaying of Claudius signals the demise of Ptolemaic geocentricism, both ends being prolonged, the former dramatically, the latter as a matter of historical fact. But the climax of the play is not the slaughter of the chief protagonists; it is the triumphal arrival of Fortinbras from Poland and his timely salute to the ambassadors from England. By means of this apparent incongruity, Shakespeare celebrates the Copernican and Diggesian models and states poetically the nature of the new universal order. I present literary and historical evidence for the present reading which, if essentially correct, suggests that Hamlet evinces a scientific cosmology no less significant than its literary and philosophical counterparts. The last year of the sixteenth century saw the martyrdom of Bruno, but the first year of the next century saw the Bard affirm that there are more things in heaven than were dreamt of in contemporary philosophy.

  14. Immediate versus delayed treatment for recently symptomatic carotid artery stenosis

    Directory of Open Access Journals (Sweden)

    Vladimir Vasconcelos

    Full Text Available ABSTRACT BACKGROUND: The timing of surgery for recently symptomatic carotid artery stenosis remains controversial. Early cerebral revascularization may prevent a disabling or fatal ischemic recurrence, but it may also increase the risk of hemorrhagic transformation, or of dislodging a thrombus. This review examined the randomized controlled evidence that addressed whether the increased risk of recurrent events outweighed the increased benefit of an earlier intervention. OBJECTIVES: To assess the risks and benefits of performing very early cerebral revascularization (within two days compared with delayed treatment (after two days for people with recently symptomatic carotid artery stenosis. METHODS: Search methods: We searched the Cochrane Stroke Group Trials Register in January 2016, the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2016, issue 1, MEDLINE (1948 to 26 January 2016, EMBASE (1974 to 26 January 2016, LILACS (1982 to 26 January 2016, and trial registers (from inception to 26 January 2016. We also handsearched conference proceedings and journals, and searched reference lists. There were no language restrictions. We contacted colleagues and pharmaceutical companies to identify further studies and unpublished trials Selection criteria: All completed, truly randomized trials (RCT that compared very early cerebral revascularization (within two days with delayed treatment (after two days for people with recently symptomatic carotid artery stenosis. Data collection and analysis: We independently selected trials for inclusion according to the above criteria, assessed risk of bias for each trial, and performed data extraction. We utilized an intention-to-treat analysis strategy. MAIN RESULTS: We identified one RCT that involved 40 participants, and addressed the timing of surgery for people with recently symptomatic carotid artery stenosis. It compared very early surgery with surgery performed after 14 days of

  15. Treatment delay of bone tumours, compilation of a sociodemographic risk profile: A retrospective study

    International Nuclear Information System (INIS)

    Schnurr, Christoph; Pippan, Mathias; Stuetzer, Hartmut; Delank, Karl S; Michael, Joern WP; Eysel, Peer

    2008-01-01

    Bone tumours are comparatively rare tumours and delays in diagnosis and treatment are common. The purpose of this study was to analyse sociodemographic risk factors for bone tumour patients in order to identify those at risk of prolonged patients delay (time span from first symptoms to consultation), professional delay (from consultation to treatment) or symptom interval (from first symptoms to treatment). Understanding these relationships might enable us to shorten time to diagnosis and therapy. We carried out a retrospective analysis of 265 patients with bone tumours documenting sociodemographic factors, patient delay, professional delay and symptom interval. A multivariate explorative Cox model was performed for each delay. Female gender was associated with a prolonged patient delay. Age under 30 years and rural living predisposes to a prolonged professional delay and symptom interval. Early diagnosis and prompt treatment are required for successful management of most bone tumour patients. We succeeded in identifying the histology independent risk factors of age under 30 years and rural habitation for treatment delay in bone tumour patients. Knowing about the existence of these risk groups age under 30 years and female gender could help the physician to diagnose bone tumours earlier. The causes for the treatment delays of patients living in a rural area have to be investigated further. If the delay initiates in the lower education of rural general physicians, further training about bone tumours might advance early detection. Hence the outcome of patients with bone tumours could be improved

  16. Delayed puberty and hypogonadotropic hypogonadism. Differential diagnosis and treatment

    NARCIS (Netherlands)

    Snoep, Marinus Cornelis

    1978-01-01

    This thesis describes a method enabling a prospecrive differential diagnosis to be made berween delayed puberty (DP) and hypogonadotropic hypogonadism (HH). The influence of androgen administration on the gonadal feedback sysrem of patients with delayed puberty was also studied. ... Zie: Summary

  17. Treatment seeking behaviour and prevalence of treatment delay among malaria patients along Thailand-Myanmar border in Tak province

    Directory of Open Access Journals (Sweden)

    Krit Sonkong

    2015-04-01

    Full Text Available Objective: To investigate treatment seeking behaviour and the prevalence of treatment delay of malaria patients. Methods: A cross-sectional study was conducted with malaria patients along the ThailandMyanmar border in Tak province, Thailand. Results: Most of patients (70.0% were treated for fever before receiving treatment at a malaria clinic or public hospital. The sources of initial treatments were self-treatment (64.0%, malaria clinics (20.0%, public hospital (11.0%, sub-district health promotion hospital (3.3%, and malaria posts (1.1%. Prevalence of patients delayed more than one day after onset of symptoms was 79.4%, but doctor delay of more than one day occurred in only 1.3%. The prevalence of treatment delay (total delay of more than one day was 79.6%. Patient delay and treatment delay were found to be significantly higher among hill tribe than Thai subjects (P=0.004 and 0.003, respectively but, there was no significant association between ethnicity and doctor delay (P=0.669. Conclusion: Patient delay in seeking treatment is a major problem along the ThailandMyanmar border in Tak province, especially in hill tribe people. Self-treatment accounted for most of initial treatment sought by patients.

  18. Delay in treatment seeking of smear positive tuberculous patients

    International Nuclear Information System (INIS)

    Bhatti, A.T.; Zahid, M.

    2010-01-01

    To assess and identify the causes and circumstances leading to delays in health seeking and diagnosis of tuberculosis patients as they often present with advance disease resulting in increased morbidity and mortality. Settings Department of Tuberculosis, DOTS clinic DHQ Hospital, Vehari. Methodology One (author) inspiration diagnosed smear positive pulmonary tuberculosis patients were included. Information was gathered through interviews and from TB-01 card. Results Maximum patients were in age group of 16-40 years. Median patient delay was 4-6 months; jobless, homeless personnel had longer delay. The main reason for delay was that the symptoms were not considered serious enough. Delay in presentation of smear positive cases may be due to the lack of awareness of patients and the incompetence of some health workers. Training and supervision of staff and awareness campaigns targeted at the population and involvement of private sector will improve TB control in Vehari. (author)

  19. A novel method for preparation of HAMLET-like protein complexes.

    Science.gov (United States)

    Permyakov, Sergei E; Knyazeva, Ekaterina L; Leonteva, Marina V; Fadeev, Roman S; Chekanov, Aleksei V; Zhadan, Andrei P; Håkansson, Anders P; Akatov, Vladimir S; Permyakov, Eugene A

    2011-09-01

    Some natural proteins induce tumor-selective apoptosis. α-Lactalbumin (α-LA), a milk calcium-binding protein, is converted into an antitumor form, called HAMLET/BAMLET, via partial unfolding and association with oleic acid (OA). Besides triggering multiple cell death mechanisms in tumor cells, HAMLET exhibits bactericidal activity against Streptococcus pneumoniae. The existing methods for preparation of active complexes of α-LA with OA employ neutral pH solutions, which greatly limit water solubility of OA. Therefore these methods suffer from low scalability and/or heterogeneity of the resulting α-LA - OA samples. In this study we present a novel method for preparation of α-LA - OA complexes using alkaline conditions that favor aqueous solubility of OA. The unbound OA is removed by precipitation under acidic conditions. The resulting sample, bLA-OA-45, bears 11 OA molecules and exhibits physico-chemical properties similar to those of BAMLET. Cytotoxic activities of bLA-OA-45 against human epidermoid larynx carcinoma and S. pneumoniae D39 cells are close to those of HAMLET. Treatment of S. pneumoniae with bLA-OA-45 or HAMLET induces depolarization and rupture of the membrane. The cells are markedly rescued from death upon pretreatment with an inhibitor of Ca(2+) transport. Hence, the activation mechanisms of S. pneumoniae death are analogous for these two complexes. The developed express method for preparation of active α-LA - OA complex is high-throughput and suited for development of other protein complexes with low-molecular-weight amphiphilic substances possessing valuable cytotoxic properties. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  20. Hamlet in Freud's Thoughts: Reinterpretations in the Psychoanalytic Literature.

    Science.gov (United States)

    Diaz de Chumaceiro, Cora L.

    1998-01-01

    Presents a selection of interpretations in the psychoanalytic literature of "Hamlet," by William Shakespeare, beginning with an extensive look at the role this literature played in Sigmund Freud's mind at the origins of psychoanalysis. Also examines later interpretations. (SR)

  1. A Sense of Worth: Seven Days with Hamlet.

    Science.gov (United States)

    Harrison, Bernard T.

    1984-01-01

    Discusses the effectiveness of a week-long teacher inservice workshop on Shakespeare's "Hamlet" in the context of an analysis of participants' responses to a 10-question evaluation of the inservice. (AEA)

  2. Knowledge, Choice and Consequence: Reading and Teaching "Hamlet."

    Science.gov (United States)

    Baumlin, James S.; Baumlin, Tita French

    1990-01-01

    Offers a Pyrrhonist reading of "Hamlet." Describes an experiment in teaching that attempts to reconstruct for literature students the prudential-ethical context of human rhetoric, placing "prudentia," or practical wisdom, at the center of their own imaginative involvement. (PRA)

  3. Delay in Presentation, Diagnosis, and Treatment for Breast Cancer Patients in Jordan.

    Science.gov (United States)

    Abu-Helalah, Ahmad Munir; Alshraideh, Hussam Ahmad; Al-Hanaqtah, Mo'tasem; Da'na, Moh'd; Al-Omari, Asim; Mubaidin, Rasmi

    2016-01-01

    Breast cancer is the most common cancer, and one of the leading causes of death for females in Jordan and many countries in the world. Studies have shown that delay in symptoms presentation, diagnosis or treatment would result in poor prognosis. There has been no published study from Jordan on delays in patient presentation, delays in diagnosis, or delays in treatment. Therefore, we conducted this study to assess these important quality indicators aiming to improve prognosis for breast cancer patients in Jordan. This project was a cross-sectional study on female breast cancer patients in Jordan. The total number of participants was 327. The proportion of patients with presentation delay, diagnosis delay, and treatment delay was 32.2%, 49.1%, or 32.4%, respectively. The main reported reasons for delay in presentation were ignorance of the nature of the problem (65.6%), limited/lack of knowledge that symptoms were suggestive of cancer diagnosis (16.7%), and misdiagnosis (16.7%). Predictors of delay and mean time for presentation, diagnosis, and treatment were identified. Our results reveal that breast cancer patients in Jordan are experiencing delays in presentation, diagnosis, and treatment. This could justify the advanced stages at diagnosis and poor outcomes for breast cancer patients in Jordan. We recommend revising the current early detection and down-staging programs in Jordan. © 2015 Wiley Periodicals, Inc.

  4. Harriot, Digges, and the Ghost in Hamlet.

    Science.gov (United States)

    Usher, P. D.

    1998-12-01

    The cosmic allegorical interpretation of Hamlet (BAAS 28, 1305, 1996; 29, 1262, 1997; Giornale di Astronomia 24:3, 27, 1998) may be regarded as a Galilean postulatum with testable consequences. It associates leading characters in the play with cosmologists from the time of Ptolemy (Claudius) to Tycho Brahe (Rosencrantz and Guildenstern) and Thomas Digges (Hamlet). Lines 3.3.8-23 describe how the concepts of geocentricism and the sphere of fixed stars shared by the Ptolemaic and Tychonic models are imperiled by the Infinite Universe of Digges. Hitherto baffling lines 5.2.100-125 list in short order at least 16 attributes of Thomas Harriot, including his short bibliography (``soul of great article'') which may explain why he receives mention only in passing. The Ghost is Thomas Digges' father Leonard, who is a ``mole'' in the ``cellarage.'' That Leonard may have gone underground following restoration of his lands is supported by the range of years (1559-1574) of his alleged death, and conspicuous absence of a gravesite. Circumstances of his disappearance have remained mysterious (N&Q 2:X, 162, 1860; 6:X, 368, 515, 1884; 8:V, 186, 1894.) I suggest that, having been saved from execution and restored to gentility, he continued to work, writing in the tradition of his confrere's father Thomas Wyatt, Sr. who pioneered the English sonnet. The first Dowden series of sonnets reflects his love for his only child. The history of the perspective glass explains lines in Sonnets 14 and 103 (``my blunt invention'') and in the I.M.S. encomium wherein he did ``rowle back the heavens'' with a ``cleere and equall surface'' that is ``reflecting ages past.'' A portrait of Tycho helps date Sonnet 16 to between 1581 and 1585. Sonnets 18 and 87 would date to 1583 and 1595. Allusions to old age are not surprising. I.M.'s words: ``Wee wondred (Shake-speare) that thou went'st so soone'' and ``An Actors Art, can dye, and liue to acte a second part'' are explained, as are sources for The

  5. Antibiotic treatment delay and outcome in acute bacterial meningitis

    DEFF Research Database (Denmark)

    Køster-Rasmussen, Rasmus; Korshin, André; Meyer, Christian N

    2008-01-01

    OBJECTIVES: To identify to what degree in-hospital delay of antibiotic therapy correlated to outcome in community acquired bacterial meningitis. METHODS: All cases of culture-positive cerebrospinal fluids in east Denmark from 2002 to 2004 were included. Medical records were collected retrospectiv......OBJECTIVES: To identify to what degree in-hospital delay of antibiotic therapy correlated to outcome in community acquired bacterial meningitis. METHODS: All cases of culture-positive cerebrospinal fluids in east Denmark from 2002 to 2004 were included. Medical records were collected......=1.30/h, CI: 1.08-1.57). The median delay to the first dose of adequate antibiotics was 1h and 39min (1h and 14min in children vs. 2h in adults, pmeningitis. CONCLUSION: The delay in antibiotic therapy correlated...

  6. HAMLET forms annular oligomers when deposited with phospholipid monolayers.

    Science.gov (United States)

    Baumann, Anne; Gjerde, Anja Underhaug; Ying, Ming; Svanborg, Catharina; Holmsen, Holm; Glomm, Wilhelm R; Martinez, Aurora; Halskau, Oyvind

    2012-04-20

    Recently, the anticancer activity of human α-lactalbumin made lethal to tumor cells (HAMLET) has been linked to its increased membrane affinity in vitro, at neutral pH, and ability to cause leakage relative to the inactive native bovine α-lactalbumin (BLA) protein. In this study, atomic force microscopy resolved membrane distortions and annular oligomers (AOs) produced by HAMLET when deposited at neutral pH on mica together with a negatively charged lipid monolayer. BLA, BAMLET (HAMLET's bovine counterpart) and membrane-binding Peptide C, corresponding to BLA residues 75-100, also form AO-like structures under these conditions but at higher subphase concentrations than HAMLET. The N-terminal Peptide A, which binds to membranes at acidic but not at neutral pH, did not form AOs. This suggests a correlation between the capacity of the proteins/peptides to integrate into the membrane at neutral pH-as observed by liposome content leakage and circular dichroism experiments-and the formation of AOs, albeit at higher concentrations. Formation of AOs, which might be important to HAMLET's tumor toxic action, appears related to the increased tendency of the protein to populate intermediately folded states compared to the native protein, the formation of which is promoted by, but not uniquely dependent on, the oleic acid molecules associated with HAMLET. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Delayed onset muscle soreness : treatment strategies and performance factors.

    Science.gov (United States)

    Cheung, Karoline; Hume, Patria; Maxwell, Linda

    2003-01-01

    Delayed onset muscle soreness (DOMS) is a familiar experience for the elite or novice athlete. Symptoms can range from muscle tenderness to severe debilitating pain. The mechanisms, treatment strategies, and impact on athletic performance remain uncertain, despite the high incidence of DOMS. DOMS is most prevalent at the beginning of the sporting season when athletes are returning to training following a period of reduced activity. DOMS is also common when athletes are first introduced to certain types of activities regardless of the time of year. Eccentric activities induce micro-injury at a greater frequency and severity than other types of muscle actions. The intensity and duration of exercise are also important factors in DOMS onset. Up to six hypothesised theories have been proposed for the mechanism of DOMS, namely: lactic acid, muscle spasm, connective tissue damage, muscle damage, inflammation and the enzyme efflux theories. However, an integration of two or more theories is likely to explain muscle soreness. DOMS can affect athletic performance by causing a reduction in joint range of motion, shock attenuation and peak torque. Alterations in muscle sequencing and recruitment patterns may also occur, causing unaccustomed stress to be placed on muscle ligaments and tendons. These compensatory mechanisms may increase the risk of further injury if a premature return to sport is attempted.A number of treatment strategies have been introduced to help alleviate the severity of DOMS and to restore the maximal function of the muscles as rapidly as possible. Nonsteroidal anti-inflammatory drugs have demonstrated dosage-dependent effects that may also be influenced by the time of administration. Similarly, massage has shown varying results that may be attributed to the time of massage application and the type of massage technique used. Cryotherapy, stretching, homeopathy, ultrasound and electrical current modalities have demonstrated no effect on the alleviation of

  8. El Juego de Mundo en Hamlet

    OpenAIRE

    Osorio, Jorge

    2013-01-01

    A partir de una lectura de Hamlet el autor plantea la relación entre el regicidio y el desorden natural, tal como lo entendieron la filosofía política medieval y su transito a la filosofía del Renacimiento. Se indaga en el vínculo de la locura, el extravío dramático y la deriva política,  y sus implicancias en la visión  moral del mundo presente en la obra. Esta lectura teatral de la política sitúa el problema de la  dialéctica ocultación/de-velación  de los textos,  como un asunto central  d...

  9. WHEN DYLAN MET THE BARD: TRANSLATING HAMLET FROM TEXT TO SCREEN (SOUND: MICHAEL ALMEREYDA’S HAMLET

    Directory of Open Access Journals (Sweden)

    Marina Gerzic

    2015-12-01

    Full Text Available Director Michael Almereyda’s diverse musical choices in the film are a threshold into understanding his cinematic interpretation of Hamlet (2000. Almereyda recontextualises Hamlet in terms of contemporary social problems. Hamlet and Ophelia are confronted with and battle against urban claustrophobia, conspiracy and global corporate power. A fragment of the Bob Dylan song ‘All Along the Watchtower’ (1966 is used as a filmic shortcut to translate Shakespeare’s iconic ‘gravedigger scene’ between Hamlet and the Gravedigger from playtext to screen. ‘All Along the Watchtower’ encapsulates certain ideas about mortality and the worth of life from the ‘gravedigger scene’ and demonstrates these issues still resonate in the contemporary urban world the film is set.

  10. The Fifth Slovene Hamlet: Return to Tradition?

    Directory of Open Access Journals (Sweden)

    Moe Marija Zlatnar

    2017-12-01

    Full Text Available Over the nearly two centuries that Hamlet has been a fixture of the Slovene cultural firmament, the complete text has been translated five times, mostly by highly esteemed figures of Slovene literature and literary translation. This article focuses on the most recent translation, which was done by the prominent Slovene drama translator Srečko Fišer for a performance at the National Theatre in Ljubljana in 2013. It examines the new translation’s relations to its source text as well as to the previous translations. After the late twentieth century, when Hamlet was regarded as a text to be challenged, this new translation indicates the return to the tradition of reverence both for the source text and its author, and for the older translations. This is demonstrated on all levels, from the choice of source text edition, which seems to bear more similarities with the older translations than with the most recent predecessors, to the style, which echoes the solutions used by the earlier translators. Fišer continues the Slovenian tradition to a far greater extent than the two translators twenty years ago, by using the same strategies as the early translators, not fixing what was not broken, and only adding his own interpretation to the existing ones, instead of challenging or ignoring them. At the same time, however, traces of subversion of the source text can be detected, not in the form of rebellion, but rather as a mild disregard. This latest translation is the first one to frequently reshuffle the text. It is also the first to subordinate meaning to style. This all indicates that despite the apparent return to tradition, the source text is no longer treated with the reverence of the past.

  11. High mortality during tuberculosis treatment does not indicate long diagnostic delays in Vietnam: a cohort study

    Directory of Open Access Journals (Sweden)

    Sy Dinh N

    2007-08-01

    Full Text Available Abstract Background Delay in tuberculosis diagnosis and treatment initiation may increase disease severity and mortality. In evaluations of tuberculosis control programmes high fatality rates during tuberculosis treatment, are used as an indicator of long delays in low HIV-prevalence settings. However, data for this presumed association between delay and fatality are lacking. We assessed the association between diagnostic delay and mortality of new smear-positive pulmonary tuberculosis patients in Vietnam. Methods Follow-up of a patient cohort included in a survey of diagnostic delay in 70 randomly selected districts. Data on diagnosis and treatment were extracted from routine registers. Patients who had died during the course of treatment were compared to those with reported cure, completed treatment or failure (survivors. Results Complete data were available for 1881/2093 (89.9% patients, of whom 82 (4.4% had died. Fatality was 4.5% for patients with ≤ 4 weeks delay, 5.0% for 5- ≤ 8 weeks delay (aOR 1.11, 95%CI 0.67–1.84 and 3.2% for > 9 weeks delay (aOR 0.69, 95%CI 0.37–1.30. Fatality tended to decline with increasing delay but this was not significant. Fatality was not associated with median diagnostic delay at district level (Spearman's rho = -0.08, P = 0.5. Conclusion Diagnostic delay is not associated with treatment mortality in Vietnam at individual nor district level, suggesting that high case fatality should not be used as an indicator of long diagnostic delay in national tuberculosis programmes.

  12. Impact of delay to treatment upon survival in 1067 patients with breast-cancer.

    Science.gov (United States)

    Rabinovich, M; Vallejo, C; Perez, J; Rodriguez, R; Cuevas, M; Machiavelli, M; Lacava, J; Leone, B; Romero, A; Mickiewicz, E; Chacon, R; Estevez, R

    1993-02-01

    The medical records of 1067 patients with breast cancer were reviewed to evaluate the influence of delay between first symptom and first treatment upon survival. Three delay intervals were considered: 6 months. At a follow-up of 120 months, survival analyses identified a statistically significant difference (p=0.029) favoring patients with 3 months delay between first symptom and first treatment. Better survival rate for patients with a short delay would obey to a greater number of patients in favorable stages and a higher proportion of women aged 50 or older in this group.

  13. Factors associated with delays in treatment initiation after tuberculosis diagnosis in two districts of India.

    Directory of Open Access Journals (Sweden)

    Durba Paul

    Full Text Available BACKGROUND: Excessive time between diagnosis and initiation of tuberculosis (TB treatment contributes to ongoing TB transmission and should be minimized. In India, Revised National TB Control Programme (RNTCP focuses on indicator start of treatment within 7 days of diagnosis for patients with sputum smear-positive PTB for monitoring DOTS implementation. OBJECTIVES: To determine length of time between diagnosis and initiation of treatment and factors associated with delays of more than 7 days in smear-positive pulmonary TB. METHODS: Using existing programme records such as the TB Register, treatment cards, and the laboratory register, we conducted a retrospective cohort study of all patients with smear-positive pulmonary TB registered from July-September 2010 in two districts in India. A random sample of patients with pulmonary TB who experienced treatment delay of more than 7 days was interviewed using structured questionnaire. RESULTS: 2027 of 3411 patients registered with pulmonary TB were smear-positive. 711(35% patients had >7 days between diagnosis and treatment and 262(13% had delays >15 days. Mean duration between TB diagnosis and treatment initiation was 8 days (range = 0-128 days. Odds of treatment delay >7 days was 1.8 times more likely among those who had been previously treated (95% confidence interval [CI] 1.5-2.3 and 1.6 (95% CI 1.3-1.8 times more likely among those diagnosed in health facilities without microscopy centers. The main factors associated with a delay >7 days were: patient reluctance to start a re-treatment regimen, patients seeking second opinions, delay in transportation of drugs to the DOT centers and delay in initial home visits. To conclude, treatment delay >7 days was associated with a number of factors that included history of previous treatment and absence of TB diagnostic services in the local health facility. Decentralized diagnostic facilities and improved referral procedures may reduce such treatment

  14. Diagnostic and treatment delay among pulmonary tuberculosis patients in Ethiopia: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Yimer Solomon

    2005-12-01

    Full Text Available Abstract Background Delayed diagnosis and treatment of tuberculosis (TB results in severe disease and a higher mortality. It also leads to an increased period of infectivity in the community. The objective of this study was to determine the length of delays, and analyze the factors affecting the delay from onset of symptoms of pulmonary tuberculosis (PTB until the commencement of treatment. Methods In randomly selected TB management units (TBMUs, i.e. government health institutions which have diagnosing and treatment facilities for TB in Amhara Region, we conducted a cross sectional study from September 1-December 31/2003. Delay was analyzed from two perspectives, 1. Period between onset of TB symptoms to first visit to any health provider (health seeking period, and from the first health provider visit to initiation of treatment (health providers' delay, and 2. Period between onset of TB symptoms to first visit to a medical provider (patients' delay, and from this visit to commencement of anti-TB treatment (health systems' delay. Patients were interviewed on the same date of diagnosis using a semi-structured questionnaire. Logistics regression analysis was applied to analyze the risk factors of delays. Results A total of 384 new smear positive PTB patients participated in the study. The median total delay was 80 days. The median health-seeking period and health providers' delays were 15 and 61 days, respectively. Conversely, the median patients' and health systems' delays were 30 and 21 days, respectively. Taking medical providers as a reference point, we found that forty eight percent of the subjects delayed for more than one month. Patients' delays were strongly associated with first visit to non-formal health providers and self treatment (P Conclusion Delay in the diagnosis and treatment of PTB is unacceptably high in Amhara region. Health providers' and health systems' delays represent the major portion of the total delay. Accessing a

  15. Treatment delay among pulmonary tuberculosis patients in pastoralist communities in Bale Zone, Southeast Ethiopia

    Directory of Open Access Journals (Sweden)

    Hussen Awol

    2012-06-01

    Full Text Available Abstract Background Tuberculosis (TB is a major public health problem in Africa with Ethiopia being the most affected. Treatment delay is an important indicator of access to TB diagnosis and treatment. However, little is known about factors associated with treatment delay of pulmonary TB among pastoralists. Health facility based cross sectional study was conducted on 129 pulmonary TB patients in pastoralist community. The study was conducted in three health centers and a hospital. Time between onset of TB symptoms and first visit to a professional health care provider (patient delay, and the time between first visits to the professional health care provider to the date of diagnosis (provider's delay were analyzed using SPSS 16.0 statistical software. Findings A total of 129 new smear positive pulmonary TB patients participated in the study. The median total delay was 97 days. The median patient and health provider delays were 63 and 34 days, respectively. Ninety six percent of the patients were delayed for more than the twenty one days cutoff point. Patient delay was positively associated with first visit to traditional healer/private clinic/drug shop, rural residence, being illiterate, living in more than 10 kilometers from health facility; severity of illness at first presentation to health facility. Provider delay was positively associated with rural residence, being illiterate, patient with good functional status, patients in contact with more than two health providers, and place of first visit being traditional healer/private clinic/drug shop. Conclusions This study showed that majority of smear positive patients delayed either for diagnosis or treatment, thus continue to serve as reservoirs of infection. This indicates that there is a need for intervention to decrease patient and provider delays. Effort to reduce delays in pastoralist communities should focus on improving access to services in rural communities, engaging traditional and

  16. Hamlet's "Globe" and the Self as Performer in England and Japan

    OpenAIRE

    Shibuya, Yu

    2004-01-01

    In his paper, "Hamlet's 'Globe' and the Self as Performer in England and Japan," Yu Shibuya argues that Hamlet sees his life as a performance. Shibuya presents examples from Tsuneari Fukuda's Japanese translation to suggest that Fukuda makes choices that emphasize the theatrical side of Hamlet's character. If Hamlet perceives himself as an actor, then his definition of theater or an actor is ultimately a definition of himself. Shibuya uses the theme of self-definition to examine Kenneth Brana...

  17. Local Stability of AIDS Epidemic Model Through Treatment and Vertical Transmission with Time Delay

    Science.gov (United States)

    Novi W, Cascarilla; Lestari, Dwi

    2016-02-01

    This study aims to explain stability of the spread of AIDS through treatment and vertical transmission model. Human with HIV need a time to positively suffer AIDS. The existence of a time, human with HIV until positively suffer AIDS can be delayed for a time so that the model acquired is the model with time delay. The model form is a nonlinear differential equation with time delay, SIPTA (susceptible-infected-pre AIDS-treatment-AIDS). Based on SIPTA model analysis results the disease free equilibrium point and the endemic equilibrium point. The disease free equilibrium point with and without time delay are local asymptotically stable if the basic reproduction number is less than one. The endemic equilibrium point will be local asymptotically stable if the time delay is less than the critical value of delay, unstable if the time delay is more than the critical value of delay, and bifurcation occurs if the time delay is equal to the critical value of delay.

  18. Delays in the diagnosis and treatment of tuberculosis patients in Vietnam: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Khanh Vu T

    2007-06-01

    Full Text Available Abstract Background Treatment delay is an important indicator of access to tuberculosis diagnosis and treatment. Analyses of patient delay (i.e. time interval between onset of symptoms and first consultation of a health care provider and health care delay (i.e. time interval between first consultation and start of treatment can inform policies to improve access. This study assesses the patient, health care provider and total delay in diagnosis and treatment of new smear-positive pulmonary tuberculosis patients, and the risk factors for long delay, in Vietnam. Methods A cross-sectional survey of new patients treated by the National Tuberculosis Control Programme was conducted in 70 randomly selected districts in Vietnam. All consecutively registered patients in one quarter of 2002 were interviewed using a pre-coded structured questionnaire. Results Median (range delay was 4 weeks (1–48 for total, 3 (1–48 weeks for patient and 1 (0–25 week for health care delay. Patients with long total delay (≥ 12 weeks, 15% accounted for 49% of the cumulative number of delay-weeks. Independent risk factors (p 5 km distance from a health facility or in the northern area. For long health care delay (≥ 6 weeks this was urban setting, residence in the central area and initial visit to a communal health post, TB hospital or the private sector. Conclusion Analyses of patient and treatment delays can indicate target groups and areas for health education and strengthening of the referral system, in particular between the private sector and the NTP.

  19. A novel design for randomized immuno-oncology clinical trials with potentially delayed treatment effects

    Directory of Open Access Journals (Sweden)

    Pei He

    2015-10-01

    Full Text Available The semi-parametric proportional hazards model is widely adopted in randomized clinical trials with time-to-event outcomes, and the log-rank test is frequently used to detect a potential treatment effect. Immuno-oncology therapies pose unique challenges to the design of a trial as the treatment effect may be delayed, which violates the proportional hazards assumption, and the log-rank test has been shown to markedly lose power under the non-proportional hazards setting. A novel design and analysis approach for immuno-oncology trials is proposed through a piecewise treatment effect function, which is capable of detecting a potentially delayed treatment effect. The number of events required for the trial will be determined to ensure sufficient power for both the overall log-rank test without a delayed effect and the test beyond the delayed period when such a delay exists. The existence of a treatment delay is determined by a likelihood ratio test with resampling. Numerical results show that the proposed design adequately controls the Type I error rate, has a minimal loss in power under the proportional hazards setting and is markedly more powerful than the log-rank test with a delayed treatment effect.

  20. Delay discounting, treatment motivation and treatment retention among substance-dependent individuals attending an in inpatient detoxification program

    NARCIS (Netherlands)

    Stevens, Laura; Verdejo-García, Antonio; Roeyers, Herbert; Goudriaan, Anna E.; Vanderplasschen, Wouter

    2015-01-01

    Recent studies consistently indicate high rates of delay discounting in drug users, which refers to a strong tendency to devaluate delayed rewards. Many addiction treatment programs however, place high demands on the ability to postpone immediate gratification. Therefore, these programs may be

  1. Successful treatment of delayed refractory chylothorax after irradiation with octreotide

    International Nuclear Information System (INIS)

    Kuroda, Hiroaki; Kawamura, Masafumi; Izumi, Yotaro; Horinouchi, Hirohisa; Matsumura, Shin-ichiro; Horiguchi, Hayanori

    2009-01-01

    A 15-year-old male, with a past history of splenic hemangioma treated with radiotherapy in his infancy, was diagnosed with idiopathic left chylothorax. Ligation of the thoracic duct at the level of Th7 was not effective, and he was admitted to our hospital. Ligation at the level of the diaphragm resulted in bilateral pleural effusion and ascites. Based on his past history, lymphangiography showing multiple points of leakage from the diaphragm and intraoperative findings of lymph proliferation along the mediastinal pleura, delayed chylothorax due to irradiation was diagnosed. Octreotide was administered for 30 days. Pleural effusions and ascites gradually decreased, and meals were started without reappearance. (author)

  2. Como os pintores “traduziram” Hamlet

    Directory of Open Access Journals (Sweden)

    Thais Flores Nogueira Diniz

    2015-04-01

    Full Text Available http://dx.doi.org/10.5007/2175-7968.2015v35n1p86 Textos literários sempre ofereceram terreno fértil para “traduções” em outros sistemas semióticos. As peças de Shakespeare não são uma exceção já que artistas vêm traduzindo semioticamente suas obras, principalmente para as artes visuais, e predominantemente para a pintura. Utilizando a terminologia de Benton & Butcher para classificar pinturas das peças de Shakespeare, este ensaio, analisa três imagens baseadas em Hamlet. Em seguida descreve o quadro de Daniel Maclise que se refere à “peça dentro da peça”, comparando-o com o de Edward Austin Abbey, com o mesmo tema, para demonstrar que cada obra “traduz”, à sua maneira, a ideia da culpa da personagem Gertrude.

  3. Topographical memory analyzed in mice using the Hamlet test, a novel complex maze.

    Science.gov (United States)

    Crouzier, Lucie; Gilabert, Damien; Rossel, Mireille; Trousse, Françoise; Maurice, Tangui

    2018-03-01

    The Hamlet test is an innovative device providing a complex environment for testing topographic memory in mice. Animals were trained in groups for weeks in a small village with a central agora, streets expanding from it towards five functionalized houses, where they can drink, eat, hide, run, interact with a stranger mouse. Memory was tested by depriving mice from water or food and analyzing their ability to locate the Drink/Eat house. Exploration and memory were analyzed in different strains, gender, and after different training periods and delays. After 2 weeks training, differences in exploration patterns were observed between strains, but not gender. Neuroanatomical structures activated by training, identified using FosB/ΔFosB immunolabelling, showed an involvement of the hippocampus-subiculum-parahippocampal gyrus axis and dopaminergic structures. Training increased hippocampal neurogenesis (cell proliferation and neuronal maturation) and modified the amnesic efficacy of muscarinic or nicotinic cholinergic antagonists. Moreover, topographical disorientation in Alzheimer's disease was addressed using intracerebroventricular injection of amyloid β 25-35 peptide in trained mice. When retested after 7 days, Aβ 25-35 -treated mice showed memory impairment. The Hamlet test specifically allows analysis of topographical memory in mice, based on complex environment. It offers an innovative tool for various ethological or pharmacological research needs. For instance, it allowed to examine topographical disorientation, a warning sign in Alzheimer's disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Predicting delay to treatment of urinary incontinence among urban community-dwelling women in China

    Directory of Open Access Journals (Sweden)

    Chen Wu

    2015-03-01

    Conclusion: Women who were older, had lower subjective UI severity, and who reported only stress or urgency UI tended to delay treatment longer; such patients should be targeted for health education and intervention regarding UI in urban communities.

  5. Why Irish women delay seeking treatment for urinary incontinence : a focus group study

    OpenAIRE

    Ni Aileasa, Mairead

    2011-01-01

    non-peer-reviewed Background: Urinary Incontinence is defined as "any involuntary leakage of urine" (Abrams et al, 2002). Living with incontinence can effect one's life greatly. Many women delay seeking treatment and often do not seek any help (Dolan et al, 1999), despite physiotherapy being an effective treatment (Neumann et al, 2005). Therefore, there is a need to discover why women delay seeking help, such as physiotherapy and continue to live with incontinence. Objectives: To establ...

  6. The inability to mourn and the inability to love in Shakespeare's Hamlet.

    Science.gov (United States)

    Bergmann, Martin S

    2009-04-01

    The author discusses the special role played by Shakespeare's masterpiece Hamlet in the history of psychoanalysis. Freud and many of his followers have treated Hamlet as if he were a real person inhibited by the Oedipus complex. In this presentation, Hamlet is understood as the embodiment of a brilliant artistic endeavor aimed at both revealing and concealing the power of this complex. The author proposes that, if Hamlet is autobiographical, it expresses Shakespeare's inability to mourn and love until a childhood homosexual memory has emerged. Hidden in Hamlet is a cure through the recall of a childhood memory.

  7. Delay in the diagnosis and treatment of pulmonary tuberculosis in Uzbekistan: a cross-sectional study.

    Science.gov (United States)

    Belkina, Tatiana V; Khojiev, Doniyor S; Tillyashaykhov, Mirzagaleb N; Tigay, Zinaida N; Kudenov, Marat U; Tebbens, Jurjen Duintjer; Vlcek, Jiri

    2014-11-25

    Early diagnosis and prompt effective therapy are crucial for the prevention of tuberculosis (TB) transmission, particularly in regions with high levels of multi-drug resistant TB. This study aimed to evaluate the extent of delay in diagnosis and treatment of TB in Uzbekistan and identify associated risk factors. A cross-sectional study was performed on hospital patients with newly diagnosed TB. The time between the onset of respiratory symptoms and initiation of anti-TB treatment was assessed and delays were divided into patient, health system and total delays. Univariable and multivariable logistic regression analysis was used to evaluate determinants of diagnostic and treatment delay. Among 538 patients enrolled, the median delay from onset of symptoms until treatment with anti-TB drugs was 50 days. Analysis of the factors affecting health-seeking behaviour and timely treatment showed the presence of the patient factor. Self-medication was the first health-seeking action for 231 (43%) patients and proved to be a significant predictor of delay (p = 0.005), as well as coughing (p = 0.009), loss of weight (p = 0.001), and visiting private and primary healthcare facilities (p = 0.03 and p = 0.02, respectively). TB diagnostic and treatment delay was mainly contributed to by patient delay and should be reduced through increasing public awareness of TB symptoms and improving public health-seeking behaviour for timely initiation of anti-TB treatment. Efforts should be made to minimise irrational use of antibiotics and support interventions to restrict over-the-counter availability of antibiotics.

  8. Open lung ventilation preserves the response to delayed surfactant treatment in surfactant-deficient newborn piglets

    NARCIS (Netherlands)

    van Veenendaal, Mariëtte B.; van Kaam, Anton H.; Haitsma, Jack J.; Lutter, René; Lachmann, Burkhard

    2006-01-01

    OBJECTIVE: Delayed surfactant treatment (>2 hrs after birth) is less effective than early treatment in conventionally ventilated preterm infants with respiratory distress syndrome. The objective of this study was to evaluate if this time-dependent efficacy of surfactant treatment is also present

  9. Factors affecting professional delay in diagnosis and treatment of oral cancer in Iran.

    Science.gov (United States)

    Esmaelbeigi, Farhad; Hadji, Maryam; Harirchi, Iraj; Omranipour, Ramesh; vand Rajabpour, Mojtaba; Zendehdel, Kazem

    2014-04-01

    Oral cancer is the most common malignant tumor among head and neck cancers. Delay in diagnosis affects the treatment and prognosis of oral cancer. We measured the professional delay in the diagnosis and its attributes in the Cancer Institute of Iran, the largest referral center for oral cancer patients in the country.  We interviewed oral cancer patients to measure the delay and used case-control approach to study association of various prognostic factors with professional delay and tumor stage. Out of 206 patients, 71.4% were diagnosed at the advanced stage. The median of the patient, professional and total delays were 45, 86 and 140 day, receptively. In the univariate model, prescription of medicines like analgesics (OR = 5.3, 95% CI 2.2-12.9) and history of dental procedure (OR=6.8, 95% CI 1.7-26.9) were associated with higher risk of delay compared to patient who were biopsied from the beginning. History of loose teeth increased risk of delay 4 times (OR = 4.0, 95% CI 1.6-9.8). Patients with primary education had 70% lower risk of delay compared to the illiterate patients (OR = 0.3, 95% CI 0.1-0.7) and the risk was lower among patients who had diploma (OR = 0.04, 95% CI 0-0.7) and college education (OR = 0.1, 95% CI 0-0.4). The delayed patients were diagnosed in more advanced stage compared to the patients without delay (OR = 2.1, 95% CI 1.0-4.4). Development of a national guideline for follow-up of oral lesions, training and awareness of health care professionals about oral cancer diagnosis may decrease the delay and improve the oral cancer outcome in Iran.

  10. Choice between delayed food and immediate opioids in rats: treatment effects and individual differences.

    Science.gov (United States)

    Panlilio, Leigh V; Secci, Maria E; Schindler, Charles W; Bradberry, Charles W

    2017-11-01

    Addiction involves maladaptive choice behavior in which immediate drug effects are valued more than delayed nondrug rewards. To model this behavior and extend our earlier work with the prescription opioid oxycodone, we allowed rats to choose between immediate intravenous delivery of the short-acting opioid remifentanil and delayed delivery of highly palatable food pellets. Treatment drugs were tested on a baseline where remifentanil was preferred over food. Treatment with a high dose of the opioid antagonist naltrexone decreased but did not reverse the preference for remifentanil. Treatment with the serotonin 5-HT 2C agonist lorcaserin decreased remifentanil and food self-administration nonselectively. Across conditions in which the alternative to delayed food was either a moderate dose of oxycodone, a moderate or high dose of remifentanil, a smaller more immediate delivery of food, or timeout with no primary reinforcement, choice was determined by both the length of the delay and the nature of the alternative option. Delayed food was discounted most steeply when the alternative was a high dose of remifentanil, which was preferred over food when food was delayed by 30 s or more. Within-subject comparisons showed no evidence for trait-like impulsivity or sensitivity to delay across these conditions. Choice was determined more by the current contingencies of reinforcement than by innate individual differences. This finding suggests that people might develop steep delay-discounting functions because of the contingencies in their environment, and it supports the use of contingency management to enhance the relative value of delayed nondrug reinforcers.

  11. Hot water treatments delay cold-induced banana peel blackening

    NARCIS (Netherlands)

    Promyou, S.; Ketsa, S.; Doorn, van W.G.

    2008-01-01

    Banana fruit of cv. Gros Michel (Musa acuminata, AAA Group, locally called cv. Hom Thong) and cv. Namwa (Musa x paradisiaca, ABB Group) were immersed for 5, 10 and 15 min in water at 42 degrees C, or in water at 25 degrees C (control), and were then stored at 4 degrees C. Hot water treatment for 15

  12. Delayed Microbial Cure of Lymphogranuloma Venereum Proctitis with Doxycycline Treatment

    NARCIS (Netherlands)

    de Vries, H.J.C.; Smelov, V.; Middelburg, J.G.; Pleijster, J.; Speksnijder, A.G.; Morré, S.A.

    2009-01-01

    Microbial cure of chlamydia proctitis (lymphogranuloma venereum [LGV] and non-LGV) with doxycycline treatment was evaluated by chlamydia DNA and RNA persistence in anal swab specimens. In LGV proctitis, RNA persisted for up to 16 days. In non-LGV chlamydia proctitis, DNA was undetectable after 7

  13. Exploring Shakespeare through the Cinematic Image: Seeing "Hamlet."

    Science.gov (United States)

    Felter, Douglas P.

    1993-01-01

    Describes an innovative approach to teaching William Shakespeare's "Hamlet" utilizing various film versions of the play. Outlines a method of showing several versions of the same scene from different film adaptations. Describes student reaction to the variations among the different films. (HB)

  14. A Country Discovered: Upper Juniors Explore Meanings in "Hamlet."

    Science.gov (United States)

    Carter, Dennis

    1989-01-01

    Describes a project in England in which a class of 9- to 11-year olds enthusiastically and successfully explored the play "Hamlet" by writing about, discussing, performing, and visually interpreting the actual text. The teacher suggests that, with a little creativity, Shakespeare is very accessible to children. (SM)

  15. Hamlet on the Macintosh: An Experimental Seminar That Worked.

    Science.gov (United States)

    Strange, William C.

    1987-01-01

    Describes experimental college Shakespeare seminar that used Macintosh computers and software called ELIZA and ADVENTURE to develop character dialogs and adventure games based on Hamlet's characters and plots. Programming languages are examined, particularly their relationship to metaphor, and the use of computers in humanities is discussed. (LRW)

  16. IDEA: An Interdisciplinary Unit Comparing "Don Quixote" to "Hamlet."

    Science.gov (United States)

    Harris, Mary J. G.

    2001-01-01

    Describes an idea for teaching language through content-based instruction in which a high school Spanish class studying a shortened abridged version of Cervantes'"Don Quixote" and an English class reading Shakespeare's "Hamlet," did a simple comparative analysis of the two texts. (Author/VWL)

  17. "Hamlet": Something Is Tragic in the State of Denmark.

    Science.gov (United States)

    Fisher, Jessica

    This unit seeks to teach Shakespeare's "Hamlet" in a way that the students will have a full understanding of the play. The unit's introduction is designed to get the students acquainted with Shakespeare's language, to motivate them to read the play, and to make them feel confident about approaching the play. Lessons in the unit are fun,…

  18. "Hamlet" Meets "Chushingura": Traditions of the Revenge Tragedy. [Lesson Plan].

    Science.gov (United States)

    2002

    This lesson seeks to sensitize students to the similarities and difference between cultures by comparing the Shakespearean and the Bunraki/Kabuki dramas of Japan. In the lesson, the focus of this comparison is the complex nature of revenge explored in "The Tragedy of Hamlet, Prince of Denmark" and "Chusingura," or "The…

  19. Curricular Deliberation about "Hamlet": An Exercise in the Practical.

    Science.gov (United States)

    Siegel, Judith Susan

    This study attempts to clarify and exploit Joseph Schwab's recent and current work on "practical" and "eclectic" curriculums in a simulated deliberation about a concrete curricular question, How might "Hamlet" be taught to one group of high school juniors? By exemplifying curricular deliberation, it aims to clarify…

  20. Can misfolded proteins be beneficial? The HAMLET case.

    Science.gov (United States)

    Pettersson-Kastberg, Jenny; Aits, Sonja; Gustafsson, Lotta; Mossberg, Anki; Storm, Petter; Trulsson, Maria; Persson, Filip; Mok, K Hun; Svanborg, Catharina

    2009-01-01

    By changing the three-dimensional structure, a protein can attain new functions, distinct from those of the native protein. Amyloid-forming proteins are one example, in which conformational change may lead to fibril formation and, in many cases, neurodegenerative disease. We have proposed that partial unfolding provides a mechanism to generate new and useful functional variants from a given polypeptide chain. Here we present HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) as an example where partial unfolding and the incorporation of cofactor create a complex with new, beneficial properties. Native alpha-lactalbumin functions as a substrate specifier in lactose synthesis, but when partially unfolded the protein binds oleic acid and forms the tumoricidal HAMLET complex. When the properties of HAMLET were first described they were surprising, as protein folding intermediates and especially amyloid-forming protein intermediates had been regarded as toxic conformations, but since then structural studies have supported functional diversity arising from a change in fold. The properties of HAMLET suggest a mechanism of structure-function variation, which might help the limited number of human protein genes to generate sufficient structural diversity to meet the diverse functional demands of complex organisms.

  1. Hamlet's Suicide Soliloquy: A Case Study in Suicide Ideology.

    Science.gov (United States)

    Jenkins, Andrew P.

    This paper presents a secondary-level teaching technique that can be used in an integrated English and health education curriculum. The exercise provides students and teachers with a case study of a suicidal person for the purpose of teaching the warning signs of suicide, appropriate questioning, and referral skills. The case study uses Hamlet's…

  2. HAMLET: HPCN Technology for Real-Time, Embedded Applications

    NARCIS (Netherlands)

    Mager, J.W.L.J.; Dam, A. ten

    1995-01-01

    Building an application by using HPCN technology makes the solution scalable and therefore more flexible. The uptake of HPCN technology for real-time, embedded applications, however, is severely hampered by the lack of real application development support. Within the Esprit project HAMLET,

  3. "The Hound of the Baskervilles" and "Hamlet": Guide for Educators.

    Science.gov (United States)

    KIDSNET, Washington, DC.

    This study guide discusses the world premiere of two made-for-television movies of classics of English literature: "The Hound of the Baskervilles" and "Hamlet." The guide first provides a synopsis of the story of "The Hound of the Baskervilles" and gives a brief biography of the author, Sir Arthur Conan Doyle. It…

  4. The Hamlet Application Design Language: introductory definition report

    NARCIS (Netherlands)

    M.R. van Steen

    1993-01-01

    textabstractThis report provides an introduction to the definition of the Hamlet Application Design Language (ADL). ADL is a graphical-based language and notation supporting the design of parallel real-time applications. Designs expressed in ADL are based on a model of processes that communicate by

  5. Text, Style, and Author in Hamlet Q1

    Directory of Open Access Journals (Sweden)

    Christy Desmet

    2016-03-01

    Full Text Available The first quarto of Hamlet has traditionally been an embarrassment to attribution studies. Textual and bibliographical studies from the 1980s and beyond have permitted suspect texts to be recovered and performed, but critical appreciation tends to focus on such matters as characterization and performance possibilities rather than the text’s rhetorical integrity and aesthetic qualities. More recently, we have seen greater critical attention to Shakespeare’s suspect texts, which has increased our appreciation for and expanded our notion of Q1 Hamlet as a ‘text’. Opinion remains divided, however, on the question of who ‘wrote’ this play. This essay addresses the authorship debate somewhat indirectly by providing a different view of Hamlet Q1 based on a stylistic analysis that is grounded in Renaissance rhetoric. It characterizes the play’s style as the rhetoric of speed, with brachylogia as its representative rhetorical figure. Through review of theories about the composition of Hamlet Q1 and a rhetorical analysis of its style, the essay seeks to examine how Hamlet’s first quarto might have a recognizable style and how that style might be related to current concepts of authorship.

  6. From HAMLET to XAMLET: The molecular complex selectively ...

    African Journals Online (AJOL)

    HAMLET (human α-lactalbumin made lethal to tumor cells) is a complex consisting of decalcinated α-lactalbumin and oleic acid. It has been shown to induce massive cell death in various cancers without serious damage to normal tissues in both in vitro and in vivo experiments. The complexity of the mechanism in the ...

  7. Targeting of nucleotide-binding proteins by HAMLET--a conserved tumor cell death mechanism.

    Science.gov (United States)

    Ho, J C S; Nadeem, A; Rydström, A; Puthia, M; Svanborg, C

    2016-02-18

    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills tumor cells broadly suggesting that conserved survival pathways are perturbed. We now identify nucleotide-binding proteins as HAMLET binding partners, accounting for about 35% of all HAMLET targets in a protein microarray comprising 8000 human proteins. Target kinases were present in all branches of the Kinome tree, including 26 tyrosine kinases, 10 tyrosine kinase-like kinases, 13 homologs of yeast sterile kinases, 4 casein kinase 1 kinases, 15 containing PKA, PKG, PKC family kinases, 15 calcium/calmodulin-dependent protein kinase kinases and 13 kinases from CDK, MAPK, GSK3, CLK families. HAMLET acted as a broad kinase inhibitor in vitro, as defined in a screen of 347 wild-type, 93 mutant, 19 atypical and 17 lipid kinases. Inhibition of phosphorylation was also detected in extracts from HAMLET-treated lung carcinoma cells. In addition, HAMLET recognized 24 Ras family proteins and bound to Ras, RasL11B and Rap1B on the cytoplasmic face of the plasma membrane. Direct cellular interactions between HAMLET and activated Ras family members including Braf were confirmed by co-immunoprecipitation. As a consequence, oncogenic Ras and Braf activity was inhibited and HAMLET and Braf inhibitors synergistically increased tumor cell death in response to HAMLET. Unlike most small molecule kinase inhibitors, HAMLET showed selectivity for tumor cells in vitro and in vivo. The results identify nucleotide-binding proteins as HAMLET targets and suggest that dysregulation of the ATPase/kinase/GTPase machinery contributes to cell death, following the initial, selective recognition of HAMLET by tumor cells. The findings thus provide a molecular basis for the conserved tumoricidal effect of HAMLET, through dysregulation of kinases and oncogenic GTPases, to which tumor cells are addicted.

  8. Diclofenac delays micropore closure following microneedle treatment in human subjects.

    Science.gov (United States)

    Brogden, Nicole K; Milewski, Mikolaj; Ghosh, Priyanka; Hardi, Lucia; Crofford, Leslie J; Stinchcomb, Audra L

    2012-10-28

    Drugs absorbed poorly through the skin are commonly delivered via injection with a hypodermic needle, which is painful and increases the risk of transmitting infectious diseases. Microneedles (MNs) selectively and painlessly permeabilize the outermost skin layer, allowing otherwise skin-impermeable drugs to cross the skin through micron-sized pores and reach therapeutic concentrations. However, rapid healing of the micropores prevents further drug delivery, blunting the clinical utility of this unique transdermal technique. We present the first human study demonstrating that micropore lifetime can be extended following MN treatment. Subjects received one-time MN treatment and daily topical application of diclofenac sodium. Micropore closure was measured with impedance spectroscopy, and area under the admittance-time curve (AUC) was calculated. AUC was significantly higher at MN+diclofenac sodium sites vs. placebo, suggesting slower rates of micropore healing. Colorimetry measurements confirmed the absence of local erythema and irritation. This mechanistic human proof-of-concept study demonstrates that micropore lifetime can be prolonged with simple topical administration of a non-specific cyclooxygenase inhibitor, suggesting the involvement of subclinical inflammation in micropore healing. These results will allow for longer patch wear time with MN-enhanced delivery, thus increasing patient compliance and expanding the transdermal field to a wider variety of clinical conditions. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Diclofenac delays micropore closure following microneedle treatment in human subjects

    Science.gov (United States)

    Brogden, Nicole K.; Milewski, Mikolaj; Ghosh, Priyanka; Hardi, Lucia; Crofford, Leslie J.; Stinchcomb, Audra L.

    2013-01-01

    Drugs absorbed poorly through the skin are commonly delivered via injection with a hypodermic needle, which is painful and increases the risk of transmitting infectious diseases. Microneedles (MNs) selectively and painlessly permeabilize the outermost skin layer, allowing otherwise skin-impermeable drugs to cross the skin through micron-sized pores and reach therapeutic concentrations. However, rapid healing of the micropores prevents further drug delivery, blunting the clinical utility of this unique transdermal technique. We present the first human study demonstrating that micropore lifetime can be extended following MN treatment. Subjects received one-time MN treatment and daily topical application of diclofenac sodium. Micropore closure was measured with impedance spectroscopy, and area under the admittance–time curve (AUC) was calculated. AUC was significantly higher at MN + diclofenac sodium sites vs. placebo, suggesting slower rates of micropore healing. Colorimetry measurements confirmed the absence of local erythema and irritation. This mechanistic human proof-of-concept study demonstrates that micropore lifetime can be prolonged with simple topical administration of a non-specific cyclooxygenase inhibitor, suggesting the involvement of subclinical inflammation in micropore healing. These results will allow for longer patch wear time with MN-enhanced delivery, thus increasing patient compliance and expanding the transdermal field to a wider variety of clinical conditions. PMID:22929967

  10. Cumulative or delayed nephrotoxicity after cisplatin (DDP) treatment.

    Science.gov (United States)

    Pinnarò, P; Ruggeri, E M; Carlini, P; Giovannelli, M; Cognetti, F

    1986-04-30

    The present retrospective study reports data regarding renal toxicity in 115 patients (63 males, 52 females; median age, 56 years) who received cumulative doses of cisplatin (DDP) greater than or equal to 200 mg/m2. DDP was administered alone or in combination at a dose of 50-70 mg/m2 in 91 patients, and at a dose of 100 mg/m2 in 22 patients. Two patients after progression of ovarian carcinoma treated with conventional doses of DDP received 4 and 2 courses, respectively, of high-dose DDP (40 mg/m2 for 5 days) in hypertonic saline. The median number of DDP courses was 6 (range 2-14), and the median cumulative dose was 350 mg/m2 (range, 200-1200). Serum creatinine and urea nitrogen were determined before initiating the treatment and again 13-16 days after each administration. The incidence of azotemia (creatinina levels that exceeded 1.5 mg/dl) was similar before (7.8%) and after (6.1%) DDP doses of 200 mg/m2. Azotemia appears to be related to the association of DDP with other potentially nephrotoxic antineoplastic drugs (methotrexate) more than to the dose per course of DDP. Of 59 patients followed for 2 months or more after discontinuing the DDP treatment, 3 (5.1%) presented creatinine values higher than 1.5 mg/dl. The data deny that the incidence of nephrotoxicity is higher in patients receiving higher cumulative doses of DDP and confirm that increases in serum creatinine levels may occur some time after discontinuation of the drug.

  11. Time Delay and Associated Factors in Diagnosis and Treatment of Pulmonary Tuberculosis in Markazi Province

    Directory of Open Access Journals (Sweden)

    Aliasghar Farazi

    2012-07-01

    Full Text Available Introduction: Delay in the diagnosis of tuberculosis increases the risk of death and enhances the transmission of disease in the community. This study aims to determine the patient and health service delay and factors affecting it in tuberculosis diagnosis. Materials & Methods: A cross-sectional survey that included all the public health centers was conducted in Markazi province from March 2009 till June 2011. Patients were interviewed after diagnosis by using a structured questionnaire. Results: One hundred and sixty-six patients aged between 9 and 87 (median; 66 years were included in the study. They comprised 87 (52.4% females and 79 (47.6% males. The median and mean of patient delay was 35 and 62 days, respectively; the median and mean of health system diagnosis delay was 34 and 53 days, respectively; the median and mean of health system treatment delay was 5 and 6 days, respectively; The median and mean of total delays were 86 and 121 days, respectively for all patients. The main determinants of delay were non education, poor economic, private sector, female gender and age≥55. Conclusion: The results of this review suggest that there is a need for revising case-finding strategies and reduction of infectious cases for better control of tuberculosis.

  12. PEMF as treatment for delayed healing of foot and ankle arthrodesis.

    Science.gov (United States)

    Saltzman, Charles; Lightfoot, Andrew; Amendola, Annunziato

    2004-11-01

    Arthrodesis is the most common surgical treatment for foot and ankle arthritis. In adults, these procedures are associated with a 5% to 10% rate of nonunion. Pulsed electromagnetic field (PEMF) stimulation was approved by the Federal Drug Administration (FDA) for treatment of delayed unions after long-bone fractures and joint arthrodesis. The purpose of this study was to examine the results of PEMF treatment for delayed healing after foot and ankle arthrodesis. Three hundred and thirty-four foot and ankle arthrodeses were done. Nineteen resulted in delayed unions that were treated with a protocol of immobilization, limited weightbearing, and PEMF stimulation for a median of 7 (range 5 to 27) months. All patients were followed clinically and radiographically. The use of PEMF, immobilization, and limited weightbearing to treat delayed union after foot and ankle arthrodesis was successful in 5 of 19 (26%) patients. Of the other 14 patients with nonunions, nine had revision surgery with autogenous grafting, continued immobilization, and PEMF stimulation. Seven of these eventually healed at a median of 5.5 (range 2 to 26) months and two did not heal. One patient had a below-knee amputation, and four refused further treatment. The protocol of PEMF, immobilization, and limited weightbearing had a relatively low success rate in this group of patients. We no longer use this protocol alone to treat delayed union after foot and ankle arthrodesis.

  13. Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system

    Directory of Open Access Journals (Sweden)

    Han Ruolan

    2008-04-01

    Full Text Available Abstract Background Cancer treatment with a variety of chemotherapeutic agents often is associated with delayed adverse neurological consequences. Despite their clinical importance, almost nothing is known about the basis for such effects. It is not even known whether the occurrence of delayed adverse effects requires exposure to multiple chemotherapeutic agents, the presence of both chemotherapeutic agents and the body's own response to cancer, prolonged damage to the blood-brain barrier, inflammation or other such changes. Nor are there any animal models that could enable the study of this important problem. Results We found that clinically relevant concentrations of 5-fluorouracil (5-FU; a widely used chemotherapeutic agent were toxic for both central nervous system (CNS progenitor cells and non-dividing oligodendrocytes in vitro and in vivo. Short-term systemic administration of 5-FU caused both acute CNS damage and a syndrome of progressively worsening delayed damage to myelinated tracts of the CNS associated with altered transcriptional regulation in oligodendrocytes and extensive myelin pathology. Functional analysis also provided the first demonstration of delayed effects of chemotherapy on the latency of impulse conduction in the auditory system, offering the possibility of non-invasive analysis of myelin damage associated with cancer treatment. Conclusions Our studies demonstrate that systemic treatment with a single chemotherapeutic agent, 5-FU, is sufficient to cause a syndrome of delayed CNS damage and provide the first animal model of delayed damage to white-matter tracts of individuals treated with systemic chemotherapy. Unlike that caused by local irradiation, the degeneration caused by 5-FU treatment did not correlate with either chronic inflammation or extensive vascular damage and appears to represent a new class of delayed degenerative damage in the CNS.

  14. Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer.

    Science.gov (United States)

    Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

    2016-07-01

    Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer.

  15. [Impact of care pathway on the delay for initiation of antituberculosis treatment in Conakry, Guinea].

    Science.gov (United States)

    Camara, A; Bah-Sow, O Y; Baldé, N M; Camara, L M; Barry, I S; Bah, B; Diallo, M; Chaperon, J; Riou, F

    2009-06-01

    Complex care pathways can result in detrimental treatment delay particularly in tuberculosis patients. The purpose of this retrospective study was to assess the care pathways followed by tuberculosis patients prior to diagnosis and to assess impact on the delay for initiation of treatment in Conakry, Guinea. A total of 112 patients were interviewed at the time of first admission for pulmonary tuberculosis with positive bacilloscopy. Based on interview data, pathways were classified as conventional (use of health care facilities only) and mixed (use of health care facilities, self-medication, and traditional medicine). The correlation between patient characteristics and type of pathway was assessed by univariate and multivariate analysis and the two groups, i.e., conventional vs. mixed, were compared with regard to delay for initiation of treatment. The care pathway was classified as mixed in two out of three patients. Multivariate analysis showed that this type of pathway was only correlated with schooling (p=0.02). The mean delay for treatment was similar, i.e., 13.4 and 12.8 weeks for conventional and mixed pathways respectively (p<0.68). The percentage of pathways including three consultations at health care facilities was significantly higher in the conventional than mixed group (72% vs. 30%, p<0.001). The main reasons given for delayed use of health care facilities were poor knowledge of tuberculosis symptoms (26%) and high cost of care (12%). The findings of this study indicate that tuberculosis patients follow a variety of care pathways that can lead to delayed treatment. An information campaign is needed to increase awareness among the population and care providers.

  16. Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial.

    Science.gov (United States)

    Hofmeijer, Jeannette; Kappelle, L Jaap; Algra, Ale; Amelink, G Johan; van Gijn, Jan; van der Worp, H Bart

    2009-04-01

    Patients with space-occupying hemispheric infarctions have a poor prognosis, with case fatality rates of up to 80%. In a pooled analysis of randomised trials, surgical decompression within 48 h of stroke onset reduced case fatality and improved functional outcome; however, the effect of surgery after longer intervals is unknown. The aim of HAMLET was to assess the effect of decompressive surgery within 4 days of the onset of symptoms in patients with space-occupying hemispheric infarction. Patients with space-occupying hemispheric infarction were randomly assigned within 4 days of stroke onset to surgical decompression or best medical treatment. The primary outcome measure was the modified Rankin scale (mRS) score at 1 year, which was dichotomised between good (0-3) and poor (4-6) outcome. Other outcome measures were the dichotomy of mRS score between 4 and 5, case fatality, quality of life, and symptoms of depression. Analysis was by intention to treat. This trial is registered, ISRCTN94237756. Between November, 2002, and October, 2007, 64 patients were included; 32 were randomly assigned to surgical decompression and 32 to best medical treatment. Surgical decompression had no effect on the primary outcome measure (absolute risk reduction [ARR] 0%, 95% CI -21 to 21) but did reduce case fatality (ARR 38%, 15 to 60). In a meta-analysis of patients in DECIMAL (DEcompressive Craniectomy In MALignant middle cerebral artery infarction), DESTINY (DEcompressive Surgery for the Treatment of malignant INfarction of the middle cerebral arterY), and HAMLET who were randomised within 48 h of stroke onset, surgical decompression reduced poor outcome (ARR 16%, -0.1 to 33) and case fatality (ARR 50%, 34 to 66). Surgical decompression reduces case fatality and poor outcome in patients with space-occupying infarctions who are treated within 48 h of stroke onset. There is no evidence that this operation improves functional outcome when it is delayed for up to 96 h after stroke onset

  17. Hamlet à l’épreuve des librettistes Hamlet: Standing the Test of Librettists

    Directory of Open Access Journals (Sweden)

    Francis Guinle

    2011-12-01

    Full Text Available On ne peut pas demander à un livret l’opéra de reproduire exactement le texte de l’ouvrage dont il s’inspire. Les prétendues « faiblesses » des livrets se justifient par le fait qu’ils n’existent que pour être mis en musique. Dans quelques rares cas où le livret suit à la lettre le texte d’origine (Francis Poulenc, Dialogues des Carmélites, la musique suit le contour des mots, mais, d’ordinaire, la musique pallie le manque de poéticité des livrets. Cela paraît particulièrement le cas dans les opéras du XIXe siècle. En conséquence, il semble impossible de parler des livrets sans prendre la musique en considération. Dans le cas d’Hamlet, comment les librettistes ont-ils abordé le texte ? Où peut-on retrouver la tragédie de Shakespeare dans l’opéra d’Ambroise Thomas ? Quelle lumière l’opéra apporte-t-il sur la réception de Shakespeare au XIXe siècle ? Voilà quelques questions auxquelles cet article tentera de répondre.An opera libretto cannot be expected to reproduce the exact text of the literary or dramatic work on which it is based. The so-called “weaknesses” of the libretti may be accounted for by the fact that they are meant to be set to music. In some rare cases, where the libretto uses part of the original text (like Francis Poulenc’s Dialogues des Carmélites, the music closely follows the shape of the words, but usually it fulfills a poetical aspect lacking in the text. This seems particularly true when we consider 19th century opera. This implies that it is impossible to deal with the libretti without taking the music into account. In the case of Hamlet, what is the librettists’ approach? Where is Shakespeare’s tragedy to be found in Ambroise Thomas’s opera? What light does the opera shed on the reception of Shakespeare in the 19th century? These are the questions this article tries to answer.

  18. "Eternal Image" of Hamlet as Prototype of Intelligent Consciousness in Novel by S. Zheromsky "Homeless"

    Directory of Open Access Journals (Sweden)

    Darya B. Smirnova

    2016-12-01

    Full Text Available It is analyzed the «eternal image» of Hamlet as a prototype of the intelligentsia layer of society in the novel by S. Zheromsky «Homeless people». It is concluded that S. Zheromsky created in his novel-variation characters of Hamlet, to which the author gave national character. This relation with Hamlet manifests the motives of loneliness, homelessness and wandering.

  19. Division delay after low x-ray doses and treatment with cyclohexionide

    International Nuclear Information System (INIS)

    Schneiderman, M.H.; Braby, L.A.; Roesch, W.C.

    1977-01-01

    Radiation-induced division delay of Chinese hamster ovary cells located in G 2 , and in G 2 between the cycloheximide and x-ray transition points, was measured by the mitotic cell selection technique. The mitotic yield (number of mitotic cells after treatment expressed as a fraction of the control) decreased with increasing radiation dose (4.5 to 34 rad). However, either because some cells were not delayed or because delayed cells recovered rapidly, the mitotic yield did not fall to zero. When cycloheximide was combined with radiation to prevent repair of the radiation damage, only cells which were past the cycloheximide transition point and not delayed by the radiation were selected. The location of the transition points determined from the combined drug plus low-dose radiation (4.5 to 34 rad) experiments indicate a dose-dependent relationship, with more cells delayed as the dose was increased. In addition, the transition point for cells treated with cycloheximide plus 150 rad of x rays was closer to division than the 150 rad of x rays alone. These results are discussed in light of a recent model for radiation-induced division delay proposed by Dewey and Highfield

  20. Hamlet vor Ödipus. Die Postmoderne als Mythos der Moderne

    OpenAIRE

    Zizek, Slavoj

    2001-01-01

    Wenn wir in der Psychoanalyse über Mythen sprechen, sprechen wir in Wahrheit über einen Mythos, den Ödipusmythos . alle anderen Freudschen Mythen (der des Urvaters, Freuds Version des Moses-Mythos) sind, wenn auch notwendige, Variationen davon. Mit der Hamlet Erzählung kompli­ziert sich jedoch die Lage: Die standardisierte, vor-Lacansche .naive. psychoanalytische Lesart von Hamlet fixiert sich bekanntlich auf Hamlets inzestuöses Begehren nach seiner Mutter. Hamlets Schock über den Tod sei...

  1. HAMLET (human alpha-lactalbumin made lethal to tumor cells) triggers autophagic tumor cell death.

    Science.gov (United States)

    Aits, Sonja; Gustafsson, Lotta; Hallgren, Oskar; Brest, Patrick; Gustafsson, Mattias; Trulsson, Maria; Mossberg, Ann-Kristin; Simon, Hans-Uwe; Mograbi, Baharia; Svanborg, Catharina

    2009-03-01

    HAMLET, a complex of partially unfolded alpha-lactalbumin and oleic acid, kills a wide range of tumor cells. Here we propose that HAMLET causes macroautophagy in tumor cells and that this contributes to their death. Cell death was accompanied by mitochondrial damage and a reduction in the level of active mTOR and HAMLET triggered extensive cytoplasmic vacuolization and the formation of double-membrane-enclosed vesicles typical of macroautophagy. In addition, HAMLET caused a change from uniform (LC3-I) to granular (LC3-II) staining in LC3-GFP-transfected cells reflecting LC3 translocation during macroautophagy, and this was blocked by the macroautophagy inhibitor 3-methyladenine. HAMLET also caused accumulation of LC3-II detected by Western blot when lysosomal degradation was inhibited suggesting that HAMLET caused an increase in autophagic flux. To determine if macroautophagy contributed to cell death, we used RNA interference against Beclin-1 and Atg5. Suppression of Beclin-1 and Atg5 improved the survival of HAMLET-treated tumor cells and inhibited the increase in granular LC3-GFP staining. The results show that HAMLET triggers macroautophagy in tumor cells and suggest that macroautophagy contributes to HAMLET-induced tumor cell death.

  2. Changes in proteasome structure and function caused by HAMLET in tumor cells.

    Science.gov (United States)

    Gustafsson, Lotta; Aits, Sonja; Onnerfjord, Patrik; Trulsson, Maria; Storm, Petter; Svanborg, Catharina

    2009-01-01

    Proteasomes control the level of endogenous unfolded proteins by degrading them in the proteolytic core. Insufficient degradation due to altered protein structure or proteasome inhibition may trigger cell death. This study examined the proteasome response to HAMLET, a partially unfolded protein-lipid complex, which is internalized by tumor cells and triggers cell death. HAMLET bound directly to isolated 20S proteasomes in vitro and in tumor cells significant co-localization of HAMLET and 20S proteasomes was detected by confocal microscopy. This interaction was confirmed by co-immunoprecipitation from extracts of HAMLET-treated tumor cells. HAMLET resisted in vitro degradation by proteasomal enzymes and degradation by intact 20S proteasomes was slow compared to fatty acid-free, partially unfolded alpha-lactalbumin. After a brief activation, HAMLET inhibited proteasome activity in vitro and in parallel a change in proteasome structure occurred, with modifications of catalytic (beta1 and beta5) and structural subunits (alpha2, alpha3, alpha6 and beta3). Proteasome inhibition was confirmed in extracts from HAMLET-treated cells and there were indications of proteasome fragmentation in HAMLET-treated cells. The results suggest that internalized HAMLET is targeted to 20S proteasomes, that the complex resists degradation, inhibits proteasome activity and perturbs proteasome structure. We speculate that perturbations of proteasome structure might contribute to the cytotoxic effects of unfolded protein complexes that invade host cells.

  3. hamlet, a binary genetic switch between single- and multiple- dendrite neuron morphology.

    Science.gov (United States)

    Moore, Adrian W; Jan, Lily Yeh; Jan, Yuh Nung

    2002-08-23

    The dendritic morphology of neurons determines the number and type of inputs they receive. In the Drosophila peripheral nervous system (PNS), the external sensory (ES) neurons have a single nonbranched dendrite, whereas the lineally related multidendritic (MD) neurons have extensively branched dendritic arbors. We report that hamlet is a binary genetic switch between these contrasting morphological types. In hamlet mutants, ES neurons are converted to an MD fate, whereas ectopic hamlet expression in MD precursors results in transformation of MD neurons into ES neurons. Moreover, hamlet expression induced in MD neurons undergoing dendrite outgrowth drastically reduces arbor branching.

  4. Early-Onset Bipolar Disorder and Treatment Delay Are Risk Factors for Poor Outcome in Adulthood

    NARCIS (Netherlands)

    Post, Robert M.; Leverich, Gabriele S.; Kupka, Ralph W.; Keck, Paul E.; McElroy, Susan L.; Altshuler, Lori L.; Frye, Mark A.; Luckenbaugh, David A.; Rowe, Michael; Grunze, Heinz; Suppes, Trisha; Nolen, Willem A.

    Objective: We examined the influence of age at onset of illness and the delay in time to first treatment on morbidity in adulthood. Method: 529 adult outpatients with a mean age of 42 years, who entered our research network from 1996 through 2001 and who were diagnosed with bipolar disorder

  5. A favorable outcome despite a 39-hour treatment delay for arterial gas embolism: case report.

    Science.gov (United States)

    Covington, Derek; Bielawski, Anthony; Sadler, Charlotte; Latham, Emi

    2016-01-01

    Cerebral arterial gas embolism (CAGE) occurs when gas enters the cerebral arterial vasculature. CAGE can occur during sitting craniotomies, cranial trauma or secondary to gas embolism from the heart. A far less common cause of CAGE is vascular entrainment of gas during endoscopic procedures. We present the case of a 49-year-old male who developed a CAGE following an esophagoduodenoscopy (EGD) biopsy. Due to a delay in diagnosis, the patient was not treated with hyperbaric oxygen (HBO₂) therapy until 39 hours after the inciting event. Despite presenting to our institution non-responsive and with decorticate posturing, the patient was eventually discharged to a rehabilitation facility, with only mild left upper extremity weakness. This delay in HBO₂ treatment represents the longest delay in treatment to our knowledge for a patient suffering from CAGE secondary to EGD. In addition to the clinical case report, we discuss the etiology of CAGE and the evidence supporting early HBO₂ treatment, as well as the data demonstrating efficacy even after considerable treatment delay. Copyright© Undersea and Hyperbaric Medical Society.

  6. Barriers and Delays in Tuberculosis Diagnosis and Treatment Services: Does Gender Matter?

    Directory of Open Access Journals (Sweden)

    Wei-Teng Yang

    2014-01-01

    Full Text Available Background. Tuberculosis (TB remains a global public health problem with known gender-related disparities. We reviewed the quantitative evidence for gender-related differences in accessing TB services from symptom onset to treatment initiation. Methods. Following a systematic review process, we: searched 12 electronic databases; included quantitative studies assessing gender differences in accessing TB diagnostic and treatment services; abstracted data; and assessed study validity. We defined barriers and delays at the individual and provider/system levels using a conceptual framework of the TB care continuum and examined gender-related differences. Results. Among 13,448 articles, 137 were included: many assessed individual-level barriers (52% and delays (42%, 76% surveyed persons presenting for care with diagnosed or suspected TB, 24% surveyed community members, and two-thirds were from African and Asian regions. Many studies reported no gender differences. Among studies reporting disparities, women faced greater barriers (financial: 64% versus 36%; physical: 100% versus 0%; stigma: 85% versus 15%; health literacy: 67% versus 33%; and provider-/system-level: 100% versus 0% and longer delays (presentation to diagnosis: 45% versus 0% than men. Conclusions. Many studies found no quantitative gender-related differences in barriers and delays limiting access to TB services. When differences were identified, women experienced greater barriers and longer delays than men.

  7. Barriers and delays in tuberculosis diagnosis and treatment services: does gender matter?

    Science.gov (United States)

    Yang, Wei-Teng; Gounder, Celine R; Akande, Tokunbo; De Neve, Jan-Walter; McIntire, Katherine N; Chandrasekhar, Aditya; de Lima Pereira, Alan; Gummadi, Naveen; Samanta, Santanu; Gupta, Amita

    2014-01-01

    Background. Tuberculosis (TB) remains a global public health problem with known gender-related disparities. We reviewed the quantitative evidence for gender-related differences in accessing TB services from symptom onset to treatment initiation. Methods. Following a systematic review process, we: searched 12 electronic databases; included quantitative studies assessing gender differences in accessing TB diagnostic and treatment services; abstracted data; and assessed study validity. We defined barriers and delays at the individual and provider/system levels using a conceptual framework of the TB care continuum and examined gender-related differences. Results. Among 13,448 articles, 137 were included: many assessed individual-level barriers (52%) and delays (42%), 76% surveyed persons presenting for care with diagnosed or suspected TB, 24% surveyed community members, and two-thirds were from African and Asian regions. Many studies reported no gender differences. Among studies reporting disparities, women faced greater barriers (financial: 64% versus 36%; physical: 100% versus 0%; stigma: 85% versus 15%; health literacy: 67% versus 33%; and provider-/system-level: 100% versus 0%) and longer delays (presentation to diagnosis: 45% versus 0%) than men. Conclusions. Many studies found no quantitative gender-related differences in barriers and delays limiting access to TB services. When differences were identified, women experienced greater barriers and longer delays than men.

  8. Os Simpsons em Hamlet: um petisco de Shakespeare

    Directory of Open Access Journals (Sweden)

    Robert Salem

    2014-07-01

    Full Text Available http://dx.doi.org/10.5007/2175-7968.2014v1n33p261 Este artigo se propõe a refletir sobre a adaptação de Hamlet em Os Simpsons no episódio Do the bard, man, a fim de observar aspectos importantes dessa recriação contemporânea. A releitura de Hamlet apresentada em Os Simpsons é uma peça dentro de outra, em que os personagens do seriado assumem os papéis dos personagens de Shakespeare.  O artigo enfatiza a inclusão de tantos elementos da peça de Shakespeare em uma adaptação de apenas cinco minutos e sugere uma solução de storyboard para incluir aspectos dos famosos solilóquios

  9. Shakespearean Tragedy Revisited: Death in Othello and Hamlet

    Directory of Open Access Journals (Sweden)

    Pr. Lhoussain SIMOUR

    2016-07-01

    Full Text Available This paper looks closely at death as a thematic concern in Shakespearean tragedy, with a focus on Othello and Hamlet. In both plays, death as a tragic ending brings the stories of heroes who are led up constantly to fall and yield to the force of circumstances that have been created and plotted. The calamities in Shakespeare‟s tragedies are not accidental. They proceed mainly from actions which beget others until this series of interconnected acts leads to a catastrophe. These acts are predominantly of great importance to the tragic ending. As the tragedy advances towards its „denouement‟, one would notice that the catastrophe follows inextricably from certain actions whose main source is a flaw in the hero‟s character. Such is the case with both Othello and Hamlet. This paper attempts to offer a critical reading and a discussion of Shakespeare‟s tragedy.

  10. Protein receptor-independent plasma membrane remodeling by HAMLET

    DEFF Research Database (Denmark)

    Nadeem, Aftab; Sanborn, Jeremy; Gettel, Douglas L.

    2015-01-01

    A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This "protein-centric" view is increasingly challenged by evidence for the involvement of specialized membrane domains...... in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range...... of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies. We identify a "receptor independent" transformation of vesicular motifs in model membranes, which is paralleled by gross remodeling of tumor cell membranes. Furthermore, we find that HAMLET...

  11. Impact of fluoroquinolone treatment on delay of tuberculosis diagnosis: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Catherine A Hogan

    2017-01-01

    Full Text Available Background: Fluoroquinolones are among the most commonly used antibiotics for the treatment of respiratory infections. Because fluoroquinolones show bactericidal activity against Mycobacterium tuberculosis, there is concern that their use can delay the diagnosis of tuberculosis. We conducted a systematic review and meta-analysis to assess whether empiric treatment with fluoroquinolones delays the diagnosis and treatment of tuberculosis in patients with respiratory tract infections. Objectives: The primary objective was to assess the delay in days in the diagnosis and treatment of tuberculosis, among patients who received quinolones, compared to those who received non-fluoroquinolone antibiotics. Methods: We included studies of adult patients treated with fluoroquinolones prior to a confirmed diagnosis of tuberculosis. We performed a literature search of 7 databases (including PubMed, Embase and Cochrane Library with no language restrictions. We calculated an unweighted mean of estimate of difference in delay across all studies. For the studies for which the estimate was available as a mean with standard deviation, a weighted average using a random effects meta-analysis model was estimated. Results: A total of 3983 citations were identified from the literature search; of these, 17 articles were selected for full-text review. A total of 10 studies were retained for the synthesis. These included 7 retrospective cohort studies and 3 case-control studies. Only one of these studies was from a high TB burden country, South Africa. The most commonly used fluoroquinolones were levofloxacin, gemifloxacin and moxifloxacin. The unweighted average of difference in delay between the fluoroquinolone group and non-fluoroquinolone group was 12.9 days (95% CI 6.1–19.7. When these differences were pooled using a random effects model, the weighted estimate was 10.9 days (95% CI 4.2–17.6. When stratified by acid-fast smear status, the delay was

  12. Delayed treatment of decompression sickness with short, no-air-break tables: review of 140 cases.

    Science.gov (United States)

    Cianci, Paul; Slade, John B

    2006-10-01

    Most cases of decompression sickness (DCS) in the U.S. are treated with hyperbaric oxygen using U.S. Navy Treatment Tables 5 and 6, although detailed analysis shows that those tables were based on limited data. We reviewed the development of these protocols and offer an alternative treatment table more suitable for monoplace chambers that has proven effective in the treatment of DCS in patients presenting to our facility. We reviewed the outcomes for 140 cases of DCS in civilian divers treated with the shorter tables at our facility from January 1983 through December 2002. Onset of symptoms averaged 9.3 h after surfacing. At presentation, 44% of the patients demonstrated mental aberration. The average delay from onset of symptoms to treatment was 93.5 h; median delay was 48 h. Complete recovery in the total group of 140 patients was 87%. When 30 patients with low probability of DCS were excluded, the recovery rate was 98%. All patients with cerebral symptoms recovered. Patients with the highest severity scores showed a high rate of complete recovery (97.5%). Short oxygen treatment tables as originally described by Hart are effective in the treatment of DCS, even with long delays to definitive recompression that often occur among civilian divers presenting to a major Divers Alert Network referral center.

  13. Delay in Diagnosis and Treatment of Breast Cancer among Women Attending a Reference Service in Brazil

    Science.gov (United States)

    Romeiro Lopes, Tiara Cristina; Gravena, Angela Andréia França; Demitto, Marcela de Oliveira; Borghesan, Deise Helena Pelloso; Dell`Agnolo, Cátia Millene; Brischiliari, Sheila Cristina Rocha; Carvalho, Maria Dalva de Barros; Pelloso, Sandra Marisa

    2017-11-26

    Background: Cancer is a major public health problem. Early diagnosis and treatment are essential for reducing mortality. This study aimed to analyze factors associated with delay in breast cancer diagnosis and treatment among women attending a reference cancer service. Methods: This retrospective, cross-sectional study was performed with data collected from medical records and interviews conducted with women diagnosed with breast cancer and treated from October 2013 to October 2014 at a cancer reference hospital in Paraná, Southern Brazil. Results: A total of 82 participants were enrolled during the study period; their average age was 58.2 ± 11.5 years. The average time taken for final diagnosis of breast cancer was 102.5 ± 165.5 days. Treatment onset was delayed in the majority of cases, and the average time elapsing from diagnostic biopsy to onset of primary treatment was 72.3 ± 54.0 days. The odds of treatment delay were higher among the women with a low educational level. Conclusions: The results underline the need for proposals aimed at early detection, identification of risk factors and timely provision of treatment by health managers that focus on this group. Creative Commons Attribution License

  14. Vygotsky’s Hamlet: the dialectic method and personality psychology

    OpenAIRE

    Bayanova L.F.

    2013-01-01

    This article presents an analysis of Vygotsky’s work on the psychology of art and his use of the image of Hamlet in the psychological analysis of personality. It also describes the capabilities of the dialectic method for assessing psychological problems. Reference to three dialectical oppositions—of the story and the plot, of the main character’s spinelessness and his insanity, and of subject and personality—allows the development of a theoretical analysis of the psychology of personality in...

  15. Requests for late termination of pregnancy: Tower Hamlets, 1983.

    OpenAIRE

    Savage, W

    1985-01-01

    The case histories of all women seeking late (more than 20 weeks' gestation) abortion in the NHS district of Tower Hamlets in 1983 were assessed. Of 12 women requesting late abortion, seven underwent termination of pregnancy. All the women had severe social or psychological problems, or both. The main reasons for late presentation were denial of pregnancy, youth, and mental disorder. In a small group of atypical women late abortion seems to be justified for reasons other than fetal abnormality.

  16. On the Alternative Use of Verse and Prose in Hamlet

    Institute of Scientific and Technical Information of China (English)

    李雷

    2008-01-01

    As a master in language,William Shakespeare is proficient in using verse and prose alternatively in his tragedies and comedies,which is regarded as the key to his success in literature by some critics.In this thesis,I would like to analyze the three criteria for the altemafion of verse and prose in Hamlet,in which a discussion of functions of the alternation will be included

  17. Gender differences in reasons patients delay in seeking treatment for acute myocardial infarction symptoms.

    Science.gov (United States)

    Moser, Debra K; McKinley, Sharon; Dracup, Kathleen; Chung, Misook L

    2005-01-01

    Patients (n = 194) with confirmed acute myocardial infarction (AMI) were interviewed to determine sociodemographic, clinical, social, behavioral, cognitive and emotional factors that contribute to delay in seeking treatment for their symptoms. Initial symptom experience was similar for men and women: both were most commonly at home when symptoms began; both were most commonly in the presence of their spouse or other family member; few patients (trouble others, and prior knowledge of thrombolytics. There was no difference in delay between men and women (median 3.08 versus 3.10 h), but there are important gender differences in the reasons patients delay and in their patterns of decision-making that may assist clinicians trying to tailor interventions.

  18. Delayed treatment of basilar thrombosis in a patient with a basilar aneurysm: a case report

    Directory of Open Access Journals (Sweden)

    Fakhouri T

    2008-11-01

    Full Text Available Abstract Introduction Acute occlusion of the basilar artery is a neurological emergency that has a high risk of severe disability and mortality. Delayed thrombolysis or endovascular therapy has been performed with some success in patients who present after 3 hours of symptom onset. Here we present the first case of delayed intra-arterial thrombolysis of a basilar artery thrombosis associated with a large saccular aneurysm. Case presentation A 73-year-old Caucasian man with a history of smoking and alcohol abuse presented to the Emergency Department complaining of diplopia and mild slurred speech and who progressed over 12 hours to coma and quadriparesis. He was found to have a large basilar tip aneurysm putting him at high risk for hemorrhage with lytic treatment. Conclusion The treatment options for basilar thrombosis are discussed. Aggressive treatment options should be considered despite long durations of clinical symptoms in basilar thrombosis, even in extremely high risk patients.

  19. Factors contributing to delay in diagnosis and start of treatment of leprosy

    DEFF Research Database (Denmark)

    Nicholls, P.G.; Chhina, N; Aaen, Karen Bro

    2005-01-01

    The objective of our research was to identify factors contributing to delay in diagnosis and start of treatment in leprosy, focussing on patients' narratives of help-seeking behaviour. Our research took place in Purulia, West Bengal, India and in Nilphamari, northern Bangladesh. Between January...... and August 2000, we conducted semi-structured interviews with 104 patients that explored each individual's narrative of help-seeking behaviour and the context of beliefs and attitudes towards leprosy. Subsequently we surveyed 356 patients currently receiving treatment for leprosy and recorded specific...... aspects of each help-seeking action and their reports of local beliefs and attitudes towards leprosy. Delay was estimated from time of first symptoms through to start of effective treatment (mean 18 months, median 9 months in Purulia and mean 20 months, median 12 months in Nilphamari). The number of help...

  20. The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting.

    Science.gov (United States)

    Palli, Swetha Rao; Grabner, Michael; Quimbo, Ralph A; Rugo, Hope S

    2015-01-01

    To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics. This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. We identified 1,832 palonosetron and 2,387 other 5-HT3 RA ("other") patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, PHEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019). Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs.

  1. Early versus delayed hormonal treatment in locally advanced or asymptomatic metastatic prostatic cancer patient dilemma.

    Science.gov (United States)

    Prezioso, Domenico; Iacono, Fabrizio; Romeo, Giuseppe; Ruffo, Antonio; Russo, Nicola; Illiano, Ester

    2014-06-01

    The objective of this work is to compare the effectiveness of hormonal treatment (luteinizing hormone-releasing hormone agonists and/or antiandrogens) as an early or as a deferred intervention for patients with locally advanced prostate cancer (LAPC) and/or asymptomatic metastasis. Systematic review of trials published in 1950-2007. Sources included MEDLINE and bibliographies of retrieved articles. Eligible trials included adults with a history of LAPC who are not suitable for curative local treatment of prostate cancer. We retrieved 22 articles for detailed review, of which 8 met inclusion criteria. The Veterans Administration Cooperative Urological Research Group suggested that delaying hormonal therapy did not compromise overall survival and that many of the patients died of causes other than prostate cancer. In European Organisation for Research and Treatment of Cancer (EORTC) 30846 trial, the median survival for delayed endocrine treatment was 6.1 year, and for immediate treatment 7.6 year, the HR for survival on delayed versus immediate treatment was 1.23 (95 % CI 0.88-1.71), indicating a 23 % nonsignificant trend in favour of early treatment. In EORTC 30891, the immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival. The protocol SAKK 08/88 showed the lack of any major advantage of immediate compared with deferred hormonal treatment regarding quality of life or overall survival. The early intervention with hormonal treatment for patients with LAPC provides important reductions in all-cause mortality, prostate cancer-specific mortality, overall progression, and distant progression compared with deferring their use until standard care has failed to halt the disease.

  2. Delays before Diagnosis and Initiation of Treatment in Patients Presenting to Mental Health Services with Bipolar Disorder.

    Science.gov (United States)

    Patel, Rashmi; Shetty, Hitesh; Jackson, Richard; Broadbent, Matthew; Stewart, Robert; Boydell, Jane; McGuire, Philip; Taylor, Matthew

    2015-01-01

    Bipolar disorder is a significant cause of morbidity and mortality. Although existing treatments are effective, there is often a substantial delay before diagnosis and treatment initiation. We sought to investigate factors associated with the delay before diagnosis of bipolar disorder and the onset of treatment in secondary mental healthcare. Retrospective cohort study using anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register on 1364 adults diagnosed with bipolar disorder between 2007 and 2012. The following predictor variables were analysed in a multivariable Cox regression analysis: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder. The outcomes were time to recorded diagnosis from first presentation to specialist mental health services (the diagnostic delay), and time to the start of appropriate therapy (treatment delay). The median diagnostic delay was 62 days (interquartile range: 17-243) and median treatment delay was 31 days (4-122). Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18-3.06) and treatment delay (4.40, 3.63-5.62). Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33-0.41) and substance misuse disorders (0.44, 0.31-0.61). Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay. Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder after initiation of specialist mental healthcare, particularly those who have prior diagnoses of alcohol and substance misuse disorders. These findings highlight a need for further study on strategies to better identify underlying symptoms and offer appropriate treatment sooner

  3. Delays before Diagnosis and Initiation of Treatment in Patients Presenting to Mental Health Services with Bipolar Disorder.

    Directory of Open Access Journals (Sweden)

    Rashmi Patel

    Full Text Available Bipolar disorder is a significant cause of morbidity and mortality. Although existing treatments are effective, there is often a substantial delay before diagnosis and treatment initiation. We sought to investigate factors associated with the delay before diagnosis of bipolar disorder and the onset of treatment in secondary mental healthcare.Retrospective cohort study using anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust (SLaM Biomedical Research Centre (BRC Case Register on 1364 adults diagnosed with bipolar disorder between 2007 and 2012. The following predictor variables were analysed in a multivariable Cox regression analysis: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder. The outcomes were time to recorded diagnosis from first presentation to specialist mental health services (the diagnostic delay, and time to the start of appropriate therapy (treatment delay.The median diagnostic delay was 62 days (interquartile range: 17-243 and median treatment delay was 31 days (4-122. Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18-3.06 and treatment delay (4.40, 3.63-5.62. Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33-0.41 and substance misuse disorders (0.44, 0.31-0.61. Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay.Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder after initiation of specialist mental healthcare, particularly those who have prior diagnoses of alcohol and substance misuse disorders. These findings highlight a need for further study on strategies to better identify underlying symptoms and offer appropriate treatment

  4. Where to Be or Not to Be: The Question of Place in "Hamlet"

    Science.gov (United States)

    Golden, John

    2009-01-01

    The author does not really like "Hamlet." He loves the play, the language, and the characters, but always finds it difficult to teach. Part of this is because he prefers to assign students scenes to perform as they read a Shakespeare text, but Hamlet does not divide nicely into manageable scenes, and he usually does not have enough teenage Ken…

  5. An Analysis of the Termination of Credit Business in Faulkner's "The Hamlet"

    Science.gov (United States)

    Huang, Xiuguo

    2015-01-01

    Flem's economic reformation especially his replacement of credit business by cash business in Varner's Store in "The Hamlet" marked the social transition from a more traditional, closer and bonded community to a rather detached, rational and mechanical commercial society. The description in "The Hamlet" to a certain extent…

  6. Stability of HAMLET--a kinetically trapped alpha-lactalbumin oleic acid complex.

    Science.gov (United States)

    Fast, Jonas; Mossberg, Ann-Kristin; Svanborg, Catharina; Linse, Sara

    2005-02-01

    The stability toward thermal and urea denaturation was measured for HAMLET (human alpha-lactalbumin made lethal to tumor cells) and alpha-lactalbumin, using circular dichroism and fluorescence spectroscopy as well as differential scanning calorimetry. Under all conditions examined, HAMLET appears to have the same or lower stability than alpha-lactalbumin. The largest difference is seen for thermal denaturation of the calcium free (apo) forms, where the temperature at the transition midpoint is 15 degrees C lower for apo HAMLET than for apo alpha-lactalbumin. The difference becomes progressively smaller as the calcium concentration increases. Denaturation of HAMLET was found to be irreversible. Samples of HAMLET that have been renatured after denaturation have lost the specific biological activity toward tumor cells. Three lines of evidence indicate that HAMLET is a kinetic trap: (1) It has lower stability than alpha-lactalbumin, although it is a complex of alpha-lactalbumin and oleic acid; (2) its denaturation is irreversible and HAMLET is lost after denaturation; (3) formation of HAMLET requires a specific conversion protocol.

  7. HAMLET triggers apoptosis but tumor cell death is independent of caspases, Bcl-2 and p53.

    Science.gov (United States)

    Hallgren, O; Gustafsson, L; Irjala, H; Selivanova, G; Orrenius, S; Svanborg, C

    2006-02-01

    HAMLET (Human alpha-lactalbumin Made Lethal to Tumor cells) triggers selective tumor cell death in vitro and limits tumor progression in vivo. Dying cells show features of apoptosis but it is not clear if the apoptotic response explains tumor cell death. This study examined the contribution of apoptosis to cell death in response to HAMLET. Apoptotic changes like caspase activation, phosphatidyl serine externalization, chromatin condensation were detected in HAMLET-treated tumor cells, but caspase inhibition or Bcl-2 over-expression did not prolong cell survival and the caspase response was Bcl-2 independent. HAMLET translocates to the nuclei and binds directly to chromatin, but the death response was unrelated to the p53 status of the tumor cells. p53 deletions or gain of function mutations did not influence the HAMLET sensitivity of tumor cells. Chromatin condensation was partly caspase dependent, but apoptosis-like marginalization of chromatin was also observed. The results show that tumor cell death in response to HAMLET is independent of caspases, p53 and Bcl-2 even though HAMLET activates an apoptotic response. The use of other cell death pathways allows HAMLET to successfully circumvent fundamental anti-apoptotic strategies that are present in many tumor cells.

  8. A parapraxis in Hamlet. A note on the aesthetic genius of William Shakespeare.

    Science.gov (United States)

    Mahon, E

    1998-01-01

    Shakespeare has placed a parapraxis in Hamlet's mouth in the soliloquy in Act I. Hamlet says, "But two months dead, nay not so much not two." The slip attributed to Hamlet is of course no slip at all when seen as an aesthetic contrivance of the bard's to suggest the tension between warring aspects of Hamlet's psychology. I argue that Shakespeare's artistic methodology, his aesthetic sleight of hand, so to speak, which layers this complex drama with meanings concealing other meanings, supports Freud's notion that an unconscious latent oedipal drama underlies the whole manifest content, imbuing it with subtle but substantial dramatic tension. The slip of the tongue is not only a window into the unconscious of Hamlet that sheds light on the hero's Oedipus complex and the complexities of his attempted resolutions, it is also an example of Shakespeare's aesthetic subtlety at its most refined.

  9. Survival of Primates in Lethal Septic Shock Following Delayed Treatment with Steroid.

    Science.gov (United States)

    1981-02-26

    TECHNICAL REPORT NO. 142 SURVIVAL OF PRIMATES IN LETHAL SEPTIC SHOCK FOLLOWING DELAYED TREAMENT WIn STEROID L. B. Hinshaw, L. T. Archer, B. K. Belier ...2. Schumer W: Steroids in the treatment of clinical septic shock. Ann Surg 184:333-341, 1976. 3. Hinshaw LB, Belier PK, Archer LT, Flournoy DJ, White...not preventable by antibiotic alone. Infect Immun ZS:538-5)7, 1979. 6. Hinshaw LB, Archer LT, Belier -Todd BK, Coalson .JJ, Flournoy DL, Passey R

  10. Diagnosis and treatment delays among elderly breast cancer patients with pre-existing mental illness.

    Science.gov (United States)

    Iglay, Kristy; Santorelli, Melissa L; Hirshfield, Kim M; Williams, Jill M; Rhoads, George G; Lin, Yong; Demissie, Kitaw

    2017-11-01

    This study aimed to compare diagnosis and treatment delays in elderly breast cancer patients with and without pre-existing mental illness. A retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results-Medicare data including 16,636 women 68+ years, who were diagnosed with stage I-IIIa breast cancer in the United States from 2005 to 2007. Mental illness was identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes recorded on inpatient and outpatient claims during the 3 years prior to breast cancer diagnosis. Patients were classified as having no mental illness, anxiety, depression, anxiety and depression, or severe mental illness (bipolar disorder, schizophrenia, and other psychotic disorder). Multivariable binomial regression was used to assess the association between mental illness and delays of ≥60 and ≥90 days after adjustment for confounders. Patients with comorbid anxiety and depression had an increased risk for diagnosis delay of ≥90 days from symptom recognition (RR 1.11; 95% CI 1.00, 1.23), and those with severe mental illness had an increased risk for initial treatment delay of ≥60 days from diagnosis (RR 1.36; 95% CI 1.06, 1.74). Patients with any mental illness experienced an increased risk for adjuvant chemotherapy delay of ≥90 days from last operation (RR 1.13; 95% CI 1.01, 1.26) and each category of mental illness, except depression, showed a non-significant trend for this association. Breast cancer patients with mental illness should be closely managed by a cross-functional care team, including a psychiatrist, a primary care physician, and an oncologist, to ensure adequate care is received within an appropriate timeframe.

  11. Role of surgery in delayed local treatment for INSS 4 neuroblastoma.

    Science.gov (United States)

    Uehara, Shuichiro; Yoneda, Akihiro; Oue, Takaharu; Nakahata, Kengo; Zenitani, Masahiro; Miyamura, Takako; Hashii, Yoshiko; Fukuzawa, Masahiro; Okuyama, Hiroomi

    2017-09-01

    The aim of the present study was to compare the efficacy, complications and outcomes of the following two surgical strategies for delayed local treatment for International Neuroblastoma Staging System (INSS) 4 neuroblastoma (NB): complete resection (CR; period A); and gross total resection/subtotal resection (GTR/STR) with local irradiation (period B). We retrospectively analyzed 17 patients with INSS 4 NB who received delayed local treatment (period A, n = 11; period B, n = 6). Eleven patients in period A received CR. Two patients underwent GTR and four patients underwent STR in period B. The amount of blood loss in period A was significantly greater than that in period B. Postoperative complications were observed in eight patients in period A (73%), but in only one patient in period B (17%; P < 0.01). Recurrence was observed in five patients in period A and in one patient in period B (45.4% vs 16.6%; P = n.s.). Distant metastasis at recurrence was observed in four patients in period A and in one patient in period B. Gross total resection/subtotal resection with local irradiation may be a safe and effective delayed local treatment for INSS 4 NB. © 2017 Japan Pediatric Society.

  12. The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting

    Directory of Open Access Journals (Sweden)

    Palli SR

    2015-06-01

    Full Text Available Swetha Rao Palli,1 Michael Grabner,1 Ralph A Quimbo,1 Hope S Rugo2 1HealthCore, Wilmington, DE, 2University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA Purpose: To determine the incidence of chemotherapy-induced nausea/vomiting (CINV and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA antiemetics. Materials and methods: This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC or moderately EC (MEC regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. Results: We identified 1,832 palonosetron and 2,387 other 5-HT3 RA (“other” patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026, and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001. Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019 and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019. Conclusion: Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with

  13. Predictors of delay in starting radiation treatment for patients with early stage breast cancer

    International Nuclear Information System (INIS)

    Benk, Veronique; Ho, Vivian; Fortin, Paul R.; Zhang, G.; Levinton, Carey; Freeman, C.R.

    1998-01-01

    Purpose: To describe the factors predicting waiting time for radiation treatment in early breast cancer. Materials and Methods: Between January 1992 and December 1993, 739 patients with Stage I and II breast cancer were treated with conservative treatment at three McGill University Hospitals. Waiting time was defined as the interval between the date of surgery and the date of the first radiation treatment. Delay was defined as a waiting time of more than 7 weeks for women who did not receive chemotherapy (Group NC, n 478), and as a waiting time of more than 24 weeks for those who received chemotherapy (Group C, n = 261). We analyzed predictive factors related to the patient (age, stage, treatment on protocol, income by postal code) and to the referring hospital (university or community hospital). Results: For the entire population, 54% of patients were delayed, 72% in Group NC and 21.4% in Group C. Univariate analysis showed an impact of referring hospital in both groups, and of stage and treatment on protocol in Group C (all p = 0.001). Multivariate analysis showed that delays were significantly less in Group NC for women referred from a community hospital (p = 0.001) and in Group C for women with Stage I disease (p = 0.06), those treated on protocol, and those referred from a university hospital (p = 0.001). Conclusion: More than half of patients with early breast cancer waited more than the recommended intervals for radiation therapy. However, lower income breast cancer patients did not wait longer for treatment than higher income patients, possibly a result of the Canadian Medicare system which provides universal access to health care

  14. Emergency or Delayed Surgical Treatment of Unstable Supracondylar Humeral Fractures in Children?

    Directory of Open Access Journals (Sweden)

    Stefanovic Branko

    2017-06-01

    Full Text Available Supracondylar humeral fractures (SCHF are the most common elbow fractures in children, representing 3% of all paediatric fractures. Treatment options for SCHF in children are based on the Gartland classification. Treatment of non-displaced fractures (type I is non-operative. Plaster immobilization for 3 to 4 weeks is recommended, depending on the age of the child and fracture healing. Treatments of displaced supracondylar fractures (type II and III of the humerus in children are still undefined in clinical practice. Because of divided opinions, the aim of this study was to evaluate whether delayed or immediate surgical treatment has an advantage in the treatment of supracondylar fractures in children. This is a prospective – retrospective clinical study. This study included 64 patients from 5 to 15 years old; 47 (73.4% were boys and 17 (26.6% were girls. The most common age range (59.4% in this study was 5-8 years old. All patients were diagnosed with supracondylar fractures at the Institute for Orthopaedic Surgery “Banjica”. We analysed 17 parameters, which were obtained either from direct patient interviews or from their medical history. All patients were divided into two groups with matched characteristics. Group I consisted of 26 patients who had immediate operations. Group II consisted of 38 patients who had delayed operations.

  15. Operative treatment of the midshaft fractures of the clavicle – does delay matter?

    Directory of Open Access Journals (Sweden)

    Matej Andoljšek

    2007-11-01

    Full Text Available Background: Fractures of the clavicle are common injuries and mostly treated non-operatively. Nearly always the fracture is clinically united within three to four weeks and functional recovery should be completed within two months. Traditionally thinking has been that operative treatment is indicated exceptionaly and that delayed surgery is less successful. In retrospective comparative study authors have asked – whether delay of surgery in middle-third clavicular fractures negatively affects functional results and – whether after delayed surgery complications are more frequent.Patients and methods: Thirty-seven of 733 fractures of the clavicle were treated operatively. Among these, 11 were fresh Allman Type I fractures (early procedure, 9 delayed- or non-unions and one malunion (late procedure. All fractures were fixed with plates and screws. In none of the reconstructive procedures composite bone grafting was performed, twice spongiotic bone graft and twice morsilized calus grafts were used. DASH and Constant scores were used for outcome evaluation.Results: Twenty-one of 22 patients were evaluated (one foreign turist missed on average 21 month after surgery. Average DASH scores for early operated patients were 14.4 and for late operated 18.5; an average Quich DASH were 16.4 and 20.5 respectively. Average Constant scores were 85.6 and 76.0. Statistically differences are not important. Three patients had early complications (two from early, one from late group. Five patients had late complications (four skin paresthesias, one non-union.Conclusions: In retrospective study, functional results of surgically treated fresh Type I fractures and after reconstructive surgery for delayed-, non- and mal-union of the midshaft of the clavicle were comparable. No significant differences in complication rates were confirmed.

  16. [Usefulness of endovascular treatment for delayed massive epistaxis following endoscopic endonasal transsphenoidal surgery: a case report].

    Science.gov (United States)

    Oka, Tetsuo; Sugiu, Kenji; Ishida, Joji; Hishikawa, Tomohito; Ono, Shigeki; Tokunaga, Koji; Date, Isao

    2012-01-01

    We report here a case of massive nasal bleeding from the sphenopalatine artery three weeks after endonasal transsphenoidal surgery. This 66-year-old male suffered from massive nasal bleeding with the status of hypovolemic shock. Under general anesthesia, an emergent angiography revealed an extravasation from the sphenopalatine artery. Trans-arterial embolization using coil and n-butyl-cyanoacrylate (NBCA) was performed following the diagnostic angiography. Complete occlusion of the injured artery was achieved. The patient showed good recovery from general anesthesia. Delayed nasal bleeding after endonasal transsphenoidal surgery is a rare but important complication. The sphenopalatine artery and its branch are located in the hidden inferior lateral corner of the sphenoid sinus and may be injured during enlargement of the sphenoid opening. When massive delayed nasal bleeding follows transsphenoidal surgery and damage of the internal carotid artery has been ruled out, endovascular treatment of the external carotid artery should be considered.

  17. Apariencia y realidad en Hamlet y Las Meninas

    Directory of Open Access Journals (Sweden)

    Antonio PRIETO MARTÍNEZ

    2009-11-01

    Full Text Available La obra de Shakespeare comenzó a ser estudiada en profundidad a finales del siglo XVII y, sobre todo, en el siglo XVIII. Desde ese siglo hasta el momento actual la investigación en torno a la obra shakesperiana se ha desarrollado hasta tal punto que resulta inabordable. De entre la obra de Shakespeare, Hamlet es probablemente la que suscita mayor interés a causa de su compleja estructura y su contenido ambiguo. Del mismo modo, la obra de Velázquez comenzó a estudiarse con rigor en el siglo XVIII, aunque hasta el siglo XX no se investigan sus características e influencias. Como en el caso de Shakespeare, la bibliografía existente en la actualidad sobre su obra resulta inaccesible para el investigador. De entre todas sus pinturas, Las Meninas, del mismo modo que Hamlet, es la que despierta mayor interés y tiene una proyección universal. Haciendo un recorrido por las investigaciones más importantes realizadas sobre ambas obras en los tres últimos siglos, intento encontrar semejanzas entre ellas, basándome fundamentalmente en su estructura. Apoyando mi investigación en la teoría deconstructivista, según la propuesta de J. Derrida, y siguiendo el esquema formal de ambas obras, propongo el tema general de apariencia y realidad como núcleo de sus semejanzas. Los puntos de analogía entre Hamlet y Las Meninas son, en síntesis, los siguientes: - Texto (expresado en el ser o no ser y el reverso del lienzo sobre el que pinta Velázquez. - El personaje del espectro en Hamlet y el personaje invisible en el cuadro (María Teresa de Austria o el espectador. - Velázquez significante representado en el cuadro y la obra dentro de la obra que representan los cómicos. - El personaje de Claudio, como símbolo del tirano y los reyes representados en el espejo. - Finalmente considero la vigencia y proyección que tienen ambas obras en el mundo actual.

  18. Interaction of low-dose irradiation with subsequent mutagenic treatment. Role of mitotic delay

    International Nuclear Information System (INIS)

    Salone, B.; Pretazzoli, V.; Bosi, A.; Olivieri, G.

    1996-01-01

    Experiments were carried out with human lymphocytes to test whether there was any relation between the changes that conditioning treatment can produce in cell progression or in mitotic delay induced by the challenge dose and the presence of an 'adaptive response' (AR). In experiments in which the cells were successively fixed after the challenge dose, the interaction between conditioning treatment and challenge was of the same sign for all the fixation times: therefore it is likely that modifications of the cytogenetic damage in primed cells is not a mere reflection of stage sensitivity. In experiments in which using 1 Gy as conditioning treatment we induced a drastic extension of G 2 , we did not observe any AR; therefore, even if conditioning treatment can induce modifications in the cell-cycle phases before and/or after challenge, there is probably no link between these modifications and the presence of an AR

  19. Patient characteristics associated with self-presentation, treatment delay and survival following primary percutaneous coronary intervention.

    Science.gov (United States)

    Austin, David; Yan, Andrew T; Spratt, James C; Kunadian, Vijay; Edwards, Richard J; Egred, Mohaned; Bagnall, Alan J

    2014-09-01

    Delayed arrival to a primary percutaneous coronary intervention (PPCI)-capable hospital following ST-elevation myocardial infarction (STEMI) is associated with poorer outcome. The influence of patient characteristics on delayed presentation during STEMI is unknown. This was a retrospective observational study. Patients presenting for PPCI from March 2008 to November 2011 in the north of England (Northumbria, Tyne and Wear) were included. The outcomes were self-presentation to a non-PPCI-capable hospital, symptom to first medical contact (STFMC) time, total ischaemic time and mortality during follow-up. STEMI patients included numbered 2297; 619 (26.9%) patients self-presented to a non-PPCI-capable hospital. STFMC of >30 min and total ischaemic time of >180 min was present in 1521 (70.7%) and 999 (44.9%) cases, respectively. Self-presentation was the strongest predictor of prolonged total ischaemic time (odds ratio, OR (95% confidence interval, CI): 5.05 (3.99-6.39)). Married patients (OR 1.38 (1.10-1.74)) and patients living closest to an Emergency Room self-presented more commonly (driving time (vs. ≤10 min) 11-20 min OR 0.66 (0.52-0.83), >20 minutes OR 0.46 (0.33-0.64). Unmarried females waited longest to call for help (OR vs. married males 1.89 (1.29-2.78) and experienced longer total ischaemic times (OR 1.51 (1.10-2.07)). Married patients had a borderline association with lower mortality (hazard ratio 0.75 (0.53-1.05), p=0.09). Unmarried female patients had the longest treatment delays. Married patients and those living closer to an Emergency Room self-present more frequently. Early and exclusive use of the ambulance service may reduce treatment delay and improve STEMI outcome. © The European Society of Cardiology 2014.

  20. Bovine lactoferrin binds oleic acid to form an anti-tumor complex similar to HAMLET.

    Science.gov (United States)

    Fang, Bing; Zhang, Ming; Tian, Mai; Jiang, Lu; Guo, Hui Yuan; Ren, Fa Zheng

    2014-04-04

    α-Lactalbumin (α-LA) can bind oleic acid (OA) to form HAMLET-like complexes, which exhibited highly selective anti-tumor activity in vitro and in vivo. Considering the structural similarity to α-LA, we conjectured that lactoferrin (LF) could also bind OA to obtain a complex with anti-tumor activity. In this study, LF-OA was prepared and its activity and structural changes were compared with α-LA-OA. The anti-tumor activity was evaluated by methylene blue assay, while the apoptosis mechanism was analyzed using flow cytometry and Western blot. Structural changes of LF-OA were measured by fluorescence spectroscopy and circular dichroism. The interactions of OA with LF and α-LA were evaluated by isothermal titration calorimetry (ITC). LF-OA was obtained by heat-treatment at pH8.0 with LD50 of 4.88, 4.95 and 4.62μM for HepG2, HT29, and MCF-7 cells, respectively, all of which were 10 times higher than those of α-LA-OA. Similar to HAMLET, LF-OA induced apoptosis in tumor cells through both death receptor- and mitochondrial-mediated pathways. Exposure of tryptophan residues and the hydrophobic regions as well as the loss of tertiary structure were observed in LF-OA. Besides these similarities, LF showed different secondary structure changes when compared with α-LA, with a decrease of α-helix and β-turn and an increase of β-sheet and random coil. ITC results showed that there was a higher binding number of OA to LF than to α-LA, while both of the proteins interacted with OA through van der Waals forces and hydrogen bonds. This study provides a theoretical basis for further exploration of protein-OA complexes. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Early identification and delay to treatment in myocardial infarction and stroke: differences and similarities

    Directory of Open Access Journals (Sweden)

    Herlitz Johan

    2010-09-01

    Full Text Available Abstract Background The two major complications of atherosclerosis are acute myocardial infarction (AMI and acute ischemic stroke. Both are life-threatening conditions characterised by the abrupt cessation of blood flow to respective organs, resulting in an infarction. Depending on the extent of the infarction, loss of organ function varies considerably. In both conditions, it is possible to limit the extent of infarction with early intervention. In both conditions, minutes count. This article aims to describe differences and similarities with regard to the way patients, bystanders and health care providers act in the acute phase of the two diseases with the emphasis on the pre-hospital phase. Method A literature search was performed on the PubMed, Embase (Ovid SP and Cochrane Library databases. Results In both conditions, symptoms vary considerably. Patients appear to suspect AMI more frequently than stroke and, in the former, there is a gender gap (men suspect AMI more frequently than women. With regard to detection of AMI and stroke at dispatch centre and in Emergency Medical Service (EMS there is room for improvement in both conditions. The use of EMS appears to be higher in stroke but the overall delay to hospital admission is shorter in AMI. In both conditions, the fast track concept has been shown to influence the delay to treatment considerably. In terms of diagnostic evaluation by the EMS, more supported instruments are available in AMI than in stroke. Knowledge of the importance of early treatment has been reported to influence delays in both AMI and stroke. Conclusion Both in AMI and stroke minutes count and therefore the fast track concept has been introduced. Time to treatment still appears to be longer in stroke than in AMI. In the future improvement in the early detection as well as further shortening to start of treatment will be in focus in both conditions. A collaboration between cardiologists and neurologists and also between

  2. The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting

    International Nuclear Information System (INIS)

    Palli, Swetha Rao; Grabner, Michael; Quimbo, Ralph A; Rugo, Hope S

    2015-01-01

    To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT 3 RA) antiemetics. This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. We identified 1,832 palonosetron and 2,387 other 5-HT 3 RA (“other”) patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019). Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT 3 RAs

  3. Conformational analysis of HAMLET, the folding variant of human alpha-lactalbumin associated with apoptosis.

    Science.gov (United States)

    Casbarra, Annarita; Birolo, Leila; Infusini, Giuseppe; Dal Piaz, Fabrizio; Svensson, Malin; Pucci, Piero; Svanborg, Catharina; Marino, Gennaro

    2004-05-01

    A combination of hydrogen/deuterium (H/D) exchange and limited proteolysis experiments coupled to mass spectrometry analysis was used to depict the conformation in solution of HAMLET, the folding variant of human alpha-lactalbumin, complexed to oleic acid, that induces apoptosis in tumor and immature cells. Although near- and far-UV CD and fluorescence spectroscopy were not able to discriminate between HAMLET and apo-alpha-lactalbumin, H/D exchange experiments clearly showed that they correspond to two distinct conformational states, with HAMLET incorporating a greater number of deuterium atoms than the apo and holo forms. Complementary proteolysis experiments revealed that HAMLET and apo are both accessible to proteases in the beta-domain but showed substantial differences in accessibility to proteases at specific sites. The overall results indicated that the conformational changes associated with the release of Ca2+ are not sufficient to induce the HAMLET conformation. Metal depletion might represent the first event to produce a partial unfolding in the beta-domain of alpha-lactalbumin, but some more unfolding is needed to generate the active conformation HAMLET, very likely allowing the protein to bind the C18:1 fatty acid moiety. On the basis of these data, a putative binding site of the oleic acid, which stabilizes the HAMLET conformation, is proposed.

  4. Extracorporeal shock wave treatment of non- or delayed union of proximal metatarsal fractures.

    Science.gov (United States)

    Alvarez, Richard G; Cincere, Brandon; Channappa, Chandra; Langerman, Richard; Schulte, Robert; Jaakkola, Juha; Melancon, Keith; Shereff, Michael; Cross, G Lee

    2011-08-01

    Nonunion or delayed union of fractures in the proximal aspect of metatarsals 1 to 4 and Zone 2 of the fifth metatarsal were treated by high energy extracorporeal shock wave treatment (ESWT) to study the safety and efficacy of this method of treatment in a FDA study of the Ossatron device. In a prospective single-arm, multi-center study, 34 fractures were treated in 32 patients (two subjects had two independent fractures) with ESWT. All fractures were at least 10 (range, 10 to 833) weeks after injury, with a median of 23 weeks. ESWT application was conducted using a protocol totaling 2,000 shocks for a total energy application of approximately 0.22 to 0.51 mJ/mm2 per treatment. The mean ESWT application time for each of the treatments was 24.6 +/- 16.6 minutes, and anesthesia time averaged 27.1 +/- 10.4 minutes. All subjects were followed for 1 year after treatment at intervals of 12 weeks, 6, 9, and 12 months. The overall success rate at the 12-week visit was 71% with low complications, significant pain improvement as well as improvement on the SF-36. The success/fail criteria was evaluated again at the 6- and 12-month followup, showing treatment success rates of 89% (23/26) and 90% (18/20), respectively. The most common adverse event was swelling in the foot, reported by five subjects (15.6%). High-energy ESWT appears to be effective and safe in patients for treatment of nonunion or a delayed healing of a proximal metatarsal, and in fifth metatarsal fractures in Zone 2.

  5. Oxytocin versus no treatment or delayed treatment for slow progress in the first stage of spontaneous labour.

    Science.gov (United States)

    Bugg, George J; Siddiqui, Farah; Thornton, Jim G

    2013-06-23

    Slow progress in the first stage of spontaneous labour is associated with an increased caesarean section rate and fetal and maternal morbidity. Oxytocin has long been advocated as a treatment for slow progress in labour but it is unclear to what extent it improves the outcomes for that labour and whether it actually reduces the caesarean section rate or maternal and fetal morbidity. This review will address the use of oxytocin and whether it improves the outcomes for women who are progressing slowly in labour compared to situations where it is not used or where its administration is delayed. To determine if the use of oxytocin for the treatment of slow progress in the first stage of spontaneous labour is associated with a reduction in the incidence of caesarean sections, or maternal and fetal morbidity compared to situations where it is not used or where its administration is delayed. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 February 2013) and bibliographies of relevant papers. Randomised controlled trials which compared oxytocin with either placebo, no treatment or delayed oxytocin in the active stage of spontaneous labour in low-risk women at term. Two authors independently assessed studies for inclusion, assessed risk of bias and extracted data. We sought additional information from trial authors. We included eight studies in the review involving a total of 1338 low-risk women in the first stage of spontaneous labour at term. Two comparisons were made; 1) the use of oxytocin versus placebo or no treatment (three trials); 2) the early use of oxytocin versus its delayed use (five trials). There were no significant differences in the rates of caesarean section or instrumental vaginal delivery in either comparison. Early use of oxytocin resulted in an increase in uterine hyperstimulation associated with fetal heart changes. However, the early use of oxytocin versus its delayed use resulted in no significant differences in a range

  6. HAMLET kills tumor cells by an apoptosis-like mechanism--cellular, molecular, and therapeutic aspects.

    Science.gov (United States)

    Svanborg, Catharina; Agerstam, Helena; Aronson, Annika; Bjerkvig, Rolf; Düringer, Caroline; Fischer, Walter; Gustafsson, Lotta; Hallgren, Oskar; Leijonhuvud, Irene; Linse, Sara; Mossberg, Ann-Kristin; Nilsson, Hanna; Pettersson, Jenny; Svensson, Malin

    2003-01-01

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex that induces apoptosis-like death in tumor cells, but leaves fully differentiated cells unaffected. This review summarizes the information on the in vivo effects of HAMLET in patients and tumor models on the tumor cell biology, and on the molecular characteristics of the complex. HAMLET limits the progression of human glioblastomas in a xenograft model and removes skin papillomas in patients. This broad anti-tumor activity includes >40 different lymphomas and carcinomas and apoptosis is independent of p53 or bcl-2. In tumor cells HAMLET enters the cytoplasm, translocates to the perinuclear area, and enters the nuclei where it accumulates. HAMLET binds strongly to histones and disrupts the chromatin organization. In the cytoplasm, HAMLET targets ribosomes and activates caspases. The formation of HAMLET relies on the propensity of alpha-lactalbumin to alter its conformation when the strongly bound Ca2+ ion is released and the protein adopts the apo-conformation that exposes a new fatty acid binding site. Oleic acid (C18:1,9 cis) fits this site with high specificity, and stabilizes the altered protein conformation. The results illustrate how protein folding variants may be beneficial, and how their formation in peripheral tissues may depend on the folding change and the availability of the lipid cofactor. One example is the acid pH in the stomach of the breast-fed child that promotes the formation of HAMLET. This mechanism may contribute to the protective effect of breastfeeding against childhood tumors. We propose that HAMLET should be explored as a novel approach to tumor therapy.

  7. The molecular motor F-ATP synthase is targeted by the tumoricidal protein HAMLET.

    Science.gov (United States)

    Ho, James; Sielaff, Hendrik; Nadeem, Aftab; Svanborg, Catharina; Grüber, Gerhard

    2015-05-22

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) interacts with multiple tumor cell compartments, affecting cell morphology, metabolism, proteasome function, chromatin structure and viability. This study investigated if these diverse effects of HAMLET might be caused, in part, by a direct effect on the ATP synthase and a resulting reduction in cellular ATP levels. A dose-dependent reduction in cellular ATP levels was detected in A549 lung carcinoma cells, and by confocal microscopy, co-localization of HAMLET with the nucleotide-binding subunits α (non-catalytic) and β (catalytic) of the energy converting F1F0 ATP synthase was detected. As shown by fluorescence correlation spectroscopy, HAMLET binds to the F1 domain of the F1F0 ATP synthase with a dissociation constant (KD) of 20.5μM. Increasing concentrations of the tumoricidal protein HAMLET added to the enzymatically active α3β3γ complex of the F-ATP synthase lowered its ATPase activity, demonstrating that HAMLET binding to the F-ATP synthase effects the catalysis of this molecular motor. Single-molecule analysis was applied to study HAMLET-α3β3γ complex interaction. Whereas the α3β3γ complex of the F-ATP synthase rotated in a counterclockwise direction with a mean rotational rate of 3.8±0.7s(-1), no rotation could be observed in the presence of bound HAMLET. Our findings suggest that direct effects of HAMLET on the F-ATP synthase may inhibit ATP-dependent cellular processes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Stressful life events predict delayed functional recovery following treatment for mania in bipolar disorder.

    Science.gov (United States)

    Yan-Meier, Leslie; Eberhart, Nicole K; Hammen, Constance L; Gitlin, Michael; Sokolski, Kenneth; Altshuler, Lori

    2011-04-30

    Identifying predictors of functional recovery in bipolar disorder is critical to treatment efforts to help patients re-establish premorbid levels of role adjustment following an acute manic episode. The current study examined the role of stressful life events as potential obstacles to recovery of functioning in various roles. 65 patients with bipolar I disorder participated in a longitudinal study of functional recovery following clinical recovery from a manic episode. Stressful life events were assessed as predictors of concurrent vs. delayed recovery of role functioning in 4 domains (friends, family, home duties, work/school). Despite clinical recovery, a subset of patients experienced delayed functional recovery in various role domains. Moreover, delayed functional recovery was significantly associated with presence of one or more stressors in the prior 3 months, even after controlling for mood symptoms. Presence of a stressor predicted longer time to functional recovery in life domains, up to 112 days in work/school. Interventions that provide monitoring, support, and problem-solving may be needed to help prevent or mitigate the effects of stress on functional recovery. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  9. Posterior treatment of delayed traumatic atlantoaxial joint dislocation with apofix internal fixation

    International Nuclear Information System (INIS)

    Qing Wei; Jiang Weimin; Shi Jinhui; Li Xuefeng; Yang Huilin; Tang Tiansi

    2010-01-01

    Objective: To assess the effect of posterior fixation and fusion with Apofix device for the treatment of delayed traumatic atlantoaxial joint dislocation. Methods: Eighteen patients with delayed traumatic atlantoaxial joint dislocation were included. Posterior fixation and fusion with Apofix device were performed. First step was one or two week skull traction. After the atlantoaxial joint dislocation had been reduced, the posterior fixation and fusion with Apofix was performed. Using local anaesthesia, atlantoaxial interval and posterior structure of atlas and dentata were exposed by midline operative approach. Apofix interlaminar clamps were placed at posterior arch of atlas and odontoid vertebral laminae, autologous iliac bone graft was placed for fusion. Then the device to proper position was pressurized and items locked. Results: All of the patients were followed up, the mean follow-up period was 38 months (13 ∼ 84 months). Fifteen patients obtained complete reduction, the others were partial reduction. Seventeen patients had successful fusion after 3 or 4 months, only 1 patient who had partial reduction had internal fixation loose and nonfusion, leading to recurrence of atlantoaxial joint dislocation. An occipitocervical fusion surgery was performed on this patient. As to neurological assessment, 16 patients had neurological deficit before operation, while 6 of them recovered completely after operation, another 10 patients' neurological status improved significantly. JOA score was improved from 9.5 pre-operative to 15.8 post-operative. Conclusion: Apofix internal fixation and fusion seems to be feasible in treatment of delayed traumatic atlantoaxial joint dislocation. Successful reduction before operation and proper treatment after operation is also important. (authors)

  10. HyperHamlet – Intricacies of Data Selection

    Directory of Open Access Journals (Sweden)

    Quassdorf, Sixta

    2009-01-01

    Full Text Available HyperHamlet is a database of allusions to and quotations from Shakespeare's Hamlet, which is supported by the Swiss National Science Foundation as a joint venture between the Departments of English and German Philology, and the Image & Media Lab at the University of Basel. The compilation of a corpus, whose aim it is to document the "Shakespeare phenomenon", is intricate on more than one level: the desired transdisciplinary approach between linguistics, literary and cultural studies entails data selection from a vast variety of sources; the pragmatic nature of intertextual traces, i.e. their dependence on and subordination to new contexts, further adds to formal heterogeneity. This is not only a challenge for annotation, but also for data selection. As the recognition of intertextual traces is more often than not based on intuition, this paper analyses the criteria which underlie intuition so that it can be operationalised for scholarly corpus compilation. An analogue to the pragmatic model of ostensive-inferential communication with its three constitutive parts of speaker's meaning, sentence meaning and hearer's meaning has been used for analytical heuristics. Authorial intent – in a concrete as well as in an abstract historical sense – origin and specific encyclopaedic knowledge have been found to be the basic assumptions underlying data selection, while quantitative factors provide supporting evidence.

  11. Delays and Refusal in Treatment for Breast Cancer Among Native American and Hispanic Women with Breast Cancer

    National Research Council Canada - National Science Library

    Saavedra, Elba

    2000-01-01

    ..., attitudinal, spiritual and demographic variables associated with delays and refusals in breast cancer treatment The focus of the semi-structured interview is to encourage the women in story-telling...

  12. 'Lost to follow up': rethinking delayed and interrupted HIV treatment among married Swazi women.

    Science.gov (United States)

    Dlamini-Simelane, Thandeka T T; Moyer, Eileen

    2017-03-01

    Through various campaigns and strategies, more women are being tested for HIV in countries with a high prevalence of the virus. Despite the ready availability of treatment at government clinics in sub-Saharan African countries like Swaziland, women consistently report difficulty in maintaining access to treatment. Drawing on two individual case studies selected from a larger study of the so-called leaky cascade in Swaziland, we illustrate the protracted journeys married women undertake to initiate treatment. We demonstrate how women manoeuvre tactically after diagnosis, highlight factors that influence their decisions related to initiating treatment, and detail the actors involved in the decision-making process. Our research shows the persistence of structural factors that inhibit access, including economic constraints, gender inequality and patriarchal social norms. Patients referred as ‘lost to follow up’ are in many cases actively pursuing treatment within a context that includes the biomedical health system, but also extends well beyond it. We argue that the phrase ‘lost to follow up’ conceals the complex social navigation required by women to initiate and maintain access to treatment. Further, we suggest that many of the logistical challenges of monitoring and tracking people with HIV can be better addressed by taking into account the structural and social aspects of delayed treatment initiative.

  13. [Re-bleeding predictors in patients with aneurysmal subarachnoid haemorrhage and delayed neurosurgical treatment].

    Science.gov (United States)

    Rivero Rodríguez, Dannys; Scherle Matamoros, Claudio; Fernández Cúe, Leda; Miranda Hernández, José Luis; Pernas Sánchez, Yanelis; Pérez Nellar, Jesús

    2016-01-01

    To evaluate the re-bleeding predictors in patients with delayed treatment of aneurysmal subarachnoid hemorrhage. A prospective cohort study enrolled 261 patients with aneurysmal subarachnoid hemorrhage, attending in Hermanos Ameijeiras Hospital from October 2005, and June 2014. An increased re-bleeding risk in the multivariate analysis was associated with grade III (OR 2.01; 95% CI; 1.06-3.84) and grade IV (OR 3.84; 95% CI; 2.06-7.31) on World Federation Neurological Surgeon (WFNS) scale; grade III (OR 2.04; 95% CI; 1.01-4.13) and grade IV (OR 2.12, 95% CI; 1.05-4.28) on the Fischer scale, aneurism location in posterior circulation (OR 2.45, 95% CI; 1.33-4.44), and anterior communicant artery (OR 1.57, 95% CI;1.00-2.46). Hypertension history was present in 60.9% (159 patients) and was also associated with risk of re-bleeding (OR 2.70, 95% CI; 1.00-7.30). Blood pressure, haematocrit, glycemic, aneurysm size, multiple aneurysms, and location in the middle cerebral artery, do not show any relationship. Hypertension history, poor grade (III and IV) on WFNS and Fisher scale and aneurysm location were independent risks factors of re-bleeding in patients with delayed aneurysmal treatment. Copyright © 2014 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  14. Delayed brain radiation necrosis: pathological review and new molecular targets for treatment.

    Science.gov (United States)

    Furuse, Motomasa; Nonoguchi, Naosuke; Kawabata, Shinji; Miyatake, Shin-Ichi; Kuroiwa, Toshihiko

    2015-12-01

    Delayed radiation necrosis is a well-known adverse event following radiotherapy for brain diseases and has been studied since the 1930s. The primary pathogenesis is thought to be the direct damage to endothelial and glial cells, particularly oligodendrocytes, which causes vascular hyalinization and demyelination. This primary pathology leads to tissue inflammation and ischemia, inducing various tissue protective responses including angiogenesis. Macrophages and lymphocytes then infiltrate the surrounding areas of necrosis, releasing inflammatory cytokines such as interleukin (IL)-1α, IL-6, and tumor necrosis factor (TNF)-α. Microglia also express these inflammatory cytokines. Reactive astrocytes play an important role in angiogenesis, expressing vascular endothelial growth factor (VEGF). Some chemokine networks, like the CXCL12/CXCR4 axis, are upregulated by tissue inflammation. Hypoxia may mediate the cell-cell interactions among reactive astrocytes, macrophages, and microglial cells around the necrotic core. Recently, bevacizumab, an anti-VEGF antibody, has demonstrated promising results as an alternative treatment for radiation necrosis. The importance of VEGF in the pathophysiology of brain radiation necrosis is being recognized. The discovery of new molecular targets could facilitate novel treatments for radiation necrosis. This literature review will focus on recent work characterizing delayed radiation necrosis in the brain.

  15. Ovarian reaction and estrus manifestation in delayed puberty gilts after treatment with equine chorionic gonadotropin

    Directory of Open Access Journals (Sweden)

    Stančić Ivan B

    2012-08-01

    Full Text Available Abstract Background Prolonged pre-insemination anestrus (i.e. delayed puberty is a major contributing factor for culling up to 30% of the replacement gilts at large breeding farm units in Vojvodina. It is imperative to determine if these gilts are acyclic (prepubertal or cyclic, but just fail to exhibit behavioural estrus. Recent investigations demonstrate that treatment with equine chorionic gonadotropin (eCG can increase the diestrous phase duration in sexually mature gilts. Based on these finding, the aim of the present studies was to determine the reproductive status of delayed puberty gilts following injection with eCG. Methods Two experiments were conducted on a swine breeding farm in Vojvodina. In Exp. 1, 20 prepubertal (acyclic gilts, and 120 sexually mature (cyclic gilts were injected with a single injection of 400 IU eCG + 200 IU human chorionic gonadotropin (hCG or with 1000 IU eCG (cyclic gilts, at d5, d11 or d17 after spontaneous estrus detection, to determine their ovarian reaction and induced estrus manifestation. In Exp. 2, sixty delayed puberty gilts (estrus not detected until 8 month of age, av. 258 days were culled from breeding herd and slaughtered to determine their reproductive status based on ovarian anatomical features. The second group of gilts (n = 60 was treated with a single 1000 IU eCG injection to determine their reproductive status, based on the interval between eCG injection to estrus detection and duration. The data were analyzed by descriptive statistics, t-test, analysis of variance and Duncan’s test in the software package Statistics 10th. Results Ovulations were induced in 90% of acyclic (sexually immature and, on average, 93.3% of cyclic (sexually mature gilts after the eCG injection. On average, 4 days after the eCG injection, estrus was detected in 85% of the treated acyclic (sexually immature gilts and in 95% (19/20 of the cyclic (sexually mature gilts, treated with eCG on day 17

  16. Surgical treatment of delayed radiation effects in the skin and its indication

    International Nuclear Information System (INIS)

    Tilkorn, H.; Drepper, H.

    1987-01-01

    Since 1960 a total of 1200 patients with skin disease as delayed radiation effects were treated at the Hornheide special clinic, 40% of whom received plastic surgery. This requires knowledge of the type of radiation applied and when it was applied, additional harmful influences, exposure, differentiation in cases of ulcers between primary, cumulative, and combination effect, early radiation effects, and late radiation effects. Secondary factors leading possibly to necrosis may be: recidivation of the primary tumours, benign or malignant neoplasms, traumatic injuries such as injections, sampling, tight clothing, chemical factors like therapeuticals for local application, allergies, infections of the skin with bacteria or fungi, osteomyelitis, non-infections skin disease, and internal disease. A precondition for successful dermatological and surgical treatment are a careful review of the previous case history and exact diagnosis. Some clinical cases serve to illustrate the theoretical explanations and point out possibilities for surgical treatment. (TRV) [de

  17. Rapid Disease Progression With Delay in Treatment of Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Mohammed, Nasiruddin; Kestin, Larry Llyn; Grills, Inga Siiner; Battu, Madhu; Fitch, Dwight Lamar; Wong, Ching-yee Oliver; Margolis, Jeffrey Harold; Chmielewski, Gary William; Welsh, Robert James

    2011-01-01

    Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

  18. On-demand SSRI treatment of premature ejaculation: pharmacodynamic limitations for relevant ejaculation delay and consequent solutions.

    Science.gov (United States)

    Waldinger, Marcel D; Schweitzer, Dave H; Olivier, Berend

    2005-01-01

    Recently, the idea has emerged that on-demand use of serotonin reuptake inhibitors (SSRIs), particularly short half-life, should be equally effective in delaying ejaculation as daily SSRI treatment of premature ejaculation. To provide evidence that SSRI-induced ejaculation delay is mainly dependent on pharmacodynamic properties of the drug and hardly on pharmacokinetic factors, and that combined SSRI administration with specific 5-hydroxytryptamine (5-HT) receptor antagonism leads acutely to stronger ejaculation delay than acute SSRI monoadministration. We performed a detailed analysis of serotonin neurotransmission and reviewed animal studies with 5-HT(1A) receptor antagonists. In addition, we critically reviewed existing on-demand SSRI treatments publications and the current debate on a definition of premature ejaculation. Intravaginal ejaculation latency time (IELT). Acute SSRI administration leads to only a mild or no increase of 5-HT neurotransmission and concomitant stimulation of postsynaptic 5-HT receptors. Existing on-demand SSRI treatment studies suffer from methodological insufficiencies, and the reported high-fold increases of ejaculation time contradict with neuropharmacological insights from serotonin metabolism. Animal studies show that SSRI coadministration with 5-HT(1A) receptor antagonists significantly increases the ejaculation time acutely compared to acute SSRI monoadministration. On-demand SSRI treatment has less ejaculation-delaying effects than daily SSRI treatment. SSRIs with a short half-life are likely leading to much less ejaculation delay than current registered SSRIs. Combined use of SSRIs with 5-HT(1A) receptor antagonists increases the likelihood of clinically relevant ejaculation delay after on-demand treatment. On-demand SSRIs with short half-life that insufficiently delay ejaculation in men with IELTs less than 1 minute should be called ejaculation-delaying drugs rather than drugs against premature ejaculation.

  19. Loss-to-follow-up and delay to treatment initiation in Pakistan's national tuberculosis control programme.

    Science.gov (United States)

    Ali, Syed Mustafa; Naureen, Farah; Noor, Arif; Fatima, Irum; Viney, Kerri; Ishaq, Muhammad; Anjum, Naveed; Rashid, Aamna; Haider, Ghulam Rasool; Khan, Muhammad Aamir; Aamir, Javariya

    2018-03-09

    Researchers and policy-makers have identified loss to follow-up as a major programmatic problem. Therefore, the objective of this study is to quantify TB related pre-treatment loss to follow up and treatment delay in private sector health care facilities in Pakistan. This was a retrospective, descriptive cohort study using routinely collected programmatic data from TB referral, diagnosis and treatment registers. Data from 48 private healthcare facilities were collected using an online questionnaire prepared in ODK Collect, for the period October 2015 to March 2016. Data were analysed using SPSS. We calculated the: (1) number and proportion of patients who were lost to follow-up during the diagnostic period, (2) number and proportion of patients with pre-treatment loss to follow-up, and (3) the number of days between diagnosis and initiation of treatment. One thousand five hundred ninety-six persons with presumptive TB were referred to the laboratory. Of these, 96% (n = 1538) submitted an on-the-spot sputum sample. Of the 1538 people, 1462 (95%) people subsequently visited the laboratory to submit the early morning (i.e. the second) sample. Hence, loss to follow-up during the diagnostic process was 8% overall (n = 134). Of the 1462 people who submitted both sputum samples, 243 (17%) were diagnosed with sputum smear-positive pulmonary TB and 231 were registered for anti-TB treatment, hence, loss in the pre-treatment phase was 4.9% (n = 12). 152 persons with TB (66%) initiated TB treatment either on the day of TB diagnosis or the next day. A further 79 persons with TB (34%) commenced TB treatment within a mean time of 7 days (range 2 to 64 days). Concentrated efforts should be made by the National TB Control Programme to retain TB patients and innovative methods such as text reminders and behavior change communication may need to be used and tested.

  20. Shakespeare Starts a New Century Travel in China: A Comparative Analysis of the Two New Chinese Re-Translations of Hamlet

    Directory of Open Access Journals (Sweden)

    Xiaonong Wang

    2013-04-01

    Full Text Available The two new 21st-century Chinese re-translations of Shakespeare’s Hamlet, one by Hongyin Wang and the other by Guobin Huang, represent continued efforts by Chinese scholars in studying and translating Shakespeare. Compared with those previous translations, these two have realized fresh achievements in such aspects as use of language with characteristics of the times, employment of new para-textual elements, visual arrangement of verse lines, and new treatment of those literary devices in the original work which usually constitute a major challenge to translators of them. And based on the latest academic research achievements with regard to Hamlet, either of them incorporates its translator’s own research findings. The two translations also show some different features. Their main differences lie in that Wang, who translates mainly for the reader, is more concerned with the overall artistic effect by giving full play to the literary and expressive force of Chinese in characterization and uses naturally used Chinese language in characterization. Also, he lifts his translation in a philosophical connotation and a literary conception. Huang’s version, far more annotated, is rendered for the stage and pays much attention to rhythm-rhyming scheme and image correspondence by concise and accurate Chinese, blending elegant and vulgar features according to the characters’ identity. The two translators have made new contribution to the international Shakespeare studies in general and Hamlet studies in particular.

  1. HAMLET interacts with lipid membranes and perturbs their structure and integrity.

    Science.gov (United States)

    Mossberg, Ann-Kristin; Puchades, Maja; Halskau, Øyvind; Baumann, Anne; Lanekoff, Ingela; Chao, Yinxia; Martinez, Aurora; Svanborg, Catharina; Karlsson, Roger

    2010-02-23

    Cell membrane interactions rely on lipid bilayer constituents and molecules inserted within the membrane, including specific receptors. HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal complex of partially unfolded alpha-lactalbumin (HLA) and oleic acid that is internalized by tumor cells, suggesting that interactions with the phospholipid bilayer and/or specific receptors may be essential for the tumoricidal effect. This study examined whether HAMLET interacts with artificial membranes and alters membrane structure. We show by surface plasmon resonance that HAMLET binds with high affinity to surface adherent, unilamellar vesicles of lipids with varying acyl chain composition and net charge. Fluorescence imaging revealed that HAMLET accumulates in membranes of vesicles and perturbs their structure, resulting in increased membrane fluidity. Furthermore, HAMLET disrupted membrane integrity at neutral pH and physiological conditions, as shown by fluorophore leakage experiments. These effects did not occur with either native HLA or a constitutively unfolded Cys-Ala HLA mutant (rHLA(all-Ala)). HAMLET also bound to plasma membrane vesicles formed from intact tumor cells, with accumulation in certain membrane areas, but the complex was not internalized by these vesicles or by the synthetic membrane vesicles. The results illustrate the difference in membrane affinity between the fatty acid bound and fatty acid free forms of partially unfolded HLA and suggest that HAMLET engages membranes by a mechanism requiring both the protein and the fatty acid. Furthermore, HAMLET binding alters the morphology of the membrane and compromises its integrity, suggesting that membrane perturbation could be an initial step in inducing cell death.

  2. Early versus delayed postoperative radiotherapy for treatment of low-grade gliomas

    Science.gov (United States)

    Sarmiento, J Manuel; Venteicher, Andrew S; Patil, Chirag G

    2015-01-01

    Background In most people with low-grade gliomas (LGG), the primary treatment regimen remains a combination of surgery followed by postoperative radiotherapy. However, the optimal timing of radiotherapy is controversial. It is unclear whether to use radiotherapy in the early postoperative period, or whether radiotherapy should be delayed until tumour progression occurs. Objectives To assess the effects of early postoperative radiotherapy versus radiotherapy delayed until tumour progression for low-grade intracranial gliomas in people who had initial biopsy or surgical resection. Search methods We searched up to September 2014 the following electronic databases: the Cochrane Register of Controlled Trials (CENTRAL, Issue 8, 2014), MEDLINE (1948 to Aug week 3, 2014), and EMBASE (1980 to Aug week 3, 2014) to identify trials for inclusion in this Cochrane review. Selection criteria We included randomised controlled trials (RCTs) that compared early versus delayed radiotherapy following biopsy or surgical resection for the treatment of people with newly diagnosed intracranial LGG (astrocytoma, oligodendroglioma, mixed oligoastrocytoma, astroblastoma, xanthoastrocytoma, or ganglioglioma). Radiotherapy may include conformal external beam radiotherapy (EBRT) with linear accelerator or cobalt-60 sources, intensity-modulated radiotherapy (IMRT), or stereotactic radiosurgery (SRS). Data collection and analysis Three review authors independently assessed the trials for inclusion and risk of bias, and extracted study data. We resolved any differences between review authors by discussion. Adverse effects were also extracted from the study report. We performed meta-analyses using a random-effects model with inverse variance weighting. Main results We included one large, multi-institutional, prospective RCT, involving 311 participants; the risk of bias in this study was unclear. This study found that early postoperative radiotherapy is associated with an increase in time to

  3. Lipids as Tumoricidal Components of Human α-Lactalbumin Made Lethal to Tumor Cells (HAMLET)

    Science.gov (United States)

    Ho, James C. S.; Storm, Petter; Rydström, Anna; Bowen, Ben; Alsin, Fredrik; Sullivan, Louise; Ambite, Inès; Mok, K. H.; Northen, Trent; Svanborg, Catharina

    2013-01-01

    Long-chain fatty acids are internalized by receptor-mediated mechanisms or receptor-independent diffusion across cytoplasmic membranes and are utilized as nutrients, building blocks, and signaling intermediates. Here we describe how the association of long-chain fatty acids to a partially unfolded, extracellular protein can alter the presentation to target cells and cellular effects. HAMLET (human α-lactalbumin made lethal to tumor cells) is a tumoricidal complex of partially unfolded α-lactalbumin and oleic acid (OA). As OA lacks independent tumoricidal activity at concentrations equimolar to HAMLET, the contribution of the lipid has been debated. We show by natural abundance 13C NMR that the lipid in HAMLET is deprotonated and by chromatography that oleate rather than oleic acid is the relevant HAMLET constituent. Compared with HAMLET, oleate (175 μm) showed weak effects on ion fluxes and gene expression. Unlike HAMLET, which causes metabolic paralysis, fatty acid metabolites were less strongly altered. The functional overlap increased with higher oleate concentrations (500 μm). Cellular responses to OA were weak or absent, suggesting that deprotonation favors cellular interactions of fatty acids. Fatty acids may thus exert some of their essential effects on host cells when in the deprotonated state and when presented in the context of a partially unfolded protein. PMID:23629662

  4. Effect of Aegle marmelos and Murraya koenigii in treatment of delayed pubertal buffaloes heifers

    Directory of Open Access Journals (Sweden)

    Mohan M. Baitule

    2016-12-01

    Full Text Available Aim: This study aims to study the estrus induction, ovulation, and conception rate of delayed puberty in buffaloes heifers by feeding a herbal plants Aegle marmelos (bael/bili/bhel leaf and Murraya koenigii (Curry leaf. Materials and Methods: Totally, 24 buffalo heifers with delayed puberty were selected for the present study and divided randomly in four equal groups (n=6. Before experiment, all animals were dewormed with albendazole at 10 mg/kg body weight to prevent them from the stress of parasitism. In the present experiment, four group taken and Group I (n=6 treated with A. marmelos, Group II (n=6 treated with M. koenigii, Group III (n=6 treated with mixture of A. marmelos and M. koenigii and fed for 9 days. Group IV (n=6 considered as control and fed with concentrate only. The blood samples were collected from all the animals on day 0 (before treatment, 4, 9 (during treatment, on the day of estrus and day 8 after the onset of estrus. The 10 ml blood was collected from the jugular vein of all the experimental animals for estimation of serum calcium, inorganic phosphorus, and progesterone (P4. The estrus response, ovulation, conception rate along with serum calcium, inorganic phosphorus, and progesterone level were determined by the standard protocol. Results: From Group III 4 heifers, from Group II 3 heifers, and from Group I and IV (Control 2 heifers each, exhibited the estrus. The estrus response was recorded as 33.33%, 50.00%, 75.00%, and 33.33% in Group I, Group II, Group III, and Group IV, respectively. In treatment Group III, serum calcium found significantly more (p<0.05 on day 8 post-estrus as compared to other groups at a similar interval. Inorganic phosphorus and progesterone show no significant difference between groups. The ovulation and conception rates are comparatively better in Group III (75% buffalo heifers than other groups. Conclusion: Herbal supplementation of A. marmelos and M. koenigii in combination, as well as M

  5. The characters God and Hamlet by Jack Miles

    Directory of Open Access Journals (Sweden)

    Tania de Fátima da Silva

    2015-04-01

    Full Text Available In the book “God - A Biography,” Jack Miles aims to introduce ourselves Creator-God as a literary character. Miles developed a narrative based on concept aristotelian, in other words, the structure of the work is made from beginning to end. This procedure established a harmony arising from the interaction between the parties, which contributes to scrutinize the precise details of the story of the main protagonist. We decided to highlight that time some characteristics of the main character of the work and compare them to the character Hamlet, by William Shakespeare, because from the beginning of the narrative to completion Miles calls the reader’s attention to the play Shakespeare.

  6. No Evidence of Delayed Parasite Clearance after Oral Artesunate Treatment of Uncomplicated Falciparum Malaria in Mali

    Science.gov (United States)

    Maiga, Amelia W.; Fofana, Bakary; Sagara, Issaka; Dembele, Demba; Dara, Antoine; Traore, Oumar Bila; Toure, Sekou; Sanogo, Kassim; Dama, Souleymane; Sidibe, Bakary; Kone, Aminatou; Thera, Mahamadou A.; Plowe, Christopher V.; Doumbo, Ogobara K.; Djimde, Abdoulaye A.

    2012-01-01

    Plasmodium falciparum resistance to artemisinins by delayed parasite clearance is present in Southeast Asia. Scant data on parasite clearance after artemisinins are available from Africa, where transmission is high, burden is greatest, and artemisinin use is being scaled up. Children 1–10 years of age with uncomplicated malaria were treated with 7 days of artesunate and followed for 28 days. Blood smears were done every 8 hours until negative by light microscopy. Results were compared with a similar study conducted in the same village in 2002–2004. The polymerase chain reaction-corrected cure rate was 100%, identical to 2002–2004. By 24 hours after treatment initiation, 37.0% of participants had cleared parasitemia, compared with 31.9% in 2002–2004 (P = 0.5). The median parasite clearance time was 32 hours. Only one participant still had parasites at 48 hours and no participant presented parasitemia at 72 hours. Artesunate was highly efficacious, with no evidence of delayed parasite clearance. We provide baseline surveillance data for the emergence or dissemination of P. falciparum resistance in sub-Saharan Africa. PMID:22764287

  7. Delayed Toxicity Associated with Soluble Anthrax Toxin Receptor Decoy-Ig Fusion Protein Treatment

    Science.gov (United States)

    Cote, Christopher; Welkos, Susan; Manchester, Marianne; Young, John A. T.

    2012-01-01

    Soluble receptor decoy inhibitors, including receptor-immunogloubulin (Ig) fusion proteins, have shown promise as candidate anthrax toxin therapeutics. These agents act by binding to the receptor-interaction site on the protective antigen (PA) toxin subunit, thereby blocking toxin binding to cell surface receptors. Here we have made the surprising observation that co-administration of receptor decoy-Ig fusion proteins significantly delayed, but did not protect, rats challenged with anthrax lethal toxin. The delayed toxicity was associated with the in vivo assembly of a long-lived complex comprised of anthrax lethal toxin and the receptor decoy-Ig inhibitor. Intoxication in this system presumably results from the slow dissociation of the toxin complex from the inhibitor following their prolonged circulation. We conclude that while receptor decoy-Ig proteins represent promising candidates for the early treatment of B. anthracis infection, they may not be suitable for therapeutic use at later stages when fatal levels of toxin have already accumulated in the bloodstream. PMID:22511955

  8. Delay to Reconstruction of the Adolescent Anterior Cruciate Ligament: The Socioeconomic Impact on Treatment.

    Science.gov (United States)

    Newman, Justin T; Carry, Patrick M; Terhune, Elizabeth B; Spruiell, Murray; Heare, Austin; Mayo, Meredith; Vidal, Armando F

    2014-08-01

    A delay in pediatric and adolescent anterior cruciate ligament (ACL) reconstruction is associated with an increase in the number of concomitant meniscal and chondral injuries. Factors that contribute to this delay have not been well described. Socioeconomic and demographic factors are related to ACL surgery timing. Cohort study; Level of evidence, 3. All subjects who underwent primary ACL reconstruction at a single tertiary pediatric hospital between 2005 and 2012 were retrospectively reviewed. Variables included concomitant knee injuries (cartilage or meniscus injuries requiring additional operative treatment) and chronologic, demographic, and socioeconomic factors. Multivariable Cox proportional-hazards analyses were used to identify factors related to ACL surgery timing. The mean age of the 272 subjects was 15.2 ± 2.12 years. Time to surgery was significantly different among subjects who required multiple additional surgical procedures at time of ACL reconstruction (median, 3.3 months) compared with subjects with 1 (median, 2.0 months) or no additional injuries (median, 1.6 months). Subjects underwent ACL reconstruction significantly sooner if they were older at the time of injury (hazard ratio [HR], 1.2 per 1 year; 95% CI, 1.1-1.2; P socioeconomic and demographic factors and ACL surgery timing to optimize outcomes.

  9. Time-delayed contrast-enhanced MRI improves detection of brain metastases and apparent treatment volumes.

    Science.gov (United States)

    Kushnirsky, Marina; Nguyen, Vinh; Katz, Joel S; Steinklein, Jared; Rosen, Lisa; Warshall, Craig; Schulder, Michael; Knisely, Jonathan P S

    2016-02-01

    Contrast-enhanced MRI is the preeminent diagnostic test for brain metastasis (BM). Detection of BMs for stereotactic radiosurgery (SRS) planning may improve with a time delay following administration of a high-relaxivity agent for 1.5-T and 3-T imaging systems. Metastasis detection with time-delayed MRI was evaluated in this study. Fifty-three volumetric MRI studies from 38 patients undergoing SRS for BMs were evaluated. All studies used 0.1-mmol/kg gadobenate dimeglumine (MultiHance; Bracco Diagnostics) immediately after injection, followed by 2 more axial T1-weighted sequences after 5-minute intervals (final image acquisition commenced 15 minutes after contrast injection). Two studies were motion limited and excluded. Two hundred eighty-seven BMs were identified. The studies were randomized and examined separately by 3 radiologists, who were blinded to the temporal sequence. Each radiologist recorded the number of BMs detected per scan. A Wilcoxon signed-rank test compared BM numbers between scans. One radiologist determined the scan on which BMs were best defined. All confirmed, visible tumors were contoured using iPlan RT treatment planning software on each of the 3 MRI data sets. A linear mixed model was used to analyze volume changes. The interclass correlations for Scans 1, 2, and 3 were 0.7392, 0.7951, and 0.7290, respectively, demonstrating excellent interrater reliability. At least 1 new lesion was detected in the second scan as compared with the first in 35.3% of subjects (95% CI 22.4%-49.9%). The increase in BM numbers between Scans 1 and 2 ranged from 1 to 10. At least 1 new lesion was detected in the third scan as compared with the second in 21.6% of subjects (95% CI 11.3%-35.3%). The increase in BM numbers between Scans 2 and 3 ranged from 1 to 9. Between Scans 1 and 3, additional tumors were seen on 43.1% of scans (increase ranged from 1 to 14). The median increase in tumor number for all comparisons was 1. There was a significant increase in number

  10. Herbs and natural supplements in the prevention and treatment of delayed-onset muscle soreness

    Directory of Open Access Journals (Sweden)

    Abbas Meamarbashi

    2017-01-01

    Full Text Available Objective:  Unaccustomed and intense eccentric exercise is a common cause of delayed-onset muscle soreness (DOMS. There are multiple remedies for the treatment of DOMS, but its clinical and laboratory pieces of evidence are scarce. Currently, the treatments proposed for DOMS are numerous and include pharmaceuticals, herbal remedies, stretching, massage, nutritional supplements, and other alternatives. To find a holistic treatment with effective pain relief and minimum side effects, complementary and alternative medicine, including herbal therapies, plays a main role.Methods: In this review, the existing published studies investigating the efficacy of herbal and natural supplementation therapies for the prevention or treatment of side effects, symptoms, and signs of DOMS are summarized.Results: Previous studies have documented the efficacy of herbal therapies to treat pain, inflammation, as well as laboratory and clinical side effects of DOMS.Conclusion: The use of herbs in DOMS seems safer and has lower side effects than pharmacotherapy. However, the potential for side effects and drug interactions should be considered.

  11. [Early versus delayed physiotherapy in the treatment of post-prostatectomy male urinary incontinence].

    Science.gov (United States)

    Tarcía Kahihara, Carina; Ferreira, Ubirajora; Nardi Pedro, Renato; Matheus, Wagner Eduardo; Rodrigues Netto, Nelson

    2006-10-01

    To analyze the importance of the starting time for pelvic floor physiotherapy in patients with post radical prostatectomy urinary incontinence. Between May 2003 and February 2004 18 patients with the diagnosis of post radical prostatectomy urinary incontinence underwent physiotherapy of the pelvic floor. Each patient received 12 sessions using kinesotherapy and electric stimulation on a weekly basis. Patients were divided into two groups: Group 1 included eight patients that started therapy within the first six months after surgery; Group 2 included 10 patients starting therapy after the sixth post operative month. All patients were evaluated by the pad test and number of incontinence pads per day. Evaluating pad tests before and after treatment, six patients in group 1 had a reduction of the amount of urine leak in comparison to seven patients in group 2. The statistical analysis showed significant differences before and after treatment for both groups (group 1: p = 0.028; group 2: p = 0.018). The evaluation of the number of pads showed: Group 1: all eight patients using pods had a reduction in the number of pads. Group 2: 5 of the eight patients using pads had a reduction and the other three continued using the same number. Statistical analysis comparing the number of pads per day before and after treatment showed a significant difference in group 1 (p = 0.004). There was no statistically significant difference in the number of pads per day before and after physiotherapy in group 2, although half of the patients showed a diminishment in the number of pads required after treatment. Results demonstrate that early indication of physiotherapy for the treatment of post radical prostatectomy urinary incontinence is better than delayed treatment. New works may be developed in the future to confirm our results.

  12. Behavior Problems in Toddlers with and without Developmental Delays: Comparison of Treatment Outcomes

    Science.gov (United States)

    Holtz, Casey A.; Carrasco, Jennifer M.; Mattek, Ryan J.; Fox, Robert A.

    2009-01-01

    The purpose of this study is to examine the effectiveness of an in-home parent management program for toddlers with behavior problems and developmental delays by comparing outcomes for a group of toddlers with developmental delays (n = 27) and a group of toddlers without developmental delays (n = 27). The majority of children lived in single…

  13. A STUDY OF IMPACT OF DETERMINANTS OF PATIENTS AND HEALTH SYSTEM DELAY ON TUBERCULOSIS DIAGNOSIS AND TREATMENT IN BANGALORE

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    Jagadish Siddalinga Devaru

    2013-01-01

    Full Text Available Setting: TU/DMCs of Bangalore city. India. All new sputum positive patients registered to the selected TU/DMCs were interviewed. A total of 468 patients aged above 20 years were enrolled. The study period was from January to June 2009. Objectives: To track the delay in diagnosis and treatment of patients reporting to tuberculosis units and microscopy centers. Design: A cross sectional study. TU/DMCs were randomly selected. A pretested questionnaire was administered to collect data. Results: The study population had 326 (69.7% males. The mean age of study population was 38.5 years. 74.4% were married, 20.7% were illiterates, 27.8% were daily wagers, 10.5% were unemployed. The median and mean total delays from development of cough to diagnosis were 41 days and 36.04 days; the median and mean patient delay was 24 days and 20.7 days, and health system delay was 18 and 15.31 days respectively. There was a significant difference among the different age group of patients with older people having longer patient delay (p<0.0001. Lower income, illiteracy, unemployment, showed significant association with patients delay (p<0.0001. Alcohol intake and smoking habit among the male patients had significant association for longer patient delay (p=0.00004. Health seeking behavior like self medication, also had longer patient delay. Other socio demographic factors had no significant influence on the patient delay. Longer health system delay was found among patients who visited general practitioners and Ayurvedic medicine. Conclusion: More specific and effective health education of the general public on tuberculosis and seeking of appropriate medical consultation are likely to improve case detection.

  14. A STUDY OF IMPACT OF DETERMINANTS OF PATIENTS AND HEALTH SYSTEM DELAY ON TUBERCULOSIS DIAGNOSIS AND TREATMENT IN BANGALORE

    Directory of Open Access Journals (Sweden)

    Jagadish Siddalinga Devaru

    2012-12-01

    Full Text Available Setting: TU/DMCs of Bangalore city. India. All new sputum positive patients registered to the selected TU/DMCs were interviewed. A total of 468 patients aged above 20 years were enrolled. The study period was from January to June 2009. Objectives: To track the delay in diagnosis and treatment of patients reporting to tuberculosis units and microscopy centers. Design: A cross sectional study. TU/DMCs were randomly selected. A pretested questionnaire was administered to collect data. Results: The study population had 326 (69.7% males. The mean age of study population was 38.5 years. 74.4% were married, 20.7% were illiterates, 27.8% were daily wagers, 10.5% were unemployed. The median and mean total delays from development of cough to diagnosis were 41 days and 36.04 days; the median and mean patient delay was 24 days and 20.7 days, and health system delay was 18 and 15.31 days respectively. There was a significant difference among the different age group of patients with older people having longer patient delay (p<0.0001. Lower income, illiteracy, unemployment, showed significant association with patients delay (p<0.0001. Alcohol intake and smoking habit among the male patients had significant association for longer patient delay (p=0.00004. Health seeking behavior like self medication, also had longer patient delay. Other socio demographic factors had no significant influence on the patient delay. Longer health system delay was found among patients who visited general practitioners and Ayurvedic medicine. Conclusion: More specific and effective health education of the general public on tuberculosis and seeking of appropriate medical consultation are likely to improve case detection.

  15. Anoxia Treatment for Delaying Skin Browning, Inhibiting Disease Development and Maintaining the Quality of Litchi Fruit

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    Yueming Jiang

    2004-01-01

    Full Text Available Litchi fruit has a very short shelf life after harvest, so marketers and consumers alike desire longer periods of storage, transportation and distribution. To extend shelf life, anoxia treatments were used for the fruit. Litchi fruit were exposed to pure N2 for 0, 3, 6, 12 or 24 h. They were then kept individually in closed but vented containers for 6 days in the dark at 20 °C and 95–100 % relative humidity. Exposure of litchi fruit to N2 for 3 or 6 h markedly delayed skin browning, reduced rot development and maintained higher concentrations of total soluble solids, titratable acidity and ascorbic acid after 6 days of storage. Anoxia treatment for 24 h reduced browning index, but it accelerated disease development, compared to the control. Thus, a pre-storage pure N2 treatment for 3 or 6 h can be an effective means of reducing rotting while maintaining the physical quality of the fruit.

  16. Delayed conifer mortality after fuel reduction treatments: Interactive effects of fuel, fire intensity, and bark beetles

    Science.gov (United States)

    Youngblood, A.; Grace, J.B.; Mciver, J.D.

    2009-01-01

    Many low-elevation dry forests of the western United States contain more small trees and fewer large trees, more down woody debris, and less diverse and vigorous understory plant communities compared to conditions under historical fire regimes. These altered structural conditions may contribute to increased probability of unnaturally severe wildfires, susceptibility to uncharacteristic insect outbreaks, and drought-related mortality. Broad-scale fuel reduction and restoration treatments are proposed to promote stand development on trajectories toward more sustainable structures. Little research to date, however, has quantified the effects of these treatments on the ecosystem, especially delayed and latent tree mortality resulting directly or indirectly from treatments. In this paper, we explore complex hypotheses relating to the cascade of effects that influence ponderosa pine (Pinus ponderosa) and Douglas-fir (Pseudotsuga menziesii) mortality using structural equation modeling (SEM). We used annual census and plot data through six growing seasons after thinning and four growing seasons after burning from a replicated, operational-scale, completely randomized experiment conducted in northeastern Oregon, USA, as part of the national Fire and Fire Surrogate study. Treatments included thin, burn, thin followed by burn (thin+burn), and control. Burn and thin+burn treatments increased the proportion of dead trees while the proportion of dead trees declined or remained constant in thin and control units, although the density of dead trees was essentially unchanged with treatment. Most of the new mortality (96%) occurred within two years of treatment and was attributed to bark beetles. Bark beetle-caused tree mortality, while low overall, was greatest in thin + burn treatments. SEM results indicate that the probability of mortality of large-diameter ponderosa pine from bark beetles and wood borers was directly related to surface fire severity and bole charring, which in

  17. Treatment-time-dependence models of early and delayed radiation injury in rat small intestine

    International Nuclear Information System (INIS)

    Denham, James W.; Hauer-Jensen, Martin; Kron, Tomas; Langberg, Carl W.

    2000-01-01

    Background: The present study modeled data from a large series of experiments originally designed to investigate the influence of time, dose, and fractionation on early and late pathologic endpoints in rat small intestine after localized irradiation. The objective was to obtain satisfactory descriptions of the regenerative response to injury together with the possible relationships between early and late endpoints. Methods: Two- and 26-week pathologic radiation injury data in groups of Sprague-Dawley rats irradiated with 27 different fractionation schedules were modeled using the incomplete repair (IR) version of the linear-quadratic model with or without various time correction models. The following time correction models were tested: (1) No time correction; (2) A simple exponential (SE) regenerative response beginning at an arbitrary time after starting treatment; and (3) A bi-exponential response with its commencement linked to accumulated cellular depletion and fraction size (the 'intelligent response model' [INTR]). Goodness of fit of the various models was assessed by correlating the predicted biological effective dose for each dose group with the observed radiation injury score. Results: (1) The incomplete repair model without time correction did not provide a satisfactory description of either the 2- or 26-week data. (2) The models using SE time correction performed better, providing modest descriptions of the data. (3) The INTR model provided reasonable descriptions of both the 2- and 26-week data, confirming a treatment time dependence of both early and late pathological endpoints. (4) The most satisfactory descriptions of the data by the INTR model were obtained when the regenerative response was assumed to cease 2 weeks after irradiation rather than at the end of irradiation. A fraction-size-dependent delay of the regenerative response was also suggested in the best fitting models. (5) Late endpoints were associated with low-fractionation sensitivity

  18. Low resolution solution structure of HAMLET and the importance of its alpha-domains in tumoricidal activity.

    Science.gov (United States)

    Ho, C S James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

    2012-01-01

    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells.

  19. Durations and Delays in Care Seeking, Diagnosis and Treatment Initiation in Uncomplicated Pulmonary Tuberculosis Patients in Mumbai, India.

    Directory of Open Access Journals (Sweden)

    Nerges Mistry

    Full Text Available Timely diagnosis and treatment initiation are critical to reduce the chain of transmission of Tuberculosis (TB in places like Mumbai, where almost 60% of the inhabitants reside in overcrowded slums. This study documents the pathway from the onset of symptoms suggestive of TB to initiation of TB treatment and examines factors responsible for delay among uncomplicated pulmonary TB patients in Mumbai.A population-based retrospective survey was conducted in the slums of 15 high TB burden administrative wards to identify 153 self-reported TB patients. Subsequently in-depth interviews of 76 consenting patients that fit the inclusion criteria were undertaken using an open-ended interview schedule. Mean total, first care seeking, diagnosis and treatment initiation duration and delays were computed for new and retreatment patients. Patients showing defined delays were divided into outliers and non-outliers for all three delays using the median values.The mean duration for the total pathway was 65 days with 29% of patients being outliers. Importantly the mean duration of first care seeking was similar in new (24 days and retreatment patients (25 days. Diagnostic duration contributed to 55% of the total pathway largely in new patients. Treatment initiation was noted to be the least among the three durations with mean duration in retreatment patients twice that of new patients. Significantly more female patients experienced diagnostic delay. Major shift of patients from the private to public sector and non-allopaths to allopaths was observed, particularly for treatment initiation.Achieving positive behavioural changes in providers (especially non-allopaths and patients needs to be considered in TB control strategies. Specific attention is required in counselling of TB patients so that timely care seeking is effected at the time of relapse. Prioritizing improvement of environmental health in vulnerable locations and provision of point of care diagnostics

  20. Durations and Delays in Care Seeking, Diagnosis and Treatment Initiation in Uncomplicated Pulmonary Tuberculosis Patients in Mumbai, India.

    Science.gov (United States)

    Mistry, Nerges; Rangan, Sheela; Dholakia, Yatin; Lobo, Eunice; Shah, Shimoni; Patil, Akshaya

    2016-01-01

    Timely diagnosis and treatment initiation are critical to reduce the chain of transmission of Tuberculosis (TB) in places like Mumbai, where almost 60% of the inhabitants reside in overcrowded slums. This study documents the pathway from the onset of symptoms suggestive of TB to initiation of TB treatment and examines factors responsible for delay among uncomplicated pulmonary TB patients in Mumbai. A population-based retrospective survey was conducted in the slums of 15 high TB burden administrative wards to identify 153 self-reported TB patients. Subsequently in-depth interviews of 76 consenting patients that fit the inclusion criteria were undertaken using an open-ended interview schedule. Mean total, first care seeking, diagnosis and treatment initiation duration and delays were computed for new and retreatment patients. Patients showing defined delays were divided into outliers and non-outliers for all three delays using the median values. The mean duration for the total pathway was 65 days with 29% of patients being outliers. Importantly the mean duration of first care seeking was similar in new (24 days) and retreatment patients (25 days). Diagnostic duration contributed to 55% of the total pathway largely in new patients. Treatment initiation was noted to be the least among the three durations with mean duration in retreatment patients twice that of new patients. Significantly more female patients experienced diagnostic delay. Major shift of patients from the private to public sector and non-allopaths to allopaths was observed, particularly for treatment initiation. Achieving positive behavioural changes in providers (especially non-allopaths) and patients needs to be considered in TB control strategies. Specific attention is required in counselling of TB patients so that timely care seeking is effected at the time of relapse. Prioritizing improvement of environmental health in vulnerable locations and provision of point of care diagnostics would be

  1. The identification of risk factors associated with patient and healthcare system delays in the treatment of tuberculosis in Tabriz, Iran.

    Science.gov (United States)

    Ebrahimi Kalan, Mohammad; Yekrang Sis, Hassan; Kelkar, Vinaya; Harrison, Scott H; Goins, Gregory D; Asghari Jafarabadi, Mohammad; Han, Jian

    2018-01-24

    Tuberculosis (TB) is a serious health concern, particularly in developing countries. Various delays, such as patient delay (PD) and healthcare system delay (HSD) in the TB process, are exacerbating the disease burden and increasing the rates of transmission and mortality in various global communities. Therefore, the aim of this study is to identify risk factors associated with PD and HSD in TB patients in Tabriz, Iran. A cross-sectional study was conducted on 173 TB patients in Tabriz, Iran from 2012 to 2014. Patients were interviewed with a semi-structured questionnaire. Frequencies and percentages were reported for patient categories of sex, age, and education. The median and interquartile range (IQR) were reported for the time intervals of delays. Univariate and multivariate logistic regressions of delay in respect to socio-demographic and clinical variables were performed. Statistical significance was set at p patients during their initial visit to the health care facilities. The knowledge generated from this study will be helpful for prioritizing and developing strategies for minimizing delays, initiating early treatment to TB patients, and improving TB-related training programs and healthcare systems in Tabriz, Iran.

  2. Temporal changes in hamlet communities (Hypoplectrus spp., Serranidae) over 17 years.

    Science.gov (United States)

    Hench, K; Mcmillan, W O; Betancur-R, R; Puebla, O

    2017-11-01

    Transect surveys of hamlet communities (Hypoplectrus spp., Serranidae) covering 14 000 m 2 across 16 reefs off La Parguera, Puerto Rico, are presented and compared with a previous survey conducted in the year 2000. The hamlet community has noticeably changed over 17 years, with a > 30% increase in relative abundance of the yellowtail hamlet Hypoplectrus chlorurus on the inner reefs at the expense of the other hamlet species. The data also suggest that the density of H. chlorurus has declined and that its distribution has shifted towards shallower depths. Considering that H. chlorurus has been previously identified as one of the few fish showing a positive association with seawater turbidity on the inner reefs of La Parguera and that sedimentation of terrestrial origin has increased over recent decades on these reefs, it is proposed that turbidity may constitute an important but so far overlooked ecological driver of hamlet communities. © 2017 The Fisheries Society of the British Isles.

  3. Protein receptor-independent plasma membrane remodeling by HAMLET: a tumoricidal protein-lipid complex.

    Science.gov (United States)

    Nadeem, Aftab; Sanborn, Jeremy; Gettel, Douglas L; James, Ho C S; Rydström, Anna; Ngassam, Viviane N; Klausen, Thomas Kjær; Pedersen, Stine Falsig; Lam, Matti; Parikh, Atul N; Svanborg, Catharina

    2015-11-12

    A central tenet of signal transduction in eukaryotic cells is that extra-cellular ligands activate specific cell surface receptors, which orchestrate downstream responses. This ''protein-centric" view is increasingly challenged by evidence for the involvement of specialized membrane domains in signal transduction. Here, we propose that membrane perturbation may serve as an alternative mechanism to activate a conserved cell-death program in cancer cells. This view emerges from the extraordinary manner in which HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) kills a wide range of tumor cells in vitro and demonstrates therapeutic efficacy and selectivity in cancer models and clinical studies. We identify a ''receptor independent" transformation of vesicular motifs in model membranes, which is paralleled by gross remodeling of tumor cell membranes. Furthermore, we find that HAMLET accumulates within these de novo membrane conformations and define membrane blebs as cellular compartments for direct interactions of HAMLET with essential target proteins such as the Ras family of GTPases. Finally, we demonstrate lower sensitivity of healthy cell membranes to HAMLET challenge. These features suggest that HAMLET-induced curvature-dependent membrane conformations serve as surrogate receptors for initiating signal transduction cascades, ultimately leading to cell death.

  4. Oleic acid is a key cytotoxic component of HAMLET-like complexes.

    Science.gov (United States)

    Permyakov, Sergei E; Knyazeva, Ekaterina L; Khasanova, Leysan M; Fadeev, Roman S; Zhadan, Andrei P; Roche-Hakansson, Hazeline; Håkansson, Anders P; Akatov, Vladimir S; Permyakov, Eugene A

    2012-01-01

    HAMLET is a complex of α-lactalbumin (α-LA) with oleic acid (OA) that selectively kills tumor cells and Streptococcus pneumoniae. To assess the contribution of the proteinaceous component to cytotoxicity of HAMLET, OA complexes with proteins structurally and functionally distinct from α-LA were prepared. Similar to HAMLET, the OA complexes with bovine β-lactoglobulin (bLG) and pike parvalbumin (pPA) (bLG-OA-45 and pPA-OA-45, respectively) induced S. pneumoniae D39 cell death. The activation mechanisms of S. pneumoniae death for these complexes were analogous to those for HAMLET, and the cytotoxicity of the complexes increased with OA content in the preparations. The half-maximal inhibitory concentration for HEp-2 cells linearly decreased with rise in OA content in the preparations, and OA concentration in the preparations causing HEp-2 cell death was close to the cytotoxicity of OA alone. Hence, the cytotoxic action of these complexes against HEp-2 cells is induced mostly by OA. Thermal stabilization of bLG upon association with OA implies that cytotoxicity of bLG-OA-45 complex cannot be ascribed to molten globule-like conformation of the protein component. Overall, the proteinaceous component of HAMLET-like complexes studied is not a prerequisite for their activity; the cytotoxicity of these complexes is mostly due to the action of OA.

  5. Effects of Samorin Treatment and Delayed Infection on the Establishment of Trypanosomes in Glossina Pallidipes

    Energy Technology Data Exchange (ETDEWEB)

    Okoth, S; Mukiria, P; Tinega, G; Murilla, G [Trypanosomiasis Research Centre, Kenya Agricultural Research Institute (TRC-KARI), Box 362, Kikuyu (Kenya)

    2012-07-15

    The protective role of Samorin (isometamidium chloride) when given with the bloodmeal, and the effect of the age of flies at infective feed, on the establishment of Trypanosoma congolense and Trypanosoma vivax in Glossina pallidipes Austen was evaluated. G. pallidipes was fed on fresh bovine blood containing 0, 6, 8, 10, 12 and 14 {mu}g of Samorin/mL of blood on day 0. A control group was fed in vivo on an infected goat as first feed on the same day (day 0). On day 3 post-Samorin treatment, the flies were infected in vivo by feeding them on a goat infected with either T. congolense or T. vivax. Similar procedures were followed for the experimental groups infected 5, 10 and 20 days post-Samorin treatment. Thereafter flies were maintained on rabbits for 15 and 20 days for the T. vivax and T. congolense groups, respectively. Fly survival was assessed, and the flies were dissected to determine infection rates. Results showed that the age of a fly at infection significantly affected the refractoriness of G. pallidipes to T. congolense ( F{sub 4,20} = 5.241; P=0.0047) and T. vivax ( F{sub 4,20} = 5.410; P=0.0040) infections. However, the effect of Samorin treatment on infection per se was not shown to be significant (F{sub 5,19} = 2.383; P=0733 and F{sub 4,20} = 1.106; P=0.3900) for T. congolense and T. vivax, respectively. The age of flies at infection significantly reduced tsetse survival (F{sub 4,20} = 7.584; P<0.001 and F{sub 4,20} = 10.755; P=0.0001) for T. congolense and T. vivax groups, respectively. However, Samorin treatment did not significantly reduce survival in both Trypanosoma groups (F{sub 5,19} = 0.642; P>0.67 and F{sub 5,19} = 0.485; P=0.783). These results indicated that, for T. congolense and T. vivax, combining Samorin treatment at a concentration of at least 8 {mu}g/mL, and delaying exposure of tsetse to infective feed for at least 3 days post emergence, induces sufficient refractoriness that may counter the increased challenge posed by the mass

  6. 6. Endovascular treatment for acute traumatic transection of the thoracic aorta: The safety of delayed stenting

    Directory of Open Access Journals (Sweden)

    Adil H. Al Kindi

    2015-10-01

    Conclusion: The delayed approach has been safe with no patients lost during the waiting period. Patients with ATT who make it to the hospital and are stable from the aortic point of view may be managed safely with delayed TEVAR if immediate therapy is not available or possible.

  7. Delayed versus immediate treatment for patients with acute hepatitis C: a randomised controlled non-inferiority trial.

    Science.gov (United States)

    Deterding, Katja; Grüner, Norbert; Buggisch, Peter; Wiegand, Johannes; Galle, Peter R; Spengler, Ulrich; Hinrichsen, Holger; Berg, Thomas; Potthoff, Andrej; Malek, Nisar; Großhennig, Anika; Koch, Armin; Diepolder, Helmut; Lüth, Stefan; Feyerabend, Sandra; Jung, Maria Christina; Rogalska-Taranta, Magdalena; Schlaphoff, Verena; Cornberg, Markus; Manns, Michael P; Wedemeyer, Heiner

    2013-06-01

    Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is very effective, with cure rates of greater than 85%. However, spontaneous clearance of HCV occurs in 10-50% of cases. We aimed to assess an alternative treatment strategy of delayed antiviral therapy in patients who do not eliminate the virus spontaneously compared with immediate treatment. In our open-label phase 3 non-inferiority trial, we enrolled adults (≥18 years) with acute hepatitis C but no HIV or hepatitis B co-infection at 72 centres in Germany. We randomly allocated patients with symptomatic acute hepatitis C (1:1) to receive immediate pegylated interferon alfa-2b treatment for 24 weeks or delayed treatment with pegylated interferon alfa-2b plus ribavirin (for 24 weeks) starting 12 weeks after randomisation if HCV RNA remained positive. We used a computer-generated randomisation sequence and block sizes of eight, stratified by bilirubin concentration. We assigned all asymptomatic patients to immediate treatment with pegylated interferon alfa-2b for 24 weeks. The primary endpoint was sustained HCV RNA negativity in all randomly allocated participants who completed screening (intention-to-treat analysis), with a non-inferiority margin of 10%. For the primary analysis, we calculated the virological response of patients in the immediate and delayed treatment groups and an absolute risk difference stratified by bilirubin status. The trial was stopped early on advice from the study advisory committee because of slow recruitment of participants. This study is registered, number ISRCTN88729946. Between April, 2004, and February, 2010, we recruited 107 symptomatic and 25 asymptomatic patients. 37 (67%) of 55 symptomatic patients randomly allocated to receive immediate treatment and 28 (54%) of 52 symptomatic patients randomly allocated to receive delayed treatment had a sustained virological response (difference 13·7%, 95% CI -4·6 to 32·0; p=0·071). 18 (72%) of 25

  8. Outcome measures in studies on the use of oxytocin for the treatment of delay in labour: A systematic review.

    LENUS (Irish Health Repository)

    Begley, Cecily M

    2014-07-01

    to identify primary and secondary outcome measures in randomised trials, and systematic reviews of randomised trials, measuring effectiveness of oxytocin for treatment of delay in the first and second stages of labour, and to identify any positive health-focussed outcomes used.

  9. Clonidine treatment delays postnatal motor development and blocks short-term memory in young mice.

    Directory of Open Access Journals (Sweden)

    Cristina Calvino-Núñez

    Full Text Available During the development of the nervous system, the perinatal period is particularly sensitive as neuronal connections are still forming in the brain of the neonate. Alpha2-adrenergic receptors are overexpressed temporarily in proliferative zones in the developing brain, reaching a peak during the first postnatal week of life. Both stimulation and blocking of these receptors during this period alter the development of neural circuits, affecting synaptic connectivity and neuronal responses. They even affect motor and cognitive skills later on in the adult. It's especially important to look for the early neurological consequences resulting from such modifications, because they may go unnoticed. The main objective of the present study has been to reaffirm the importance of the maturation of alpha-adrenergic system in mice, by carrying out a comprehensive examination of motor, behavioral and cognitive effects in neonates, during early postnatal development, following chronic administration of the drug Clonidine, an alpha2 adrenergic system agonist. Our study shows that mice treated postnatally with clonidine present a temporal delay in the appearance of developmental markers, a slow execution of vestibular reflexes during first postnatal week of life and a blockade of the short term memory in the novel object recognition task. Shortly after the treatment the startle response is hyperreactive.

  10. Oedipus the King and Hamlet: A Descent to the Fathers

    Directory of Open Access Journals (Sweden)

    Chiara Lombardi

    2017-11-01

    Full Text Available Sulla base delle letture freudiane e di alcune ipotesi circa la circolazione del teatro greco nell’Europa e nell’Inghilterra del Cinquecento e sulla possibile ricezione shakespeariana, questo contributo propone alcune tangenze tra Sofocle e Shakespeare. L’analisi si concentra non tanto su una figura del mito, quanto sull’intreccio di più vettori e di più personaggi ad esso attinti: il ricorso a Edipo, ad esempio, si intravvede non soltanto nel palinsesto di Hamlet – come è stato ampiamente e variamente dimostrato –  ma anche dietro al Lear, mentre Elettra diventa un ulteriore, meno indagato, punto di riferimento della costruzione psicologica e drammaturgica di Amleto.  Si vorrebbe così dimostrare come Shakespeare ricorra al modello tragico greco e, nello specifico, di Sofocle, nel momento in cui l’intreccio della tragedia, nei suoi momenti di maggiore tensione (e incertezza conoscitiva, richiede una sorta di interrogazione e di mobilitazione di archetipi e, in particolare, di quelli collegati alle figure dei padri e al loro rapporto con il potere.

  11. Qualitative study of men's perceptions of why treatment delays occur in the UK for those with testicular cancer.

    Science.gov (United States)

    Chapple, Alison; Ziebland, Sue; McPherson, Ann

    2004-01-01

    Many studies (but not all) have shown that for men with testicular cancer a longer treatment delay is associated with additional treatments, greater morbidity, and shorter survival. This paper explores patients' perspectives on why treatment delays occur. Qualitative study using narrative interviews Interviews in patient's homes throughout the United Kingdom (UK). Interviews with a maximum variation sample of 45 men with testicular cancer, recruited through general practitioners (GPs), urologists, support groups, and charities. Those who sought help relatively quickly responded to symptoms, had heard about testicular cancer in the media, had seen leaflets in GPs' surgeries, or knew others with this disease. Men delayed because they did not recognise signs and symptoms; feared appearing weak, a hypochondriac, or lacking in masculinity; recalled past illness or painful examinations; were embarrassed; feared the consequences of treatment; or lacked time to consult their doctors. Beliefs about symptoms and pessimistic associations with cancer also led to delay. Treatment delays also resulted from misdiagnosis or waiting lists. Whether or not men should be taught to examine themselves routinely to check for testicular cancer is much debated. This study suggests that it is important that men are aware of the normal shape and feel of their testicles, and may benefit from information about signs and symptoms of testicular cancer and the excellent cure rate. Information, provided in surgeries where men feel welcome, might encourage men to seek help promptly when a problem arises. Our study also suggests that GPs may need to accept a low threshold for ultrasound investigation of testicular symptoms and that the ultrasound service needs to be improved. These measures may further reduce mortality and morbidity.

  12. Acute and delayed deferoxamine treatment attenuates long-term sequelae after germinal matrix hemorrhage in neonatal rats.

    Science.gov (United States)

    Klebe, Damon; Krafft, Paul R; Hoffmann, Clotilde; Lekic, Tim; Flores, Jerry J; Rolland, William; Zhang, John H

    2014-08-01

    This study investigated if acute and delayed deferoxamine treatment attenuates long-term sequelae after germinal matrix hemorrhage (GMH). Bacterial collagenase (0.3 U) was infused intraparenchymally into the right hemispheric ganglionic eminence in P7 rat pups to induce GMH. GMH animals received either deferoxamine or vehicle twice a day for 7 consecutive days. Deferoxamine administration was initiated at either 1 hour or 72 hours post-GMH. Long-term neurocognitive deficits and motor coordination were assessed using Morris water maze, rotarod, and foot fault tests between day 21 to 28 post-GMH. At 28 days post-GMH, brain morphology was assessed and extracellular matrix protein (fibronectin and vitronectin) expression was determined. Acute and delayed deferoxamine treatment improved long-term motor and cognitive function at 21 to 28 days post-GMH. Attenuated neurofunction was paralleled with improved overall brain morphology at 28 days post-GMH, reducing white matter loss, basal ganglia loss, posthemorrhagic ventricular dilation, and cortical loss. GMH resulted in significantly increased expression of fibronectin and vitronectin, which was reversed by acute and delayed deferoxamine treatment. Acute and delayed deferoxamine administration ameliorated long-term sequelae after GMH. © 2014 American Heart Association, Inc.

  13. Women And Visual Representations Of Space In Two Chinese Film Adaptations Of Hamlet

    Directory of Open Access Journals (Sweden)

    CHEANG WAI FONG

    2014-12-01

    Full Text Available This paper studies two Chinese film adaptations of Shakespeare’s Hamlet, Xiaogang Feng’s The Banquet (2006 and Sherwood Hu’s Prince of the Himalayas (2006, by focusing on their visual representations of spaces allotted to women. Its thesis is that even though on the original Shakespearean stage details of various spaces might not be as vividly represented as in modern film productions, spaces are still crucial dramatic elements imbued with powerful significations. By analyzing the two Chinese film adaptations alongside the original Hamlet text, the paper attempts to reinterpret their different representations of spaces in relation to their different historical-cultural gender notions.

  14. The Hamlet Project in Goethe’s Wilhelm Meister’s Years of Apprenticeship

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    Kullmann Thomas

    2017-09-01

    – The project itself, as represented by Wilhelm, appears to be informed by a cultural movement towards emancipation from French culture: The character of Hamlet was interpreted as representing a role model for young Germans.– Informed by a theatrical practice based on French conventions, the manager objects to the lack of dramaturgical coherence of the Shakespeare play. As a compromise, Wilhelm composes an adapted version in which references to Wittenberg, Poland, France and England as well as several minor characters are cut, but the Hamlet scenes and speeches are retained.– Wilhelm and his friends also take account of German audiences’ preferences and capacities.

  15. The Tragedy of Hamlet, Son of an Organic Chemist of Denmark

    Science.gov (United States)

    Brisbois, Ronald G.

    2004-04-01

    Once faced with structure reactivity relationships in the context of nucleophilic substitution at sp 3 carbon, introductory organic chemistry students must compare and contrast the various attributes and ramifications of S N 2 versus S N 1 reaction pathways. The dramatic (even melodramatic) way in which some students ask such comparative questions inspired a parody of Hamlet's famous to be or not to be soliloquy. Herein, Hamlet (the son of an organic chemist of Denmark) is the surrogate of any and every student as he uses a thoroughly Shakespearian approach to sorting out some of the key distinguishing features of S N 2 versus S N 1 reactions.

  16. Delayed treatment with ADAMTS13 ameliorates cerebral ischemic injury without hemorrhagic complication.

    Science.gov (United States)

    Nakano, Takafumi; Irie, Keiichi; Hayakawa, Kazuhide; Sano, Kazunori; Nakamura, Yoshihiko; Tanaka, Masayoshi; Yamashita, Yuta; Satho, Tomomitsu; Fujioka, Masayuki; Muroi, Carl; Matsuo, Koichi; Ishikura, Hiroyasu; Futagami, Kojiro; Mishima, Kenichi

    2015-10-22

    Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, delayed tPA treatment increases the risk of cerebral hemorrhage and can result in exacerbation of nerve injury. ADAMTS13, a von Willebrand factor (VWF) cleaving protease, has a protective effect against ischemic brain injury and may reduce bleeding risk by cleaving VWF. We examined whether ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA in mice subjected to middle cerebral artery occlusion (MCAO). ADAMTS13 (0.1mg/kg) or tPA (10mg/kg) was administered i.v., immediately after reperfusion of after 2-h or 4-h MCAO for comparison of the therapeutic time windows in ischemic stroke. Infarct volume, hemorrhagic volume, plasma high-mobility group box1 (HMGB1) levels and cerebral blood flow were measured 24h after MCAO. Both ADAMTS13 and tPA improved the infarct volume without hemorrhagic complications in 2-h MCAO mice. On the other hand, ADAMTS13 reduced the infarct volume and plasma HMGB1 levels, and improved cerebral blood flow without hemorrhagic complications in 4-h MCAO mice, but tPA was not effective and these animals showed massive intracerebral hemorrhage. These results indicated that ADAMTS13 has a longer therapeutic time window in ischemic stroke than tPA, and ADAMTS13 may be useful as a new therapeutic agent for ischemic stroke. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. The effect of duration of untreated psychosis and treatment delay on the outcomes of prolonged early intervention in psychotic disorders.

    Science.gov (United States)

    Albert, Nikolai; Melau, Marianne; Jensen, Heidi; Hastrup, Lene Halling; Hjorthøj, Carsten; Nordentoft, Merete

    2017-09-26

    The duration of untreated psychosis (DUP) has been shown to have an effect on outcome after first-episode psychosis. The premise of specialized early intervention (SEI) services is that intervention in the early years of illness can affect long-term outcomes. In this study, we investigate whether DUP affects treatment response after 5 years of SEI treatment compared to 2 years of SEI treatment. As part of a randomized controlled trial testing the effect of prolonged SEI treatment 400 participants diagnosed within the schizophrenia spectrum were recruited. For this specific study participants were dichotomized based on DUP, treatment delay, and time from first symptom until start of SEI treatment. The groups were analyzed with regard to treatment response on psychopathology, level of functioning, and cognitive functioning. The participants with a short DUP had a tendency to respond better to the prolonged treatment with regards to disorganized and negative dimension. For participants with short duration from first symptom until start of SEI treatment there was a significant difference on the negative dimension favoring the prolonged OPUS treatment. The finding of an effect of prolonged treatment for participants with a short total treatment delay could mean that prolonged SEI treatment is more beneficial than treatment as usual (TAU) so long as it is provided in the early years of illness and not just in the early years after diagnosis. THE EARLIER THE BETTER: The duration of untreated psychosis influences the long-term outcomes of treatment. Nikolai Albert, at the Copenhagen Mental Health Centre, and a team of Danish researchers have investigated the effects of a specialized early intervention program (OPUS) in 400 patients diagnosed with schizophrenia spectrum disorders and compared the effects of OPUS after two and five years. Their findings suggest that five years of specialized early intervention was most beneficial when the total duration from symptom start to

  18. Healthcare-seeking behavior, treatment delays and its determinants among pulmonary tuberculosis patients in rural Nigeria: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Ukwaja Kingsley N

    2013-01-01

    Full Text Available Abstract Background Nigeria ranks fourth among 22 high tuberculosis (TB burden countries. Although it reached 99% DOTS coverage in 2008, current case detection rate is 40%. Little is known about delays before the start of TB therapy and health-seeking behaviour of TB patients in rural resource-limited settings. We aimed to: 1 assess healthcare-seeking behaviour and delay in treatment of pulmonary TB patients, 2 identify the determinants of the delay in treatment of pulmonary TB. Methods We conducted a cross-sectional study of adult new pulmonary TB patients notified to the National Tuberculosis Control Programme (NTP by three rural (two mission/one public hospitals. Data on health-seeking and delays were collected using a standardised questionnaire. We defined patient delay as the interval (weeks between the onset of cough and the first visit to any health provider, and health system delay as the time interval (weeks between patient's first attendance to any health provider, and the onset of treatment. Total delay is the sum of both delays. Multiple linear regression models using nine exposure variables were built to identify determinants of delays. Results Of 450 patients (median age 30 years enrolled, most were males (55%, subsistent farmers (49%, rural residents (78%; and 39% had no formal education. About 84% of patients reported first consulting a non-NTP provider. For such patients, the first facilities visited after onset of symptoms were drug shops (79%, traditional healers (10%, and private hospitals (10%. The median total delay was 11 (IQR 9–16 weeks, patient delay 8 (IQR 8–12 and health system (HS delay 3 (IQR 1–4 weeks. Factors associated with increased patient delay were older age (P Conclusion Overall, TB treatment delays were high; and needs to be reduced in Nigeria. This may be achieved through improved access to care, further education of patients, engagement of informal care providers, and strengthening of existing public

  19. Treatment of displaced talar neck fractures using delayed procedures of plate fixation through dual approaches.

    Science.gov (United States)

    Xue, Youdi; Zhang, Hui; Pei, Fuxing; Tu, Chongqi; Song, Yueming; Fang, Yue; Liu, Lei

    2014-01-01

    Treatment of talar neck fractures is challenging. Various surgical approaches and fixation methods have been documented. Clinical outcomes are often dissatisfying due to inadequate reduction and fixation with high rates of complications. Obtaining satisfactory clinical outcomes with minimum complications remains a hard task for orthopaedic surgeons. In the period from May 2007 to September 2010, a total of 31 cases with closed displaced talar neck fractures were treated surgically in our department. Injuries were classified according to the Hawkins classification modified by Canale and Kelly. Under general anaesthesia with sufficient muscle relaxation, urgent closed reduction was initiated once the patients were admitted; if the procedure failed, open reduction and provisional stabilisation with Kirschner wires through an anteromedial approach with tibiometatarsal external fixation were performed. When the soft tissue had recovered, definitive fixation was performed with plate and screws through dual approaches. The final follow-up examination included radiological analysis, clinical evaluation and functional outcomes which were carried out according to the Ankle-Hindfoot Scale of the American Orthopaedic Foot and Ankle Society (AOFAS), patient satisfaction and SF-36. Twenty-eight patients were followed up for an average of 25 months (range 18-50 months) after the injury. Only two patients had soft tissue complications, and recovery was satisfactory with conservative treatment. All of the fractures healed anatomically without malunion and nonunion, and the average union time was 14 weeks (range 12-24 weeks). Post-traumatic arthritis developed in ten cases, while six patients suffered from avascular necrosis of the talus. Secondary procedures included three cases of subtalar arthrodesis, one case of ankle arthrodesis and one case of total ankle replacement. The mean AOFAS hindfoot score was 78 (range 65-91). According to the SF-36, the average score of the

  20. Speech and Language Delay

    Science.gov (United States)

    ... OTC Relief for Diarrhea Home Diseases and Conditions Speech and Language Delay Condition Speech and Language Delay Share Print Table of Contents1. ... Treatment6. Everyday Life7. Questions8. Resources What is a speech and language delay? A speech and language delay ...

  1. The Long-Term Outcome Comparison of Different Time-Delayed Kallikrein Treatments in a Mouse Cerebral Ischemic Model

    Directory of Open Access Journals (Sweden)

    Yaohui Ni

    2018-01-01

    Full Text Available Delayed administration of kallikrein after cerebral infarction can improve neurological function. However, the appropriate kallkrein treatment time after ischemic stroke has not been illuminated. In this study, we compared the long-term outcome among three kallikrein therapeutic regimens starting at different time points following mouse cerebral ischemia. Furthermore, the protective mechanisms involving neurogenesis, angiogenesis, and AKT-GSK3β-VEGF signaling pathway were analyzed. Human tissue kallikrein was injected through the tail vein daily starting at 8 h, 24 h, or 36 h after right middle cerebral artery occlusion (MCAO until the 28th day. Three therapeutic regimens all protected against neurological dysfunction, but kallikrein treatment starting at 8 h after MCAO had the best efficacy. Additionally, kallikrein treatment at 8 h after MCAO significantly enhanced cell proliferation including neural stem cell and induced differentiation of neural stem cell into mature neuron. Kallikrein treatment starting at 8 h also promoted more angiogenesis than other two treatment regimens, which was associated with AKT-GSK3β-VEGF signaling pathway. Thus, we confirm that three delayed kallikrein treatments provide protection against cerebral infarction and furthermore suggest that kallikrein treatment starting at 8 h had a better effect than that at 24 h and 36 h. These findings provide the experimental data contributing to better clinical application of exogenous kallikrein.

  2. Structure and function of human α-lactalbumin made lethal to tumor cells (HAMLET)-type complexes.

    Science.gov (United States)

    Mossberg, Ann-Kristin; Hun Mok, Kenneth; Morozova-Roche, Ludmilla A; Svanborg, Catharina

    2010-11-01

    Human α-lactalbumin made lethal to tumor cells (HAMLET) and equine lysozyme with oleic acid (ELOA) are complexes consisting of protein and fatty acid that exhibit cytotoxic activities, drastically differing from the activity of their respective proteinaceous compounds. Since the discovery of HAMLET in the 1990s, a wealth of information has been accumulated, illuminating the structural, functional and therapeutic properties of protein complexes with oleic acid, which is summarized in this review. In vitro, both HAMLET and ELOA are produced by using ion-exchange columns preconditioned with oleic acid. However, the complex of human α-lactalbumin with oleic acid with the antitumor activity of HAMLET was found to be naturally present in the acidic fraction of human milk, where it was discovered by serendipity. Structural studies have shown that α-lactalbumin in HAMLET and lysozyme in ELOA are partially unfolded, 'molten-globule'-like, thereby rendering the complexes dynamic and in conformational exchange. HAMLET exists in the monomeric form, whereas ELOA mostly exists as oligomers and the fatty acid stoichiometry varies, with HAMLET holding an average of approximately five oleic acid molecules, whereas ELOA contains a considerably larger number (11- 48). Potent tumoricidal activity is found in both HAMLET and ELOA, and HAMLET has also shown strong potential as an antitumor drug in different in vivo animal models and clinical studies. The gain of new, beneficial function upon partial protein unfolding and fatty acid binding is a remarkable phenomenon, and may reflect a significant generic route of functional diversification of proteins via varying their conformational states and associated ligands. © 2010 The Authors Journal compilation © 2010 FEBS.

  3. Apoptosis and tumor cell death in response to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

    Science.gov (United States)

    Hallgren, Oskar; Aits, Sonja; Brest, Patrick; Gustafsson, Lotta; Mossberg, Ann-Kristin; Wullt, Björn; Svanborg, Catharina

    2008-01-01

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a molecular complex derived from human milk that kills tumor cells by a process resembling programmed cell death. The complex consists of partially unfolded alpha-lactalbumin and oleic acid, and both the protein and the fatty acid are required for cell death. HAMLET has broad antitumor activity in vitro, and its therapeutic effect has been confirmed in vivo in a human glioblastoma rat xenograft model, in patients with skin papillomas and in patients with bladder cancer. The mechanisms of tumor cell death remain unclear, however. Immediately after the encounter with tumor cells, HAMLET invades the cells and causes mitochondrial membrane depolarization, cytochrome c release, phosphatidyl serine exposure, and a low caspase response. A fraction of the cells undergoes morphological changes characteristic of apoptosis, but caspase inhibition does not rescue the cells and Bcl-2 overexpression or altered p53 status does not influence the sensitivity of tumor cells to HAMLET. HAMLET also creates a state of unfolded protein overload and activates 20S proteasomes, which contributes to cell death. In parallel, HAMLET translocates to tumor cell nuclei, where high-affinity interactions with histones cause chromatin disruption, loss of transcription, and nuclear condensation. The dying cells also show morphological changes compatible with macroautophagy, and recent studies indicate that macroautophagy is involved in the cell death response to HAMLET. The results suggest that HAMLET, like a hydra with many heads, may interact with several crucial cellular organelles, thereby activating several forms of cell death, in parallel. This complexity might underlie the rapid death response of tumor cells and the broad antitumor activity of HAMLET.

  4. Treatment with Docosahexaenoic Acid, but Not Eicosapentaenoic Acid, Delays Ca2+-Induced Mitochondria Permeability Transition in Normal and Hypertrophied Myocardium

    OpenAIRE

    Khairallah, Ramzi J.; O'Shea, Karen M.; Brown, Bethany H.; Khanna, Nishanth; Des Rosiers, Christine; Stanley, William C.

    2010-01-01

    Intake of fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) prevents heart failure; however, the mechanisms are unclear. Mitochondrial permeability transition pore (MPTP) opening contributes to myocardial pathology in cardiac hypertrophy and heart failure, and treatment with DHA + EPA delays MPTP opening. Here, we assessed: 1) whether supplementation with both DHA and EPA is needed for optimal prevention of MPTP opening, and 2) whether this benefit occurs in hyper...

  5. Effects of music therapy in the treatment of children with delayed speech development - results of a pilot study.

    Science.gov (United States)

    Gross, Wibke; Linden, Ulrike; Ostermann, Thomas

    2010-07-21

    Language development is one of the most significant processes of early childhood development. Children with delayed speech development are more at risk of acquiring other cognitive, social-emotional, and school-related problems. Music therapy appears to facilitate speech development in children, even within a short period of time. The aim of this pilot study is to explore the effects of music therapy in children with delayed speech development. A total of 18 children aged 3.5 to 6 years with delayed speech development took part in this observational study in which music therapy and no treatment were compared to demonstrate effectiveness. Individual music therapy was provided on an outpatient basis. An ABAB reversal design with alternations between music therapy and no treatment with an interval of approximately eight weeks between the blocks was chosen. Before and after each study period, a speech development test, a non-verbal intelligence test for children, and music therapy assessment scales were used to evaluate the speech development of the children. Compared to the baseline, we found a positive development in the study group after receiving music therapy. Both phonological capacity and the children's understanding of speech increased under treatment, as well as their cognitive structures, action patterns, and level of intelligence. Throughout the study period, developmental age converged with their biological age. Ratings according to the Nordoff-Robbins scales showed clinically significant changes in the children, namely in the areas of client-therapist relationship and communication. This study suggests that music therapy may have a measurable effect on the speech development of children through the treatment's interactions with fundamental aspects of speech development, including the ability to form and maintain relationships and prosodic abilities. Thus, music therapy may provide a basic and supportive therapy for children with delayed speech development

  6. Classical conditioning for preserving the effects of short melatonin treatment in children with delayed sleep: a pilot study

    Directory of Open Access Journals (Sweden)

    van Maanen A

    2017-03-01

    Full Text Available Annette van Maanen,1 Anne Marie Meijer,1 Marcel G Smits,2 Frans J Oort1 1Research Institute Child Development and Education, University of Amsterdam, Amsterdam, 2Centre for Sleep-Wake Disorders and Chronobiology, Hospital Gelderse Vallei, Ede, the Netherlands Abstract: Melatonin treatment is effective in treating sleep onset problems in children with delayed melatonin onset, but effects usually disappear when treatment is discontinued. In this pilot study, we investigated whether classical conditioning might help in preserving treatment effects of melatonin in children with sleep onset problems, with and without comorbid attention deficit hyperactivity disorder (ADHD or autism. After a baseline week, 16 children (mean age: 9.92 years, 31% ADHD/autism received melatonin treatment for 3 weeks and then gradually discontinued the treatment. Classical conditioning was applied by having children drink organic lemonade while taking melatonin and by using a dim red light lamp that was turned on when children went to bed. Results were compared with a group of 41 children (mean age: 9.43 years, 34% ADHD/autism who received melatonin without classical conditioning. Melatonin treatment was effective in advancing dim light melatonin onset and reducing sleep onset problems, and positive effects were found on health and behavior problems. After stopping melatonin, sleep returned to baseline levels. We found that for children without comorbidity in the experimental group, sleep latency and sleep start delayed less in the stop week, which suggests an effect of classical conditioning. However, classical conditioning seems counterproductive in children with ADHD or autism. Further research is needed to establish these results and to examine other ways to preserve melatonin treatment effects, for example, by applying morning light. Keywords: melatonin, classical conditioning, children, delayed sleep

  7. Hamlet - little known piece by Enriko Josif: Literary-theoretical, philosophical and musicological views

    Directory of Open Access Journals (Sweden)

    Marjanović Nataša

    2011-01-01

    Full Text Available Hamlet is well-known as the most famous tragedy written by William Shakespeare. This dramatic work has, throughout the centuries, lead numerous writers, poets, literary-critics and philosophers to think about universal issues of life, human nature, love, loyalty and friendship. Hamlet has not just been the subject of discussion from the point of view of the theory of literature and human psychology and philosophy, it has also directly inspired the creation of many artistic works. One of those works which forms the main subject-matter of this paper is the almost unknown music for Hamlet by Enriko Josif. Enriko Josif was an extraordinary figure, a versatile artist and thinker, almost a kind of philosopher. In his opinion and in accordance with his inner feeling, art was a matter of divine creation first of all. He admired those artists who dealt with difficult issues of life in their works of art and William Shakespeare was to him one of the most prominent among them. In general terms, we have highlighted certain general points about Josif’s views on an artist’s life and work and have presented our notions about his piece. Specifically, we have tried to point out personal views that Josif held about Hamlet, as well as the most important features of Josif’s music, which are broadly in accordance with the literary, ethical, philosophical and theological critical tradition surrounding this masterpiece.

  8. "The Lion King" and "Hamlet": A Homecoming for the Exiled Child.

    Science.gov (United States)

    Gavin, Rosemarie

    1996-01-01

    Explains how the movie "The Lion King" may be used to elucidate Shakespeare's "Hamlet," a play about a prince who does not always seem heroic to modern audiences. Gives specific points of comparison between the two works concerning heroes, characters, conflicts, themes, ending scenes, and archetypal patterns. (TB)

  9. Hip-Hop Hamlet: Hybrid Interpretive Discourse in a Suburban High School English Class

    Science.gov (United States)

    Anglin, Joanna L.; Smagorinsky, Peter

    2014-01-01

    This study investigates the collaborative composing processes of a group of five high school seniors who constructed interpretations of each of the five acts of Shakespeare's Hamlet through the medium of spoken word performances. The group composing processes were analyzed to identify how the students drew on conventions from the spoken word…

  10. Constructing Knowledge from an Ill-Structured Domain: Testing a Multimedia Hamlet.

    Science.gov (United States)

    Barnes, William G. W.

    How a multimedia program that employs concept maps and hypertext for teaching "Hamlet" facilitated comprehension in an undergraduate course is described. Results suggest factors that instructional designers should take into account to improve learning. Thirty-six upper-division college students were enrolled in a course on Shakespeare at…

  11. "Hamlet" and the Elizabethan Revenge Ethic in Text and Film. [Lesson Plan].

    Science.gov (United States)

    2002

    This lesson seeks to sensitize students to the complex nature of revenge as it is portrayed in William Shakespeare's "The Tragedy of Hamlet, Prince of Denmark." In the lesson, students learn how Shakespeare's play interprets Elizabethan attitudes toward revenge, as reflected in the structure of the Elizabethan revenge tragedy, one of the…

  12. An Analysis of Ophelia in Hamlet from the Perspective of Feminist Care Ethic

    Institute of Scientific and Technical Information of China (English)

    张洁

    2015-01-01

    Through the ages,Ophelia in Hamlet has long been regarded as a childish maid.This thesis will give an analysis of Ophelia's growth from the perspective of feminist care ethic developmental stages theory,trying to illustrate that in the play Ophelia has experienced ethical development and has arrived at ethical maturity in the end.

  13. Ecological wisdom of Hindu-Javanese community settlement in Cetho Hamlet, Lawu Mountains, Central Java, Indonesia

    Science.gov (United States)

    Ikhsan, Fauzan Ali; Setioko, Bambang; Suprapti, Atiek

    2017-12-01

    Dwelling culture of Java community has a long history. In Javanese community point of view, Javanese culture is not a homogeneous entity. There is a diversity characteristic of a regional nature of Javanese culture, which is caused by differences in the natural environment on the island of Java. Dwelling Culture settled in the mountains is a variant form of Javanese culture that has its own uniqueness. This study aimed to describe the local values of the rural settlement structure of in Lawu mountains with Hindu-Javanese culture background. This study used a qualitative approach with case study strategy. The locus of research is in the Cetho hamlet on the slopes of Mount Lawu Karanganyar, Central Java. The results showed that local values in the neighborhoods of Cetho hamlet is based on the Memayu Hayuning Bawana philosophy. These concepts are abstracted into various aspects of settlements in Cetho hamlet such as aspects of dwelling house setting, water management, and ritual activities related to environmental management. Memayu Hayuning Bawana philosophy becomes a cultural space coloring the ecological action of the population of Cetho hamlet. The comprehensive motivation of ecological action ultimately leads to one final goal, namely the desire to maintain a harmonic atmosphere with the surroundings.

  14. Does Hamlet Belong in Freshman Composition? The Debatable Role of Canonical Literature in Composition

    Science.gov (United States)

    Fitzwilliam, Marie A.

    2006-01-01

    The question of whether "Hamlet" belongs in a freshman composition classroom is one that institutions are making easier to answer, though perhaps for political rather than pedagogical reasons. This article describes a project in which Marie Fitzwilliam and her colleagues were asked to engage in a dialogue with the administration on…

  15. The Hamlet design entry system: on the implementation of synchronous channels

    NARCIS (Netherlands)

    M.R. van Steen

    1994-01-01

    textabstractThe graphical Hamlet Application Design Language (ADL) has been developed to support the construction of parallel applications. The language is based on a notion of processes communicating by means of message-passing. One of the goals of ADL is that its implementation should allow

  16. "To be or not to be" - Hamlets monolog i danske oversættelser

    DEFF Research Database (Denmark)

    Onsberg, Merete

    2008-01-01

    Tolv danske oversættelser af Hamlets monolog To be or not to be fra 1807 til i dag undersøges metrisk for at give et signalement af blankverset på dansk. Der argumenteres for at opfatte det danske blankvers som bisyllabiske femslagsrækker med fire slag og trisyllabler som variationer, hvorimod...

  17. Disjointed Confessions: Adikia and Radical Deradicalization in Schlingensief’s Hamlet

    Directory of Open Access Journals (Sweden)

    Janus C. Currie

    2017-01-01

    Full Text Available In 2001, in Zürich Switzerland, German director Christoph Schlingensief staged a version of Shakespeare’s Hamlet. In this version’s famous mousetrap scene, in which Hamlet wants to force his uncle to confess to fratricide, all the players of the mise en abyme are portrayed by a group of neo-Nazis endeavouring to separate themselves from the right–wing scene. In a dramatic break from Shakespeare’s text the group go on to share their own personal experiences with the audience. The production attempted to comment on and create debate about the ‘rottenness’ of the State, not just Switzerland, amid the rise in approval ratings and growing influence of far-right parties in the surrounding countries. I posit that Schlingensief’s project is a form of radical deradicalization (i.e., a radical method of deradicalizing neo-Nazis. This paper analyses Schlingensief’s Hamlet by utilizing the concepts of adikia (disjointure, dislocation, injustice and dike (jointure, ordering, justice, which go back to the oldest extant Greek text: the Anaximander fragment. Drawing on Martin Heidegger and Jacques Derrida’s reinterpretations of adikia and dike I endeavour to illustrate how Schlingensief’s work attempts to intervene in the disjointure caused by the contemporary politics of fear by bringing adikia to the production of Hamlet itself.

  18. The "Strange Alteration" of "Hamlet": Comic Books, Adaptation and Constructions of Adolescent Literacy

    Science.gov (United States)

    Sabeti, Shari

    2014-01-01

    This article examines two comic book adaptations of Shakespeare's "Hamlet" produced for teenage readers and used in school classrooms. It seeks to understand the ways in which particular kinds of literacy are being implied and constructed through the textual practice of multimodal adaptation. It presents a close reading of sections of…

  19. Chronic sleep reduction in adolescents with Delayed Sleep Phase Disorder and effects of melatonin treatment

    NARCIS (Netherlands)

    van Maanen, Annette; Dewald-Kaufmann, Julia F.; Smits, Marcel G.; Oort, Frans J.; Meijer, Anne Marie

    2013-01-01

    Homeostatic and circadian changes that occur during adolescence can result in chronic sleep reduction. This may particularly be true for adolescents with Delayed Sleep Phase Disorder (DSPD), which is associated with late Dim Light Melatonin Onset (DLMO). This study assessed the influence of

  20. Delayed unpaired extinction as a treatment for hyperarousal of the rabbit nictitating membrane response and its implications for treating PTSD.

    Science.gov (United States)

    Schreurs, Bernard G; Smith-Bell, Carrie A; Burhans, Lauren B

    2018-04-01

    Treatment for PTSD (Post-traumatic stress disorder) is rarely available immediately after trauma and often delayed for weeks or months after an event. In a rabbit eyeblink conditioning model of PTSD, we have previously shown that presentations of a tone conditioned stimulus (CS) and shock unconditioned stimulus (US) in an explicitly unpaired manner known as unpaired extinction is effective in reducing CS responding and US hyperarousal even if shock intensity is reduced eight-fold and elicits only minimal responding. Here we determined if delayed delivery of unpaired extinction would still be effective in extinguishing hyperarousal. Rabbits were tested for sensitivity to shock before CS-US pairings and after six days of unpaired extinction presented a day, a week or a month after CS-US pairings. Hyperarousal was extinguished a day and a week after conditioning but not after a month suggesting a significant delay in "treatment" can make hyperarousal persist. We next assessed if this persistence of hyperarousal was associative by comparing rabbits given CS-US pairings to those given explicitly unpaired CS and US presentations, measuring hyperarousal a day and a month later, followed by unpaired extinction and hyperarousal assessment. After four weeks, there was an increase in responding for all rabbits but only rabbits receiving CS-US pairings showed a significant increase in associatively-mediated hyperarousal. Importantly, both paired and unpaired groups showed increased levels of responding after unpaired extinction suggesting treatment delayed for too long may no longer be effective and could cause generalized hyperarousal. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. TO ACT OR NOT TO ACT: HOW COLERIDGE CHANGED THE WAY WE SEE "HAMLET"

    Directory of Open Access Journals (Sweden)

    Svetozar Poštić

    2014-10-01

    Full Text Available Exactly 200 years ago, from 1811 to 1819, Samuel Taylor Coleridge, one of the most famous English Romantic poets, held a series of influential lectures about William Shakespeare and his plays. His presentation of "Hamlet", a play hitherto not only negatively appraised, but even viewed quite negatively by the leading critics, most notably Samuel Johnson, was especially significant. His insightful analysis helped to change the general opinion about the play, and pointed to the qualities of "Hamlet" that made it into perhaps the best known and most frequently played drama in the next 200 years. In this paper, I examine the way Coleridge was able to recognize the neglected features of Shakespeare’s profound tragedy up to that point. First of all, he identified with the main protagonist of the play, the Prince of Denmark, and described the unbridgeable gap between ambitions and power of imagination on the one hand, and inability to act on the other. Like Hamlet, Coleridge had "great, enormous, intellectual activity, and a consequent proportionate aversion to real action" (Coleridge 2014: 345. Aware of this shortcoming, but unable to correct it, the extremely talented and educated Coleridge presented it in fascinating detail. Secondly, he used his knowledge of the most influential contemporary philosophers, especially Kant, Locke and Hobbes, and the increasingly popular psychological approach to character analysis in order to paint an internal portrait of leading characters of the play. Due to the increasingly popular trend in recent literary theory and analysis focusing on the political and material context of an art work, the universal qualities of Coleridge's intepretation of "Hamlet" that contributed to the lasting influence of his critique have been largely neglected. This article intends, therefore, to re-establish the significance of Coleridge's "Hamlet" lectures.

  2. Total Delay Is Associated with Unfavorable Treatment Outcome among Pulmonary Tuberculosis Patients in West Gojjam Zone, Northwest Ethiopia: A Prospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Senedu Bekele Gebreegziabher

    Full Text Available delay in diagnosis and treatment of tuberculosis (TB may worsen the disease, increase mortality and enhance transmission in the community. This study aimed at assessing the association between total delay and unfavorable treatment outcome among newly diagnosed pulmonary TB (PTB patients.A prospective cohort study was conducted in West Gojjam Zone, Amhara Region of Ethiopia from October 2013 to May 2015. Newly diagnosed PTB patients who were ≥15 years of age were consecutively enrolled in the study from 30 randomly selected public health facilities. Total delay (the time period from onset of TB symptoms to first start of anti-TB treatment was measured. Median total delay was calculated. Mixed effect logistics regression was used to analyze factors associated with unfavorable treatment outcome.Seven hundred six patients were enrolled in the study. The median total delay was 60 days. Patients with total delay of > 60 days were more likely to have unfavorable TB treatment outcome than patients with total delay of ≤ 60 days (adjusted odds ratio [AOR], 2.33; 95% confidence interval [CI], 1.04-5.26. Human immunodeficiency virus (HIV positive TB patients were 8.46 times more likely to experience unfavorable treatment outcome than HIV negative TB patients (AOR, 8.46; 95% CI, 3.14-22.79.Long total delay and TB/HIV coinfection were associated with unfavorable treatment outcome. Targeted interventions that can reduce delay in diagnosis and treatment of TB, and early comprehensive management of TB/HIV coinfection are needed to reduce increased risk of unfavorable treatment outcome.

  3. Delayed Encephalopathy of Carbon Monoxide Intoxication and Treatment with Hyperbaric Oxygen: A Case Report

    Directory of Open Access Journals (Sweden)

    Fatma Polat

    2012-09-01

    Full Text Available Delayed encephalopathy (DE is a neuropsychiatric syndrome that can arise generally within 20 days of acute carbon monoxide (CO intoxication after apparent recovery and involves variable degrees of cognitive deficits, personality changes, movement disorders and focal neurologic deficits. We report a 35-year-old female patient with delayed encephalopathy due to CO intoxication, presenting with cognitive impairment and mild parkinsonism despite receiving hyberbaric oxigen therapy (HBO. Magnetic resonance imaging showed abnormal signal intensity and decreased diffusivity at both caudate nuclei and globus pallidus. She continued to receive additional HBO therapy and complete recovery was reached within six months. The positive effect of early HBO therapy of selected patients in reversing the acute effects of CO intoxication is appearant. We here also review the beneficial effect of HBO in preventing or limitating the late neurocognitive deficits associated with severe CO intoxication

  4. Experience of Comamonas Acidovorans Keratitis with Delayed Onset and Treatment Response in Immunocompromised Cornea

    OpenAIRE

    Lee, Sang Mok; Kim, Mee Kum; Lee, Jae Lim; Wee, Won Ryang; Lee, Jin Hak

    2008-01-01

    Purpose To report 2 cases of Comamonas Acidovorans keratitis in immunocompromised cornea. Methods A complete review of the medical records of the two cases of Comamonas acidovorans keratitis. Results We found some similarities in clinical courses of two cases. Both of them showed development of keratitis during the management with corticosteroids, delayed onset, slow response to antibiotics, and relatively less affected corneal epithelium. Conclusions Comamonas Acidovorans is known as a less ...

  5. Empowerment Of Position And Roles Of Traditional Leaders In The Development Of Livestock Hamlet In The Banten Province

    Directory of Open Access Journals (Sweden)

    Kedi Suradisastr

    2011-06-01

    Full Text Available Developing livestock village is a suitable effort to enhance meat production for fulfilling increasing of the product demand. Developing livestock village in form of Sheep Hamlet in the Regency of Pandeglang, Province of Banten, is also function as forest and environmental buffer zone. Another target of such a livestock development center is to improve farmer’s income by at least 50% of Banten’s Minimum Regional Wage. The success of Sheep Hamlet so far depends upon the following socio-cultural factors: (a the basic culture of the Bantams, (b local leadership, and (c decision making pattern and process. The development of livestock hamlet depends on the roles of local informal figure in the respective area. Such a local leader can help accelerating the success of a livestock development in a sustainable fashion. The existence of a respected local figure is a crucial entry point in the process of livestock hamlet development in the such area.

  6. Effect of Delayed Reinforcement on Skill Acquisition during Discrete-Trial Instruction: Implications for Treatment-Integrity Errors in Academic Settings

    Science.gov (United States)

    Carroll, Regina A.; Kodak, Tiffany; Adolf, Kari J.

    2016-01-01

    We used an adapted alternating treatments design to compare skill acquisition during discrete-trial instruction using immediate reinforcement, delayed reinforcement with immediate praise, and delayed reinforcement for 2 children with autism spectrum disorder. Participants acquired the skills taught with immediate reinforcement; however, delayed…

  7. G-CSF in solid tumor chemotherapy: a tailored regimen reduces febrile neutropenia, treatment delays and direct costs.

    Science.gov (United States)

    Tsavaris, Nicolas; Kosmas, Christos; Gouveris, Panagiotis; Vadiak, Maria; Dimitrakopoulos, Antonis; Karadima, Dimitra; Pagouni, Efterpi; Panagiotakopoulos, George; Tzima, Evanthia; Ispoglou, Sevasti; Sakelariou, Dimitris; Koufos, Christos

    2004-02-01

    Current guidelines do not recommend G-CSF for patients with risk factors for neutropenia. One-hundred patients undergoing chemotherapy were randomized to treatment with G-CSF at 5 Kg/kg for established febrile neutropenia (ANC <1000/microl) (Group A) or G-CSF at 263 Kg/day if ANC was 1500/microl or less on the day of the expected nadir, with the duration of treatment determined by the severity of neutropenia (Group B). The number of doses of G-CSF was similar in the two groups. There were 34 cases of febrile neutropenia in Group A, but none in Group B (p=0.0001). Hospital admission for febrile neutropenia, antibiotic use and delays in chemotherapy were all significantly more common in Group A. Total direct costs were estimated to be 66, 646 for Group A and 47, 119 for Group B. Tailoring treatment does not increase G-CSF use, but significantly reduces febrile neutropenia and treatment delays and lowers direct costs.

  8. Structure and Potential Cellular Targets of HAMLET-like Anti-Cancer Compounds made from Milk Components.

    Science.gov (United States)

    Rath, Emma M; Duff, Anthony P; Håkansson, Anders P; Vacher, Catherine S; Liu, Guo Jun; Knott, Robert B; Church, William Bret

    2015-01-01

    The HAMLET family of compounds (Human Alpha-lactalbumin Made Lethal to Tumours) was discovered during studies on the properties of human milk, and is a class of protein-lipid complexes having broad spectrum anti-cancer, and some specific anti-bacterial properties. The structure of HAMLET-like compounds consists of an aggregation of partially unfolded protein making up the majority of the compound's mass, with fatty acid molecules bound in the hydrophobic core. This is a novel protein-lipid structure and has only recently been derived by small-angle X-ray scattering analysis. The structure is the basis of a novel cytotoxicity mechanism responsible for anti-cancer activity to all of the around 50 different cancer cell types for which the HAMLET family has been trialled. Multiple cytotoxic mechanisms have been hypothesised for the HAMLET-like compounds, but it is not yet clear which of those are the initiating cytotoxic mechanism(s) and which are subsequent activities triggered by the initiating mechanism(s). In addition to the studies into the structure of these compounds, this review presents the state of knowledge of the anti-cancer aspects of HAMLET-like compounds, the HAMLET-induced cytotoxic activities to cancer and non-cancer cells, and the several prospective cell membrane and intracellular targets of the HAMLET family. The emerging picture is that HAMLET-like compounds initiate their cytotoxic effects on what may be a cancer-specific target in the cell membrane that has yet to be identified. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  9. Sensitization of Staphylococcus aureus to methicillin and other antibiotics in vitro and in vivo in the presence of HAMLET.

    Directory of Open Access Journals (Sweden)

    Laura R Marks

    Full Text Available HAMLET (human alpha-lactalbumin made lethal to tumor cells is a protein-lipid complex from human milk with both tumoricidal and bactericidal activities. HAMLET exerts a rather specific bactericidal activity against some respiratory pathogens, with highest activity against Streptococcus pneumoniae, but lacks activity against most other bacterial pathogens, including Staphylococci. Still, ion transport associated with death in S. pneumoniae is also detected to a lower degree in insensitive organisms. In this study we demonstrate that HAMLET acts as an antimicrobial adjuvant that can increase the activity of a broad spectrum of antibiotics (methicillin, vancomycin, gentamicin and erythromycin against multi-drug resistant Staphylococcus aureus, to a degree where they become sensitive to those same antibiotics, both in antimicrobial assays against planktonic and biofilm bacteria and in an in vivo model of nasopharyngeal colonization. We show that HAMLET exerts these effects specifically by dissipating the proton gradient and inducing a sodium-dependent calcium influx that partially depolarizes the plasma membrane, the same mechanism induced during pneumococcal death. These effects results in an increased cell associated binding and/or uptake of penicillin, gentamicin and vancomycin, especially in resistant stains. Finally, HAMLET inhibits the increased resistance of methicillin seen under antibiotic pressure and the bacteria do not become resistant to the adjuvant, which is a major advantageous feature of the molecule. These results highlight HAMLET as a novel antimicrobial adjuvant with the potential to increase the clinical usefulness of antibiotics against drug resistant strains of S. aureus.

  10. Sensitization of Staphylococcus aureus to methicillin and other antibiotics in vitro and in vivo in the presence of HAMLET.

    Science.gov (United States)

    Marks, Laura R; Clementi, Emily A; Hakansson, Anders P

    2013-01-01

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a protein-lipid complex from human milk with both tumoricidal and bactericidal activities. HAMLET exerts a rather specific bactericidal activity against some respiratory pathogens, with highest activity against Streptococcus pneumoniae, but lacks activity against most other bacterial pathogens, including Staphylococci. Still, ion transport associated with death in S. pneumoniae is also detected to a lower degree in insensitive organisms. In this study we demonstrate that HAMLET acts as an antimicrobial adjuvant that can increase the activity of a broad spectrum of antibiotics (methicillin, vancomycin, gentamicin and erythromycin) against multi-drug resistant Staphylococcus aureus, to a degree where they become sensitive to those same antibiotics, both in antimicrobial assays against planktonic and biofilm bacteria and in an in vivo model of nasopharyngeal colonization. We show that HAMLET exerts these effects specifically by dissipating the proton gradient and inducing a sodium-dependent calcium influx that partially depolarizes the plasma membrane, the same mechanism induced during pneumococcal death. These effects results in an increased cell associated binding and/or uptake of penicillin, gentamicin and vancomycin, especially in resistant stains. Finally, HAMLET inhibits the increased resistance of methicillin seen under antibiotic pressure and the bacteria do not become resistant to the adjuvant, which is a major advantageous feature of the molecule. These results highlight HAMLET as a novel antimicrobial adjuvant with the potential to increase the clinical usefulness of antibiotics against drug resistant strains of S. aureus.

  11. External fixation combined with delayed internal fixation in treatment of tibial plateau fractures with dislocation.

    Science.gov (United States)

    Tao, Xingguang; Chen, Nong; Pan, Fugen; Cheng, Biao

    2017-10-01

    The aim of this study was to evaluate the clinical efficacy of external fixation, delayed open reduction, and internal fixation in treating tibial plateau fracture with dislocation.Clinical data of 34 patients diagnosed with tibial plateau fracture complicated with dislocation between January 2009 and May 2015 were retrospectively analyzed. Fifteen patients in group A underwent early calcaneus traction combined with open reduction and internal fixation and 19 in group B received early external fixation combined with delayed open reduction and internal fixation. Operation time, postoperative complication, bone healing time, knee joint range of motion, initial weight-bearing time, Rasmussen tibial plateau score, and knee function score (HSS) were statistically compared between 2 groups.The mean follow-up time was 18.6 months (range: 5-24 months). The mean operation time in group A was 96 minutes, significantly longer than 71 minutes in group B (P  .05). In group A, initial weight-bearing time in group A was (14.0 ± 3.6) weeks, significantly differing from (12.9 ± 2.8) weeks in group B (P  0.05). Rasmussen tibial plateau score in group A was slightly lower than that in group B (P > .05). The excellent rate of knee joint function in group A was 80% and 84.21% in group B (P > .05).External fixation combined with delayed open reduction and internal fixation is a safer and more efficacious therapy of tibial plateau fracture complicated with dislocation compared with early calcaneus traction and open reduction and internal fixation.

  12. Early versus delayed rehabilitation treatment in hemiplegic patients with ischemic stroke: proprioceptive or cognitive approach?

    Science.gov (United States)

    Morreale, Manuela; Marchione, Pasquale; Pili, Antonio; Lauta, Antonella; Castiglia, Stefano F; Spallone, Aldo; Pierelli, Francesco; Giacomini, Patrizia

    2016-02-01

    Early/intensive mobilization may improve functional recovery after stroke but it is not clear which kind of "mobilization" is more effective. Proprioceptive neuromuscular facilitation (PNF) and cognitive therapeutic exercise (CTE) are widespread applied in post-stroke rehabilitation but their efficacy and safety have not been systematically investigated. To compare PNF and CTE methods in a two different time setting (early versus standard approach) in order to evaluate different role of time and techniques in functional recovery after acute ischemic stroke. We designed a prospectical multicenter blinded interventional study of early versus standard approach with two different methods by means of both PNF and CTE. A discrete stroke-dedicated area for out-of-thrombolysis patients, connected with two different comprehensive stroke centres in two different catchment areas. Three hundred and forty consecutive stroke patient with first ever sub-cortical ischemic stroke in the mean cerebral artery (MCA) territory and contralateral hemiplegia admitted within 6 and 24 hours from symptoms onset. All patients were randomly assigned by means of a computer generated randomization sequence in blocks of 4 to one to the 4 interventional groups: early versus delayed rehabilitation programs with Kabat's schemes or Perfetti's technique. Patients in both delayed group underwent to a standard protocol in the acute phase. disability at 3-12 months. Disability measures: modified Rankin Score and Barthel Index. Safety outcome: immobility-related adverse events. Six-Minute Walking Test, Motricity Index, Mini-Mental State Examination, Beck Depression Inventory. Disability was not different between groups at 3 months but Barthel Index significantly changed between early versus delayed groups at 12 months (P=0.01). Six-Minute Walking Test (P=0.01) and Motricity Index in both upper (P=0.01) and lower limbs (P=0.001) increased in early versus delayed groups regardless rehabilitation schedule. A

  13. Experience of Comamonas acidovorans keratitis with delayed onset and treatment response in immunocompromised cornea.

    Science.gov (United States)

    Lee, Sang Mok; Kim, Mee Kum; Lee, Jae Lim; Wee, Won Ryang; Lee, Jin Hak

    2008-03-01

    To report 2 cases of Comamonas acidovorans keratitis in immunocompromised cornea. A complete review of the medical records of the two cases of Comamonas acidovorans keratitis. We found some similarities in clinical courses of two cases. Both of them showed development of keratitis during the management with corticosteroids, delayed onset, slow response to antibiotics, and relatively less affected corneal epithelium. Comamonas acidovorans is known as a less virulent organism. However it can cause an indolent infection that responds slowly even to adequate antibiotics therapy in immunocompromised corneas.

  14. Effects of music therapy in the treatment of children with delayed speech development - results of a pilot study

    Science.gov (United States)

    2010-01-01

    Background Language development is one of the most significant processes of early childhood development. Children with delayed speech development are more at risk of acquiring other cognitive, social-emotional, and school-related problems. Music therapy appears to facilitate speech development in children, even within a short period of time. The aim of this pilot study is to explore the effects of music therapy in children with delayed speech development. Methods A total of 18 children aged 3.5 to 6 years with delayed speech development took part in this observational study in which music therapy and no treatment were compared to demonstrate effectiveness. Individual music therapy was provided on an outpatient basis. An ABAB reversal design with alternations between music therapy and no treatment with an interval of approximately eight weeks between the blocks was chosen. Before and after each study period, a speech development test, a non-verbal intelligence test for children, and music therapy assessment scales were used to evaluate the speech development of the children. Results Compared to the baseline, we found a positive development in the study group after receiving music therapy. Both phonological capacity and the children's understanding of speech increased under treatment, as well as their cognitive structures, action patterns, and level of intelligence. Throughout the study period, developmental age converged with their biological age. Ratings according to the Nordoff-Robbins scales showed clinically significant changes in the children, namely in the areas of client-therapist relationship and communication. Conclusions This study suggests that music therapy may have a measurable effect on the speech development of children through the treatment's interactions with fundamental aspects of speech development, including the ability to form and maintain relationships and prosodic abilities. Thus, music therapy may provide a basic and supportive therapy for

  15. Effects of music therapy in the treatment of children with delayed speech development - results of a pilot study

    Directory of Open Access Journals (Sweden)

    Linden Ulrike

    2010-07-01

    Full Text Available Abstract Background Language development is one of the most significant processes of early childhood development. Children with delayed speech development are more at risk of acquiring other cognitive, social-emotional, and school-related problems. Music therapy appears to facilitate speech development in children, even within a short period of time. The aim of this pilot study is to explore the effects of music therapy in children with delayed speech development. Methods A total of 18 children aged 3.5 to 6 years with delayed speech development took part in this observational study in which music therapy and no treatment were compared to demonstrate effectiveness. Individual music therapy was provided on an outpatient basis. An ABAB reversal design with alternations between music therapy and no treatment with an interval of approximately eight weeks between the blocks was chosen. Before and after each study period, a speech development test, a non-verbal intelligence test for children, and music therapy assessment scales were used to evaluate the speech development of the children. Results Compared to the baseline, we found a positive development in the study group after receiving music therapy. Both phonological capacity and the children's understanding of speech increased under treatment, as well as their cognitive structures, action patterns, and level of intelligence. Throughout the study period, developmental age converged with their biological age. Ratings according to the Nordoff-Robbins scales showed clinically significant changes in the children, namely in the areas of client-therapist relationship and communication. Conclusions This study suggests that music therapy may have a measurable effect on the speech development of children through the treatment's interactions with fundamental aspects of speech development, including the ability to form and maintain relationships and prosodic abilities. Thus, music therapy may provide a basic

  16. Delayed cerebral radiation necrosis following treatment for a plasmacytoma of the skull.

    Science.gov (United States)

    Chambless, Lola B; Angel, Federica B; Abel, Ty W; Xia, Fen; Weaver, Kyle D

    2010-10-25

    Cerebral radiation necrosis is a relatively common complication of radiation therapy for intracranial malignancies which can also rarely be encountered after radiation of extracranial lesions of the head and neck. We present the first reported case of cerebral radiation necrosis in a patient who underwent radiation therapy for a plasmacytoma of the skull. A 68-year-old male with multiple myeloma presented with an enhancing right frontal mass, 8 years after receiving radiation therapy for a plasmacytoma of the left frontal skull. The patient underwent a diagnostic and therapeutic craniotomy for a presumed neoplastic lesion. The pathologic diagnosis made in this case was delayed radiation necrosis. The patient was followed for over a year during which this process continued to evolve before the ultimate resolution of his clinical symptoms and radiographic abnormality. This case highlights the importance of considering radiation necrosis in the differential diagnosis of any patient with an intracranial mass and a history of radiation for an extracranial head and neck malignancy, regardless of timing and laterality. This case also provides unique insights into the ongoing debate regarding the role of the aberrant immune response in the pathogenesis of delayed cerebral radiation necrosis.

  17. Diabetes guidelines may delay timely adjustments during treatment and might contribute to clinical inertia.

    Science.gov (United States)

    Pimazoni-Netto, Augusto; Zanella, Maria Teresa

    2014-11-01

    Clinical inertia and poor knowledge by many physicians play an important role in delaying diabetes control. Among other guidelines, the Position Statement of the American Diabetes Association/European Association for the Study of Diabetes on Management of Hyperglycemia in Type 2 Diabetes is a respected guideline with high impact on this subject in terms of influencing physicians in the definition of strategic approach to overcome poor glycemic control. But, on the other hand, it carries a recommendation that might contribute to clinical inertia because it can delay the needed implementation of more vigorous, intensive, and effective strategies to overcome poor glycemic control within a reasonable time frame during the evolution of the disease. The same is true with other respected algorithms from different diabetes associations. Together with pharmacological interventions, diabetes education and more intensive blood glucose monitoring in the initial phases after the diagnosis are key strategies for the effective control of diabetes. The main reason why a faster glycemic control should be implemented in an effective and safe way is to boost the confidence and the compliance of the patient to the recommendations of the diabetes care team. Better and faster results in glycemic control can only be safely achieved with educational strategies, structured self-monitoring of blood glucose, and adequate pharmacological therapy in the majority of cases.

  18. Delayed Stimulus-Specific Improvements in Discourse Following Anomia Treatment Using an Intentional Gesture

    Science.gov (United States)

    Altmann, Lori J. P.; Hazamy, Audrey A.; Carvajal, Pamela J.; Benjamin, Michelle; Rosenbek, John C.; Crosson, Bruce

    2014-01-01

    Purpose: In this study, the authors assessed how the addition of intentional left-hand gestures to an intensive treatment for anomia affects 2 types of discourse: picture description and responses to open-ended questions. Method: Fourteen people with aphasia completed treatment for anomia comprising 30 treatment sessions over 3 weeks. Seven…

  19. Conversion of neurons and glia to external-cell fates in the external sensory organs of Drosophila hamlet mutants by a cousin-cousin cell-type respecification.

    Science.gov (United States)

    Moore, Adrian W; Roegiers, Fabrice; Jan, Lily Y; Jan, Yuh-Nung

    2004-03-15

    The Drosophila external sensory organ forms in a lineage elaborating from a single precursor cell via a stereotypical series of asymmetric divisions. HAMLET transcription factor expression demarcates the lineage branch that generates two internal cell types, the external sensory neuron and thecogen. In HAMLET mutant organs, these internal cells are converted to external cells via an unprecedented cousin-cousin cell-fate respecification event. Conversely, ectopic HAMLET expression in the external cell branch leads to internal cell production. The fate-determining signals NOTCH and PAX2 act at multiple stages of lineage elaboration and HAMLET acts to modulate their activity in a branch-specific manner.

  20. A "Shark Encounter": Delayed Primary Closure and Prophylactic Antibiotic Treatment of a Great White Shark Bite.

    Science.gov (United States)

    Popa, Daniel; Van Hoesen, Karen

    2016-11-01

    Shark bites are rare but sensational injuries that are covered in the lay press but are not well described in the medical literature. We present the case of a 50-year-old man who sustained two deep puncture wounds to his thigh from a great white shark in the waters surrounding Isla de Guadalupe off the coast of Baja California, Mexico, during a caged SCUBA dive. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We discuss our strategy of closing the wounds in a delayed primary fashion 24 hours after injury, our antibiotic choices, and the patient's course and review marine pathogens and appropriate antibiotic coverage. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Distribution of intraarterially administered papaverine in endovascular treatment of delayed cerebral vasospasm

    Energy Technology Data Exchange (ETDEWEB)

    Touho, Hajime; Fukuoka, Norihiko; Karasawa, Jun [Osaka Neurological Inst., Toyonaka (Japan)

    1997-02-01

    The distribution of selectively administered papaverine was determined in nine patients with delayed cerebral vasospasm in the territories of the anterior (ACA) and/or middle cerebral arteries (MCA) secondary to aneurysmal subarachnoid hemorrhage by simultaneous infusion with technetium-99m-hexamethyl-propyleneamine oxime ({sup 99m}Tc-HMPAO). Four of the nine patients had a ruptured anterior communicating artery aneurysm, four had an internal carotid artery aneurysm, and the remaining one had a MCA aneurysm. Trapping of anterior communicating artery was carried out in one case and clipping of aneurysms in other eight cases. Neurological deterioration with hemiparesis, paraparesis, and/or somnolence appeared between postsurgical days 8 and 13 due to delayed cerebral vasospasm in all patients. Intraarterial infusion of 40 mg of papaverine containing 37 MBq of {sup 99m}Tc-HMPAO was performed from the C{sub 1} segment in seven of the nine patients and from the C{sub 4} segment in the other two patients. {sup 99m}Tc-HMPAO was distributed in the territories of the ACA and MCA in the two patients who were treated with intraarterial infusion of papaverine from the C{sub 4} segment, but was distributed only to the territory of the ACA in four patients who were treated with intraarterial infusion of papaverine from the C{sub 1} segment at 1 ml/min. In contrast, {sup 99m}Tc-HMPAO was distributed in the territories of the ACA and MCA in the three patients who were treated with papaverine from the C{sub 1} segment at 2 ml/min, although most {sup 99m}Tc-HMPAO was distributed in the territory of the ACA. Vasospasm of the ACA can be treated by intraarterial infusion of papaverine from the C{sub 1} segment at 1 ml/min when selective catheterization to the ACA is difficult to perform. (author)

  2. "To Thine Own Self Be True": Existentialism in Hamlet and The Blind Owl

    Directory of Open Access Journals (Sweden)

    Masoud Farahmandfar

    2015-04-01

    Full Text Available This article aims at exploring the key concepts of Existential thought in two masterpieces of the world literature, namely, William Shakespeare’s Hamlet and Sadeq Hedayat’s The Blind Owl (Buf-e Kur. Freedom, free will, authenticity, self-realization, self-becoming, and awareness of death are among the main concerns of both writers. Shakespeare depicts authenticity in the character of Hamlet, and it is in contrast to him that the reader finds many instances of inauthenticity. The Danish prince has no tolerance whatsoever for inauthentic or self-deceiving. The same thing is visible in The Blind Owl in which the narrator-protagonist feels himself above all the low, petty desires of mankind. All in all, both characters’ main challenge is to live authentically. Keywords: Existential philosophy, authenticity, angst, death, being, existence, self-realization

  3. Interweaving Stories. Hamlet in Jerusalem by Gabriele Vacis and Marco Paolini

    Directory of Open Access Journals (Sweden)

    Franco Nasi

    2017-12-01

    Full Text Available In march 2016, playwright and director Gabriele Vacis, together with Marco Paolini and a group of young Palestinian and Italian actors staged Amleto in Jerusalem, the last production of a “school of theater” for adolescents, directed by Vacis and Paolini. Moving from a brief introduction to the pedagogical and aesthetic philosophy that inspired this educational experience, this article offers a critical description of the structurally complex performance, in which two different theatrical genres, storytelling and tragedy, are continuously intermingled.  In the performance the text by Shakespeare is revisited, deconstructed,  and represented through fragments, which becomes the fundamental dialectical reference for a reflection on problems crucial to the young Palestinian actors, as identity, relations, vengeance, oblivion. Situating this extraordinary theatrical event in relation to the reception of Hamlet in the Arab world, this article explores the narrative development of the reflection urged by an always contemporary Hamlet.

  4. The Simpsons' Shakespeare: Hamlet Today. Possible Meanings and Consequences of a Parodic Appropriaton

    Directory of Open Access Journals (Sweden)

    Maria Elisa Montironi

    2012-12-01

    Full Text Available Within a theoretical framework which includes receptions theory and the theories on the afterlife of Shakespeare, this paper aims at illustrating how Shakespeare’s Hamlet has been formatted for contemporary audience by “The Simpsons”, the successful animated sitcom that shares with the English playwright more than one feature, primarily the fact of being a worldwide icon, thus a global phenomenon. First of all, the figure of Shakespeare will be described, as it is shown in many episodes of the series, among the hundreds aired till now. Furthermore, the parody of Hamlet played by the beloved and well known yellow characters of the cartoon will be described, mainly pointing out the contemporary reading of the Renaissance text, and the way in which it influences its circulation in our society.

  5. Municipalities' Priority Problems and Prospect of Establishing Ordinance to Measures for Marginal Hamlets

    Science.gov (United States)

    Nakanishi, Mayumi; Hoshino, Satoshi; Hashimoto, Shizuka; Kuki, Yasuaki

    The problems of Marginal Hamlets are getting worse, in which more than half of the population is over 65 and community-based life is difficult. To contribute to effective policy making, we conducted a questionnaire survey to members of the National Liaison Council of ‘Suigen no Sato’ constituted to share information about problems and effective counter measures for marginal hamlets. Our study clarified that first, most of respondents had common problems such as lack of job-opportunities and animal damage on farm, and second, though most of respondents recognized the effectiveness of selecting target communities in policy implementations, it is difficult for municipal governments to establish such ordinance provided that councilors and those who were not living in areas of policy target wouldn't agree with it. Finally, we pointed out the roles of national and prefectural governments to help municipal governments effectively cope with such entangled situations.

  6. Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

    Science.gov (United States)

    Grinsztejn, Beatriz; Hosseinipour, Mina C; Ribaudo, Heather J; Swindells, Susan; Eron, Joseph; Chen, Ying Q; Wang, Lei; Ou, San-San; Anderson, Maija; McCauley, Marybeth; Gamble, Theresa; Kumarasamy, Nagalingeshwaran; Hakim, James G; Kumwenda, Johnstone; Pilotto, Jose H S; Godbole, Sheela V; Chariyalertsak, Suwat; de Melo, Marineide Gonçalves; Mayer, Kenneth H; Eshleman, Susan H; Piwowar-Manning, Estelle; Makhema, Joseph; Mills, Lisa A; Panchia, Ravindre; Sanne, Ian; Gallant, Joel; Hoffman, Irving; Taha, Taha E; Nielsen-Saines, Karin; Celentano, David; Essex, Max; Havlir, Diane; Cohen, Myron S

    2014-01-01

    Summary Background Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes. Methods The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00074581. Findings 1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373–522) cells per μL in patients assigned to the early treatment group and 428 (357–522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group

  7. An Intervention That Delays Institutionalization of Alzheimer's Disease Patients: Treatment of Spouse-Caregivers.

    Science.gov (United States)

    Mittelman, Mary S.; And Others

    1993-01-01

    Randomly assigned spouse-caregivers of Alzheimer's disease patients to treatment group (individual and family counseling, support group participation, and ad hoc consultation) or control group (only routine support). Treatment group had less than half as many nursing home placements as control group. Placement also was affected by patient's need…

  8. The budget impact of introducing delayed-release dimethyl fumarate for treatment of relapse-remitting multiple sclerosis in Canada.

    Science.gov (United States)

    Dorman, Emily; Kansal, Anuraag R; Sarda, Sujata

    2015-01-01

    Multiple sclerosis (MS) causes significant disability globally and is especially prevalent in Canada. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) is an orally administered disease-modifying treatment (DMT) for patients with relapsing-remitting MS (RRMS) that is currently on the market in the US, Australia, Canada, and Europe. A budget impact model (BIM) was developed to assess the financial consequences of introducing DMF for treatment of RRMS in Canada. A BIM calculated the financial consequences of introducing DMF in Canada over 3 years based on RRMS prevalence, treatment market share, and clinical effects. RRMS prevalence in Canada was derived from published literature and natural relapse rates, and disease state distribution from clinical trial data. It was conservatively assumed that 100% of RRMS patients were treated with a DMT. DMF was assumed to absorb market share proportionally from the following current treatments: interferon beta-1a-IM, interferon beta-1a-SC, interferon beta-1b, and glatiramer acetate. Treatment efficacy, in terms of relapse rate reductions and treatment discontinuation rates, was determined from mixed treatment comparison. Treatment costs (including costs of acquisition, monitoring, and administration) and cost of relapse were considered. Deterministic one-way sensitivity analyses were conducted to assess the most sensitive input parameters. Over 3 years, the introduction of DMF resulted in an average annual increase of CAD417 per treated patient per year, with reductions in costs associated with relapses (CAD192/patient/year) partially offsetting increased drug acquisition costs (CAD602/patient/year). On a population level, the average annual cost increase was CAD24,654,237, a CAD 0.68 increase per population covered by the Canadian healthcare system. The main drivers of budget impact were drop-out rates, proportion of RRMS patients treated, and market share assumptions. The acquisition costs of DMF for

  9. ["I am but mad north-north-west"--Hamlet's portrayed delusion].

    Science.gov (United States)

    Schulte Herbrüggen, H

    1996-01-01

    Whereas science refers to the real world existing independently and conditioned by cause and effect, the world of literature is fictitious, created by the artist in our imagination by means of language, an artefact conditioned by aesthetic laws, a world sui generis. Accordingly, Hamlet is no person, but a literary figure, doing, saying, thinking and feeling only what the poet dictated him word for word. The essential difference between the two worlds is often overlooked. That "blind spot" has a long-standing tradition in European intellectual history and goes back i.a. to the German "Hamlet experience" in the eighteenth, the "Hamlet fever" and the felt spiritual kinship (Seelenverwandtschaft) in the nineteenth century. Teleological literary criticism, centering around Hamlet's "character" and isolating his psychologically evaluated monologues (e.g. Bradley), refrained from Hamlet's fictionality and role-play and led to blurring beyond recognition the boundaries between real person and literary figure (e.g. Freud, Jones) and assisted in reducing a dramatic role to a medical case history. Speaking of Hamlet, one has to start from Shakespeare's text, our subject matter. A dramatic play being a plot turned into dialogue, the poet's vocabulary used (but indirectly also the vocabulary not used) is particularly informative. When referring to Hamlet's "antic disposition", Shakespeare uses a wide range of over 20 different terms, the most frequented being mad/madness (44 times). Evidence of primary importance are the five occasions after the apparition of his father's ghost, when Hamlet speaks of hist "madness" as an assumed role. In Act I "madness occurs first as a mere possibility when Hamlet informs his friends, he might "put an antic disposition on"; in Act II vis-a-vis Rosencrantz and Guildenstern ("I am but mad north-north-west") it is his deliberate action under certain conditions; in Act III it occurs thrice, first in his declaration of intent ("They are coming to

  10. p18(Hamlet) mediates different p53-dependent responses to DNA-damage inducing agents.

    Science.gov (United States)

    Lafarga, Vanesa; Cuadrado, Ana; Nebreda, Angel R

    2007-10-01

    Cells organize appropriate responses to environmental cues by activating specific signaling networks. Two proteins that play key roles in coordinating stress responses are the kinase p38alpha (MAPK14) and the transcription factor p53 (TP53). Depending on the nature and the extent of the stress-induced damage, cells may respond by arresting the cell cycle or by undergoing cell death, and these responses are usually associated with the phosphorylation of particular substrates by p38alpha as well as the activation of specific target genes by p53. We recently characterized a new p38alpha substrate, named p18(Hamlet) (ZNHIT1), which mediates p53-dependent responses to different genotoxic stresses. Thus, cisplatin or UV light induce stabilization of the p18(Hamlet) protein, which then enhances the ability of p53 to bind to and activate the promoters of pro-apoptotic genes such as NOXA and PUMA leading to apoptosis induction. In a similar way, we report here that p18(Hamlet) can also mediate the cell cycle arrest induced in response to gamma-irradiation, by participating in the p53-dependent upregulation of the cell cycle inhibitor p21(Cip1) (CDKN1A).

  11. Adverse events in diabetic foot infections: a case control study comparing early versus delayed medical treatment after home remedies

    Directory of Open Access Journals (Sweden)

    Cawich SO

    2014-11-01

    outcomes when patients delay conventional medical therapy in favour of home remedies to treat diabetic foot infections. These treatments need not be mutually exclusive. We encourage persons with diabetes who wish to try home remedies to seek medical advice in addition as a part of holistic care. Keywords: diabetic foot infections, adverse events, medical treatment, home remedies

  12. Continuous quality improvement process pin-points delays, speeds STEMI patients to life-saving treatment.

    Science.gov (United States)

    2011-11-01

    Using a multidisciplinary team approach, the University of California, San Diego, Health System has been able to significantly reduce average door-to-balloon angioplasty times for patients with the most severe form of heart attacks, beating national recommendations by more than a third. The multidisciplinary team meets monthly to review all cases involving patients with ST-segment-elevation myocardial infarctions (STEMI) to see where process improvements can be made. Using this continuous quality improvement (CQI) process, the health system has reduced average door-to-balloon times from 120 minutes to less than 60 minutes, and administrators are now aiming for further progress. Among the improvements instituted by the multidisciplinary team are the implementation of a "greeter" with enough clinical expertise to quickly pick up on potential STEMI heart attacks as soon as patients walk into the ED, and the purchase of an electrocardiogram (EKG) machine so that evaluations can be done in the triage area. ED staff have prepared "STEMI" packets, including items such as special IV tubing and disposable leads, so that patients headed for the catheterization laboratory are prepared to undergo the procedure soon after arrival. All the clocks and devices used in the ED are synchronized so that analysts can later review how long it took to complete each step of the care process. Points of delay can then be targeted for improvement.

  13. Toxicity profile and treatment delays in NOPHO ALL2008-comparing adults and children with Philadelphia chromosome-negative acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Toft, Nina; Birgens, Henrik; Abrahamsson, Jonas

    2016-01-01

    OBJECTIVES: Cure rates improve when adolescents and young adults with acute lymphoblastic leukemia (ALL) are treated according to pediatric protocols. Assumed risks of toxicities and associated delays in treatment have played a role in setting upper age limits. The aim of this study was to examine...... the toxicity profile and treatment delays in NOPHO ALL2008 comparing children and adults. METHODS: We collected information on 19 treatment-related toxicities, systematically captured at 3-month intervals throughout therapy, and time intervals between 12 consecutive treatment phases for 1076 patients aged 1......-45 yrs treated according to the Nordic/Baltic ALL2008 protocol. RESULTS: No adults died during induction. The duration of induction therapy and postinduction treatment phases did not differ between children and adults, except for patients 18-45 yrs being significantly delayed during two of nine high...

  14. Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment.

    Science.gov (United States)

    Sinha, Sanjeev; Shekhar, Rahul C; Singh, Gurjeet; Shah, Nipam; Ahmad, Hafiz; Kumar, Narendra; Sharma, Surendra K; Samantaray, J C; Ranjan, Sanjai; Ekka, Meera; Sreenivas, Vishnu; Mitsuyasu, Ronald T

    2012-07-31

    For antiretroviral therapy (ART) naive human immunodeficiency virus (HIV) infected adults suffering from tuberculosis (TB), there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART) after starting antituberculosis treatment (ATT), in order to minimize mortality, HIV disease progression, and adverse events. In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS) for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART) and 62 after 8-12 weeks (delayed ART) of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045). Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05). Rates of adverse events were similar. Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. CTRI/2011/12/002260.

  15. Early versus delayed initiation of antiretroviral therapy for Indian HIV-Infected individuals with tuberculosis on antituberculosis treatment

    Directory of Open Access Journals (Sweden)

    Sinha Sanjeev

    2012-07-01

    Full Text Available Abstract Background For antiretroviral therapy (ART naive human immunodeficiency virus (HIV infected adults suffering from tuberculosis (TB, there is uncertainty about the optimal time to initiate highly active antiretroviral therapy (HAART after starting antituberculosis treatment (ATT, in order to minimize mortality, HIV disease progression, and adverse events. Methods In a randomized, open label trial at All India Institute of Medical Sciences, New Delhi, India, eligible HIV positive individuals with a diagnosis of TB were randomly assigned to receive HAART after 2-4 or 8-12 weeks of starting ATT, and were followed for 12 months after HAART initiation. Participants received directly observed therapy short course (DOTS for TB, and an antiretroviral regimen comprising stavudine or zidovudine, lamivudine, and efavirenz. Primary end points were death from any cause, and progression of HIV disease marked by failure of ART. Findings A total of 150 patients with HIV and TB were initiated on HAART: 88 received it after 2-4 weeks (early ART and 62 after 8-12 weeks (delayed ART of starting ATT. There was no significant difference in mortality between the groups after the introduction of HAART. However, incidence of ART failure was 31% in delayed versus 16% in early ART arm (p = 0.045. Kaplan Meier disease progression free survival at 12 months was 79% for early versus 64% for the delayed ART arm (p = 0.05. Rates of adverse events were similar. Interpretation Early initiation of HAART for patients with HIV and TB significantly decreases incidence of HIV disease progression and has good tolerability. Trial registration CTRI/2011/12/002260

  16. Delayed tooth replantation after root surface treatment with sodium hypochlorite and sodium fluoride: histomorphometric analysis in rats.

    Science.gov (United States)

    Sottovia, André Dotto; Sonoda, Celso Koogi; Poi, Wilson Roberto; Panzarini, Sônia Regina; Lauris, José Roberto Pereira

    2006-04-01

    In cases of delayed tooth replantation, non-vital periodontal ligament remnants have been removed with sodium hypochlorite in an attempt to control root resorption. Nevertheless, reports of its irritating potential in contact with the alveolar connective tissue have been described. Therefore, this study evaluated the healing process on delayed replantation of rat teeth, after periodontal ligament removal by different treatment modalities. Twenty-four rats, assigned to 3 groups (n=8), had their upper right incisor extracted and left on the workbench for desiccation during 60 min. Afterwards, the teeth in group I were immersed in saline for 2 min. In group II, root surfaces were scrubbed with gauze soaked in saline for 2 min; and in group III, scrubbing was done with gauze soaked in 1% sodium hypochlorite solution. Thereafter, root surfaces were etched with 37% phosphoric acid and immersed in 2% acidulate-phosphate sodium fluoride solution, at pH 5.5. Root canals were filled with a calcium hydroxide-based paste and the teeth were replanted. The animals were sacrificed 60 days postoperatively and the pieces containing the replanted teeth were processed and paraffin- embedded. Semi-serial transversally sections were obtained from the middle third of the root and stained with hematoxylin and eosin for histomorphometric analysis. Data were analyzed statistically using Kruskal-Wallis and Dunn's tests. The results showed that root structure and cementum extension were more affected by resorption in group III (p<0.05). All groups were affected by root resorption but the treatment performed in group III was the least effective for its control. The treatment accomplished in groups I and II yielded similar results to each other.

  17. Who is Mr. HAMLET? Interaction of human alpha-lactalbumin with monomeric oleic acid.

    Science.gov (United States)

    Knyazeva, Ekaterina L; Grishchenko, Valery M; Fadeev, Roman S; Akatov, Vladimir S; Permyakov, Sergei E; Permyakov, Eugene A

    2008-12-09

    A specific state of the human milk Ca(2+) binding protein alpha-lactalbumin (hLA) complexed with oleic acid (OA) prepared using an OA-pretreated ion-exchange column (HAMLET) triggers several cell death pathways in various tumor cells. The possibility of preparing a hLA-OA complex with structural and cytotoxic properties similar to those of the HAMLET but under solution conditions has been explored. The complex was formed by titration of hLA by OA at pH 8.3 up to OA critical micelle concentration. We have shown that complex formation strongly depends on calcium, ionic strength, and temperature; the optimal conditions were established. The spectrofluorimetrically estimated number of OA molecules irreversibly bound per hLA molecule (after dialysis of the OA-loaded preparation against water followed by lyophilization) depends upon temperature: 2.9 at 17 degrees C (native apo-hLA; resulting complex referred to as LA-OA-17 state) and 9 at 45 degrees C (thermally unfolded apo-hLA; LA-OA-45). Intrinsic tryptophan fluorescence measurements revealed substantially decreased thermal stability of Ca(2+)-free forms of HAMLET, LA-OA-45, and OA-saturated protein. The irreversibly bound OA does not affect the Ca(2+) association constant of the protein. Phase plot analysis of fluorimetric and CD data indicates that the OA binding process involves several hLA intermediates. The effective pseudoequilibrium OA association constants for Ca(2+)-free hLA were estimated. The far-UV CD spectra of Ca(2+)-free hLA show that all OA-bound forms of the protein are characterized by elevated content of alpha-helical structure. The various hLA-OA complexes possess similar cytotoxic activities against human epidermoid larynx carcinoma cells. Overall, the LA-OA-45 complex possesses physicochemical, structural, and cytotoxic properties closely resembling those of HAMLET. The fact that the HAMLET-like complex can be formed in aqueous solution makes the process of its preparation more transparent and

  18. The pharmaceutical sector inquiry: 'Hamlet' in a nutshell.

    Science.gov (United States)

    den Exter, André

    2010-03-01

    In July 2009, the European Commission (DG Competition) published a Communication on the pharmaceutical sector. This inquiry was launched because there were some indications that competition in the pharmaceutical market in the European Union might not be working well. The report examines the reasons for the observed delay. This article analyses the outcomes from a critical standpoint, arguing in favour of enhanced 'soft law' accountability mechanisms in the pharmaceutical sector, defending conditional patenting and the introduction of a Community patent.

  19. Factors associated with patient and provider delays for tuberculosis diagnosis and treatment in Asia: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jing Cai

    Full Text Available Delays in tuberculosis (TB diagnosis and treatment is a major barrier to effective management of the disease. Determining the factors associated with patient and provider delay of TB diagnosis and treatment in Asia may contribute to TB prevention and control.We searched the PubMed, EMBASE and Web of Science for studies that assessed factors associated with delays in care-seeking, diagnosis, or at the beginning of treatment, which were published from January 1992 to September 2014. Two reviewers independently identified studies that were related to our meta-analysis and extracted data from each study. Independent variables were categorized in separate tables for patient and provider delays.Among 45 eligible studies, 40 studies assessed patient delay whereas 30 assessed provider delay. Cross-sectional surveys were used in all but two articles, which included 17 countries and regions. Socio-demographic characteristics, TB-related symptoms and medical examination, and conditions of seeking medical care in TB patients were frequently reported. Male patients and long travel time/distance to the first healthcare provider led to both shorter patient delays [odds ratio (OR (95% confidence intervals, CI = 0.85 (0.78, 0.92; 1.39 (1.08, 1.78] and shorter provider delays [OR (95%CI = 0.96 (0.93, 1.00; 1.68 (1.12, 2.51]. Unemployment, low income, hemoptysis, and positive sputum smears were consistently associated with patient delay [ORs (95%CI = 1.18 (1.07, 1.30, 1.23 (1.02, 1.49, 0.64 (0.40, 1.00, 1.77 (1.07, 2.94, respectively]. Additionally, consultation at a public hospital was associated with provider delay [OR (95%CI = 0.43 (0.20, 0.91].We propose that the major opportunities to reduce delays involve enabling socio-demographic factors and medical conditions. Male, unemployed, rural residence, low income, hemoptysis, positive sputum smear, and long travel time/distance significantly correlated with patient delay. Male, long travel time/distance and

  20. Delay in treatment of biliary disease during pregnancy increases morbidity and can be avoided with safe laparoscopic cholecystectomy.

    Science.gov (United States)

    Muench, J; Albrink, M; Serafini, F; Rosemurgy, A; Carey, L; Murr, M M

    2001-06-01

    Recent reports indicate that laparoscopic cholecystectomy in pregnancy is safe. The aim of this study was to evaluate whether delays in definitive treatment of symptomatic cholelithiasis increase morbidity. We reviewed the records of 16 women who underwent laparoscopic cholecystectomy during pregnancy between 1992 and 1999. Mean age was 24 +/- 5 years (mean +/- standard error). Symptom onset was during the first trimester in nine patients, second trimester in six patients, and third trimester in one patient. Patients had abdominal pain (93%), nausea (93%), emesis (80%), and fever (66%) for a median of 45 days (range 1-195 days) before cholecystectomy. Nine of 11 women who underwent cholecystectomy more than 5 weeks after onset of symptoms experienced recurrent attacks necessitating 15 hospital admissions and four emergency room visits. Moreover four women who developed symptoms in the first and second trimesters but whose operations were delayed to the third trimester had 11 hospital admissions and four emergency room visits; three of those four (75%) women developed premature contractions necessitating tocolytics. Cholecystectomy was completed laparoscopically in 14 women. There was no hospital infant or maternal mortality or morbidity. We recommend prompt laparoscopic cholecystectomy in pregnant women with symptomatic biliary disease because it is safe and it reduces hospital admissions and frequency of premature labor.

  1. Combination of butylphthalide with umbilical mesenchymal stem cells for the treatment of delayed encephalopathy after carbon monoxide poisoning.

    Science.gov (United States)

    Wang, Huanjun; Li, Yan; Wu, Qiang; Xu, Chenglong; Liu, Qingran

    2016-12-01

    Delayed encephalopathy after carbon monoxide (CO) poisoning (DEACMP) is still a clinical challenge. This study aimed to investigate the efficacy of combined therapy of mesenchymal stem cell (MSC) transplantation and butylphthalide in DEACMP patients.Forty-two DEACMP patients were treated with 1 of the 3 therapies: combined therapy of MSC transplantation and butylphthalide; MSC transplantation alone; or hyperbaric oxygen therapy. The MSCs were alternatively injected into the subarachnoid space and the carotid artery using a self-made high-pressure injector. The Mini-Mental State Examination and the Barthel index of activities of daily living were administered before the treatment, and at 1 month, 3 months, and 6 months after the treatment. Computed tomography and magnetic resonance imaging results before and after the treatment were compared.At 1 month, 3 months, and 6 months after the treatment, the Mini-Mental State Examination scores and the Barthl scores were significantly higher in patients with the combined therapy of MSC transplantation and butylphthalide than those in patients with MSC transplantation alone or hyperbaric oxygen therapy (all P < 0.0001). No significant adverse events occurred.The combination of MSC transplantation and butylphthalide is safe and effective in treating DEACMP.

  2. Medial Canthoplasty Combined with Conjunctivodacryocystorhinostomy for the Treatment of Delayed Medial Telecanthal Deformity

    Directory of Open Access Journals (Sweden)

    Hua Sun

    2017-01-01

    Conclusions: Medial canthoplasty combined with CDCR is an effective surgical method for treatment of patients with medial telecanthal deformity and lacrimal drainage system obstruction. The study indicates that medial canthoplasty combined with CDCR surgery rebuilds normal appearance of eyelid and contour of the medial canthus and successfully repairs the function of the lacrimal drainage system.

  3. ‘Lost to follow up’ : Rethinking delayed and interrupted HIV treatment among married Swazi women

    NARCIS (Netherlands)

    Dlamini-Simelane, T.T.T.; Moyer, E.

    2017-01-01

    Through various campaigns and strategies, more women are being tested for HIV in countries with a high prevalence of the virus. Despite the ready availability of treatment at government clinics in sub-Saharan African countries like Swaziland, women consistently report difficulty in maintaining

  4. Geodesic curve-of-sight formulae for the cosmic microwave background: a unified treatment of redshift, time delay, and lensing

    International Nuclear Information System (INIS)

    Saito, Ryo; Naruko, Atsushi; Hiramatsu, Takashi; Sasaki, Misao

    2014-01-01

    In this paper, we introduce a new approach to a treatment of the gravitational effects (redshift, time delay and lensing) on the observed cosmic microwave background (CMB) anisotropies based on the Boltzmann equation. From the Liouville's theorem in curved spacetime, the intensity of photons is conserved along a photon geodesic when non-gravitational scatterings are absent. Motivated by this fact, we derive a second-order line-of-sight formula by integrating the Boltzmann equation along a perturbed geodesic (curve) instead of a background geodesic (line). In this approach, the separation of the gravitational and intrinsic effects are manifest. This approach can be considered as a generalization of the remapping approach of CMB lensing, where all the gravitational effects can be treated on the same footing

  5. Chitosan Coating: A Postharvest Treatment to Delay Oxidative Stress in Loquat Fruits during Cold Storage

    Directory of Open Access Journals (Sweden)

    Giuseppina Adiletta

    2018-04-01

    Full Text Available Loquat is a non-climacteric fruit consumed fresh for its essential nutrients and phytochemical compounds. In this study, the effects of chitosan coating (1% w/v on changes in the enzymatic antioxidant and membrane damage in three loquat selections (CREAFRC-S18; CREAFRC-S35 and CREAFRC-S36 and three loquat cultivars (Golden Nugget, Algerie and Nespolone rosso di Trabia stored at 7 °C over 21 days were evaluated. Chitosan treatment enhanced the activities of superoxide dismutase, catalase and ascorbate peroxidase. Moreover, this treatment inhibited polyphenol oxidase and guaiacol peroxidase activities, extending the storage life of loquat. Chitosan also preserved membrane integrity by inhibiting lipoxygenase activity and malondialdehyde accumulation. Principal component analysis provided a global view of the responses of both loquat selections and cultivars to the postharvest chitosan coating and storage temperature. These findings suggest that chitosan treatment could be a valid tool for improving the activity of antioxidant enzymes, preserving the enzymatic browning of loquat fruits.

  6. Termination of short term melatonin treatment in children with delayed Dim Light Melatonin Onset: effects on sleep, health, behavior problems, and parenting stress

    NARCIS (Netherlands)

    van Maanen, Annette; Meijer, Anne Marie; Smits, Marcel G.; Oort, Frans J.

    2011-01-01

    To investigate the effects of termination of short term melatonin treatment on sleep, health, behavior, and parenting stress in children with delayed Dim Light Melatonin Onset. Forty-one children (24 boys, 17 girls; mean age=9.43 years) entered melatonin treatment for 3 weeks and then discontinued

  7. Delayed pan-hypopituitarism as a complication following endovascular treatment of bilateral internal carotid artery aneurysms. A case report and review.

    Science.gov (United States)

    Hall, Jonathan; Caputo, Carmela; Chung, Carlos; Holt, Michael; Wang, Yi Yuen

    2015-04-01

    Pan-hypopituitarism has been reported in patients who are subsequently found to have a cerebral aneurysm and there have been reports of pituitary dysfunction immediately following both surgical and endovascular treatment. The authors report a rare case of delayed pan-hypopituitarism following endovascular treatment of bilateral internal carotid artery aneurysms with coil embolisation and flow-diverting stents.

  8. The 808 nm Laser-Assisted Surgery as an Adjunct to Orthodontic Treatment of Delayed Tooth Eruption.

    Science.gov (United States)

    Seifi, Massoud; Vahid-Dastjerdi, Elahe; Ameli, Nazila; Badiee, Mohammad-Reza; Younessian, Farnaz; Amdjadi, Parisa

    2013-01-01

    Failure of teeth to erupt from gingival tissues at usual developmental time is called delayed tooth eruption (DTE). Delayed tooth eruption lead to prolonged fixed orthodontic treatment and its eventual complications. The purpose of the present study was to evaluate the effect of laser-assisted (808 nm) surgical uncovering, on the tooth emergence and orthodontic treatment of DTE. A total of 16 orthodontic patients were included in this study and were equally assigned to an experimental and a control group. Subjects for experiment consisted of eight patients (6 girls and 2 boys) with a mean age of 14±0.9 years. All patients exhibited delayed second premolar eruption. The laser wavelength was 810 nm and it was set in a continuous wave mode at a power output of 1.6 watt with a 0.3-mm diameter fiber tip. When the target tissue was sufficiently anesthetized, the tip was directed at an angle of 10 to 20 degrees to the tissue (light contact mode); and was applied continuously for approximately 12 Seconds until an acceptable tooth exposure area was visible. The facial axis of the clinical crown (FACC) line represents the most prominent portion of the facial central lobe for premolars. All orthodontic brackets are aligned along this reference and are located on FA (Facial Axis) point. The standard for adequate tooth eruption was the accessibility of facial axis of the clinical crown (FACC) for bonding the brackets. Data gathered from the patients were statistically surveyed and compared by means of Tukey's Test and Analysis of Variance (ANOVA). All patients showed good gingival status, no significant bleeding during or immediately after the surgery, and acceptable level of healing after laser surgery. The biologic width of the teeth was preserved and no violation of this important periodontal parameter was observed. The average time for accessing the FA point in experimental group was 11±1.1 weeks and the mentioned period was increased to 25±1.8 weeks in control group

  9. The Dialogue with Hamlet: Paul-Eerik Rummo’s “Hamlet’s Songs” as an Example of the Existential Paradigm in Estonian Culture

    Directory of Open Access Journals (Sweden)

    Anneli Mihkelev

    2013-06-01

    Full Text Available The article demonstrates different meanings of the motif of Hamlet in the Estonian culture. Hamlet as a literary figure has been very important and influential, a symbol of will and a fighter in a hopeless situation. Paul-Eerik Rummo’s poem “Hamlet’s Songs” (1964 forms the centre around which revolve not only written texts but also many such cultural texts as theatre performances and music, all connected by allusions to Hamlet. Rummo’s poem is one of the most innovative poems from the 1960s in Estonian literature. The generation of the 1960s was influenced by several important contemporary theories, including existentialism. Many young writers systematically undermined the Soviet regime in their works. The use of the motif of Hamlet reveals a similarity between the existential and romantic rebellions. Rummo’s dialogue with Hamlet in his poem expresses optimism in a hopeless situation in a way different from Shakespeare’s.

  10. Percutaneous treatment of delayed post-atherectomy superficial femoral artery pseudoaneurysm.

    Science.gov (United States)

    Akkus, Nuri Ilker; Fay, Matt; Varma, Jai

    2012-10-01

    SilverHawk atherectomy is commonly used in lower extremity percutaneous interventions. Minor perforations during SilverHawk atherectomy procedures are reported at a range of 0.8%. There are few reported cases in the literature about very late pseuodoaneursym formation after SilverHawk atherectomy. Herein we report a very unusual, late, concealed, acute rupture of superficial femoral artery with a large, painful pseuodoaneursym formation, 1 week after Silver- Hawk atherectomy and its treatment with Viabahn stent graft (W.L. Gore & Associates).

  11. Conservative treatment of an ankylosed tooth after delayed replantation: a case report.

    Science.gov (United States)

    Díaz, Jaime Andrés; Sandoval, Hector Paulo; Pineda, Patricia Irene; Junod, Pablo Antonio

    2007-10-01

    An 8-year-old boy sustained avulsion of his upper right maxillary central incisor and lateral luxation of his upper left maxillary incisors. Subsequently, the upper right maxillary central incisor developed replacement resorption, and both upper left maxillary incisors developed pulpal canal obliteration. In the ankylosed tooth, decoronation procedure was performed, and in the 44-month follow-up period the involved alveolar site showed vertical apposition of bone and continuing replacement resorption. Decoronation is a surgical procedure that allows preservation of the bone volume for the future, avoiding aesthetic disturbances and more aggressive treatments in cases where other therapeutic alternatives are not feasible.

  12. Molecular Mechanisms of the Cytotoxicity of Human α-Lactalbumin Made Lethal to Tumor Cells (HAMLET) and Other Protein-Oleic Acid Complexes*

    Science.gov (United States)

    Nakamura, Takashi; Aizawa, Tomoyasu; Kariya, Ryusho; Okada, Seiji; Demura, Makoto; Kawano, Keiichi; Makabe, Koki; Kuwajima, Kunihiro

    2013-01-01

    Although HAMLET (human α-lactalbumin made lethal to tumor cells), a complex formed by human α-lactalbumin and oleic acid, has a unique apoptotic activity for the selective killing of tumor cells, the molecular mechanisms of expression of the HAMLET activity are not well understood. Therefore, we studied the molecular properties of HAMLET and its goat counterpart, GAMLET (goat α-lactalbumin made lethal to tumor cells), by pulse field gradient NMR and 920-MHz two-dimensional NMR techniques. We also examined the expression of HAMLET-like activities of complexes between oleic acid and other proteins that form a stable molten globule state. We observed that both HAMLET and GAMLET at pH 7.5 were heterogeneous, composed of the native protein, the monomeric molten globule-like state, and the oligomeric species. At pH 2.0 and 50 °C, HAMLET and GAMLET appeared in the monomeric state, and we identified the oleic acid-binding site in the complexes by two-dimensional NMR. Rather surprisingly, the binding site thus identified was markedly different between HAMLET and GAMLET. Furthermore, canine milk lysozyme, apo-myoglobin, and β2-microglobulin all formed the HAMLET-like complex with the anti-tumor activity, when the protein was treated with oleic acid under conditions in which their molten globule states were stable. From these results, we conclude that the protein portion of HAMLET, GAMLET, and the other HAMLET-like protein-oleic acid complexes is not the origin of their cytotoxicity to tumor cells and that the protein portion of these complexes plays a role in the delivery of cytotoxic oleic acid molecules into tumor cells across the cell membrane. PMID:23580643

  13. Molecular mechanisms of the cytotoxicity of human α-lactalbumin made lethal to tumor cells (HAMLET) and other protein-oleic acid complexes.

    Science.gov (United States)

    Nakamura, Takashi; Aizawa, Tomoyasu; Kariya, Ryusho; Okada, Seiji; Demura, Makoto; Kawano, Keiichi; Makabe, Koki; Kuwajima, Kunihiro

    2013-05-17

    Although HAMLET (human α-lactalbumin made lethal to tumor cells), a complex formed by human α-lactalbumin and oleic acid, has a unique apoptotic activity for the selective killing of tumor cells, the molecular mechanisms of expression of the HAMLET activity are not well understood. Therefore, we studied the molecular properties of HAMLET and its goat counterpart, GAMLET (goat α-lactalbumin made lethal to tumor cells), by pulse field gradient NMR and 920-MHz two-dimensional NMR techniques. We also examined the expression of HAMLET-like activities of complexes between oleic acid and other proteins that form a stable molten globule state. We observed that both HAMLET and GAMLET at pH 7.5 were heterogeneous, composed of the native protein, the monomeric molten globule-like state, and the oligomeric species. At pH 2.0 and 50 °C, HAMLET and GAMLET appeared in the monomeric state, and we identified the oleic acid-binding site in the complexes by two-dimensional NMR. Rather surprisingly, the binding site thus identified was markedly different between HAMLET and GAMLET. Furthermore, canine milk lysozyme, apo-myoglobin, and β2-microglobulin all formed the HAMLET-like complex with the anti-tumor activity, when the protein was treated with oleic acid under conditions in which their molten globule states were stable. From these results, we conclude that the protein portion of HAMLET, GAMLET, and the other HAMLET-like protein-oleic acid complexes is not the origin of their cytotoxicity to tumor cells and that the protein portion of these complexes plays a role in the delivery of cytotoxic oleic acid molecules into tumor cells across the cell membrane.

  14. Delayed Diagnosis of Vesicouterine Fistula After Treatment for Mixed Urinary Incontinence: Menstrual Cup Management and Diagnosis.

    Science.gov (United States)

    Goldberg, Leah; Elsamra, Sammy; Hutchinson-Colas, Juana; Segal, Saya

    2016-01-01

    A vesicouterine fistula is a rare form of urogenital fistula, yet there is increasing prevalence in the United States because of the rising rate of cesarean deliveries. Vesicouterine fistulas have various presentations including menouria, hematuria, or urinary incontinence. A 39-year-old multiparous woman presented with urine leakage after her third cesarean delivery. She had been treated for mixed urinary incontinence with overactive bladder medications and a midurethral sling with continued complaints of urine leakage. The patient noticed her symptoms of urine leakage improved during menses when she used a menstrual cup. After confirmation of vesicouterine fistula, the patient underwent robotic-assisted surgery and her symptoms of insensible urine leakage resolved. When evaluating women with urinary incontinence and a history of cesarean deliveries, use of menstrual cup may aid in the diagnosis of vesicouterine fistula. Robotic-assisted laparoscopic repair with tissue interposition flap is an efficacious minimally invasive method for treatment of vesicouterine fistula.

  15. Delayed Tension Pneumothorax - Identification and Treatment in Traumatic Bronchial Injury: An Interesting Presentation.

    Science.gov (United States)

    Gupta, Amit; Rattan, Amulya; Kumar, Sunil; Rathi, Vinita

    2017-09-01

    A 13-year-old girl, who did not receive any treatment for few hours following Road Traffic Injury (RTI), reported to the Casualty Department and found to have patent airway with clinically normal C spine, air-hunger (RR 42/minute), trachea deviated to left, distended neck veins and absent breath sounds on the right side. The chest X-ray she carried, done immediately after the injury, showed right sided tension pneumothorax. She was put on oxygen at 11 L/minute and an Intercostal chest tube drainage (ICD) was inserted on right side. Her oxygen saturation (40%) failed to improve. ICD bag showed continuous bubbling and air entry remained absent on the right side. An urgent right thoracotomy was done which revealed right main bronchus tear; the tear was repaired using interrupted Prolene ® sutures. Patient recovered well and was discharged 10 days later in a stable condition.

  16. Delayed surgical treatment for neglected or mal-reduced talar fractures.

    Science.gov (United States)

    Huang, Peng-Ju; Cheng, Yuh-Min

    2005-10-01

    From 1993 to 2002, we treated nine patients for neglected or mal-reduced talar fractures. Average patient age was 39 (20-64) years and average follow-up 53 months. The time interval between injury and index operation ranged from 4 weeks to 4 years. Surgical procedures included open reduction with or without bone grafting in six cases, open reduction combined with ankle fusion in one case, talar neck osteotomy in one case, and talar neck osteotomy combined with subtalar fusion in one case. All cases had solid bone union. One patient developed avascular necrosis of the talus needing subsequent ankle arthrodesis. In six patients, adjacent hindfoot arthrosis occurred. The overall AOFAS ankle-hindfoot score was in average 77.4. We conclude that in neglected and mal-reduced talar fractures, surgical treatment can lead to a favourable outcome if the hindfoot joints are not arthritic.

  17. Diabetic foot infections: Current treatment and delaying the 'post-antibiotic era'.

    Science.gov (United States)

    Lipsky, Benjamin A

    2016-01-01

    Treatment for diabetic foot infections requires properly diagnosing infection, obtaining an appropriate specimen for culture, assessing for any needed surgical procedures and selecting an empiric antibiotic regimen. Therapy will often need to be modified based on results of culture and sensitivity testing. Because of excessive and inappropriate use of antibiotics for treating diabetic foot infections, resistance to the usually employed bacteria has been increasing to alarming levels. This article reviews recommendations from evidence-based guidelines, informed by results of systematic reviews, on treating diabetic foot infections. Data from the pre-antibiotic era reported rates of mortality of about 9% and of high-level leg amputations of about 70%. Outcomes have greatly improved with appropriate antibiotic therapy. While there are now many oral and parenteral antibiotic agents that have demonstrated efficacy in treating diabetic foot infections, the rate of infection with multidrug-resistant pathogens is growing. This problem requires a multi-focal approach, including providing education to both clinicians and patients, developing robust antimicrobial stewardship programmes and using new diagnostic and therapeutic technologies. Recently, new methods have been developed to find novel antibiotic agents and to resurrect old treatments, like bacteriophages, for treating these difficult infections. Medical and political leaders have recognized the serious global threat posed by the growing problem of antibiotic resistance. By a multipronged approach that includes exerting administrative pressure on clinicians to do the right thing, investing in new technologies and encouraging the profitable development of new antimicrobials, we may be able to stave off the coming 'post-antibiotic era'. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Transfer between hospitals as a predictor of delay in diagnosis and treatment of patients with Non-Small Cell Lung Cancer

    DEFF Research Database (Denmark)

    Iachina, Maria; Jakobsen, Erik; Fallesen, Anne Kudsk

    2017-01-01

    with treatment facilities during the care pathway. We wanted to investigate whether this organizational set-up influenced the time that patients wait for the diagnosis and treatment. Therefore, the objective of this study was to uncover the impact of transfer between hospitals on the delay in the diagnosis......BACKGROUND: Lung cancer is the second most frequent cancer diagnosis in Denmark. Although improved during the last decade, the prognosis of lung cancer is still poor with an overall 5-year survival rate of approximately 12%. Delay in diagnosis and treatment of lung cancer has been suggested...... and incomplete data on the dates of referral, diagnosis and treatment were excluded. RESULTS: A total of 11 273 patients were included for further analyses. Transfer patients waited longer for treatment after the diagnosis, (Hazard ratio (HR) 0.81 (0.68-0.96)) and in total time from referral to treatment (HR 0...

  19. Reducing treatment delay for early intervention: evaluation of a community based crisis helpline

    Directory of Open Access Journals (Sweden)

    Shrivastava Amresh K

    2012-07-01

    Full Text Available Abstract Background A limited number of studies have assessed the pathways to care of patients experiencing psychosis for the first time. Helpline/clinic programs may offer patients who are still functional but have potential for crisis an alternative that is free from judgment. Methods In this study we report on patient calling a round-the-clock crisis helpline for suicide prevention supported by psychiatric facilities in Mumbai, India. Chi-square and test of mean differences were used to compare outcomes between first-episode patients and those with a previous history. Results Within five years, the helpline received 15,169 calls. Of those callers, 2341 (15.4% experienced suicidal ideation. Two hundred and thirty four patients opting for counseling lasting 12 months agreed to a psychiatric assessment. Of those, 32 were fist time psychosis sufferers, whereas, 54 had previously been psychotic. Of all psychiatric assessments, the clinic received 94 patients with ‘first-episode psychosis’. We found that the duration of illness was significantly shorter (17 vs. 28 months and suicide attempts were fewer (16 vs. 21 in first-time psychosis sufferers compared to those with a treatment history. Conclusions We conclude that some first-episode patients of schizophrenia and other disorders do access services by using helplines. We also argue that helplines may be somewhat immune to stigma, allowing patients a safe alternative when finding help.

  20. Electrophysiologic changes following treatment with organophosphorus-induced delayed neuropathy-producing agents in the adult hen.

    Science.gov (United States)

    Robertson, D G; Schwab, B W; Sills, R D; Richardson, R J; Anderson, R J

    1987-03-15

    Although clinical, pathological, and biochemical effects of organophosphorus-induced delayed neuropathy (OPIDN) have been intensively investigated in the adult hen, detailed electrophysiological studies are lacking. Adult white leghorn hens were treated with a single oral dose of either 30 mg/kg tri-2-cresyl phosphate (TOCP), 750 mg/kg TOCP, 4 mg/kg di-n-butyl-2,2-dichlorovinyl phosphate (DBCV), or 30 mg/kg di-n-butyl-2,2-dichlorovinyl phosphinate (DBCV-P). The 750 mg/kg TOCP and DBCV, but not the 30 mg/kg TOCP and DBCV-P, treatments resulted in clinical signs of OPIDN and mild to marked damage of the tibial nerve 21 days after dose. Twenty-four hr lymphocyte neurotoxic esterase (NTE) inhibition was used as an index of brain NTE inhibition for the various organophosphorus compound (OP) treatment. Twenty-four hr lymphocyte NTE inhibition for 30 mg/kg TOCP, 750 mg/kg TOCP, DBCV, and DBCV-P was 54.1, 87.1, 84.8, and 68.3%, respectively. Twenty-one days after dose, the TOCP-treated hens exhibited some abnormalities in conduction velocity and action potential duration in the tibial or sciatic nerves. No abnormalities were observed in action potential parameters of either the DBCV or DBCV-P treatments. Neurotoxic OP (TOCP and DBCV) treatment resulted in decreased refractoriness in the tibial nerve, increased refractoriness in the sciatic nerve, and elevated strength duration threshold for both nerves. These changes were not present in nerves from DBCV-P (a non-neurotoxic NTE inhibitor)-treated hens. These results suggest that refractory period and strength duration abnormalities in peripheral nerve correlate well with the production of OPIDN and are evident without coincident clinical signs or histopathology.

  1. Delayed release pancrelipase for treatment of pancreatic exocrine insufficiency associated with chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Devi Mukkai Krishnamurty

    2009-07-01

    Full Text Available Devi Mukkai Krishnamurty,1 Atoosa Rabiee,2 Sanjay B Jagannath,1 Dana K Andersen2Johns Hopkins University School of Medicine; 1Department of Medicine; 2Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA; 2Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD, USAAbstract: Pancreatic enzyme supplements (PES are used in chronic pancreatitis (CP for correction of pancreatic exocrine insufficiency (PEI as well as pain and malnutrition. The use of porcine pancreatic enzymes for the correction of exocrine insufficiency is governed by the pathophysiology of the disease as well as pharmacologic properties of PES. Variability in bioequivalence of PES has been noted on in vitro and in vivo testing and has been attributed to the differences in enteric coating and the degree of micro-encapsulation. As a step towards standardizing pancreatic enzyme preparations, the Food and Drug Administration now requires the manufacturers of PES to obtain approval of marketed formulations by April 2010. In patients with treatment failure, apart from evaluating drug and dietary interactions and compliance, physicians should keep in mind that patients may benefit from switching to a different formulation. The choice of PES (enteric coated versus non-enteric coated and the need for acid suppression should be individualized. There is no current standard test for evaluating adequacy of therapy in CP patients and studies have shown that optimization of therapy based on symptoms may be inadequate. Goals of therapy based on overall patient presentation and specific laboratory tests rather than mere correction of steatorrhea are needed.Keywords: pancreatic exocrine insufficiency, chronic pancreatitis, pancreatic enzyme supplement

  2. Delayed release dexlansoprazole in the treatment of GERD and erosive esophagitis

    Directory of Open Access Journals (Sweden)

    Eric T Wittbrodt

    2009-11-01

    Full Text Available Eric T Wittbrodt1, Charles Baum2, David A Peura31Takeda Pharmaceuticals North America, Inc., 2Takeda Pharmaceuticals International, Inc., Deerfield, IL, USA; 3University of Virginia, School of Medicine, Charlottesville, VA, USAAbstract: Although proton pump inhibitors (PPI have a record of remarkable effectiveness and safety in the management of gastroesophageal reflux disease (GERD, several treatment challenges with PPI have emerged. Dexlansoprazole MR is the (R-enantiomer of lansoprazole contained in a formulation that produces two distinct releases of drug and significantly extends the duration of active plasma concentrations and % time pH > 4 beyond that of conventional singlerelease PPI. Dexlansoprazole MR can be administered without regard to meals or the timing of meals in most patients. Dexlansoprazole MR 60 mg demonstrated similar efficacy for healing of erosive esophagitis at 8 weeks compared with lansoprazole 30 mg, and dexlansoprazole MR 30 mg was superior to placebo for maintenance of healed erosive esophagitis at 6 months with 99% of nights and 96% of days heartburn-free over 6 months in patients taking dexlansoprazole MR 30 mg. Superior relief of heartburn occurred in patients taking dexlansoprazole MR 30 mg (55% heartburn-free 24-hour periods vs placebo (14% for symptomatic nonerosive GERD. The safety profile of dexlansoprazole MR is similar to that of lansoprazole. The extended pharmacodynamic effects, added convenience, and efficacy and safety of dexlansoprazole MR offer a novel approach to gastric pH control in patients with acid-related disorders.Keywords: dexlansoprazole MR, gastroesophageal reflux disease, GERD, erosive esophagitis, TAK-390MR

  3. Systemic treatment with CAR-engineered T cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice

    International Nuclear Information System (INIS)

    Hillerdal, Victoria; Ramachandran, Mohanraj; Leja, Justyna; Essand, Magnus

    2014-01-01

    Adoptive transfer of T cells genetically engineered with a chimeric antigen receptor (CAR) has successfully been used to treat both chronic and acute lymphocytic leukemia as well as other hematological cancers. Experimental therapy with CAR-engineered T cells has also shown promising results on solid tumors. The prostate stem cell antigen (PSCA) is a protein expressed on the surface of prostate epithelial cells as well as in primary and metastatic prostate cancer cells and therefore a promising target for immunotherapy of prostate cancer. We developed a third-generation CAR against PSCA including the CD28, OX-40 and CD3 ζ signaling domains. T cells were transduced with a lentivirus encoding the PSCA-CAR and evaluated for cytokine production (paired Student’s t-test), proliferation (paired Student’s t-test), CD107a expression (paired Student’s t-test) and target cell killing in vitro and tumor growth and survival in vivo (Log-rank test comparing Kaplan-Meier survival curves). PSCA-CAR T cells exhibit specific interferon (IFN)-γ and interleukin (IL)-2 secretion and specific proliferation in response to PSCA-expressing target cells. Furthermore, the PSCA-CAR-engineered T cells efficiently kill PSCA-expressing tumor cells in vitro and systemic treatment with PSCA-CAR-engineered T cells significantly delays subcutaneous tumor growth and prolongs survival of mice. Our data confirms that PSCA-CAR T cells may be developed for treatment of prostate cancer

  4. Apoptosis-like death in bacteria induced by HAMLET, a human milk lipid-protein complex.

    Directory of Open Access Journals (Sweden)

    Anders P Hakansson

    Full Text Available BACKGROUND: Apoptosis is the primary means for eliminating unwanted cells in multicellular organisms in order to preserve tissue homeostasis and function. It is characterized by distinct changes in the morphology of the dying cell that are orchestrated by a series of discrete biochemical events. Although there is evidence of primitive forms of programmed cell death also in prokaryotes, no information is available to suggest that prokaryotic death displays mechanistic similarities to the highly regulated programmed death of eukaryotic cells. In this study we compared the characteristics of tumor and bacterial cell death induced by HAMLET, a human milk complex of alpha-lactalbumin and oleic acid. METHODOLOGY/PRINCIPAL FINDINGS: We show that HAMLET-treated bacteria undergo cell death with mechanistic and morphologic similarities to apoptotic death of tumor cells. In Jurkat cells and Streptococcus pneumoniae death was accompanied by apoptosis-like morphology such as cell shrinkage, DNA condensation, and DNA degradation into high molecular weight fragments of similar sizes, detected by field inverse gel electrophoresis. HAMLET was internalized into tumor cells and associated with mitochondria, causing a rapid depolarization of the mitochondrial membrane and bound to and induced depolarization of the pneumococcal membrane with similar kinetic and magnitude as in mitochondria. Membrane depolarization in both systems required calcium transport, and both tumor cells and bacteria were found to require serine protease activity (but not caspase activity to execute cell death. CONCLUSIONS/SIGNIFICANCE: Our results suggest that many of the morphological changes and biochemical responses associated with apoptosis are present in prokaryotes. Identifying the mechanisms of bacterial cell death has the potential to reveal novel targets for future antimicrobial therapy and to further our understanding of core activation mechanisms of cell death in eukaryote cells.

  5. Apoptosis-like death in bacteria induced by HAMLET, a human milk lipid-protein complex.

    Science.gov (United States)

    Hakansson, Anders P; Roche-Hakansson, Hazeline; Mossberg, Ann-Kristin; Svanborg, Catharina

    2011-03-10

    Apoptosis is the primary means for eliminating unwanted cells in multicellular organisms in order to preserve tissue homeostasis and function. It is characterized by distinct changes in the morphology of the dying cell that are orchestrated by a series of discrete biochemical events. Although there is evidence of primitive forms of programmed cell death also in prokaryotes, no information is available to suggest that prokaryotic death displays mechanistic similarities to the highly regulated programmed death of eukaryotic cells. In this study we compared the characteristics of tumor and bacterial cell death induced by HAMLET, a human milk complex of alpha-lactalbumin and oleic acid. We show that HAMLET-treated bacteria undergo cell death with mechanistic and morphologic similarities to apoptotic death of tumor cells. In Jurkat cells and Streptococcus pneumoniae death was accompanied by apoptosis-like morphology such as cell shrinkage, DNA condensation, and DNA degradation into high molecular weight fragments of similar sizes, detected by field inverse gel electrophoresis. HAMLET was internalized into tumor cells and associated with mitochondria, causing a rapid depolarization of the mitochondrial membrane and bound to and induced depolarization of the pneumococcal membrane with similar kinetic and magnitude as in mitochondria. Membrane depolarization in both systems required calcium transport, and both tumor cells and bacteria were found to require serine protease activity (but not caspase activity) to execute cell death. Our results suggest that many of the morphological changes and biochemical responses associated with apoptosis are present in prokaryotes. Identifying the mechanisms of bacterial cell death has the potential to reveal novel targets for future antimicrobial therapy and to further our understanding of core activation mechanisms of cell death in eukaryote cells.

  6. Acetylcholinesterase inhibitor treatment alleviated cognitive impairment caused by delayed encephalopathy due to carbon monoxide poisoning: Two case reports and a review of the literature.

    Science.gov (United States)

    Yanagiha, Kumi; Ishii, Kazuhiro; Tamaoka, Akira

    2017-02-01

    Delayed encephalopathy due to carbon monoxide (CO) poisoning can even occur in patients with mild symptoms of acute CO poisoning. Some cases taking conventional hyperbaric oxygen (HBO) therapy or steroid-pulse therapy may be insufficient, and AchEI may be effective. We report two cases of delayed encephalopathy after acute CO poisoning involving two women aged 69 (Case 1) and 60 years (Case 2) whose cognitive function improved with acetylcholinesterase inhibitor (AchEI) treatment. Delayed encephalopathy occurred 25 and 35 days after acute CO poisoning in Case 1 and Case 2, respectively. Both patients demonstrated cognitive impairment, apathy, and hypokinesia on admission. Although hyperbaric oxygen therapy did not yield any significant improvements, cognitive dysfunction improved substantially. This was evidenced by an improved Mini-Mental State Examination score ffom 9 to 28 points in Case 1 and an improved Hasegawa's dementia rating scale score from 4 to 25 points in Case 2 after administration of an AchEI. In Case 1, we administered galantamine hydrobromide, which was related with improved white matter lesions initially detected on brain magnetic resonance imaging. However, in Case 2 white matter lesions persisted despite AchEI treatment. AchEI treatment may result in improved cognitive and frontal lobe function by increasing low acetylcholine concentrations in the hippocampus and frontal lobe caused by decreased nicotinic acetylcholine receptor levels in delayed encephalopathy after CO poisoning. Physicians should consider AchEIs for patients demonstrating delayed encephalopathy due to CO poisoning.

  7. Patient perspectives on delays in diagnosis and treatment of cancer: a qualitative analysis of free-text data.

    Science.gov (United States)

    Parsonage, Rachel K; Hiscock, Julia; Law, Rebecca-Jane; Neal, Richard D

    2017-01-01

    Earlier cancer diagnosis is crucial in improving cancer survival. The International Cancer Benchmarking Partnership Module 4 (ICBP4) is a quantitative survey study that explores the reasons for delays in diagnosis and treatment of breast, colorectal, lung, and ovarian cancer. To further understand the associated diagnostic processes, it is also important to explore the patient perspectives expressed in the free-text comments. To use the free-text data provided by patients completing the ICBP4 survey to augment the understanding of patients' perspectives of their diagnostic journey. Qualitative analysis of the free-text data collected in Wales between October 2013 and December 2014 as part of the ICBP4 survey. Newly-diagnosed patients with either breast, ovarian, colorectal, or lung cancer were identified from registry data and then invited by their GPs to participate in the survey. A thematic framework was used to analyse the free-text comments provided at the end of the ICBP4 survey. Of the 905 patients who returned a questionnaire, 530 included comments. The free-text data provided information about patients' perspectives of the diagnostic journey. Analysis identified factors that acted as either barriers or facilitators at different stages of the diagnostic process. Some factors, such as screening, doctor-patient familiarity, and private treatment, acted as both barriers and facilitators depending on the context. Factors identified in this study help to explain how existing models of cancer diagnosis (for example, the Pathways to Treatment Model) work in practice. It is important that clinicians are aware of how these factors may interact with individual clinical cases and either facilitate, or act as a barrier to, subsequent cancer diagnosis. Understanding and implementing this knowledge into clinical practice may result in quicker cancer diagnoses. © British Journal of General Practice 2017.

  8. Treatment with 24 h-delayed normo- and hyperbaric oxygenation in severe sepsis induced by cecal ligation and puncture in rats

    DEFF Research Database (Denmark)

    Bærnthsen, Nina Falcon; Hansen, Marco Bo; Wahl, Anna Mygind

    2017-01-01

    uncertain. We investigated the effects of 24 h delayed normobaric oxygen (NBO2) and HBO2treatment on the endogenous production of the inflammatory markers interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-10, and on mortality in rats with cecal ligation and puncture (CLP) induced sepsis. Method...

  9. Psychosocial and cultural reasons for delay in seeking help and nonadherence to treatment in Indonesian women with breast cancer: A qualitative study.

    NARCIS (Netherlands)

    Iskandarsyah, A.; Klerk, C.D.; Suardi, D.R.; Soemitro, M.P.; Sadarjoen, S.S.; Passchier, J.

    2014-01-01

    Objective: The aim of this study was to explore reasons for delay in seeking medical help and nonadherence to treatment in Indonesian women with breast cancer. Method: Semistructured interviews were conducted by purposive sampling, using a consecutive sample of 50 breast cancer patients who were

  10. Treatment with a non-toxic, self-replicating anti-prion delays or prevents prion disease in vivo.

    Science.gov (United States)

    Diaz-Espinoza, R; Morales, R; Concha-Marambio, L; Moreno-Gonzalez, I; Moda, F; Soto, C

    2018-03-01

    Transmissible spongiform encephalopathies (TSEs) are fatal neurological disorders caused by prions, which are composed of a misfolded protein (PrP Sc ) that self-propagates in the brain of infected individuals by converting the normal prion protein (PrP C ) into the pathological isoform. Here, we report a novel experimental strategy for preventing prion disease based on producing a self-replicating, but innocuous PrP Sc -like form, termed anti-prion, which can compete with the replication of pathogenic prions. Our results show that a prophylactic inoculation of prion-infected animals with an anti-prion delays the onset of the disease and in some animals completely prevents the development of clinical symptoms and brain damage. The data indicate that a single injection of the anti-prion eliminated ~99% of the infectivity associated to pathogenic prions. Furthermore, this treatment caused significant changes in the profile of regional PrP Sc deposition in the brains of animals that were treated, but still succumbed to the disease. Our findings provide new insights for a mechanistic understanding of prion replication and support the concept that prion replication can be separated from toxicity, providing a novel target for therapeutic intervention.

  11. Delayed orgasm and anorgasmia.

    Science.gov (United States)

    Jenkins, Lawrence C; Mulhall, John P

    2015-11-01

    Delayed orgasm/anorgasmia defined as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation, which causes personal distress. Delayed orgasm and anorgasmia are associated with significant sexual dissatisfaction. A focused medical history can shed light on the potential etiologies, which include medications, penile sensation loss, endocrinopathies, penile hyperstimulation, and psychological etiologies. Unfortunately, there are no excellent pharmacotherapies for delayed orgasm/anorgasmia, and treatment revolves largely around addressing potential causative factors and psychotherapy. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Hip-Hop Hamlet: Hybrid Interpretive Discourse in a Suburban High School English Class

    Directory of Open Access Journals (Sweden)

    Joanna L. Anglin

    2014-07-01

    Full Text Available This study investigates the collaborative composing processes of a group of five high school seniors who constructed interpretations of each of the five acts of Shakespeare’s Hamlet through the medium of spoken word performances. The group composing processes were analyzed to identify how the students drew on conventions from the spoken word tradition to phrase and perform their interpretations. Findings indicate that across the five spoken word performances, the retelling of the Hamlet narrative involved a set of decisions that were both constrained and afforded by the rap medium. The students’ discussion of how to rewrite the story in the condensed poetic form of a rap required them to clarify events from Shakespeare’s version and both summarize them and interpret them both in their discussion and in their own text. Their interpretive work involved the incorporation of a variety of rap and other pop culture conventions such that their deliberation regarding word choice and accompanying performative elements necessitated careful consideration of the meaning that they found in Shakespeare’s version of the story, itself an adaptation from extant cultural narratives. The study concludes with a consideration of their spoken word interpretations as comprising a hybrid discourse that enabled exploratory interpretive talk that contributed to their understanding of the drama through the collaborative composition of their own representational text.

  13. Speaking to the yet unknowing world: Hamlet, Horatio and the problem of imperfect witness.

    Science.gov (United States)

    Phillips, Christine

    2010-12-01

    Every day doctors bear witness to others about the experiences, needs and feelings of their patients, drawing on what they have learnt from clinical consultations. This paper considers the medical task of bearing honourable and truthful witness through an examination of the role and actions of Horatio in Hamlet. Horatio is simultaneously located among the background machinery of the play, separate from the lives of the protagonists, and in the foreground, where his authoritative witness is repeatedly called upon by the play's characters. Horatio is invited to watch an unfolding disaster, his warnings are not heard, and at its conclusion he stands apart from the drama to give its account. The tensions between engagement and observation, and between partial and impartial accounting echo those faced by doctors in everyday clinical practice. The act of bearing witness, Shakespeare suggests, even for those who are tasked with being objective, is necessarily imperfect, and not dispassionate. Those people, including doctors, who are expected to construct authoritative accounts of the motives and actions of others may find in Hamlet a small lesson on the need to approach their summary narratives about others more humbly, aware of the narrowness and partiality of their perspective.

  14. ANÁLISE DOS EFEITOS DE FALA DO CONSELHEIRO REAL EM HAMLET

    Directory of Open Access Journals (Sweden)

    Thiago Martins Prado (UNEB

    2017-05-01

    Full Text Available

    Tomando por base como se realiza e qual a motivação das falas do personagem Polônio, o estudo investiga a composição do conselheiro real da peça Hamlet, de William Shakespeare. Os efeitos de fala de Polônio são classificados a fim de aprofundar a análise da argumentação desse personagem. Paralelamente, confrontam-se hipóteses levantadas por Stephen Greenblatt (2011 e por Manoel Hygino dos Santos (1965 sobre a relação entre acontecimentos históricos que influenciaram a escrita shakespeariana a respeito da concepção do conselheiro Polônio. Para combater as interpretações redutoras sobre o personagem Polônio, o estudo valoriza a complexidade dos contextos de fala do conselheiro.

    Palavras-chave: Conselheiro Polônio. Argumentação do conselheiro real em Hamlet. Mapeamento de efeitos de fala. Shakespeare.

  15. Determinants of delay in malaria treatment-seeking behaviour for under-five children in south-west Ethiopia: a case control study

    Directory of Open Access Journals (Sweden)

    Deribew Amare

    2010-11-01

    Full Text Available Abstract Background Prompt diagnosis and timely treatment of malaria within 24 hours after onset of first symptoms can reduce illness progression to severe stages and therefore, decrease mortality. The reason why mothers/caretakers delay in malaria diagnosis and treatment for under-five children is not well studied in Ethiopia. The objective of this study was to assess determinants of malaria treatment delay in under-five children in three districts of south-west Ethiopia. Methods A case control study was conducted from March 15 to April 20, 2010. Cases were under-five children who had clinical malaria and sought treatment after 24 hours of developing sign and symptom, and controls were under-five children who had clinical malaria and sought treatment within 24 hours of developing sign and symptom of malaria. Data were collected by trained enumerators using structured questionnaire. Data were entered in to Epi Info version 6.04 and analyzed using SPSS version 16.0. To identify determinants, multiple logistic regression was done. Results A total of 155 mothers of cases and 155 mothers of controls were interviewed. Mothers of children who were in a monogamous marriage (OR = 3.41, 95% CI: 1.39, 8.34, who complained about the side effects of anti-malarial drugs (OR = 4.96, 95% CI: 1.21, 20.36, who had no history of child death (OR = 3.50, 95% CI: 1.82, 6.42 and who complained about the higher cost of transportation to reach the health institutions (OR = 2.01, 95% CI: 1.17, 3.45 were more likely to be late for the treatment of malaria in under-five children. Conclusion Effective malaria control programmes should address reducing delayed presentation of children for treatment. Efforts to reduce delay should address transport cost, decentralization of services and increasing awareness of the community on early diagnosis and treatment.

  16. «Eu era Hamlet»: o desejo de substituição em Hamletmaschine, de Heiner Müller

    OpenAIRE

    Gomes, Miguel Ramalhete

    2009-01-01

    «I was Hamlet»: desire for substitution in Heiner Müller’s Hamletmaschine. In this essay I propose a reading of Heiner Müller’s play Hamletmaschine (1977) as a radical exercise in rewriting William Shakespeare’s Hamlet. As a follow-up to his translation of Hamlet into German, Müller writes this nine-page play as a comment to the political situation in Eastern Europe in the 1960’s and 1970’s. Because of its size, the play strikes us as a dense form, close to the fragment form, foreshadow...

  17. Cognitive factors that influence delayed decision to seek treatment among older patients with acute myocardial infarction in Korea.

    Science.gov (United States)

    Hwang, Seon Young; Jeong, Myung Ho

    2012-06-01

    The incidence of acute myocardial infarction (AMI) is rapidly increasing among older adults in Korea. However, the factors associated with a delayed decision to visit a hospital and the reasons for this delay have not been explored adequately among older patients. To determine factors predicting a prehospital delay time of > 6 h and to identify the cognitive barriers in the delayed decision of AMI patients aged ≥ 65 years. This study adopted a mixed methodological approach using quantitative and qualitative analyses. The sample included 94 male and 71 female patients hospitalized for first-time AMI at a university hospital in Korea. Thematic content analysis was used to identify the themes from the qualitative interview data, and multiple logistic regression analysis was used to predict delayed hospital presentation by > 6 h. The median prehospital delay time was 12 h. Low education level, presence of preinfarction angina pain, and attribution of symptoms to a non-cardiac origin were found to be the predicting factors. From the qualitative data, four meaningful themes including 10 subthemes that influenced the delayed decision were identified. Some culturally peculiar themes were found in this Korean sample. Educational strategies that focus on these cognitive decision-making barriers should be planned for elderly Korean at high risk for AMI.

  18. Effects of music therapy in the treatment of children with delayed speech development - results of a pilot study

    OpenAIRE

    Linden Ulrike; Groß Wibke; Ostermann Thomas

    2010-01-01

    Abstract Background Language development is one of the most significant processes of early childhood development. Children with delayed speech development are more at risk of acquiring other cognitive, social-emotional, and school-related problems. Music therapy appears to facilitate speech development in children, even within a short period of time. The aim of this pilot study is to explore the effects of music therapy in children with delayed speech development. Methods A total of 18 childr...

  19. From Shakespeare to Kierkegaard: An Existential Reading of Hamlet = Shakespeare'den Kierkegaard'a: Varoluşçuluk Işığında

    Directory of Open Access Journals (Sweden)

    Aslı TEKİNAY

    2001-06-01

    Full Text Available Shakespeare's Hamlet yields conveniently to an existential reading. Hamlet may be seen as the prototype of the modern European man who struggles in a "rotten" world. In Denmark, he finds himself in a Sartrean "void". As he struggles to overcome his "nausea" by trying to unmask men, strip them of their fine appearances and show them in their true nature, Hamlet passes through the three stages of life described by Kierkegaard: the aesthetic, the ethical and the religious. Since these stages are in contradiction with one another, there is a basic choice, an "either/or" facing man. Hamlet's actions or non-actions in the play can be studied within the framework of this context.

  20. Delayed fission

    Energy Technology Data Exchange (ETDEWEB)

    Hatsukawa, Yuichi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1997-07-01

    Delayed fission is a nuclear decay process that couples {beta} decay and fission. In the delayed fission process, a parent nucleus undergoes {beta} decay and thereby populates excited states in the daughter. If these states are of energies comparable to or greater than the fission barrier of the daughter, then fission may compete with other decay modes of the excited states in the daughter. In this paper, mechanism and some experiments of the delayed fission will be discussed. (author)

  1. HAMLET -Matroshka IIA and IIB experiments aboard the ISS: comparison of organ doses

    Science.gov (United States)

    Kato, Zoltan; Reitz, Guenther; Berger, Thomas; Bilski, Pawel; Hajek, Michael; Sihver, Lembit; Palfalvi, Jozsef K.; Hager, Luke; Burmeister, Soenke

    The Matroshka experiments and the related FP7 HAMLET project aimed to study the dose burden of the cosmic rays in the organs of the crew working inside and outside the ISS. Two of the experiments will be discussed. They were performed in two different locations inside the ISS: during the Matroshka 2A (in 2006) the phantom was stored in the Russian Docking Module (Pirs), while during the Matroshka 2B (in 2007-08) it was inside the Russian Service Module (Zvezda). Both experiments were performed in the decreasing phase of the solar cycle. Solid state nuclear track detectors (SSNTD) were applied to investigate the dose contribution of the high LET radiation above ˜10 keV/µm. Two configurations of SSNTDs stacks were constructed: one for the exposure in the so called organ dose boxes (in the lung and kidney), another one for the skin dose measurements, embedded in the nomex poncho of the Phantom. In addition a reference package was placed outside the phantom. After exposure the detectors were transferred to the Earth for data evaluation. Short and long etching procedures were applied to distinguish the high and low LET particles, respectively. The particle tracks were evaluated by a semi automated image analyzer. Addi-tionally manual track parameter measurements were performed on very long tracks. As the result of measurements the LET spectra were deduced. Based on these spectra, the absorbed dose, the dose equivalent and the mean quality factor were calculated. The configuration of the stacks, the methods of the calibration and evaluation and finally the results will be presented and compared. The multiple etching and the combined evaluation method allowed to determine the fraction of the dose originated from HZE particles (Z>2 and range > major axis). Further on, data eval-uation was performed to separate the secondary particles (target fragments) from the primary particles. Although the number of high LET particles above a ˜80 keV/µm was found to be higher during

  2. HAMLET -Human Model MATROSHKA for Radiation Exposure Determination of Astronauts -Current status and results

    Science.gov (United States)

    Reitz, Guenther; Berger, Thomas; Bilski, Pawel; Burmeister, Soenke; Labrenz, Johannes; Hager, Luke; Palfalvi, Jozsef K.; Hajek, Michael; Puchalska, Monika; Sihver, Lembit

    The exploration of space as seen in specific projects from the European Space Agency (ESA) acts as groundwork for human long duration space missions. One of the main constraints for long duration human missions is radiation. The radiation load on astronauts and cosmonauts in space (as for the ISS) is a factor of 100 higher than the natural radiation on Earth and will further increase should humans travel to Mars. In preparation for long duration space missions it is important to evaluate the impact of space radiation in order to secure the safety of the astronauts and minimize their radiation risks. To determine the radiation risk on humans one has to measure the radiation doses to radiosensitive organs within the human body. One way to approach this is the ESA facility MATROSHKA (MTR), under the scientific and project lead of DLR. It is dedicated to determining the radiation load on astronauts within and outside the International Space Station (ISS), and was launched in January 2004. MTR is currently preparing for its fourth experimental phase inside the Japanese Experimental Module (JEM) in summer 2010. MTR, which mimics a human head and torso, is an anthropomorphic phantom containing over 6000 radiation detectors to determine the depth dose and organ dose distribution in the body. It is the largest international research initiative ever performed in the field of space dosimetry and combines the expertise of leading research institutions around the world, thereby generating a huge pool of data of potentially immense value for research. Aiming at optimal scientific exploitation, the FP7 project HAMLET aims to process and compile the data acquired individually by the participating laboratories of the MATROSHKA experiment. Based on experimental input from the MATROSHKA experiment phases as well as on radiation transport calculations, a three-dimensional model for the distribution of radiation dose in an astronaut's body will be built up. The scientific achievements

  3. Maternal prepregnancy obesity and insulin treatment during pregnancy are independently associated with delayed lactogenesis in women with recent gestational diabetes mellitus.

    Science.gov (United States)

    Matias, Susana L; Dewey, Kathryn G; Quesenberry, Charles P; Gunderson, Erica P

    2014-01-01

    The timely onset of stage II lactogenesis (OL) is important for successful breastfeeding and newborn health. Several risk factors for delayed OL are common in women with a history of gestational diabetes mellitus (GDM), which may affect their chances for successful breastfeeding outcomes. We investigated the prevalence and risk factors associated with delayed OL in a racially and ethnically diverse cohort of postpartum women with recent GDM. We analyzed data collected in the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy (SWIFT), which is a prospective cohort of women diagnosed with GDM who delivered at Kaiser Permanente Northern California hospitals from 2008 to 2011. At 6-9 wk postpartum, delayed OL was assessed by maternal report of breast fullness and defined as occurring after 72 h postpartum. We obtained data on prenatal course and postdelivery infant feeding practices from electronic medical records and in-person surveys. We used multivariable logistic regression models to estimate associations of delayed OL with prenatal, delivery, and postnatal characteristics. The analysis included 883 SWIFT participants who initiated breastfeeding and did not have diabetes at 6-9 wk postpartum. Delayed OL was reported by 33% of women and was associated with prepregnancy obesity (OR: 1.56; 95% CI: 1.07, 2.29), older maternal age (OR: 1.05; 95% CI: 1.01, 1.08), insulin GDM treatment (OR: 3.11; 95% CI: 1.37, 7.05), and suboptimal in-hospital breastfeeding (OR: 1.65; 95% CI: 1.20, 2.26). A higher gestational age was associated with decreased odds of delayed OL but only in multiparous mothers (OR: 0.79; 95% CI: 0.67, 0.94). One-third of women with recent GDM experienced delayed OL. Maternal obesity, insulin treatment, and suboptimal in-hospital breastfeeding were key risk factors for delayed OL. Early breastfeeding support for GDM women with these risk factors may be needed to ensure successful lactation. This trial was registered at clinicaltrials

  4. What role do traditional beliefs play in treatment seeking and delay for Buruli ulcer disease?--insights from a mixed methods study in Cameroon.

    Directory of Open Access Journals (Sweden)

    Koen Peeters Grietens

    Full Text Available Victims of Buruli ulcer disease (BUD frequently report to specialized units at a late stage of the disease. This delay has been associated with local beliefs and a preference for traditional healing linked to a reportedly mystical origin of the disease. We assessed the role beliefs play in determining BUD sufferers' choice between traditional and biomedical treatments.Anthropological fieldwork was conducted in community and clinical settings in the region of Ayos and Akonolinga in Central Cameroon. The research design consisted of a mixed methods study, triangulating a qualitative strand based on ethnographic research and quantitative data obtained through a survey presented to all patients at the Ayos and Akonolinga hospitals (N = 79 at the time of study and in four endemic communities (N = 73 belonging to the hospitals' catchment area.The analysis of BUD sufferers' health-seeking behaviour showed extremely complex therapeutic itineraries, including various attempts and failures both in the biomedical and traditional fields. Contrary to expectations, nearly half of all hospital patients attributed their illness to mystical causes, while traditional healers admitted patients they perceived to be infected by natural causes. Moreover, both patients in hospitals and in communities often combined elements of both types of treatments. Ultimately, perceptions regarding the effectiveness of the treatment, the option for local treatment as a cost prevention strategy and the characteristics of the doctor-patient relationship were more determinant for treatment choice than beliefs.The ascription of delay and treatment choice to beliefs constitutes an over-simplification of BUD health-seeking behaviour and places the responsibility directly on the shoulders of BUD sufferers while potentially neglecting other structural elements. While more efficacious treatment in the biomedical sector is likely to reduce perceived mystical involvement in the

  5. Lipids as tumoricidal components of human α-lactalbumin made lethal to tumor cells (HAMLET): unique and shared effects on signaling and death.

    Science.gov (United States)

    Ho, James C S; Storm, Petter; Rydström, Anna; Bowen, Ben; Alsin, Fredrik; Sullivan, Louise; Ambite, Inès; Mok, K H; Northen, Trent; Svanborg, Catharina

    2013-06-14

    Long-chain fatty acids are internalized by receptor-mediated mechanisms or receptor-independent diffusion across cytoplasmic membranes and are utilized as nutrients, building blocks, and signaling intermediates. Here we describe how the association of long-chain fatty acids to a partially unfolded, extracellular protein can alter the presentation to target cells and cellular effects. HAMLET (human α-lactalbumin made lethal to tumor cells) is a tumoricidal complex of partially unfolded α-lactalbumin and oleic acid (OA). As OA lacks independent tumoricidal activity at concentrations equimolar to HAMLET, the contribution of the lipid has been debated. We show by natural abundance (13)C NMR that the lipid in HAMLET is deprotonated and by chromatography that oleate rather than oleic acid is the relevant HAMLET constituent. Compared with HAMLET, oleate (175 μm) showed weak effects on ion fluxes and gene expression. Unlike HAMLET, which causes metabolic paralysis, fatty acid metabolites were less strongly altered. The functional overlap increased with higher oleate concentrations (500 μm). Cellular responses to OA were weak or absent, suggesting that deprotonation favors cellular interactions of fatty acids. Fatty acids may thus exert some of their essential effects on host cells when in the deprotonated state and when presented in the context of a partially unfolded protein.

  6. Routine delayed voiding cystourethography after initial successful endoscopic treatment with Dextranomer/Hialuronic Acid Copolimer (Dx/HA) of vesicoureteral reflux (VUR). Is it necessary?

    Science.gov (United States)

    García-Aparicio, L; Blázquez-Gómez, E; Vila Santandreu, A; Camacho Diaz, J A; Vila-Cots, J; Ramos Cebrian, M; de Haro, I; Martin, O; Tarrado, X

    2016-12-01

    Some guidelines recommend an early voiding cystourethrography (VCUG) after endoscopic treatment of vesicoureteral reflux (VUR), but there's no consensus if it's necessary a long-term follow-up in these patients. The aim of our study is analyze if it's necessary a delayed VCUG after initial successful treatment with Dx/HA. We have reviewed all medical charts of patients that underwent Dx/HA treatment from 2006 to 2010. We have selected patients with initial successful treatment and more than 3 years of radiological and clinical follow-up. We have analyzed late clinical and radiological outcomes. One hundred and sixty children with 228 refluxing ureters underwent Dx/HA endoscopic treatment with a mean follow-up of 52.13 months. Early VCUG was performed in 215 ureters with an initial successful rate of 84.1%. The group of study was 94/215 ureters with more than 3 years of follow-up with a delayed VCUG. VUR was still resolved in 79,8% of the ureters. Clinical success rate was 91.7%. The incidence of febrile urinary tract infection in those patients with cured VUR and those with a relapsed VUR was 8 and 15%, respectively; but there were no significant differences. We have not found any variable related with relapsed VUR except those ureters that initially received 2 injections (P<.05). If our objective in the treatment of VUR is to reduce the incidence of febrile urinary tract infection it is not necessary to perform a delayed VCUG even though the long-term radiological outcomes is worse than clinical outcome. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Yo, Hamlet!

    Science.gov (United States)

    Whelan, Debra Lau

    2007-01-01

    This article presents Alan Sitomer, an English teacher at Lynwood High School, and how he teaches his students classic literature through hip-hop. These at-risk students attend a severely overcrowded, low-performing school in East Los Angeles that's surrounded by what Sitomer describes as "gangs, guns, and drugs." Prostitutes work the…

  8. Gender Identity and Gender Performativity in Shakespeare’s Selected Plays: Macbeth, Hamlet and Merry Wives of Windsor

    Directory of Open Access Journals (Sweden)

    Mehdi Amiri

    2017-08-01

    Full Text Available The main argument of this article is focused on three plays by William Shakespeare, Macbeth, Hamlet and Merry Wives of Windsor. There are several points in these plays which deal with woman and their rights. This article deals with Shakespeare’s plays in relation to feminism, which pays more attention to the rights of women and their true identity. In all societies women are defined in terms of their relations to men as the center of power to which women have limited or no access. Judith Butler's performativity is significance on understandings of gender identity. Butler believes that gender is produced in society; also it can be changed in society. Feminism should aim to create a society in which, one's sexual anatomy is irrelevant to who one is, and what one does. Shakespeare’s view of a woman is shown through his representation of female characters in his plays specifically in Macbeth, Hamlet and Merry Wives of Windsor.

  9. The Genius of Shakespeare’s “Plagiarisms”. Case Studies: Hamlet, Othello, King Lear and Macbeth

    Directory of Open Access Journals (Sweden)

    Cuțitaru Codrin Liviu

    2017-06-01

    Full Text Available This paper aims at exploring the cultural ambiguity which William Shakespeare remarkably extracts from the sources of his major plays, turning it, eventually, into an essential instrument of the tragic and the tragedy. What in normal/modern circumstances would easily count as “plagiarism”, becomes here, paradoxically, a token of artistic genius and brilliant creation. Our examples will be from the four outstanding tragedies—Hamlet, Othello, King Lear and Macbeth. The sources selected by our research will be Saxo Grammaticus’s Histoires tragiques, Cinthio’s Un Capitano Moro, the Celtic legend Leir of Britain and, obviously, Holinshed’s Chronicles. We shall try to demonstrate that the so-called cultural ambiguity adopts various forms in Shakespeare’s plays, going from the clash of civilisations (Hamlet and Othello to the crisis of identity (Lear and Macbeth.

  10. Tròpics de Shakespeare : orígens i originalitat del Hamlet català

    OpenAIRE

    Buffery, Helena

    2009-01-01

    Hamlet és una de les obres que més ha inspirat autors, actors, directors i dramaturgs catalans. De fet, es podria dir, com en altres cultures europees, que és l'obra que determina tota traducció i representació posterior de Shakespeare, i que marca els orígens de la seva influència en la tradició cultural europea. Aquest article presenta la història retòrica del Hamlet català mitjançant les traduccions, les adaptacions i altres formes de reescritura de l'obra, a més de la seva representació t...

  11. Toxicity profile and treatment delays in NOPHO ALL2008-comparing adults and children with Philadelphia chromosome-negative acute lymphoblastic leukemia.

    Science.gov (United States)

    Toft, Nina; Birgens, Henrik; Abrahamsson, Jonas; Griškevičius, Laimonas; Hallböök, Helene; Heyman, Mats; Klausen, Tobias Wirenfeldt; Jónsson, Ólafur Gísli; Palk, Katrin; Pruunsild, Kaie; Quist-Paulsen, Petter; Vaitkeviciene, Goda; Vettenranta, Kim; Asberg, Ann; Helt, Louise Rold; Frandsen, Thomas; Schmiegelow, Kjeld

    2016-02-01

    Cure rates improve when adolescents and young adults with acute lymphoblastic leukemia (ALL) are treated according to pediatric protocols. Assumed risks of toxicities and associated delays in treatment have played a role in setting upper age limits. The aim of this study was to examine the toxicity profile and treatment delays in NOPHO ALL2008 comparing children and adults. We collected information on 19 treatment-related toxicities, systematically captured at 3-month intervals throughout therapy, and time intervals between 12 consecutive treatment phases for 1076 patients aged 1-45 yrs treated according to the Nordic/Baltic ALL2008 protocol. No adults died during induction. The duration of induction therapy and postinduction treatment phases did not differ between children and adults, except for patients 18-45 yrs being significantly delayed during two of nine high-risk blocks (median number of days for patients 1-9, 10-17, and 18-45 yrs; the glucocorticosteroid/antimetabolite-based block B1: 24, 26, and 29 d, respectively, P = 0.001, and Block 5 (in most cases also a B block): 29, 29, and 37 d, respectively, P = 0.02). A higher incidence of thrombosis with increasing age was found; highest odds ratio 5.4 (95% CI: (2.6;11.0)) for patients 15-17 yrs compared with children 1-9 yrs (P children, although thrombosis and avascular osteonecrosis was most common among adolescents. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Delayed Ejaculation

    Science.gov (United States)

    ... cases, it is due to a combination of physical and psychological concerns. Psychological causes of delayed ejaculation include: Depression, anxiety or other mental health conditions Relationship problems due to stress, poor communication ...

  13. Delayed growth

    Science.gov (United States)

    ... Slow rate of growth; Retarded growth and development; Growth delay Images Toddler development References Cooke DW, Divall SA, Radovick S. Normal and aberrant growth in children. In: Melmed S, Polonsky KS, Larsen PR, ...

  14. "A little more than kin" - Quotations as a linguistic phenomenon : a study based on quotations from Shakespeare's Hamlet

    OpenAIRE

    Quassdorf, Sixta

    2016-01-01

    Quotations "oscillate between the occasional and the conventional" as Burger/Buhofer/Sialm (1982) once succinctly formulated. Developed from a PhD thesis, this book explores precisely this "oscillating" character of quotations: It discusses the nature of quotations and the relationship between common quotations and phraseology from a theoretical and an empirical perspective. Shakespeare's Hamlet was chosen as a canonical text whose frequently quoted traces can be followed across centuries. Sc...

  15. A study on stability and medical implications for a complex delay model for CML with cell competition and treatment.

    Science.gov (United States)

    Rădulescu, I R; Cândea, D; Halanay, A

    2014-12-21

    We study a mathematical model describing the dynamics of leukemic and normal cell populations (stem-like and differentiated) in chronic myeloid leukemia (CML). This model is a system of four delay differential equations incorporating three types of cell division. The competition between normal and leukemic stem cell populations for the common microenvironment is taken into consideration. The stability of one steady state is investigated. The results are discussed via their medical interpretation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Re: What is the best treatment to reduce the need for caesarean section in nulliparous women at term with delayed first stage of labour?

    DEFF Research Database (Denmark)

    Boie, Sidsel; Glavind, Julie; Uldbjerg, Niels

    2017-01-01

    The authors pose the question - What is the best treatment to reduce the need for caesarean section in nulliparous women at term with delayed first stage of labour? and state in their paper that "There is no consensus on the optimal dose regimen of oxytocin for delay in the first stage of labour...... in nulliparous women at term (37-42 weeks’ gestation) to reduce unplanned caesarean section and increase vaginal birth with minimal adverse events". However, they describe only low and high dose oxytocin regimens and fail to acknowledge that no oxytocin at all is associated with a spontaneous delivery just...... as often as when oxytocin is given (1,2) or that discontinuation of oxytocin once the active phase of labour is reached can result in higher spontaneous delivery rates than continuing oxytocin (3,4). The paper in its list of trials (box 2) only describes those addressing high and low dose oxytocin, which...

  17. Bad Boys Meet the Swan of Avon: A Re-Visioning of Hamlet in Sons of Anarchy

    Directory of Open Access Journals (Sweden)

    Burzyńska Katarzyna

    2017-12-01

    Full Text Available This article investigates the intersections between Shakespeare’s Hamlet and a popular TV series Sons of Anarchy (SOA, loosely based on the Shakespearean original. The crime drama series revolves around an outlaw motorcycle club that literally “rules” a fictional town in California like an old royal family with its own brutal dynastic power squabbles and dark family secrets. The club is governed by an unscrupulous President Clay and an equally violent, though more conflicted, Vice President Jax Teller, the son of the late President, who had died in mysterious circumstances. In the article I argue that the popularity of the series lies not in its graphic scenes of violence, over-the-top Harley chases, and sex intrigues, but rather in its Shakespearean and Renaissance structure. SOA, dubbed as “Hamlet on Harleys”1, is an appropriation rather than an adaptation of Shakespeare’s tragedy, which makes it a truly transmedial phenomenon. The article investigates a fascinating blend of seemingly marginal elements of modern American culture and the canonical British tragedy. It also addresses the connections between the lifestyles of the so called outlaw MC clubs and the early modern family structure as presented in Hamlet, focusing on the issues of power and gender relations.

  18. Motor skill delays in pre-school children with leukemia one year after treatment: Hematopoietic stem cell transplantation therapy as an important risk factor.

    Science.gov (United States)

    Taverna, Livia; Tremolada, Marta; Bonichini, Sabrina; Tosetto, Barbara; Basso, Giuseppe; Messina, Chiara; Pillon, Marta

    2017-01-01

    CNS-directed therapies for the treatment of leukemia can adversely affect the acquisition of new skills, such as reading/writing and math. Two years after the end of treatments, children show gross and fine motor skill delays that may persist even when patients are considered healed. The goal of the present study was to assess motor skills difficulties in pre-school children with leukemia one year after treatment. Particular attention has been paid to those patients who had undergone Hematopoietic Stem Cell Transplantation (HSCT) and to the relationship between motor delays and age bands. Participants were 60 children (median age of 5; inter quartile range: 3.07-5.76), including 31 females and 29 males, 91.7% of them were affected by acute lymphoblastic leukemia (ALL), and 8.3% by acute myeloid leukemia (AML). Five children had undergone HCST. Parents were interviewed by Vineland Adaptive Behavior Scales (VABS) on children's motor skills and filled in the Italian Temperament Questionnaire (QUIT). VABS's total scores were converted into equivalent mental age scores (EMA). A score difference of at least three months between current age and equivalent mental age was considered a developmental delay. Non-parametric analyses were run to understand if HSCT treatment and a specific age band influence children's motor skills. Significant delays were found in global motor skills (56.7%) as well as in fine and gross motor domains. Mann Whitney U tests showed that children with HSCT were reported to have lower gross motor mean ranks (U = 62; p = 0.004; Mean rank = 15.40) than peers without HSCT (Mean rank = 31.87) and lower mean rank values on motor temperament scale (U = 9; p = 0.003; HSCT Mean rank = 4.75 versus no HSCT Mean rank = 27.81). Kruskal Wallis' tests identified the high risk treatment showing that HSCT experience negatively impacted the motor skills and temperamental motor activity of pre-school children one year after the diagnosis of leukemia.

  19. Motor skill delays in pre-school children with leukemia one year after treatment: Hematopoietic stem cell transplantation therapy as an important risk factor.

    Directory of Open Access Journals (Sweden)

    Livia Taverna

    Full Text Available CNS-directed therapies for the treatment of leukemia can adversely affect the acquisition of new skills, such as reading/writing and math. Two years after the end of treatments, children show gross and fine motor skill delays that may persist even when patients are considered healed. The goal of the present study was to assess motor skills difficulties in pre-school children with leukemia one year after treatment. Particular attention has been paid to those patients who had undergone Hematopoietic Stem Cell Transplantation (HSCT and to the relationship between motor delays and age bands. Participants were 60 children (median age of 5; inter quartile range: 3.07-5.76, including 31 females and 29 males, 91.7% of them were affected by acute lymphoblastic leukemia (ALL, and 8.3% by acute myeloid leukemia (AML. Five children had undergone HCST. Parents were interviewed by Vineland Adaptive Behavior Scales (VABS on children's motor skills and filled in the Italian Temperament Questionnaire (QUIT. VABS's total scores were converted into equivalent mental age scores (EMA. A score difference of at least three months between current age and equivalent mental age was considered a developmental delay. Non-parametric analyses were run to understand if HSCT treatment and a specific age band influence children's motor skills. Significant delays were found in global motor skills (56.7% as well as in fine and gross motor domains. Mann Whitney U tests showed that children with HSCT were reported to have lower gross motor mean ranks (U = 62; p = 0.004; Mean rank = 15.40 than peers without HSCT (Mean rank = 31.87 and lower mean rank values on motor temperament scale (U = 9; p = 0.003; HSCT Mean rank = 4.75 versus no HSCT Mean rank = 27.81. Kruskal Wallis' tests identified the high risk treatment showing that HSCT experience negatively impacted the motor skills and temperamental motor activity of pre-school children one year after the diagnosis of leukemia.

  20. Motor skill delays in pre-school children with leukemia one year after treatment: Hematopoietic stem cell transplantation therapy as an important risk factor

    Science.gov (United States)

    Bonichini, Sabrina; Tosetto, Barbara; Basso, Giuseppe; Messina, Chiara; Pillon, Marta

    2017-01-01

    CNS-directed therapies for the treatment of leukemia can adversely affect the acquisition of new skills, such as reading/writing and math. Two years after the end of treatments, children show gross and fine motor skill delays that may persist even when patients are considered healed. The goal of the present study was to assess motor skills difficulties in pre-school children with leukemia one year after treatment. Particular attention has been paid to those patients who had undergone Hematopoietic Stem Cell Transplantation (HSCT) and to the relationship between motor delays and age bands. Participants were 60 children (median age of 5; inter quartile range: 3.07–5.76), including 31 females and 29 males, 91.7% of them were affected by acute lymphoblastic leukemia (ALL), and 8.3% by acute myeloid leukemia (AML). Five children had undergone HCST. Parents were interviewed by Vineland Adaptive Behavior Scales (VABS) on children’s motor skills and filled in the Italian Temperament Questionnaire (QUIT). VABS’s total scores were converted into equivalent mental age scores (EMA). A score difference of at least three months between current age and equivalent mental age was considered a developmental delay. Non-parametric analyses were run to understand if HSCT treatment and a specific age band influence children’s motor skills. Significant delays were found in global motor skills (56.7%) as well as in fine and gross motor domains. Mann Whitney U tests showed that children with HSCT were reported to have lower gross motor mean ranks (U = 62; p = 0.004; Mean rank = 15.40) than peers without HSCT (Mean rank = 31.87) and lower mean rank values on motor temperament scale (U = 9; p = 0.003; HSCT Mean rank = 4.75 versus no HSCT Mean rank = 27.81). Kruskal Wallis’ tests identified the high risk treatment showing that HSCT experience negatively impacted the motor skills and temperamental motor activity of pre-school children one year after the diagnosis of leukemia. PMID

  1. THE TREATMENT OF INTERSEX AND THE PROBLEM OF DELAY: THE AUSTRALIAN SENATE INQUIRY INTO INTERSEX SURGERY AND CONFLICTING HUMAN RIGHTS FOR CHILDREN.

    Science.gov (United States)

    O'Connor, Mike

    2016-03-01

    When a child is born with indeterminate genitalia (so-called intersex or disordered sex development), it becomes very difficult to balance the child's right to determine their own sexual future against the problems of living as a child with an indeterminate gender. Moreover, the initial assignment of gender may prove to be inappropriate and major psychological disturbances in the recipient can arise during adolescence and adult life. The problems of these children were explained to the Australian Senate Committee during its inquiry into intersex surgery in 2013. As a result, the Committee made a number of recommendations, including a proposal that all surgery be deferred until the child is able to consent to treatment. The author argues that the Committee's proposal to delay all modifications of indeterminate genitalia is impractical. The inclusion in the definition of intersex of common conditions (such as hypospadias in genetic male infants) means that necessary and uncontroversial surgery will be delayed until after puberty. This delay may be harmful and adverse to some children's best interests.

  2. [Mental health of children, adolescents and young adults--part 1: prevalence, illness persistence, adversities, service use, treatment delay and consequences].

    Science.gov (United States)

    Lambert, M; Bock, T; Naber, D; Löwe, B; Schulte-Markwort, M; Schäfer, I; Gumz, A; Degkwitz, P; Schulte, B; König, H H; Konnopka, A; Bauer, M; Bechdolf, A; Correll, C; Juckel, G; Klosterkötter, J; Leopold, K; Pfennig, A; Karow, A

    2013-11-01

    Numerous birth-control studies, epidemiological studies, and observational studies have investigated mental health and health care in childhood, adolescence and early adulthood, including prevalence, age at onset, adversities, illness persistence, service use, treatment delay and course of illness. Moreover, the impact of the burden of illness, of deficits of present health care systems, and the efficacy and effectiveness of early intervention services on mental health were evaluated. According to these data, most mental disorders start during childhood, adolescence and early adulthood. Many children, adolescents and young adults are exposed to single or multiple adversities, which increase the risk for (early) manifestations of mental diseases as well as for their chronicity. Early-onset mental disorders often persist into adulthood. Service use by children, adolescents and young adults is low, even lower than for adult patients. Moreover, there is often a long delay between onset of illness and first adequate treatment with a variety of linked consequences for a poorer psychosocial prognosis. This leads to a large burden of illness with respect to disability and costs. As a consequence several countries have implemented so-called "early intervention services" at the interface of child and adolescent and adult psychiatry. Emerging studies show that these health-care structures are effective and efficient. Part 1 of the present review summarises the current state of mental health in childhood, adolescence and early adulthood, including prevalence, age at onset, adversities, illness persistence, service use, and treatment delay with consequences. © Georg Thieme Verlag KG Stuttgart · New York.

  3. The effect of duration of untreated psychosis and treatment delay on the outcomes of prolonged early intervention in psychotic disorders

    DEFF Research Database (Denmark)

    Albert, Nikolai; Melau, Marianne; Jensen, Heidi

    2017-01-01

    to the prolonged treatment with regards to disorganized and negative dimension. For participants with short duration from first symptom until start of SEI treatment there was a significant difference on the negative dimension favoring the prolonged OPUS treatment. The finding of an effect of prolonged treatment......The duration of untreated psychosis (DUP) has been shown to have an effect on outcome after first-episode psychosis. The premise of specialized early intervention (SEI) services is that intervention in the early years of illness can affect long-term outcomes. In this study, we investigate whether...... DUP affects treatment response after 5 years of SEI treatment compared to 2 years of SEI treatment. As part of a randomized controlled trial testing the effect of prolonged SEI treatment 400 participants diagnosed within the schizophrenia spectrum were recruited. For this specific study participants...

  4. Effect of magnesium treatment and glucose levels on delayed cerebral ischemia in patients with subarachnoid hemorrhage : A substudy of the Magnesium in Aneurysmal Subarachnoid Haemorrhage trial (MASH-II)

    NARCIS (Netherlands)

    Leijenaar, Jolien F.; Dorhout Mees, Sanne M.; Algra, Ale; van den Bergh, Walter M.; Rinkel, Gabriel J. E.

    2015-01-01

    Background: Magnesium treatment did not improve outcome in patients with aneurysmal subarachnoid haemorrhage in the Magnesium in Aneurysmal Subarachnoid Haemorrhage II trial. We hypothesized that high glucose levels may have offset a potential beneficial effect to prevent delayed cerebral ischemia.

  5. Developmental delay

    Science.gov (United States)

    Nutrition support is essential for the care of the child with developmental delay. After a thorough evaluation, an individualized intervention plan that accounts for the child’s nutrition status, feeding ability, and medical condition may be determined. Nutrition assessments may be performed at leas...

  6. Laryngotracheoesophageal Cleft Type 3 and Severe Laryngotracheomalacia; Delayed Surgical Repair, a Treatment Challenge with an Excellent Outcome

    Directory of Open Access Journals (Sweden)

    Ahmad Khaleghnejad

    Full Text Available Laryngotracheoesophageal clefts (LTEC are rare malformations which involve the upper respiratory and digestive tract. Surgical repair should be undertaken promptly to maintain a secure airway and prevent serious pulmonary aspiration. This paper reports the first case of LTEC type 3 with severe laryngotracheomalacia that was brought to Mofid children's hospital in late infancy with a poor health status. Delayed defect correction was our team strategy for the patient when she had achieved good weight gain. At the age of 22 months in collaboration with the pediatric surgical and otolaryngologist team, the repair of the laryngeal cleft was done with lateral open approach method. She was discharged with tracheostomy and gastrostomy. In the next six months follow up after the surgery tracheostomy decannulation and gastrostomy tube removal were done and the infant is now in regular follow-up. Keywords: Laryngotracheoesophageal clefts, Laryngotracheomalacia, Surgical repair

  7. Transcultural Hamlet: Representations of Ophelia and Gertrud in 21st-century Iran

    Directory of Open Access Journals (Sweden)

    Robabeh Jalayer

    2017-01-01

    Full Text Available Multitudes of intermedial Shakespearean adaptations, especially since 1975, have captured Iranian theatrical stage, cinema or radio as the Bard’s texts are frequently modernized, transfigured and indigenized in order to add to his globalization. Hamlet works well in the mechanisms of temporality, spatiality, power, control and sexuality, socio-political discourses, economic upheaval, female self and gender struggles even in the twentieth and twenty-first centuries. Hence, Iranian directors such as Varuzh Karim-Masihi and Arash Dadgar as well as the British director Gregory Doran have re-interpreted this text based on new ideological grounds in which the characters are at times similar or different. In this article, the transformation and characterization of major characters, especially female ones such as Gertrud/Mah-Tal’at and Ophelia/Mahtab, are analyzed based on Hutcheon’s Adaptation Theory to see how they are represented in an Asian society whose Islamic ideology necessitates a unique transcultural, transhistorical rendition.

  8. Cognitive-Behavioral Treatment for Specific Phobias with a Child Demonstrating Severe Problem Behavior and Developmental Delays

    Science.gov (United States)

    Davis, Thompson E., III; Kurtz, Patricia F.; Gardner, Andrew W.; Carman, Nicole B.

    2007-01-01

    Cognitive-behavioral treatments (CBTs) are widely used for anxiety disorders in typically developing children; however, there has been no previous attempt to administer CBT for specific phobia (in this case study, one-session treatment) to developmentally or intellectually disabled children. This case study integrates both cognitive-behavioral and…

  9. Alpha-lactalbumin unfolding is not sufficient to cause apoptosis, but is required for the conversion to HAMLET (human alpha-lactalbumin made lethal to tumor cells).

    Science.gov (United States)

    Svensson, Malin; Fast, Jonas; Mossberg, Ann-Kristin; Düringer, Caroline; Gustafsson, Lotta; Hallgren, Oskar; Brooks, Charles L; Berliner, Lawrence; Linse, Sara; Svanborg, Catharina

    2003-12-01

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a complex of human alpha-lactalbumin and oleic acid (C18:1:9 cis) that kills tumor cells by an apoptosis-like mechanism. Previous studies have shown that a conformational change is required to form HAMLET from alpha-lactalbumin, and that a partially unfolded conformation is maintained in the HAMLET complex. This study examined if unfolding of alpha-lactalbumin is sufficient to induce cell death. We used the bovine alpha-lactalbumin Ca(2+) site mutant D87A, which is unable to bind Ca(2+), and thus remains partially unfolded regardless of solvent conditions. The D87A mutant protein was found to be inactive in the apoptosis assay, but could readily be converted to a HAMLET-like complex in the presence of oleic acid. BAMLET (bovine alpha-lactalbumin made lethal to tumor cells) and D87A-BAMLET complexes were both able to kill tumor cells. This activity was independent of the Ca(2+)site, as HAMLET maintained a high affinity for Ca(2+) but D87A-BAMLET was active with no Ca(2+) bound. We conclude that partial unfolding of alpha-lactalbumin is necessary but not sufficient to trigger cell death, and that the activity of HAMLET is defined both by the protein and the lipid cofactor. Furthermore, a functional Ca(2+)-binding site is not required for conversion of alpha-lactalbumin to the active complex or to cause cell death. This suggests that the lipid cofactor stabilizes the altered fold without interfering with the Ca(2+)site.

  10. Effects of Two-stage Heat Treatment on Delayed Coke and Study of Their Surface Texture Characteristics

    Science.gov (United States)

    Im, Ui-Su; Kim, Jiyoung; Lee, Seon Ho; Lee, Byung-Rok; Peck, Dong-Hyun; Jung, Doo-Hwan

    2017-12-01

    In the present study, surface texture features and chemical properties of two types of cokes, made from coal tar by either 1-stage heat treatment or 2-stage heat treatment, were researched. The relationship between surface texture characteristics and the chemical properties was identified through molecular weight distribution, insolubility of coal tar, weight loss with temperature increase, coking yield, and polarized light microscope analysis. Rapidly cleared anisotropy texture in cokes was observed in accordance with the coking temperature rise. Quinoline insolubility and toluene insolubility of coal tar increased with a corresponding increases in coking temperature. In particular, the cokes produced by the 2-stage heat treatment (2S-C) showed surface structure of needle cokes at a temperature approximately 50°C lower than the 1-stage heat treatment (1S-C). Additionally, the coking yield of 2S-C increased by approximately 14% in comparison with 1S-C.

  11. Hamlet no cinema: as adaptações fílmicas de Laurence Olivier (1948 e Franco Zeffirelli (1990

    Directory of Open Access Journals (Sweden)

    Rogério Tomaz

    2011-10-01

    Full Text Available As inter-relações entre as artes traduzem-se numa discussão bastante recente. Um dos elementos que compõem esse quadro é a tradução intersemiótica que consiste na relação entre sistemas signícos. Este artigo propõe a análise da abordagem intersemiótica na adaptação da peça de teatro Hamlet, Príncipe da Dinamarca, de William Shakespeare para o cinema nos filmes de Laurence Olivier e Franco Zeffirelli.

  12. Applications of site-specific labeling to study HAMLET, a tumoricidal complex of α-lactalbumin and oleic acid.

    Science.gov (United States)

    Mercer, Natalia; Ramakrishnan, Boopathy; Boeggeman, Elizabeth; Qasba, Pradman K

    2011-01-01

    Alpha-lactalbumin (α-LA) is a calcium-bound mammary gland-specific protein that is found in milk. This protein is a modulator of β1,4-galactosyltransferase enzyme, changing its acceptor specificity from N-acetyl-glucosamine to glucose, to produce lactose, milk's main carbohydrate. When calcium is removed from α-LA, it adopts a molten globule form, and this form, interestingly, when complexed with oleic acid (OA) acquires tumoricidal activity. Such a complex made from human α-LA (hLA) is known as HAMLET (Human A-lactalbumin Made Lethal to Tumor cells), and its tumoricidal activity has been well established. In the present work, we have used site-specific labeling, a technique previously developed in our laboratory, to label HAMLET with biotin, or a fluoroprobe for confocal microscopy studies. In addition to full length hLA, the α-domain of hLA (αD-hLA) alone is also included in the present study. We have engineered these proteins with a 17-amino acid C-terminal extension (hLA-ext and αD-hLA-ext). A single Thr residue in this extension is glycosylated with 2-acetonyl-galactose (C2-keto-galactose) using polypeptide-α-N-acetylgalactosaminyltransferase II (ppGalNAc-T2) and further conjugated with aminooxy-derivatives of fluoroprobe or biotin molecules. We found that the molten globule form of hLA and αD-hLA proteins, with or without C-terminal extension, and with and without the conjugated fluoroprobe or biotin molecule, readily form a complex with OA and exhibits tumoricidal activity similar to HAMLET made with full-length hLA protein. The confocal microscopy studies with fluoroprobe-labeled samples show that these proteins are internalized into the cells and found even in the nucleus only when they are complexed with OA. The HAMLET conjugated with a single biotin molecule will be a useful tool to identify the cellular components that are involved with it in the tumoricidal activity.

  13. Biobreeding rat islets exhibit reduced antioxidative defense and N-acetyl cysteine treatment delays type 1 diabetes

    Science.gov (United States)

    Bogdani, Marika; Henschel, Angela M.; Kansra, Sanjay; Fuller, Jessica M.; Geoffrey, Rhonda; Jia, Shuang; Kaldunski, Mary L.; Pavletich, Scott; Prosser, Simon; Chen, Yi-Guang; Lernmark, Åke; Hessner, Martin J.

    2014-01-01

    Islet-level oxidative stress has been proposed as a trigger for type 1 diabetes (T1D), and release of cytokines by infiltrating immune cells further elevates reactive oxygen species (ROS), exacerbating β cell duress. To identify genes/mechanisms involved with diabeto-genesis at the β cell level, gene expression profiling and targeted follow-up studies were used to investigate islet activity in the biobreeding (BB) rat. Forty-day-old spontaneously diabetic lymphopenic BB DRlyp/lyp rats (before T cell insulitis) as well as nondiabetic BB DR+/+ rats, nondiabetic but lymphopenic F344lyp/lyp rats, and healthy Fischer (F344) rats were examined. Gene expression profiles of BB rat islets were highly distinct from F344 islets and under-expressed numerous genes involved in ROS metabolism, including glutathione S-transferase (GST) family members (Gstm2, Gstm4, Gstm7, Gstt1, Gstp1, and Gstk1), superoxide dismutases (Sod2 and Sod3), peroxidases, and peroxiredoxins. This pattern of under-expression was not observed in brain, liver, or muscle. Compared with F344 rats, BB rat pancreata exhibited lower GST protein levels, while plasma GST activity was found significantly lower in BB rats. Systemic administration of the antioxidant N-acetyl cysteine to DRlyp/lyp rats altered abundances of peripheral eosinophils, reduced severity of insulitis, and significantly delayed but did not prevent diabetes onset. We find evidence of β cell dysfunction in BB rats independent of T1D progression, which includes lower expression of genes related to antioxidative defense mechanisms during the pre-onset period that may contribute to overall T1D susceptibility. PMID:23111281

  14. Can exercise ameliorate treatment toxicity during the initial phase of testosterone deprivation in prostate cancer patients? Is this more effective than delayed rehabilitation?

    Directory of Open Access Journals (Sweden)

    Newton Robert U

    2012-09-01

    Full Text Available Abstract Background There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. However, all interventions to date have been of rehabilitative intent being implemented after a minimum of 3 months since initiation of androgen deprivation, by which time considerable physical and psychological health problems have manifested. The pressing question is whether it is more efficacious to commence exercise therapy at the same time as initiating androgen deprivation, so treatment induced adverse effects can be immediately attenuated or indeed prevented. Methods/design We are proposing a multi-site randomized controlled trial with partial crossover to examine the effects of timing of exercise implementation (immediate or delayed on preserving long-term skeletal health, reversing short- and long-term metabolic and cardiovascular risk factors, and supporting mental health in men receiving androgen deprivation therapy. 124 men who are about to initiate androgen deprivation for prostate cancer will be randomized to immediate or delayed groups. Immediate will commence a 6-month exercise program within 7–10 days of their first dose. Delayed will receive usual care for 6 months and then commence the exercise program for 6 months (partial cross-over. Immediate will be free to adopt the lifestyle of their choosing following the initial 6-month intervention. Measurements for primary and

  15. Can exercise ameliorate treatment toxicity during the initial phase of testosterone deprivation in prostate cancer patients? Is this more effective than delayed rehabilitation?

    International Nuclear Information System (INIS)

    Newton, Robert U; Taaffe, Dennis R; Spry, Nigel; Cormie, Prue; Chambers, Suzanne K; Gardiner, Robert A; Shum, David HK; Joseph, David; Galvão, Daniel A

    2012-01-01

    There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. However, all interventions to date have been of rehabilitative intent being implemented after a minimum of 3 months since initiation of androgen deprivation, by which time considerable physical and psychological health problems have manifested. The pressing question is whether it is more efficacious to commence exercise therapy at the same time as initiating androgen deprivation, so treatment induced adverse effects can be immediately attenuated or indeed prevented. We are proposing a multi-site randomized controlled trial with partial crossover to examine the effects of timing of exercise implementation (immediate or delayed) on preserving long-term skeletal health, reversing short- and long-term metabolic and cardiovascular risk factors, and supporting mental health in men receiving androgen deprivation therapy. 124 men who are about to initiate androgen deprivation for prostate cancer will be randomized to immediate or delayed groups. Immediate will commence a 6-month exercise program within 7–10 days of their first dose. Delayed will receive usual care for 6 months and then commence the exercise program for 6 months (partial cross-over). Immediate will be free to adopt the lifestyle of their choosing following the initial 6-month intervention. Measurements for primary and secondary endpoints will take place at baseline, 6

  16. Delayed Puberty

    DEFF Research Database (Denmark)

    Kolby, Nanna; Busch, Alexander Siegfried; Juul, Anders

    2017-01-01

    . The underlying reasons for the large variation in the age at pubertal onset are not fully established; however, nutritional status and socioeconomic and environmental factors are known to be influencing, and a significant amount of influencing genetic factors have also been identified. The challenges...... optimal in discriminating especially CDGP from HH. Management of the delayed puberty depends on the etiology. For boys with CDGP an observational period will often reveal imminent puberty. If puberty is not progressing spontaneously, sex steroid replacement is effective in stimulating the development...

  17. Role of membrane technology to achieve ALARA concept in reprocessing plant: utilization of low pressure reverse osmosis for treatment of delay tank solutions

    International Nuclear Information System (INIS)

    Pabby, Anil K.; Sonawane, J.V.; Rathore, N.S.; Gupta, S.K.; Roy, S.C.; Venugopalan, A.K.; Chagrani, R.D.; Dey, P.K.; Prabhakar, S.; Tiwari, P.K.

    2004-01-01

    Reverse osmosis is a well-developed technology. The systems have been used in industrial settings for many years with applications to separation, concentration of product streams and waste water treatment. The technology has been used for removal of the radionuclides from low-level liquid wastes, such as waste streams at nuclear power plants. Because reverse osmosis rejects nearly all contaminants from a solution the high purity product water may be recycled within the power plant, or is usually of such low activity that it is suitable for discharge to the environment. This technology will help in achieving ALARA concept which will be beneficial for the environment. In the present study, the removal of alpha and beta activities from delay tank solution is planned

  18. Delayed Treatment with a Small Pigment Epithelium Derived Factor (PEDF Peptide Prevents the Progression of Diabetic Renal Injury.

    Directory of Open Access Journals (Sweden)

    Alaa S Awad

    Full Text Available Our recent publication showed that a small bioactive pigment epithelium derived factor (PEDF peptide (P78-PEDF prevents the development of diabetic nephropathy (DN. However, its effects on the progression of established DN were not clear. Therefore, the purpose of this study was to determine the effect of P78-PEDF in the progression of DN and to compare the effects of P78-PEDF and an ACE inhibitor (ACEi, a standard of care in DN. Experiments were conducted in Ins2(Akita mice treated with P78-PEDF or captopril starting at 6 wks of age for 12 wks (early treatment or starting at 12 wks of age for 6 wks (late treatment. We first established the optimal dose of the P78-PEDF peptide to ameliorate DN in Ins2(Akita mouse for a 6 wk study period and found that the peptide was effective at 0.1- 0.5 µg/g/day. We next showed that early or late treatment with P78-PEDF resulted in protection from DN as indicated by reduced albuminuria, kidney macrophage recruitment, histological changes, inflammatory cytokines and fibrotic markers (kidney TNF-α, fibronectin, VEGFA and EGFR, and restored nephrin expression compared with vehicle-treated Ins2(Akita mice. Interestingly, only early but not late treatment with captopril was as effective as P78-PEDF in reducing most DN complications, despite its lack of effect on nephrin, VEGFA and EGFR expression. These findings highlight the importance of P78-PEDF peptide as a potential therapeutic modality in both the development and progression of diabetic renal injury.

  19. [Treatment of the infected wound with exposed silver-ring vascular graft and delayed Thiersch method of skin transplant covering ].

    Science.gov (United States)

    Nenezić, Dragoslav; Pandaitan, Simon; Ilijevski, Nenad; Matić, Predrag; Gajin, Predag; Radak, Dorde

    2005-01-01

    Although the incidence of prosthetic infection is low (1%-6%), the consequences (limb loss or death) are dramatic for a patient, with high mortality rate (25%-75%) and limb loss in 40%-75% of cases. In case of Szilagyi's grade III infection, standard procedure consists of the excision of prosthesis and wound debridement. Alternative method is medical treatment. This is a case report of a patient with prosthetic infection of Silver-ring graft, used for femoropopliteal reconstruction, in whom an extreme skin necrosis developed in early postoperative period. This complication was successfully treated medically. After repeated debridement and wound-packing, the wound was covered using Thiersch skin graft.

  20. Delayed-release oral suspension of omeprazole for the treatment of erosive esophagitis and gastroesophageal reflux disease in pediatric patients: a review

    Directory of Open Access Journals (Sweden)

    Alice Monzani

    2010-03-01

    Full Text Available Alice Monzani, Giuseppina Oderda1Department of Pediatrics, Università del Piemonte Orientale, Novara, ItalyAbstract: Omeprazole is a proton-pump inhibitor indicated for gastroesophageal reflux disease and erosive esophagitis treatment in children. The aim of this review was to evaluate the efficacy of delayed-release oral suspension of omeprazole in childhood esophagitis, in terms of symptom relief, reduction in reflux index and/or intragastric acidity, and endoscopic and/or histological healing. We systematically searched PubMed, Cochrane and EMBASE (1990 to 2009 and identified 59 potentially relevant articles, but only 12 articles were suitable to be included in our analysis. All the studies evaluated symptom relief and reported a median relief rate of 80.4% (range 35%–100%. Five studies reported a significant reduction of the esophageal reflux index within normal limits (<7% in all children, and 4 studies a significant reduction of intra-gastric acidity. The endoscopic healing rate, reported by 9 studies, was 84% after 8-week treatment and 95% after 12-week treatment, the latter being significantly higher than the histological healing rate (49%. In conclusion, omeprazole given at a dose ranging from 0.3 to 3.5 mg/kg once daily (median 1 mg/kg once daily for at least 12 weeks is highly effective in childhood esophagitis.Keywords: proton pump inhibitors, children, ranitidine, H2-blockers

  1. Comparison of the response of various TLDs to cosmic radiation and ion beams: Current results of the HAMLET project

    International Nuclear Information System (INIS)

    Bilski, P.; Berger, T.; Hajek, M.; Reitz, G.

    2011-01-01

    HAMLET is an European Commission research project aiming at optimal scientific exploitation of the data produced within the space experiment MATROSHKA. During phase 1 of this experiment a human phantom equipped with several thousands of radiation detectors (mainly TLDs) was exposed outside the International Space Station for 1.5 years. Besides the measurements realized in Earth orbit, the HAMLET project includes also a ground-based program of intercomparison of detector response to high-energy ion beams. Within the paper, the relative response of main glow-curve peaks of various TLDs (mostly based on LiF) used in frame of the MATROSHKA experiment by three laboratories (DLR Cologne, ATI Vienna and IFJ Krakow) for radiation in space and several ion beams, has been compared. For LiF:Mg,Ti detectors a very good agreement between results obtained by the three laboratories was observed, both for space and accelerator-based exposures. This should be considered a remarkable result, taking into account that the studied TLDs originated from six different batches, manufactured by two producers exploiting different production techniques and were processed by three laboratories, using significantly different protocols (annealing, readout, calibration, glow-curve analysis). Another type of TL detectors, LiF:Mg,Cu,P, was found to show response to cosmic radiation lower than that of LiF:Mg,Ti by 5%–18%.

  2. Calibration of solid state nuclear track detectors at high energy ion beams for cosmic radiation measurements: HAMLET results

    International Nuclear Information System (INIS)

    Szabó, J.; Pálfalvi, J.K.

    2012-01-01

    The MATROSHKA experiments and the related HAMLET project funded by the European Commission aimed to study the dose burden of the crew working on the International Space Station (ISS). During these experiments a human phantom equipped with several thousands of radiation detectors was exposed to cosmic rays inside and outside the ISS. Besides the measurements realized in Earth orbit, the HAMLET project included also a ground-based program of calibration and intercomparison of the different detectors applied by the participating groups using high-energy ion beams. The Space Dosimetry Group of the Centre for Energy Research (formerly Atomic Energy Research Institute) participated in these experiments with passive solid state nuclear track detectors (SSNTDs). The paper presents the results of the calibration experiments performed in the years 2008–2011 at the Heavy Ion Medical Accelerator (HIMAC) of the National Institute of Radiological Sciences (NIRS), Chiba, Japan. The data obtained serve as update and improvement for the previous calibration curves which are necessary for the evaluation of the SSNTDs exposed in unknown space radiation fields.

  3. Calibration of solid state nuclear track detectors at high energy ion beams for cosmic radiation measurements: HAMLET results

    Energy Technology Data Exchange (ETDEWEB)

    Szabo, J., E-mail: julianna.szabo@energia.mta.hu [Hungarian Academy of Sciences, Centre for Energy Research, Konkoly Thege Miklos ut 29-33, 1525 Budapest 114, P.O. Box 49 (Hungary); Palfalvi, J.K. [Hungarian Academy of Sciences, Centre for Energy Research, Konkoly Thege Miklos ut 29-33, 1525 Budapest 114, P.O. Box 49 (Hungary)

    2012-12-01

    The MATROSHKA experiments and the related HAMLET project funded by the European Commission aimed to study the dose burden of the crew working on the International Space Station (ISS). During these experiments a human phantom equipped with several thousands of radiation detectors was exposed to cosmic rays inside and outside the ISS. Besides the measurements realized in Earth orbit, the HAMLET project included also a ground-based program of calibration and intercomparison of the different detectors applied by the participating groups using high-energy ion beams. The Space Dosimetry Group of the Centre for Energy Research (formerly Atomic Energy Research Institute) participated in these experiments with passive solid state nuclear track detectors (SSNTDs). The paper presents the results of the calibration experiments performed in the years 2008-2011 at the Heavy Ion Medical Accelerator (HIMAC) of the National Institute of Radiological Sciences (NIRS), Chiba, Japan. The data obtained serve as update and improvement for the previous calibration curves which are necessary for the evaluation of the SSNTDs exposed in unknown space radiation fields.

  4. Hamlet e a hermenêutica: Das muitas interpretações da triste estória do príncipe da Dinamarca

    Directory of Open Access Journals (Sweden)

    Marcelo Bolshaw Gomes

    2016-08-01

    Full Text Available Analisa-se aqui quatro adaptações de Hamlet, de William Shakespeare, para o cinema: Laurence Olivier (1948; Franco Zeffirelli (1990; Kenneth Branagh (1996 e Michael Almereyda (2000. E se discutem as relações da narrativa com a psicanálise e com a hermenêutica.

  5. The Breach and the Observance : Theatre retranslation as a strategy of artistic differentiation, with special reference to retranslations of Shakespeare's Hamlet (1777-2001)

    NARCIS (Netherlands)

    Mathijssen, J.W.

    2007-01-01

    The subject of "The Breach and the Observance" is retranslation for the theatre. Besides offering a model that incorporates the findings of previous scholarship, it casts new light on the motivation behind retranslation, using the case of translations of Shakespeare's Hamlet on the Dutch stage.

  6. Effect of non-specific prophylaxis of thrombogenic complications on delayed results of combined treatment of bladder carcinoma

    International Nuclear Information System (INIS)

    Popov, A.I.

    1987-01-01

    Altogether 106 patients with bladder carcinoma (Stage T 3 N x M 0 ) after combined treatment were followed-up for 5 yrs. Nicotonic acid and aspirin at common doses were adminstrated to 51 patients (the 1st group) during pre- and postoperative radiation therapy. The other 55 patients (the 2nd group) did not receive these drugs. Relapses were noted in 33.3% of the patients of the 1st group and in 76.3% of the patients of the 2nd group. The 5-year survival in the 1st group was 72.5% and in the 2nd group 27.4%. The administration of nicotonic acid and aspirin to patients during pre- and postoperative γ-beam therapy was shown to raise the body antitumor resistance

  7. Effect of magnesium treatment and glucose levels on delayed cerebral ischemia in patients with subarachnoid hemorrhage: a substudy of the Magnesium in Aneurysmal Subarachnoid Haemorrhage trial (MASH-II).

    Science.gov (United States)

    Leijenaar, Jolien F; Dorhout Mees, Sanne M; Algra, Ale; van den Bergh, Walter M; Rinkel, Gabriel J E

    2015-10-01

    Magnesium treatment did not improve outcome in patients with aneurysmal subarachnoid haemorrhage in the Magnesium in Aneurysmal Subarachnoid Haemorrhage II trial. We hypothesized that high glucose levels may have offset a potential beneficial effect to prevent delayed cerebral ischemia. We investigated if magnesium treatment led to less delayed cerebral ischemia and if glucose levels interacted with magnesium treatment in the Magnesium in Aneurysmal Subarachnoid Haemorrhage II trial. To investigate the effect of magnesium treatment on occurrence of delayed cerebral ischemia and the interaction between glucose levels and magnesium treatment in subarachnoid hemorrhage patients. The Magnesium in Aneurysmal Subarachnoid Haemorrhage was a phase III randomized placebo-controlled trial assessing the effect of magnesium sulphate on clinical outcome in aneurysmal subarachnoid hemorrhage patients. For the current study, we included only the patients admitted to the University Medical Centre-Utrecht. We calculated hazard ratios for occurrence of delayed cerebral ischemia in patients treated with magnesium vs. placebo for the entire study population, and separately in the subgroups of patients with high and low mean fasting and mean daily glucose levels until onset of delayed cerebral ischemia. We used the cross-product of magnesium and glucose in the regression analysis to evaluate whether an interaction between magnesium and glucose existed. We included 616 patients: 307 received magnesium and 309 placebo; 156 patients had delayed cerebral ischemia. Hazard ratio for magnesium on occurrence of delayed cerebral ischemia was 1·0 (95% confidence interval: 0·7-1·4). Results were similar in patients with low or high fasting or daily glucose levels. We found no interactions between magnesium treatment and high fasting (P = 0·54) and daily glucose (P = 0·60). Magnesium treatment did not reduce the risk of delayed cerebral ischemia in patients with aneurysmal

  8. Impact of antiviral treatment and hospital admission delay on risk of death associated with 2009 A/H1N1 pandemic influenza in Mexico

    Directory of Open Access Journals (Sweden)

    Chowell Gerardo

    2012-04-01

    Mexican Social Security system, April-December 2009. We considered a spectrum of disease severity encompassing outpatient visits, hospitalizations, and deaths, and recorded demographic and geographic information on individual patients. We assessed the impact of neuraminidase inhibitor treatment and hospital admission delay (≤ > 2 days after disease onset on the risk of death by multivariate logistic regression. Results Approximately 50% of all A/H1N1-positive patients received antiviral medication during the Spring and Summer 2009 pandemic waves in Mexico while only 9% of A/H1N1 cases received antiviral medications during the fall wave (P  Conclusions Our findings underscore the potential impact of decreasing admission delays and increasing antiviral use to mitigate the mortality burden of future influenza pandemics.

  9. Clinical outcome comparison of immediate blanket treatment versus a delayed pathogen-based treatment protocol for clinical mastitis in a New York dairy herd.

    Science.gov (United States)

    Vasquez, A K; Nydam, D V; Capel, M B; Eicker, S; Virkler, P D

    2017-04-01

    The purpose was to compare immediate intramammary antimicrobial treatment of all cases of clinical mastitis with a selective treatment protocol based on 24-h culture results. The study was conducted at a 3,500-cow commercial farm in New York. Using a randomized design, mild to moderate clinical mastitis cases were assigned to either the blanket therapy or pathogen-based therapy group. Cows in the blanket therapy group received immediate on-label intramammary treatment with ceftiofur hydrochloride for 5 d. Upon receipt of 24 h culture results, cows in the pathogen-based group followed a protocol automatically assigned via Dairy Comp 305 (Valley Agricultural Software, Tulare, CA): Staphylococcus spp., Streptococcus spp., or Enterococcus spp. were administered on-label intramammary treatment with cephapirin sodium for 1 d. Others, including cows with no-growth or gram-negative results, received no treatment. A total of 725 cases of clinical mastitis were observed; 114 cows were not enrolled due to severity. An additional 122 cases did not meet inclusion criteria. Distribution of treatments for the 489 qualifying events was equal between groups (pathogen-based, n = 246; blanket, n = 243). The proportions of cases assigned to the blanket and pathogen-based groups that received intramammary therapy were 100 and 32%, respectively. No significant differences existed between blanket therapy and pathogen-based therapy in days to clinical cure; means were 4.8 and 4.5 d, respectively. The difference in post-event milk production between groups was not statistically significant (blanket therapy = 34.7 kg; pathogen-based = 35.4 kg). No differences were observed in test-day linear scores between groups; least squares means of linear scores was 4.3 for pathogen-based cows and 4.2 for blanket therapy cows. Odds of survival 30 d postenrollment was similar between groups (odds ratio of pathogen-based = 1.6; 95% confidence interval: 0.7-3.7) as was odds of survival to 60 d (odds ratio

  10. Delayed traumatic intracranial hematoma

    International Nuclear Information System (INIS)

    Tomita, Hiroki

    1984-01-01

    CT was performed serially within 24 hours after head injury in 64 patients having Glasgow Coma Scale of 14 or less or cranial fracture shown on roentgenogram. Delayed traumatic extradural hematoma was observed within 7-12 hours after head injury in 6 cases (9.4%). This was prominent in the frontal and occipital regions (67%). Good recovery was seen in 83.3%. Delayed traumatic intracerebral hematoma was observed within 6-24 hours after head injury in 17 cases (26.6%). This higher incidence was related to contre coup injury. Conservative treatment was possible in 14 of the 17 patients (82.4%), showing good recovery in 70%. (Namekawa, K.)

  11. Treatment with anti-C5aR mAb leads to early-onset clinical and mechanistic effects in the murine delayed-type hypersensitivity arthritis model

    DEFF Research Database (Denmark)

    Atkinson, Sara Marie; Nansen, Anneline; Usher, Pernille A.

    2015-01-01

    Blockade of the complement cascade at the C5a/C5a receptor (C5aR)-axis is believed to be an attractive treatment avenue in rheumatoid arthritis (RA). However, the effects of such interventions during the early phases of arthritis remain to be clarified. In this study we use the murine delayed-typ...

  12. Effect of magnesium treatment and glucose levels on delayed cerebral ischemia in patients with subarachnoid hemorrhage : a substudy of the Magnesium in Aneurysmal Subarachnoid Haemorrhage trial (MASH-II)

    NARCIS (Netherlands)

    Leijenaar, Jolien F.; Mees, Sanne M. Dorhout; Algra, Ale; van den Bergh, Walter M.; Rinkel, Gabriel J. E.

    2015-01-01

    BackgroundMagnesium treatment did not improve outcome in patients with aneurysmal subarachnoid haemorrhage in the Magnesium in Aneurysmal Subarachnoid Haemorrhage II trial. We hypothesized that high glucose levels may have offset a potential beneficial effect to prevent delayed cerebral ischemia. We

  13. Detailed Analysis of Apoptosis and Delayed Luminescence of Human Leukemia Jurkat T Cells after Proton Irradiation and Treatments with Oxidant Agents and Flavonoids

    Directory of Open Access Journals (Sweden)

    Irina Baran

    2012-01-01

    Full Text Available Following previous work, we investigated in more detail the relationship between apoptosis and delayed luminescence (DL in human leukemia Jurkat T cells under a wide variety of treatments. We used menadione and hydrogen peroxide to induce oxidative stress and two flavonoids, quercetin, and epigallocatechin gallate, applied alone or in combination with menadione or H2O2. 62 MeV proton beams were used to irradiate cells under a uniform dose of 2 or 10 Gy, respectively. We assessed apoptosis, cell cycle distributions, and DL. Menadione, H2O2 and quercetin were potent inducers of apoptosis and DL inhibitors. Quercetin decreased clonogenic survival and the NAD(PH level in a dose-dependent manner. Proton irradiation with 2 Gy but not 10 Gy increased the apoptotic rate. However, both doses induced a substantial G2/M arrest. Quercetin reduced apoptosis and prolonged the G2/M arrest induced by radiation. DL spectroscopy indicated that proton irradiation disrupted the electron flow within Complex I of the mitochondrial respiratory chain, thus explaining the massive necrosis induced by 10 Gy of protons and also suggested an equivalent action of menadione and quercetin at the level of the Fe/S center N2, which may be mediated by their binding to a common site within Complex I, probably the rotenone-binding site.

  14. Efficacy of a store-based environmental change intervention compared with a delayed treatment control condition on store customers' intake of fruits and vegetables.

    Science.gov (United States)

    Ayala, Guadalupe X; Baquero, Barbara; Laraia, Barbara A; Ji, Ming; Linnan, Laura

    2013-11-01

    The present store-based intervention was designed to promote sales of fruits and vegetables (F&V) to increase intake among store customers--specifically customers of tiendas, small-to-medium-sized Latino food stores. Four tiendas were randomized to a 2-month environmental change intervention or a delayed treatment control condition. Employees and managers were trained to promote F&V sales, including how to implement a food marketing campaign and installing store equipment to promote fresh fruits and vegetables. The primary outcome was self-reported daily intake of F&V among a convenience sample of customers (at least forty per store) collected at baseline prior to randomization and then 4 months later. In addition, changes in availability of F&V in the tiendas, using unobtrusive observational methods, provided evidence of intervention fidelity. Tiendas in central North Carolina. Participants included 179 customers who were recent immigrants from Mexico and Central America. A group-by-time interaction approached significance on daily servings of F&V; intervention customers reported an increase in F&V intake over time and as a function of the intervention (P customers’ reported F&V intake. Such strategies can have a public health impact on underserved populations.

  15. Predictors of Delayed Antiretroviral Therapy Initiation, Mortality, and Loss to Followup in HIV Infected Patients Eligible for HIV Treatment: Data from an HIV Cohort Study in India

    Directory of Open Access Journals (Sweden)

    Gerardo Alvarez-Uria

    2013-01-01

    Full Text Available Studies from Sub-Saharan Africa have shown that a substantial number of HIV patients eligible for antiretroviral therapy (ART do not start treatment. However, data from other low- or middle-income countries are scarce. In this study, we describe the outcomes of 4105 HIV patients who became ART eligible from January 2007 to November 2011 in an HIV cohort study in India. After three years of ART eligibility, 78.4% started ART, 9.3% died before ART initiation, and 10.3% were lost to followup. Diagnosis of tuberculosis, being homeless, lower CD4 count, longer duration of pre-ART care, belonging to a disadvantaged community, being widowed, and not living near a town were associated with delayed ART initiation. Diagnosis of tuberculosis, being homeless, lower CD4 count, shorter duration of pre-ART care, belonging to a disadvantaged community, illiteracy, and age >45 years were associated with mortality. Being homeless, being single, not living near a town, having a CD4 count <150 cells/μL, and shorter duration of pre-ART care were associated with loss to followup. These results highlight the need to improve the timely initiation of ART in HIV programmes in India, especially in ART eligible patients with tuberculosis, low CD4 counts, living in rural areas, or having a low socioeconomic status.

  16. The Unbearable Lightness of Memory: From Hamlet, Prince of Denmark to Jorge Luis Borges’ Shakespeare’s Memory

    Directory of Open Access Journals (Sweden)

    Raducanu Adriana

    2015-12-01

    Full Text Available The Romantic poet Novalis once rhetorically asked: “Where are we really going?” “Always home.” For a Shakespearean scholar like Borges’ Sörgel in “Shakespeare’s Memory”, the path towards “home” turns out to be the exploration of a most unusual gift, the very memory of the great Elizabethan. The process is similar although not identical in scope to Hamlet’s attempt to realign time through keeping alive the memory of his murdered father. My aim in this paper is to explore the process of preserving memory and its relation to identity, mourning and dread in “Hamlet, Prince of Denmark” and Borges’ “Shakespeare’s Memory”. The theoretical framework is defined by the concept of “eternal return”, as examined by Nietzsche and Mircea Eliade.

  17. Effect of treatment with cyclophosphamide in low doses upon the onset of delayed type hypersensitivity in mice chronically infected with Trypanosoma cruzi: involvement of heart interstitial dendritic cells

    Directory of Open Access Journals (Sweden)

    Torriceli Souza The

    2013-09-01

    Full Text Available Acute infection with Trypanosoma cruzi results in intense myocarditis, which progresses to a chronic, asymptomatic indeterminate form. The evolution toward this chronic cardiac form occurs in approximately 30% of all cases of T. cruzi infection. Suppression of delayed type hypersensitivity (DTH has been proposed as a potential explanation of the indeterminate form. We investigated the effect of cyclophosphamide (CYCL treatment on the regulatory mechanism of DTH and the participation of heart interstitial dendritic cells (IDCs in this process using BALB/c mice chronically infected with T. cruzi. One group was treated with CYCL (20 mg/kg body weight for one month. A DTH skin test was performed by intradermal injection of T. cruzi antigen (3 mg/mL in the hind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skin test revealed increased thickness in antigen-injected footpads, which was more evident in the mice treated with CYCL than in those mice that did not receive treatment. The thickened regions were characterised by perivascular infiltrates and areas of necrosis. Intense lesions of the myocardium were present in three/16 cases and included large areas of necrosis. Morphometric evaluation of lymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelled with specific antibodies (CD11b and CD11c and T. cruzi antigens were detected using a specific anti-T. cruzi antibody. Identification of T. cruzi antigens, sequestered in these cells using specific anti-T. cruzi antibodies was done, showing a significant increase in the number of these cells in treated mice. These results indicate that IDCs participate in the regulatory mechanisms of DTH response to T. cruzi infection.

  18. Structural characterization of more potent alternatives to HAMLET, a tumoricidal complex of α-lactalbumin and oleic acid.

    Science.gov (United States)

    Nemashkalova, Ekaterina L; Kazakov, Alexei S; Khasanova, Leysan M; Permyakov, Eugene A; Permyakov, Sergei E

    2013-09-10

    HAMLET is a complex of human α-lactalbumin (hLA) with oleic acid (OA) that kills various tumor cells and strains of Streptococcus pneumoniae. More potent protein-OA complexes were previously reported for bovine α-lactalbumin (bLA) and β-lactoglobulin (bLG), and pike parvalbumin (pPA), and here we explore their structural features. The concentration dependencies of the tryptophan fluorescence of hLA, bLA, and bLG complexes with OA reveal their disintegration at protein concentrations below the micromolar level. Chemical cross-linking experiments provide evidence that association with OA shifts the distribution of oligomeric forms of hLA, bLA, bLG, and pPA toward higher-order oligomers. This effect is confirmed for bLA and bLG using the dynamic light scattering method, while pPA is shown to associate with OA vesicles. Like hLA binding, OA binding increases the affinity of bLG for small unilamellar dipalmitoylphosphatidylcholine vesicles, while pPA efficiently binds to the vesicles irrespective of OA binding. The association of OA with bLG and pPA increases their α-helix and cross-β-sheet content and resistance to enzymatic proteolysis, which is indicative of OA-induced protein structuring. The lack of excess heat sorption during melting of bLG and pPA in complex with OA and the presence of a cooperative thermal transition at the level of their secondary structure suggest that the OA-bound forms of bLG and pPA lack a fixed tertiary structure but exhibit a continuous thermal transition. Overall, despite marked differences, the HAMLET-like complexes that were studied exhibit a common feature: a tendency toward protein oligomerization. Because OA-induced oligomerization has been reported for other proteins, this phenomenon is inherent to many proteins.

  19. Delayed puberty in girls

    Science.gov (United States)

    ... sexual development - girls; Pubertal delay - girls; Constitutional delayed puberty ... In most cases of delayed puberty, growth changes just begin later than usual, sometimes called a late bloomer. Once puberty begins, it progresses normally. This pattern runs ...

  20. Delayed Puberty (For Teens)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Delayed Puberty KidsHealth / For Teens / Delayed Puberty What's in this ... wonder if there's anything wrong. What Is Delayed Puberty? Puberty is the time when your body grows ...

  1. Delayed entry into HIV care after diagnosis in two specialized care and treatment centres in Cameroon: the influence of CD4 count and WHO staging

    Directory of Open Access Journals (Sweden)

    Noah F. Takah

    2016-07-01

    Full Text Available Abstract Background Delayed entry into HIV care has complicated the challenges faced in sub-Saharan Africa due to the high HIV burden. A clear knowledge of the factors affecting delayed entry will be essential in directing interventions towards reducing delayed entry into HIV care. There exist very limited data on delayed entry in Cameroon despite its relevance; hence this study was conducted to determine the rate of delayed entry and its associated factors in HIV programmes in Cameroon. Methods Data used for this study was routine data obtained from the files of HIV patients who were diagnosed between January 1, 2015 and June 30, 2015 at Limbe and Buea regional hospital HIV centers in the South West region of Cameroon. Data analysis was done using SPSS version 20. Results Of the 223 patients included in the study, nearly one-quarter of patients (22.4 % delayed to enter HIV care within 3 months. Those who delayed to enter care were less likely to present at first diagnosis (using HIV rapid test with symptoms such as fever > 1 month (5 % versus 30 %, p = 0.01 and weight loss > 10 % (13 % versus 48 %, p < 0.001. Alcohol consumption, WHO stage and CD4 count levels were also associated with delayed entry in bivariate analysis. In multivariate analysis only CD4 count greater than 500cells/μl and WHO stages I and II were independently associated with delayed entry into HIV care within 3 months. Conclusion In the South West region of Cameroon, approximately 1 out of 4 patients delay to enter HIV care. This high proportion of patients who delay to enter care correlates to the findings recorded by other studies in sub Saharan Africa. Interventions tackling delayed entry into HIV care might need to be favorably directed towards patients that have high CD4 counts and are at very early WHO clinical stages.

  2. Hamlet, Macbeth, Othello and King Lear in the English Teaching at School: a methodological approach - doi: 10.4025/actascieduc.v34i2.15070

    Directory of Open Access Journals (Sweden)

    Valdomiro Polidório

    2012-11-01

    Full Text Available In this article we will talk about the relevance of dramatic texts in schools. Therefore we will approach the tragedies Hamlet, Macbeth, Otelo e King Lear de William Shakespeare and how teachers can explore them as a help in the teaching of languages without forgetting that they are dramatic and literary texts. When we refer to languages, we want to say any language, because Shakespearean texts are ageless, may have many meanings and deal with human nature. The theatre is in our lives and in this case it is relevant to quote William Shakespeare himself that said that “life is a stage and we are actors”. Starting from this, we will consider the best ways of using the tragedies Hamlet, Macbeth, Otelo e King Lear in the classroom.  

  3. A Novel Initiation Mechanism of Death in Streptococcus pneumoniae Induced by the Human Milk Protein-Lipid Complex HAMLET and Activated during Physiological Death*

    Science.gov (United States)

    Clementi, Emily A.; Marks, Laura R.; Duffey, Michael E.; Hakansson, Anders P.

    2012-01-01

    To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets. PMID:22700972

  4. A novel initiation mechanism of death in Streptococcus pneumoniae induced by the human milk protein-lipid complex HAMLET and activated during physiological death.

    Science.gov (United States)

    Clementi, Emily A; Marks, Laura R; Duffey, Michael E; Hakansson, Anders P

    2012-08-03

    To cause colonization or infection, most bacteria grow in biofilms where differentiation and death of subpopulations is critical for optimal survival of the whole population. However, little is known about initiation of bacterial death under physiological conditions. Membrane depolarization has been suggested, but never shown to be involved, due to the difficulty of performing such studies in bacteria and the paucity of information that exists regarding ion transport mechanisms in prokaryotes. In this study, we performed the first extensive investigation of ion transport and membrane depolarization in a bacterial system. We found that HAMLET, a human milk protein-lipid complex, kills Streptococcus pneumoniae (the pneumococcus) in a manner that shares features with activation of physiological death from starvation. Addition of HAMLET to pneumococci dissipated membrane polarity, but depolarization per se was not enough to trigger death. Rather, both HAMLET- and starvation-induced death of pneumococci specifically required a sodium-dependent calcium influx, as shown using calcium and sodium transport inhibitors. This mechanism was verified under low sodium conditions, and in the presence of ionomycin or monensin, which enhanced pneumococcal sensitivity to HAMLET- and starvation-induced death. Pneumococcal death was also inhibited by kinase inhibitors, and indicated the involvement of Ser/Thr kinases in these processes. The importance of this activation mechanism was made evident, as dysregulation and manipulation of physiological death was detrimental to biofilm formation, a hallmark of bacterial colonization. Overall, our findings provide novel information on the role of ion transport during bacterial death, with the potential to uncover future antimicrobial targets.

  5. Questioning the ‘of’ in Performance-as-translation: Multimedia as a Subtext in the 2003 Pécs Performance ‘of’ Hamlet

    Directory of Open Access Journals (Sweden)

    Minier Márta

    2017-12-01

    Full Text Available This article explores a theatre performance (National Theatre Pécs, 2003, dir. Iván Hargitai working with a 1999 Hungarian translation of Hamlet by educator, scholar, translator and poet Ádám Nádasdy as a structural transformation (Fischer-Lichte 1992 of the dramatic text for the stage. The performance is perceived as an intersemiotic translation but not as one emerging from a source-to-target one-way route. The study focuses on certain substructures such as the set design and the multimedial nature of the performance (as defined by Giesekam 2007, and by highlighting intertextual and hypertextual ways of accessing this performance-as-translation it questions the ‘of’ in the ‘performance of Hamlet (or insert other dramatic title’ phrase. This experimentation with the terminology around performance-as-translation also facilitates the unveiling of a layer of the complex Hungarian Hamlet palimpsest, which, as a multi-layered cultural phenomenon, consists of much more than literary texts: its fabric includes theatre performance and other creative works.

  6. Manuel Tamayo y Baus’s Un Drama Nuevo (1867 and the Reception of Hamlet in 19th-Century Spain

    Directory of Open Access Journals (Sweden)

    Rocío G. Sumillera

    2013-05-01

    Full Text Available The present article discusses how Tamayo y Baus appropriates and refashions in Un drama nuevo (1867 the figures of Shakespeare and Yorick, as well as different elements of a number of tragedies by Shakespeare (Hamlet, Romeo and Juliet, Othello, in order to render homage to Shakespearean drama by means of a play that, even if set at the beginning of 17th-century England, particularly addresses the tastes and concerns of 19th-century Spanish audiences. Additionally, this article considers the extent to which the contemporary audience of Tamayo y Baus was acquainted with Shakespeare and Hamlet, taking into account both the translations into Spanish of the play and its performances in Spain up until 1867. The purpose of such an analysis is to speculate on the reception and interpretation of Un drama nuevo at the time of its release, and on the role it had in raising or renewing interest in Hamlet within the Spanish-speaking world.

  7. Pseudotumoral delayed cerebral radionecrosis

    International Nuclear Information System (INIS)

    Ciaudo-Lacroix, C.; Lapresle, J.

    1985-01-01

    A 60 year-old woman with a scalp epithelioma underwent radiotherapy, the dose being 57 Gray. A first epileptic seizure occurred twenty months later. Neurological examination revealed signs of left hemisphere involvement. γEG, angiography, CT scans, demonstrated a pseudotumoral avascular process. On account of the localisation, the patient being right-handed, no surgical procedure was performed. In spite of corticotherapy and anticonvulsive treatment, seizures recurred and neurological signs slowly progressed. The patient died, 22 months after the first seizure, of an associated disseminated carcinoma with cachexia. Neuropathological examination showed a massive lesion presenting all the features of delayed radionecrosis in the left hemisphere: situated mainly in the white matter; numerous vascular abnormalities; wide-spread demyelination; disappearance of oligoglial cells. The Authors recall the clinical and anatomical aspects of this condition for which the only successful treatment is surgical removal when location and size of the lesion permit. Finally, the mechanisms which have been proposed to explain this delayed cerebral radionecrosis are discussed [fr

  8. Pseudotumoral delayed cerebral radionecrosis

    Energy Technology Data Exchange (ETDEWEB)

    Ciaudo-Lacroix, C; Lapresle, J [Centre Hospitalier de Bicetre, 94 - Le Kremlin-Bicetre (France)

    1985-01-01

    A 60 year-old woman with a scalp epithelioma underwent radiotherapy, the dose being 57 Gray. A first epileptic seizure occurred twenty months later. Neurological examination revealed signs of left hemisphere involvement. ..gamma..EG, angiography, CT scans, demonstrated a pseudotumoral avascular process. On account of the localisation, the patient being right-handed, no surgical procedure was performed. In spite of corticotherapy and anticonvulsive treatment, seizures recurred and neurological signs slowly progressed. The patient died, 22 months after the first seizure, of an associated disseminated carcinoma with cachexia. Neuropathological examination showed a massive lesion presenting all the features of delayed radionecrosis in the left hemisphere: situated mainly in the white matter; numerous vascular abnormalities; wide-spread demyelination; disappearance of oligoglial cells. The Authors recall the clinical and anatomical aspects of this condition for which the only successful treatment is surgical removal when location and size of the lesion permit. Finally, the mechanisms which have been proposed to explain this delayed cerebral radionecrosis are discussed.

  9. Patient reported delays in seeking treatment for Tuberculosis (TB among adult and pediatric TB patients and TB patients co-infected with HIV in Lima, Peru: a qualitative study

    Directory of Open Access Journals (Sweden)

    Valerie A Paz-Soldan

    2014-12-01

    Full Text Available Abstract: Tuberculosis (TB remains a significant public health challenge worldwide, and particularly in Peru with one of the highest incidence rates in Latin America. TB patient behavior has a direct influence on whether a patient will receive timely diagnosis and successful treatment of their illness. Objectives: The objective was to understand the complex factors that can impact TB patient health seeking behavior. Methods: In-depth interviews were conducted with adult and parents of pediatric patients receiving TB treatment (n=43, within that group a sub-group was also co-infected with HIV (n=11. Results: Almost all of the study participants recognized delays in seeking either their child’s or their own diagnosis of their TB symptoms. The principal reasons for treatment-seeking delays were lack of knowledge and confusion of tuberculosis symptoms, fear and embarrassment of receiving a TB diagnosis, and a patient tendency to self-medicate prior to seeking formal medical attention.Conclusions: Health promotion activities that target patient delays have the potential to improve individual patient outcomes and mitigate the spread of TB at a community level.

  10. Effect of EI-treatment in relation to physiological and biochemical traits in rice: delay in germination and its recovery with provision of glucose

    International Nuclear Information System (INIS)

    Inoue, M.; Hasegawa, H.; Hori, S.

    1975-01-01

    Rice seeds treated with 0.2 to 1.2 v/v % of ethyleneimine (EI) demonstrated increasingly delayed germination concomitant with increasing dose. At the time of germination, the release of storage products was slightly inhibited at lower doses and completely reduced at higher doses. With increasing time after germination the development of shoot length, content of reducing sugar and free amino acid, and synthesis of nucleic acid and protein in treated seeds, showed the same response pattern as the control, although at reduced levels in the treated seeds. Consequently, it is interpreted that the delay of germination is due to physiological dormancy, i.e. impaired release of dormancy which would normally yield active forms of enzymes. When treated seeds were cultured in [ 14 C]-glucose medium, the specific activity of [ 14 C]-glucose was higher in late-germinating seeds than in early-germinating seeds. Furthermore, the provision of glucose prevented the delay of germination, resulting in about a 10% increase in germination rate (survival rate), and yet had no effect on subsequent growth. Finally, it is concluded that the damage resulting in delayed germination and reduction of survival differs from the damage leading to inhibition of subsequent growth in that the former can be compensated for by provision of glucose while the latter cannot. (author)

  11. Early versus delayed endocrine treatment of pN1-3 M0 prostate cancer without local treatment of the primary tumor: results of European Organisation for the Research and Treatment of Cancer 30846--a phase III study

    NARCIS (Netherlands)

    Schröder, Fritz H.; Kurth, Karl Heinz; Fosså, Sophie D.; Hoekstra, Wytze; Karthaus, Peter P. M.; Debois, Muriel; Collette, Laurence

    2004-01-01

    The timing of endocrine treatment for prostate cancer remains controversial. The issue is addressed in protocol 30846 of the European Organisation for Research and Treatment of Cancer for patients with lymph node positive cancer without local treatment of the primary tumor. A total of 302 patients

  12. UAVs and Control Delays

    National Research Council Canada - National Science Library

    de Vries, S. C

    2005-01-01

    .... Delays of about 250-300 ms often lead to unacceptable airplane handling qualities. Techniques such as filtering and predictive displays may extend the range of acceptable delays up to about 400 ms...

  13. Delayed puberty in boys

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/007695.htm Delayed puberty in boys To use the sharing features on this page, please enable JavaScript. Delayed puberty in boys is when puberty does not begin ...

  14. Beta delayed particle emission in light nuclei

    International Nuclear Information System (INIS)

    Riisager, K.; Gabelmann, H.

    1991-01-01

    A short discussion of theoretical treatments of beta delayed particle emission is followed by a presentation of data on the newly found beta delayed deuteron decay of 6 He. This decay cannot be described properly with existing theories. (author) 8 refs.; 3 figs

  15. Delayed Orgasm and Anorgasmia

    OpenAIRE

    Jenkins, Lawrence C.; Mulhall, John P.

    2015-01-01

    Delayed orgasm/anorgasmia defined as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation, which causes personal distress. Delayed orgasm and anorgasmia are associated with significant sexual dissatisfaction. A focused medical history can shed light on the potential etiologies; which include: medications, penile sensation loss, endocrinopathies, penile hyperstimulation and psychological etiologies, amongst others. Unfortunately, ...

  16. Delays in the management of retroperitoneal sarcomas

    DEFF Research Database (Denmark)

    Seinen, Jojanneke; Almquist, Martin; Styring, Emelie

    2010-01-01

    Retroperitoneal sarcomas are rare and treatment should optimally be centralized. Despite successful centralization with 90% of the patients referred prior to surgery, delays occur, which led us to assess lead times in a population-based series. Method. Patients diagnosed with retroperitoneal...... sarcoma in the southern Sweden health care region 2003-2009 were eligible for the study. Data on referrals and diagnostic investigations were collected from clinical files from primary health care, local hospitals, and from the sarcoma centre. Lead times were divided into patient delays and health care...... delays caused by primary health care, local hospitals, or procedures at the sarcoma centre. Results. Complete data were available from 33 patients and demonstrated a median patient delay of 23¿days (0-17¿months) and median health care delay of 94¿days (1-40¿months) with delays of median 15¿days...

  17. No need to be HAMLET or BAMLET to interact with histones: binding of monomeric alpha-lactalbumin to histones and basic poly-amino acids.

    Science.gov (United States)

    Permyakov, Serge E; Pershikova, Irina V; Khokhlova, Tatyana I; Uversky, Vladimir N; Permyakov, Eugene A

    2004-05-18

    The ability of a specific complex of human alpha-lactalbumin with oleic acid (HAMLET) to induce cell death with selectivity for tumor and undifferentiated cells was shown recently to be mediated by interaction of HAMLET with histone proteins irreversibly disrupting chromatin structure [Duringer, C., et al. (2003) J. Biol. Chem. 278, 42131-42135]. Here we show that monomeric alpha-lactalbumin (alpha-LA) in the absence of fatty acids is also able to bind efficiently to the primary target of HAMLET, histone HIII, regardless of Ca(2+) content. Thus, the modification of alpha-LA by oleic acid is not required for binding to histones. We suggest that interaction of negatively charged alpha-LA with the basic histone stabilizes apo-alpha-LA and destabilizes the Ca(2+)-bound protein due to compensation for excess negative charge of alpha-LA's Ca(2+)-binding loop by positively charged residues of the histone. Spectrofluorimetric curves of titration of alpha-LA by histone H3 were well approximated by a scheme of cooperative binding of four alpha-LA molecules per molecule of histone, with an equilibrium dissociation constant of 1.0 microM. Such a stoichiometry of binding implies that the binding process is not site-specific with respect to histone and likely is driven by just electrostatic interactions. Co-incubation of positively charged poly-amino acids (poly-Lys and poly-Arg) with alpha-LA resulted in effects which were similar to those caused by histone HIII, confirming the electrostatic nature of the alpha-LA-histone interaction. In all cases that were studied, the binding was accompanied by aggregation. The data indicate that alpha-lactalbumin can be used as a basis for the design of antitumor agents, acting through disorganization of chromatin structure due to interaction between alpha-LA and histone proteins.

  18. Analysis of Decadal-Scale Shoreline Change along the Hamlet of Paulatuk (Canadian Arctic), using Landsat Satellite Imagery and GIS techniques from 1984 to 2014.

    Science.gov (United States)

    Sankar, R. D.; Murray, M. S.; Wells, P.

    2016-12-01

    Increased accuracy in estimating coastal change along localized segments of the Canadian Arctic coast is essential, in order to identify plausible adaptation initiatives to deal with the effects of climate change. This paper quantifies rates of shoreline movement along an 11 km segment of the Hamlet of Paulatuk (Northwest Territories, Canada), using an innovative modelling technique - Analyzing Moving Boundaries Using R (AMBUR). Approximately two dozen shorelines, obtained from high-resolution Landsat satellite imagery were analyzed. Shorelines were extracted using the band ratio method and compiled in ArcMapTM to determine decadal trends of coastal change. The unique geometry of Paulatuk facilitated an independent analysis of the western and eastern sections of the study area. Long-term (1984-2014) and short-term (1984-2003) erosion and accretion rates were calculated using the Linear Regression and End Point Rate methods respectively. Results reveal an elevated rate of erosion for the western section of the hamlet over the long-term (-1.1 m/yr), compared to the eastern portion (-0.92 m/yr). The study indicates a significant alongshore increase in the rates of erosion on both portions of the study area, over the short-term period 1984 to 2003. Mean annual erosion rates increased over the short-term along the western segment (-1.4 m/yr), while the eastern shoreline retreated at a rate of -1.3 m/yr over the same period. The analysis indicates that an amalgamation of factors may be responsible for the patterns of land loss experienced along Paulatuk. These include increased sea-surface temperature coupled with dwindling arctic ice and elevated storm hydrodynamics. The analysis further reveals that the coastline along the eastern portion of the hamlet, where the majority of the population reside, is vulnerable to a high rate of shoreline erosion.

  19. The impact of place of enrollment and delay to reperfusion on 90-day post-infarction mortality in the ASSENT-4 PCI trial: assessment of the safety and efficacy of a new treatment strategy with percutaneous coronary intervention.

    Science.gov (United States)

    Ross, Allan M; Huber, Kurt; Zeymer, Uwe; Armstrong, Paul W; Granger, Christopher B; Goldstein, Patrick; Bogaerts, Kris; Van de Werf, Frans

    2009-10-01

    We have performed a retrospective analysis of the data stratified by time to treatment and by enrollment site: percutaneous coronary intervention hospitals (PCIH), nonpercutaneous coronary intervention hospitals (NoPCIH), or in a pre-hospital setting (PreH). The ASSENT-4 PCI (Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention) trial intended to test the hypothesis that in ST-segment elevation myocardial infarction (STEMI) patients an upfront fibrinolytic bolus before PCI ("facilitated PCI") compared with primary PCI would benefit STEMI patients facing a long pre-PCI delay. Seven hundred forty-nine patients (45%) presented directly to PCIH, 578 (34%) presented to NoPCIH, and 334 (20%) were randomized and initially treated in the PreH setting. Patients in the PreH-facilitated group had the shortest delays (pain-to-fibrinolytic treatment 125 min) and the lowest 90-day mortality (3.1%). Among patients randomized to primary PCI, the shortest time from pain to first balloon was similarly in the PreH group (223 min). They had the lowest mortality of the primary PCI patient groups (4.1%). The highest mortality (8.4%) was in patients presenting to a PCIH and assigned to the facilitated strategy. Their pain-to-lysis time was 174 min and pain-to-PCI time 266 min (or 92 min after lysis). Few patients fit the target population, long delays to PCI for whom facilitated PCI was designed. Patients treated early after pain onset in the PreH setting do well after a facilitated approach. Despite limitations of post hoc subgroup analysis, these observations suggest caution in extrapolating the results of the ASSENT-4 trial to the "real world" where many patients might have potentially short pain-to-fibrinolysis time but are facing a long transport time to primary PCI.

  20. Sexual development and reproductive pattern of the Mutton hamlet, Alphestes afer (Teleostei: Epinephelidae: a dyandric, hermaphroditic reef fish

    Directory of Open Access Journals (Sweden)

    Simone Marques

    Full Text Available There is little knowledge on the reproduction of the genus Alphestes. The reproduction of the Mutton hamlet, Alphestes afer, sampled in Pernambuco reefs (Brazil was studied based on macroscopic analysis during reproductive period and histological analysis of gonad material from March 2008 to October 2009. This study showed that A. afer is a diandric, protogynous hermaphrodite. Sex change followed protogynous mode in two pathways: primary males formed from immature female individuals or secondary males formed from resting, ripe or spent female individuals. The numerical distribution of gonad classes by size indicated that females from 11-18 cm L T were immature while females from 16-25 cm L T and males from 12-22 cm L T were in various stages of gonadal development. Individuals identified as immature bisexual and transitional (presenting both ovarian and sperm tissue were sized from 16-24 cm L T. Size of first reproduction for females was 18 cm L T and for males was 12 cm L T. Alphestes afer showed multiple spawning, with spawning season period from August to December 2008 and from August to October 2009. The sex-ratio (females: males in 2008 and 2009 was 0.94:1 during the months of spawning season. Males were smaller than females, reaching maximum size of 22 cm compared to 25 cm observed for females. Males showed a high sperm competition rank (3.8, suggesting intense sperm competition. This latter is a possible indication of a shift in the mating group structure from paired to group spawning. The presence of small males added to high sperm competition index, suggest that this species, while retaining the protogynous pattern, has a reproductive strategy similar to gonochorist epinephelids.

  1. Effect on treatment delay of prehospital teletransmission of 12-lead electrocardiogram to a cardiologist for immediate triage and direct referral of patients with ST-segment elevation acute myocardial infarction to primary percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Sejersten, M.; Sillesen, M.; Hansen, Peter Riis

    2008-01-01

    the hospital. The primary study purpose was to determine whether delays could be decreased in an urban area by transmitting a prehospital 12-lead ECG directly to the attending cardiologist's mobile telephone for rapid triage and transport to a primary percutaneous coronary intervention (PCI) center, bypassing......, including 2 deaths (1%) caused by treatment-resistant arrhythmia. In conclusion, transmission of a prehospital 12-lead ECG directly to the attending cardiologist's mobile telephone decreased door-to-PCI time by >1 hour when patients were transported directly to PCI centers, bypassing local hospitals...

  2. Teriparatide Induced Delayed Persistent Hypercalcemia

    Directory of Open Access Journals (Sweden)

    Nirosshan Thiruchelvam

    2014-01-01

    Full Text Available Teriparatide, a recombinant PTH, is an anabolic treatment for osteoporosis that increases bone density. Transient hypercalcemia is a reported side effect of teriparatide that is seen few hours following administration of teriparatide and resolves usually within 16 hours of drug administration. Persistent hypercalcemia, although not observed in clinical trials, is rarely reported. The current case describes a rare complication of teriparatide induced delayed persistent hypercalcemia.

  3. Association of Knowledge and Cultural Perceptions of Malaysian Women with Delay in Diagnosis and Treatment of Breast Cancer: a Systematic Review.

    Science.gov (United States)

    Khan, Tahir Mehmood; Leong, Jamie Pik Yan; Ming, Long Chiau; Khan, Amer Hayat

    2015-01-01

    Breast cancer is the most common cancer and the leading cause of cancer mortality among women of all ethnic and age groups in Malaysia. Delay in seeking help for breast cancer symptoms is preventable and by identifying possible factors for delayed diagnosis, patient prognosis and survival rates could be improved. This narrative review aimed to understand and evaluate the level of in-depth breast cancer knowledge in terms of clinical breast examination and breast self-examination, and other important aspects such as side-effects and risk factors in Malaysian females. Since Malaysia is multicultural, this review assessed social perceptions, cultural beliefs and help-seeking behaviour in respect to breast cancer among different ethnic groups, since these may impinge on efforts to 'avoid' the disease. A comprehensive literature search of seven databases was performed from December 2015 to January 2015. Screening of relevant published journals was also undertaken to identify available information related to the knowledge, perception and help-seeking behaviour of Malaysian women in relation to breast cancer. A total of 42 articles were appraised and included in this review. Generally, women in Malaysia had good awareness of breast cancer and its screening tools, particularly breast self-examination, but only superficial in-depth knowledge about the disease. Women in rural areas had lower levels of knowledge than those in urban areas. It was also shown that books, magazines, brochures and television were among the most common sources of breast cancer information. Delay in presentation was attributed mainly to a negative social perception of the disease, poverty, cultural and religion practices, and a strong influence of complementary and alternative medicine, rather than a lack of knowledge. This review highlighted the need for an intensive and in-depth breast cancer education campaigns using media and community health programmes, even with the existing good awareness of

  4. The Defence of Moratín’s «Hamlet» in the «Continuación del Semanario de Salamanca»

    Directory of Open Access Journals (Sweden)

    Philip DEACON

    2015-05-01

    Full Text Available In volume 12 of Cuadernos Dieciochistas Professor Pedro Álvarez de Miranda revealed the existence of an issue of the Continuación del Semanario de Salamanca, dated 19 April 1800, which included a Letter in defence of the translation by Leandro Fernández de Moratín of Shakespeare’s tragedy Hamlet.The Letter, signed by a mysterious P. Ozerín-Jáuregui y Z., attacks the Examen of Moratín’s volume published by the Mallorcan man of letters Cristóbal Cladera and sets out a series of objections which in effect defend the quality of the translation and the historical information accompanying it. The present article attempts to place the newly-discovered critical text in its literary and historical contexts, analyzing its arguments and approach, and evaluating its contribution to the on-going debate over the quality of Moratín’s Hamlet. The article includes, by way of appendix, an annotated transcription of the complete Letter as published in the Continuación del Semanario de Salamanca.

  5. Immediate versus Delayed Treatment in the Anterior Maxilla Using Single Implants with a Laser-Microtextured Collar: 3-Year Results of a Case Series on Hard- and Soft-Tissue Response and Esthetics.

    Science.gov (United States)

    Guarnieri, Renzo; Belleggia, Fabrizio; Grande, Maurizio

    2016-02-01

    To compare peri-implant marginal bone loss, soft tissue response, and esthetics following single immediate implant treatment (IIT) and delayed implant treatment (DIT) in the esthetic zone of the maxilla in well-selected patients. Adequate bone volume and ideal soft tissue level/contour were considered requirements for implant therapy, with additional prerequisites for IIT of residual alveolar bone wall integrity and a thick gingival biotype. IIT included immediate placement and provisionalization, while DIT included extraction socket preservation followed by implant placement and provisionalization 4 months later. Cortical bone levels and peri-implant mucosal conditions were evaluated at regular intervals. The esthetic outcome was objectively rated after 3 years using the pink esthetic score (PES) and white esthetic score (WES). Twelve patients received an immediate Laser-Lok® implant, and 13 patients received a delayed Laser-Lok® implant. No significant differences were found between the study groups regarding survival rate (100%). The mean bone level from the implant/abutment interface was 0.35 ± 0.18 mm for IIT and 0.42 ± 0.21 mm for DIT after 3 years (p > 0.05). Mesial and distal papillae remained stable over time in DIT. A tendency for regrowth of mesial and distal papillae was found following IIT (p esthetics, DIT and IIT with single Laser-Lok® implants in the anterior maxilla are comparable and predictable options for well-selected patients. © 2015 by the American College of Prosthodontists.

  6. American Dream Delayed

    DEFF Research Database (Denmark)

    Khorunzhina, Natalia; Miller, Robert A.

    This paper investigates the delay in homeownership and a subsequent reduction in homeownership rate observed over the past decades. We focus on the delay in giving birth to children and increased labor market participation as contributing factors to homeownership dynamics for prime-age female hou...

  7. Prehospital delay in acute coronary syndrome--an analysis of the components of delay

    DEFF Research Database (Denmark)

    Ottesen, Michael Mundt; Dixen, Ulrik; Torp-Pedersen, Christian

    2004-01-01

    BACKGROUND: Prompt hospital admission is essential when treating acute coronary syndrome. Delay prior to admission is unnecessarily long. Therefore, a thorough scrutiny of the influence of characteristics, circumstantial and subjective variables on elements of prehospital delay among patients...... admitted with acute coronary syndrome is warranted. METHODS: A structured interview was conducted on 250 consecutive patients admitted alive with acute coronary syndrome. RESULTS: Median prehospital, decision, physician and transportation delays were 107, 74, 25 and 22 min, respectively. Women (n=77) had...... of acute coronary syndrome among women, and thereby contributes to unnecessary long delay to treatment. The patient's prior experience and interpretation has a significant influence on behaviour....

  8. Impact of treatment delay on mortality in ST-segment elevation myocardial infarction (STEMI) patients presenting with and without haemodynamic instability: results from the German prospective, multicentre FITT-STEMI trial.

    Science.gov (United States)

    Scholz, Karl Heinrich; Maier, Sebastian K G; Maier, Lars S; Lengenfelder, Björn; Jacobshagen, Claudius; Jung, Jens; Fleischmann, Claus; Werner, Gerald S; Olbrich, Hans G; Ott, Rainer; Mudra, Harald; Seidl, Karlheinz; Schulze, P Christian; Weiss, Christian; Haimerl, Josef; Friede, Tim; Meyer, Thomas

    2018-04-01

    The aim of this study was to investigate the effect of contact-to-balloon time on mortality in ST-segment elevation myocardial infarction (STEMI) patients with and without haemodynamic instability. Using data from the prospective, multicentre Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction (FITT-STEMI) trial, we assessed the prognostic relevance of first medical contact-to-balloon time in n = 12 675 STEMI patients who used emergency medical service transportation and were treated with primary percutaneous coronary intervention (PCI). Patients were stratified by cardiogenic shock (CS) and out-of-hospital cardiac arrest (OHCA). For patients treated within 60 to 180 min from the first medical contact, we found a nearly linear relationship between contact-to-balloon times and mortality in all four STEMI groups. In CS patients with no OHCA, every 10-min treatment delay resulted in 3.31 additional deaths in 100 PCI-treated patients. This treatment delay-related increase in mortality was significantly higher as compared to the two groups of OHCA patients with shock (2.09) and without shock (1.34), as well as to haemodynamically stable patients (0.34, P < 0.0001). In patients with CS, the time elapsing from the first medical contact to primary PCI is a strong predictor of an adverse outcome. This patient group benefitted most from immediate PCI treatment, hence special efforts to shorten contact-to-balloon time should be applied in particular to these high-risk STEMI patients. NCT00794001.

  9. Combined supra-transorbital keyhole approach for treatment of delayed intraorbital encephalocele: A minimally invasive approach for an unusual complication of decompressive craniectomy

    Science.gov (United States)

    di Somma, Lucia; Iacoangeli, Maurizio; Nasi, Davide; Balercia, Paolo; Lupi, Ettore; Girotto, Riccardo; Polonara, Gabriele; Scerrati, Massimo

    2016-01-01

    Background: Intraorbital encephalocele is a rare entity characterized by the herniation of cerebral tissue inside the orbital cavity through a defect of the orbital roof. In patients who have experienced head trauma, intraorbital encephalocele is usually secondary to orbital roof fracture. Case Description: We describe here a case of a patient who presented an intraorbital encephalocele 2 years after severe traumatic brain injury, treated by decompressive craniectomy and subsequent autologous cranioplasty, without any evidence of orbital roof fracture. The encephalocele removal and the subsequent orbital roof reconstruction were performed by using a modification of the supraorbital keyhole approach, in which we combine an orbital osteotomy with a supraorbital minicraniotomy to facilitate view and access to both the anterior cranial fossa and orbital compartment and to preserve the already osseointegrated autologous cranioplasty. Conclusions: The peculiarities of this case are the orbital encephalocele without an orbital roof traumatic fracture, and the combined minimally invasive approach used to fix both the encephalocele and the orbital roof defect. Delayed intraorbital encephalocele is probably a complication related to an unintentional opening of the orbit during decompressive craniectomy through which the brain herniated following the restoration of physiological intracranial pressure gradients after the bone flap repositioning. The reconstruction of the orbital roof was performed by using a combined supra-transorbital minimally invasive approach aiming at achieving adequate surgical exposure while preserving the autologous cranioplasty, already osteointegrated. To the best of our knowledge, this approach has not been previously used to address intraorbital encephalocele. PMID:26862452

  10. One-stage treatment of delayed 'jersey finger' by Z-step lengthening of the flexor digitorum profundus tendon at the wrist.

    Science.gov (United States)

    Sawaya, Elias T; Choughri, Hussein; Pelissier, Philippe

    2012-02-01

    The authors report the case of a 19-year-old female with delayed presentation of a type II 'jersey finger' of the fourth dominant digit. A surgical approach was performed, revealing a retracted flexor digitorum profundus tendon within a still patent sheath. The resulting loss of tendon length overruled any possibility of direct reinsertion of the tendon. A lengthening "Z-step" tendinoplasty was then performed on the tendon at the wrist, thus enabling reinsertion at the base of the distal phalanx. The patient then underwent conventional splinting and physiotherapy. Total Active Motion was measured at 220° with a 6-month follow-up. Even though there is no clear consensus concerning management of such cases, different techniques have been described, such as one- or two-stage grafting, or tenotomy at the musculotendinous junction. Lengthening tendinoplasties have been applied by certain authors but only to the flexor pollicis longus tendon. To our knowledge, this is the only reported case of lengthening Z-step applied to a long digit for the repair of type II 'jersey finger' lesions. The satisfactory functional and cosmetic outcome encourages us to consider this one-stage technique in other select cases, in order to gather more formal evidence. Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  11. Diagnosis delay in tuberculosis and its consequences

    International Nuclear Information System (INIS)

    Habibullah, S.; Sheikh, M.A.; Sadiq, A.; Anwar, T.

    2004-01-01

    Objective: To find out the average duration from onset of symptoms to the diagnosis and treatment of tuberculosis, reasons for diagnostic delay, its consequences, association of variables and formulation of recommendations. Results: In this study it was found that average time from onset of initial symptoms to diagnosis and treatment of tuberculosis was 120 days. In 64% of the patients medical practitioners were responsible for delaying the diagnosis of tuberculosis. Loss of weight in 40% and haemoptysis is 21% were the consequences of diagnostic delay of tuberculosis. Delay in the diagnosis of tuberculosis was statistically significant in those patients who consulted private practitioners, and consequences of tuberculosis were severe in those patients who consulted late. (author)

  12. Delayed power analysis

    International Nuclear Information System (INIS)

    Adamovich, L.A.; Azarov, V.V.

    1999-01-01

    Time dependent core power behavior in a nuclear reactor is described with well-known neutron kinetics equations. At the same time, two portions are distinguished in energy released from uranium nuclei fission; one released directly at fission and another delayed (residual) portion produced during radioactive decay of fission products. While prompt power is definitely described with kinetics equations, the delayed power presentation still remains outstanding. Since in operation the delayed power part is relatively small (about 6%) operation, it can be neglected for small reactivity disturbances assuming that entire power obeys neutron kinetics equations. In case of a high negative reactivity rapidly inserted in core (e.g. reactor scram initiation) the prompt and delayed components can be calculated separately with practically no impact on each other, employing kinetics equations for prompt power and known approximation formulas for delayed portion, named residual in this specific case. Under substantial disturbances the prompt component in the dynamic process becomes commensurable with delayed portion, thus making necessary to take into account their cross impact. A system of differential equations to describe time-dependent behavior of delayed power is presented. Specific NPP analysis shows a way to significantly simplify the task formulation. (author)

  13. Delayed encephalopathy after acute carbon monoxide poisoning

    Directory of Open Access Journals (Sweden)

    Mehmet İbrahim Turan

    2014-03-01

    Full Text Available Carbon monoxide poisoning is a major cause of death following attempted suicide and accidental exposures. Although clinical presentation depends on the duration and the intensity of exposure, the assessment of the severity of intoxication is difficult. A small percentage of patients who show complete initial recovery may develop delayed neurological deficits. Delayed encephalopathy after acute carbon monoxide poisoning is a rare and poor prognosis neurologic disorders and there is no specific treatment. We present a case with early onset of delayed encephalopathy after acute carbon monoxide poisoning with typical cranial imaging findings in a child with atypical history and clinical presentation.

  14. Neutron delayed choice experiments

    International Nuclear Information System (INIS)

    Bernstein, H.J.

    1986-01-01

    Delayed choice experiments for neutrons can help extend the interpretation of quantum mechanical phenomena. They may also rule out alternative explanations which static interference experiments allow. A simple example of a feasible neutron test is presented and discussed. (orig.)

  15. Quad nanosecond delay module

    International Nuclear Information System (INIS)

    McDonald, R.J.; Hunter, J.B.; Wozniak, G.J.

    1986-04-01

    Four nanosecond (ns) delay units have been designed to fit in a single-width NIM module. This module is particularly suited for use in conjunction with quad constant fraction timing discriminators (CFTDs) since it has four delay units that can be placed adjacent to the four units of the CFTD. A series of different length cables connected via DIP toggle switches provide delays of 0.60 ns in 4 ns increments. Thus, the CFTD delay can be optimized for pulses of different rise times from approx.10-100 ns. Design work for the PC board and silkscreening of the front panel were done with the MacDraw program on the Apple Mackintosh computer and printed with the Lasewriter printer. 6 refs

  16. Availability of stage at diagnosis, cancer treatment delay and compliance with cancer guidelines as cancer registry indicators for cancer care in Europe: Results of EUROCHIP-3 survey

    NARCIS (Netherlands)

    Siesling, Sabine; Kwast, A.; Gavin, A.; Baili, P.; Otter, R.

    2013-01-01

    EUROCHIP (European Cancer Health Indicators Project) focuses on understanding inequalities in the cancer burden, care and survival by the indicators “stage at diagnosis,” “cancer treatment delay” and “compliance with cancer guidelines” as the most important indicators. Our study aims at providing

  17. Delayed rule following

    OpenAIRE

    Schmitt, David R.

    2001-01-01

    Although the elements of a fully stated rule (discriminative stimulus [SD], some behavior, and a consequence) can occur nearly contemporaneously with the statement of the rule, there is often a delay between the rule statement and the SD. The effects of this delay on rule following have not been studied in behavior analysis, but they have been investigated in rule-like settings in the areas of prospective memory (remembering to do something in the future) and goal pursuit. Discriminative even...

  18. Vernier Delay Unit

    International Nuclear Information System (INIS)

    Pierce, W.B.

    1984-10-01

    This module will accept differential ECL pulses from the auxiliary rear panel or NIM level pulses from the front panel. The pulses are produced at the output with a fixed delay that is software programmable in steps of 0.1 ns over the range of 0.1 to 10.5 ns. Multiple outputs are available at the front panel. Minimum delay through the module is 9 ns

  19. Quad precision delay generator

    International Nuclear Information System (INIS)

    Krishnan, Shanti; Gopalakrishnan, K.R.; Marballi, K.R.

    1997-01-01

    A Quad Precision Delay Generator delays a digital edge by a programmed amount of time, varying from nanoseconds to microseconds. The output of this generator has an amplitude of the order of tens of volts and rise time of the order of nanoseconds. This was specifically designed and developed to meet the stringent requirements of the plasma focus experiments. Plasma focus is a laboratory device for producing and studying nuclear fusion reactions in hot deuterium plasma. 3 figs

  20. Modelling delays in pharmacokinetics

    International Nuclear Information System (INIS)

    Farooqi, Z.H.; Lambrecht, R.M.

    1990-01-01

    Linear system analysis has come to form the backbone of pharmacokinetics. Natural systems usually involve time delays, thus models incorporating them would be an order closer approximation to the real world compared to those that do not. Delays may be modelled in several ways. The approach considered in this study is to have a discrete-time delay dependent rate with the delay respresenting the duration between the entry of a drug into a compartment and its release in some form (may be as a metabolite) from the compartment. Such a delay may be because of one or more of several physiological reasons, like, formation of a reservoir, slow metabolism, or receptor binding. The mathematical structure this gives rise to is a system of delay-differential equations. Examples are given of simple one and two compartment systems with drugs like bumetanide, carbamazepine, and quinolone-caffeine interaction. In these examples generally a good fit is obtained and the suggested models form a good approximation. 21 refs., 6 figs

  1. Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity arthritis (DTHA) model

    DEFF Research Database (Denmark)

    Atkinson, Sara Marie; Bleil, Janine; Maier, Rene

    2016-01-01

    . Periarticular bone formation was observed from day 10. Induction of new bone formation indicated by enhanced Runx2, collagen X, osteocalcin, MMP2, MMP9, and MMP13 mRNA expression was observed only between days 8 and 11. Anti-RANKL treatment resulted in a modest reduction in paw and ankle swelling...... and bone formation were analyzed by mRNA deep sequencing. Serum concentrations of tartrate-resistant acid phosphatase 5b, carboxy-terminal telopeptide I (CTX-I), matrix metalloproteinase 3 (MMP3), and serum amyloid P component (SAP) were determined by enzyme-linked immunosorbent assay. Anti......-RANKL monoclonal antibody treatment was initiated at the time of immunization. Results: Bone destruction (MMP3 serum levels, cathepsin B activity, and RANKL mRNA) peaked at day 3 after arthritis induction, followed by a peak in cartilage destruction and bone erosion on day 5 after arthritis induction...

  2. Design of a PWR gaseous effluent treatment system combining delay-storage vessels, volume-reduction and activated-charcoal beds

    International Nuclear Information System (INIS)

    Nuyt, G.; Glibert, R.; Lahaye, J.P.

    1986-01-01

    The usual technique for the treatment of gaseous effluents is to store them in radioactive decay tanks and to carry out a range of operations such as recycling, volume-reduction and discharge. Although presenting undeniable advantages, this technique has a number of weaknesses which have become apparent with experience. This paper describes and analyses a system designed to alleviate these difficulties and to permit greater flexibility in gaseous effluent treatment, especially for power stations in the load-following mode of operation, by means of a combination of storage techniques and retention of short-lived isotopes in activated charcoal beds. The attractiveness of the proposed system is apparent from an analysis of operational, maintenance, safety and cost aspects. (author)

  3. Grape berry ripening delay induced by a pre-véraison NAA treatment is paralleled by a shift in the expression pattern of auxin- and ethylene-related genes.

    Science.gov (United States)

    Ziliotto, Fiorenza; Corso, Massimiliano; Rizzini, Fabio Massimo; Rasori, Angela; Botton, Alessandro; Bonghi, Claudio

    2012-10-09

    Auxins act as repressors of ripening inception in grape (véraison), while ethylene and abscisic acid (ABA) play a positive role as inducers of the syndrome. Despite the increasing amount of information made available on this topic, the complex network of interactions among these hormones remains elusive. In order to shed light on these aspects, a holistic approach was adopted to evaluate, at the transcriptomic level, the crosstalk between hormones in grape berries, whose ripening progression was delayed by applying naphtalenacetic acid (NAA) one week before véraison. The NAA treatment caused significant changes in the transcription rate of about 1,500 genes, indicating that auxin delayed grape berry ripening also at the transcriptional level, along with the recovery of a steady state of its intracellular concentration. Hormone indices analysis carried out with the HORMONOMETER tool suggests that biologically active concentrations of auxins were achieved throughout a homeostatic recovery. This occurred within 7 days after the treatment, during which the physiological response was mainly unspecific and due to a likely pharmacological effect of NAA. This hypothesis is strongly supported by the up-regulation of genes involved in auxin conjugation (GH3-like) and action (IAA4- and IAA31-like). A strong antagonistic effect between auxin and ethylene was also observed, along with a substantial 'synergism' between auxins and ABA, although to a lesser extent. This study suggests that, in presence of altered levels of auxins, the crosstalk between hormones involves diverse mechanisms, acting at both the hormone response and biosynthesis levels, creating a complex response network.

  4. Natural History and Factors Associated with Early and Delayed Mortality in HIV-Infected Patients Treated of Tuberculosis under Directly Observed Treatment Short-Course Strategy: A Prospective Cohort Study in India

    Directory of Open Access Journals (Sweden)

    Gerardo Alvarez-Uria

    2012-01-01

    Full Text Available Despite the impressive global results of DOTS in India, the effectiveness of DOTS for the treatment of tuberculosis in HIV-infected patients is not well known. This is an observational prospective cohort study performed in Anantapur District, Andhra Pradesh, India. The study included 1000 DOTS antituberculosis treatment (ATT episodes and 840 person-years. CD4 lymphocyte count was below 200 cells/mm3 in 77% of the cases, and 21% were retreatments. Two thirds were presented with extrapulmonary tuberculosis, and the most common form of extrapulmonary tuberculosis was tuberculous meningitis followed by pleuritis, abdominal tuberculosis, and lymphadenitis. Cumulative incidence of mortality was 16%, 26%, 39%, and 46% at 1, 3, 12, and 24 months, respectively. Factors associated with three-month (early mortality were being homeless, having low CD4+ lymphocyte count, having tuberculous meningitis, belonging to a socially disadvantaged community, having more than 35 years, and being on an antiretroviral therapy at the moment of initiating the ATT. Factors associated with delayed mortality were having low CD4+ lymphocyte count, belonging to a socially disadvantaged community, receiving a category II ATT because of a previous episode of ATT and having acid fast bacilli in sputum before the ATT initiation. These findings indicate that there is an urgent need to improve the treatment of tuberculosis in HIV-infected patients in India.

  5. Variables influencing delay in antenatal clinic attendance among ...

    African Journals Online (AJOL)

    A delay in deciding to seek antenatal care is predominant among pregnant teenagers in Lesotho. This subsequently leads to delay in reaching treatment and in receiving adequate treatment. Early antenatal care attendance plays a major role in detecting and treating complications of pregnancy and forms a good basis for ...

  6. Analysing the Concepts of Vengeance and Hono(ur in Shakespeare´s Hamlet and Sumarokov´s Gamlet: A Corpus-based Approach to Literature

    Directory of Open Access Journals (Sweden)

    Irina Keshabyan

    2009-12-01

    Full Text Available The present paper aims at carrying out structural and lexical analysis of two contrasting plays –Shakespeare´s Hamlet and Sumarokov´s Gamlet- in a specific linguistic domain. In this contribution, we will attempt to gain some insight into two essential content words: vengeance and hono(ur, their derivatives and related words, through quantitative analysis of these words and qualitative analysis of their collocates and concordances. Collocational approach will be used to analyse and compare the ways the authors perceive the concepts of vengeance and hono(ur. In general, the findings will indicate important similarities and/or differences between the structures of the plays per acts and both texts´ basic contents in relation to two important topics -vengeance and hono(ur.El presente artículo tiene como objetivo un análisis estructural y léxico de dos obras contrastivas –Hamlet de Shakespeare y Gamlet de Sumarokov- en un dominio lingüístico específico. En esta contribución, intentaremos adentrarse en el estudio de dos sustantivos: venganza y honor, sus derivados y palabras relacionadas- a través de un análisis cuantitativo de las mismas y el análisis cualitativo de sus colocados y concordancias. El método de los colocados será utilizado para analizar y comparar el modo en que los autores perciben los conceptos de venganza y honor. En general, los resultados van a señalar las similitudes y/o diferencias importantes entre las estructuras de las obras por actos y los contenidos básicos de ambos textos en relación con dos temas importantes, tal como, venganza y honor.

  7. Robotic surgery twice performed in the treatment of hilar cholangiocarcinoma with deep jaundice: delayed right hemihepatectomy following the right-hepatic vascular control.

    Science.gov (United States)

    Zhu, Zhenyu; Liu, Quanda; Chen, Junzhou; Duan, Weihong; Dong, Maosheng; Mu, Peiyuan; Cheng, Di; Che, Honglei; Zhang, Tao; Xu, Xiaoya; Zhou, Ningxin

    2014-10-01

    To explore and find a new method to treat hilar cholangiocarcinoma with deep jaundice assisted by Da Vinci robot. A hilar cholangiocarcinoma patient of type Bismuch-Corlette IIIa was found with deep jaundice (total bilirubin: 635 µmol/L). On the first admission, we performed Da Vinci robotic surgery including drainage of left hepatic duct, dissection of right hepatic vessels (right portal vein and right hepatic artery), and placement of right-hepatic vascular control device. Three weeks later on the second admission when the jaundice disappeared we occluded right-hepatic vascular discontinuously for 6 days and then sustained later. On the third admission after 3 weeks of right-hepatic vascular control, the right hemihepatectomy was performed by Da Vinci robot for the second time. The future liver remnant after the right-hepatic vascular control increased from 35% to 47%. The volume of left lobe increased by 368 mL. When the total bilirubin and liver function were all normal, right hemihepatectomy was performed by Da Vinci robot 10 weeks after the first operation. The removal of atrophic right hepatic lobe with tumor in bile duct was found with no pathologic cancer remaining in the margin. The patient was followed up at our outpatient clinic every 3 months and no tumor recurrence occurs by now (1 y). Under the Da Vinci robotic surgical system, a programmed treatment can be achieved: first, the hepatic vessels were controlled gradually together with biliary drainage, which results in liver's partial atrophy and compensatory hypertrophy in the other part. Then a radical hepatectomy could be achieved. Such programmed hepatectomy provides a new treatment for patients of hilar cholangiocarcinoma with deep jaundice who have the possibility of radical heptolobectomy.

  8. Optimal Joint Expected Delay Forwarding in Delay Tolerant Networks

    OpenAIRE

    Jia Xu; Xin Feng; Wen Jun Yang; Ru Chuan Wang; Bing Qing Han

    2013-01-01

    Multicopy forwarding schemes have been employed in delay tolerant network (DTN) to improve the delivery delay and delivery rate. Much effort has been focused on reducing the routing cost while retaining high performance. This paper aims to provide an optimal joint expected delay forwarding (OJEDF) protocol which minimizes the expected delay while satisfying a certain constant on the number of forwardings per message. We propose a comprehensive forwarding metric called joint expected delay (JE...

  9. Hamlet and economics

    International Nuclear Information System (INIS)

    Shiffer, J.D.

    1994-01-01

    The Department of Energy seems to understand the difference between readiness and realization very well. It has a clear and realistic view of the situation; the DOE believes in getting ready. It takes the view that we live in a unpredictable world. DOE knows that today, after 20 years of commitment to the nation's energy independence, we are more independent on imported oil than we were in 1973

  10. [Cost-effectiveness analysis of delayed-release dimethyl-fumarate in the treatment of relapsing-remitting multiple sclerosis in Italy

    Directory of Open Access Journals (Sweden)

    Gianluca Furneri

    2016-06-01

    RESULTS: In the base-case analysis, DMF was more efficacious than alternatives, in terms of both survival (19.496 vs. 19.297-19.461 discounted LYs, respectively, and QALYs (6.548 vs. 5.172- 6.212 discounted QALYs, respectively. Per-patient lifetime costs with DMF amounted to € 276,500, similarly to the other options. DMF was the drug with the largest effect of disability cost reduction. DMF was dominant vs. IFN beta-1a 44 mcg and cost-effective vs. all other IFNs, GA and teriflunomide, with incremental cost-effectiveness ratio (ICERs between € 11,272 and € 23,409. All ICER values were lower than the € 50,000 per QALY threshold. One-way sensitivity analysis showed that, for all tested scenarios, ICER of DMF vs. therapeutic alternatives remained favourable (≤ 50.000 €/QALY gained and the results of probabilistic sensitivity analysis showed that the probability for DMF of being favourable (≤ 50.000 €/QALY gained was between around 70% and 93%, thus ensuring robustness of the results. CONCLUSIONS: The results of this economic analysis show that, at the current price and the described assumptions, DMF represents a cost-effective option vs. other available first-line treatments indicated in RRMS in the perspective of the Italian NHS. [Article in Italian

  11. Delayed post-treatment with bone marrow-derived mesenchymal stem cells is neurorestorative of striatal medium-spiny projection neurons and improves motor function after neonatal rat hypoxia-ischemia.

    Science.gov (United States)

    Cameron, Stella H; Alwakeel, Amr J; Goddard, Liping; Hobbs, Catherine E; Gowing, Emma K; Barnett, Elizabeth R; Kohe, Sarah E; Sizemore, Rachel J; Oorschot, Dorothy E

    2015-09-01

    Perinatal hypoxia-ischemia is a major cause of striatal injury and may lead to cerebral palsy. This study investigated whether delayed administration of bone marrow-derived mesenchymal stem cells (MSCs), at one week after neonatal rat hypoxia-ischemia, was neurorestorative of striatal medium-spiny projection neurons and improved motor function. The effect of a subcutaneous injection of a high-dose, or a low-dose, of MSCs was investigated in stereological studies. Postnatal day (PN) 7 pups were subjected to hypoxia-ischemia. At PN14, pups received treatment with either MSCs or diluent. A subset of high-dose pups, and their diluent control pups, were also injected intraperitoneally with bromodeoxyuridine (BrdU), every 24h, on PN15, PN16 and PN17. This permitted tracking of the migration and survival of neuroblasts originating from the subventricular zone into the adjacent injured striatum. Pups were euthanized on PN21 and the absolute number of striatal medium-spiny projection neurons was measured after immunostaining for DARPP-32 (dopamine- and cAMP-regulated phosphoprotein-32), double immunostaining for BrdU and DARPP-32, and after cresyl violet staining alone. The absolute number of striatal immunostained calretinin interneurons was also measured. There was a statistically significant increase in the absolute number of DARPP-32-positive, BrdU/DARPP-32-positive, and cresyl violet-stained striatal medium-spiny projection neurons, and fewer striatal calretinin interneurons, in the high-dose mesenchymal stem cell (MSC) group compared to their diluent counterparts. A high-dose of MSCs restored the absolute number of these neurons to normal uninjured levels, when compared with previous stereological data on the absolute number of cresyl violet-stained striatal medium-spiny projection neurons in the normal uninjured brain. For the low-dose experiment, in which cresyl violet-stained striatal medium-spiny neurons alone were measured, there was a lower statistically

  12. Assessing delay discounting in mice

    OpenAIRE

    Mitchell, Suzanne H.

    2014-01-01

    Delay discounting (also intertemporal choice or impulsive choice) is the process by which delayed outcomes, such as delayed food delivery, are valued less than the same outcomes delivered immediately or with a shorter delay. This process is of interest because many psychopathologies, including substance dependence, pathological gambling, attention deficit hyperactivity disorder and conduct disorder, are characterized by heightened levels of delay discounting. Some of these disorders are herit...

  13. Estimating Delays In ASIC's

    Science.gov (United States)

    Burke, Gary; Nesheiwat, Jeffrey; Su, Ling

    1994-01-01

    Verification is important aspect of process of designing application-specific integrated circuit (ASIC). Design must not only be functionally accurate, but must also maintain correct timing. IFA, Intelligent Front Annotation program, assists in verifying timing of ASIC early in design process. This program speeds design-and-verification cycle by estimating delays before layouts completed. Written in C language.

  14. Permissible Delay in Payments

    Directory of Open Access Journals (Sweden)

    Yung-Fu Huang

    2007-01-01

    Full Text Available The main purpose of this paper wants to investigate the optimal retailer's lot-sizing policy with two warehouses under partially permissible delay in payments within the economic order quantity (EOQ framework. In this paper, we want to extend that fully permissible delay in payments to the supplier would offer the retailer partially permissible delay in payments. That is, the retailer must make a partial payment to the supplier when the order is received. Then the retailer must pay off the remaining balance at the end of the permissible delay period. In addition, we want to add the assumption that the retailer's storage space is limited. That is, the retailer will rent the warehouse to store these exceeding items when the order quantity is larger than retailer's storage space. Under these conditions, we model the retailer's inventory system as a cost minimization problem to determine the retailer's optimal cycle time and optimal order quantity. Three theorems are developed to efficiently determine the optimal replenishment policy for the retailer. Finally, numerical examples are given to illustrate these theorems and obtained a lot of managerial insights.

  15. Delayed neutrons in ANSTO

    International Nuclear Information System (INIS)

    Wall, T.

    1988-01-01

    Delayed neutron analysis carried out at the Australian Nuclear Scientific and Technology Organization facilities, provides a fast, high sensitivity, low cost, reliable method, particularly suitable for large batches of samples, and for non destructive analysis of a range of materials. While its main use has been in uranium exploration, other applications include archeological investigations, agriculture, oceanography and biology

  16. Diagnosis delay in Libyan female breast cancer

    Directory of Open Access Journals (Sweden)

    Ermiah Eramah

    2012-08-01

    Full Text Available Abstract Aims To study the diagnosis delay and its impact on stage of disease among women with breast cancer on Libya. Methods 200 women, aged 22 to 75 years with breast cancer diagnosed during 2008–2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. This period (diagnosis time was categorized into 3 periods: 6 months. If diagnosis time was longer than 3 months, the diagnosis was considered delayed (diagnosis delay. Consultation time was the time taken to visit the general practitioner after the first symptoms. Retrospective preclinical and clinical data were collected on a form (questionnaire during an interview with each patient and from medical records. Results The median of diagnosis time was 7.5 months. Only 30.0% of patients were diagnosed within 3 months after symptoms. 14% of patients were diagnosed within 3–6 months and 56% within a period longer than 6 months. A number of factors predicted diagnosis delay: Symptoms were not considered serious in 27% of patients. Alternative therapy (therapy not associated with cancer was applied in 13.0% of the patients. Fear and shame prevented the visit to the doctor in 10% and 4.5% of patients, respectively. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was associated with initial breast symptom(s that did not include a lump (p  Diagnosis delay was associated with bigger tumour size (p Conclusions Diagnosis delay is very serious problem in Libya. Diagnosis delay was associated with complex interactions between several factors and with advanced stages. There is a need for improving breast cancer awareness and training of general practitioners to reduce breast cancer mortality by promoting early detection. The treatment guidelines should pay more attention to the early phases of breast cancer. Especially, guidelines for good practices in managing

  17. REASONS FOR PATIENT DELAYS & HEALTH SYSTEM DELAYS FOR TUBERCULOSIS IN SOUTH INDIA

    Directory of Open Access Journals (Sweden)

    Kapil Goel

    2011-12-01

    Full Text Available Background: Globally, the burden of Tuberculosis is escalating. Early diagnosis and prompt initiation of tuberculosis treatment is essential for an effective tuberculosis control programme. Objectives: To study the self reported reasons for patient and health system (diagnosis & treatment delays in Tuberculosis patients. Methods: A community based cross sectional study was conducted among 98 new sputum positive TB cases aged > 15 years registered under RNTCP from Oct 2006 to June 2007 & receiving treatment under DOTS in Udupi taluk by interviewing them. Results: Total 98 patients were recruited and 68% were males. Out of 17 patients with patient delays, 82% felt that their symptoms were not severe, 71% felt that patient delay was due to lack of awareness and 71% did not take it seriously. Out of 86 patients with health system delays, 82.6% of patients mentioned that doctor has not advised for sputum examination, 76.7% of patients told that they first consulted a private doctor, 21% of them mentioned that doctor was unaware to diagnose TB. Conclusion: Symptoms not severe is the main reason for the patient delay and doctor didn’t advise for sputum examination is the main reason for health system delays.

  18. Topological Acoustic Delay Line

    Science.gov (United States)

    Zhang, Zhiwang; Tian, Ye; Cheng, Ying; Wei, Qi; Liu, Xiaojun; Christensen, Johan

    2018-03-01

    Topological protected wave engineering in artificially structured media is at the frontier of ongoing metamaterials research that is inspired by quantum mechanics. Acoustic analogues of electronic topological insulators have recently led to a wealth of new opportunities in manipulating sound propagation with strikingly unconventional acoustic edge modes immune to backscattering. Earlier fabrications of topological insulators are characterized by an unreconfigurable geometry and a very narrow frequency response, which severely hinders the exploration and design of useful devices. Here we establish topologically protected sound in reconfigurable phononic crystals that can be switched on and off simply by rotating its three-legged "atoms" without altering the lattice structure. In particular, we engineer robust phase delay defects that take advantage of the ultrabroadband reflection-free sound propagation. Such topological delay lines serve as a paradigm in compact acoustic devices, interconnects, and electroacoustic integrated circuits.

  19. Elite athletes and pubertal delay.

    Science.gov (United States)

    Kapczuk, Karina

    2017-10-01

    Intensive physical training and participation in competitive sports during childhood and early adolescence may affect athletes' pubertal development. On the other hand, pubertal timing, early or late, may impact on an athlete selection for a particular sport. Genetic predisposition, training load, nutritional status and psychological stress determine athletes' pubertal timing. Athletes that practice esthetic sports, especially gymnasts, are predisposed to a delay in pubertal development. The growing evidence indicates that energy deficiency, not a systemic training per se, plays a crucial role in the pathogenesis of functional hypothalamic hypogonadism in female athletes. Metabolic and psychologic stress activate hypothalamic-pituitary-adrenal axis and suppress hypothalamic-pituitary-ovarian axis. Female athletes who do not begin secondary sexual development by the age of 14 or menstruation by the age of 16 warrant a comprehensive evaluation and a targeted treatment. Somatic growth and sexual maturation of elite female athletes are largely sport-specific since each sport favors a particular somatotype and requires a specific training. Chronic negative energy balance resulting from a systemic physical training and inadequate energy intake may delay pubertal development in elite athletes. Youth athletes, especially those engaged in competitive sports that emphasize prepubertal or lean appearance, are at risk of developing relative energy deficiency in sport associated with disordered eating or eating disorders. Management strategies should address the complex conditions underlying functional hypothalamic hypogonadism.

  20. Time-Delay Interferometry

    Directory of Open Access Journals (Sweden)

    Massimo Tinto

    2014-08-01

    Full Text Available Equal-arm detectors of gravitational radiation allow phase measurements many orders of magnitude below the intrinsic phase stability of the laser injecting light into their arms. This is because the noise in the laser light is common to both arms, experiencing exactly the same delay, and thus cancels when it is differenced at the photo detector. In this situation, much lower level secondary noises then set the overall performance. If, however, the two arms have different lengths (as will necessarily be the case with space-borne interferometers, the laser noise experiences different delays in the two arms and will hence not directly cancel at the detector. In order to solve this problem, a technique involving heterodyne interferometry with unequal arm lengths and independent phase-difference readouts has been proposed. It relies on properly time-shifting and linearly combining independent Doppler measurements, and for this reason it has been called time-delay interferometry (TDI. This article provides an overview of the theory, mathematical foundations, and experimental aspects associated with the implementation of TDI. Although emphasis on the application of TDI to the Laser Interferometer Space Antenna (LISA mission appears throughout this article, TDI can be incorporated into the design of any future space-based mission aiming to search for gravitational waves via interferometric measurements. We have purposely left out all theoretical aspects that data analysts will need to account for when analyzing the TDI data combinations.

  1. Delays in the management of retroperitoneal sarcomas

    DEFF Research Database (Denmark)

    Seinen, Jojanneke; Almquist, Martin; Styring, Emelie

    2010-01-01

    Retroperitoneal sarcomas are rare and treatment should optimally be centralized. Despite successful centralization with 90% of the patients referred prior to surgery, delays occur, which led us to assess lead times in a population-based series. Method. Patients diagnosed with retroperitoneal...... sarcoma in the southern Sweden health care region 2003-2009 were eligible for the study. Data on referrals and diagnostic investigations were collected from clinical files from primary health care, local hospitals, and from the sarcoma centre. Lead times were divided into patient delays and health care...... at the general practitioner, 36 days at local hospitals, and 55 days at the sarcoma centre. Conclusion. Centralization per se is not sufficient for optimized and efficient management. Our findings suggest that delays can be minimized by direct referral of patients from primary health care to sarcoma centers...

  2. Abdominal CT findings of delayed postoperative complications

    Energy Technology Data Exchange (ETDEWEB)

    Zissin, R.; Osadchy, A. [Sapir Medical Center, Dept. of Diagnostic Imaging, Kfar Saba (Israel)]. E-mail: zisinrivka@clalit.org.il; Gayer, G. [Assaf Harofe Medical Center, Dept. of Diagnostic Imaging, Zrifin (Israel)

    2007-10-15

    Despite progress in surgical techniques and modern medical treatment, postoperative complications occur not infrequently and vary according to type of surgery, clinical setting, and time elapsed since surgery. In general, they can be divided into early and delayed complications. Delayed postoperative complications can be classified as specific and nonspecific. The common nonspecific delayed complications are incisional hernia and postoperative bowel obstruction. Bowel obstruction can be further categorized as obstruction related to benign or neoplastic etiology, the latter occurring in oncology patients in whom the primary surgery was related to an underlying abdominal neoplasm. Gossypiboma is another, fortunately rare, postoperative complication. Specific complications appear after specific operations and include the following: Splenosis - following splenectomy. Retained gallstones and spilled gallstones - following cholecystectomy, mainly laparoscopic. Dropped appendicolith and stump appendicitis - following appendectomy, mainly laparoscopic. Obturation obstruction by a bezoar - following gastric surgery. Afferent loop syndrome (ALS) - following Bilroth II gastrectomy. (author)

  3. Delayed child-bearing.

    Science.gov (United States)

    Johnson, Jo-Ann; Tough, Suzanne

    2012-01-01

    To provide an overview of delayed child-bearing and to describe the implications for women and health care providers. Delayed child-bearing, which has increased greatly in recent decades, is associated with an increased risk of infertility, pregnancy complications, and adverse pregnancy outcome. This guideline provides information that will optimize the counselling and care of Canadian women with respect to their reproductive choices. Maternal age is the most important determinant of fertility, and obstetric and perinatal risks increase with maternal age. Many women are unaware of the success rates or limitations of assisted reproductive technology and of the increased medical risks of delayed child-bearing, including multiple births, preterm delivery, stillbirth, and Caesarean section. This guideline provides a framework to address these issues. Studies published between 2000 and August 2010 were retrieved through searches of PubMed and the Cochrane Library using appropriate key words (delayed child-bearing, deferred pregnancy, maternal age, assisted reproductive technology, infertility, and multiple births) and MeSH terms (maternal age, reproductive behaviour, fertility). The Internet was also searched using similar key words, and national and international medical specialty societies were searched for clinical practice guidelines and position statements. Data were extracted based on the aims, sample, authors, year, and results. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). The Society of Obstetricians and Gynaecologists of Canada. RECOMMENDATIONS 1. Women who delay child-bearing are at increased risk of infertility. Prospective parents, especially women, should know that their fecundity and fertility begin to decline significantly after 32 years of age. Prospective parents should know that assisted reproductive technologies cannot guarantee a live birth or completely

  4. Delaying information search

    Directory of Open Access Journals (Sweden)

    Yaniv Shani

    2012-11-01

    Full Text Available In three studies, we examined factors that may temporarily attenuate information search. People are generally curious and dislike uncertainty, which typically encourages them to look for relevant information. Despite these strong forces that promote information search, people sometimes deliberately delay obtaining valuable information. We find they may do so when they are concerned that the information might interfere with future pleasurable activities. Interestingly, the decision to search or to postpone searching for information is influenced not only by the value and importance of the information itself but also by well-being maintenance goals related to possible detrimental effects that negative knowledge may have on unrelated future plans.

  5. Vehicle barrier with access delay

    Science.gov (United States)

    Swahlan, David J; Wilke, Jason

    2013-09-03

    An access delay vehicle barrier for stopping unauthorized entry into secure areas by a vehicle ramming attack includes access delay features for preventing and/or delaying an adversary from defeating or compromising the barrier. A horizontally deployed barrier member can include an exterior steel casing, an interior steel reinforcing member and access delay members disposed within the casing and between the casing and the interior reinforcing member. Access delay members can include wooden structural lumber, concrete and/or polymeric members that in combination with the exterior casing and interior reinforcing member act cooperatively to impair an adversarial attach by thermal, mechanical and/or explosive tools.

  6. Delayed rule following.

    Science.gov (United States)

    Schmitt, D R

    2001-01-01

    Although the elements of a fully stated rule (discriminative stimulus [S(D)], some behavior, and a consequence) can occur nearly contemporaneously with the statement of the rule, there is often a delay between the rule statement and the S(D). The effects of this delay on rule following have not been studied in behavior analysis, but they have been investigated in rule-like settings in the areas of prospective memory (remembering to do something in the future) and goal pursuit. Discriminative events for some behavior can be event based (a specific setting stimulus) or time based. The latter are more demanding with respect to intention following and show age-related deficits. Studies suggest that the specificity with which the components of a rule (termed intention) are stated has a substantial effect on intention following, with more detailed specifications increasing following. Reminders of an intention, too, are most effective when they refer specifically to both the behavior and its occasion. Covert review and written notes are two effective strategies for remembering everyday intentions, but people who use notes appear not to be able to switch quickly to covert review. By focusing on aspects of the setting and rule structure, research on prospective memory and goal pursuit expands the agenda for a more complete explanation of rule effects.

  7. Morte e ressurreição: uma reflexão sobre as adaptações fílmicas "Dom Quixote" e "Hamlet", de Kozintsev

    Directory of Open Access Journals (Sweden)

    Thayane Morais Silva

    2017-03-01

    Full Text Available RESUMOAo considerar os “400 anos da morte de Shakespeare e Cervantes”, é impossível não associar as obras desses respectivos autores à questão da autoria, tema tão recorrente nos Estudos Literários, amplamente discutido por Barthes Foucault e Agamben. Se passaram 400 anos desde a morte do corpo, e não da morte do legado artístico –é sempre bom lembrar, desses dois escritores.  Entretanto, diante de tantas reproduções técnicas que desencadearam a destruição da aura da obra de arte, propomos estabelecer uma relação entre a morte autoral desses dois autores e os conceitos que Walter Benjamin delineou para esclarecer a situação da obra de arte na era de sua reprodutibilidade técnica. A fim de exemplificar como a autoria de Cervantes e de Shakespeare é mortificada a partir de suas próprias obras, iremos investigar duas adaptações cinematográficas, Dom Quixote e Hamlet, ambas dirigidas por Grigori Kozintsev.PALAVRAS-CHAVE: Shakespeare; Cervantes; Autoria; Reprodutibilidade técnica; Adaptação cinematográfica.

  8. DE-MYTHOLOGIZING THE BARD: APPROPRIATION OF SHAKESPEARE IN TOM STOPPARD’S DOGG’S HAMLET, CAHOOT’S MACBETH

    Directory of Open Access Journals (Sweden)

    Ifeta Ciric-Fazlija

    2014-11-01

    Full Text Available One of the most entrenched myths that dramatic authors need to contest and adjust to is the Shakespeare myth, a long-lasting and all-pervasive influence that Shakespeare’s name and texts have exerted since the late 16th century, being perceived as “represent[ing] truths that transcend particular circumstances” (Sinfield, 1998: 129. In order to be actively involved in the “making of culture” (Sinfield, 1998: 128 and for the purpose of establishing and (redefining one’s own position within and against the canonical (transnational texts, many British dramatists, including Tom Stoppard, have alluded to, quoted, or incorporated portions of Shakespeare’s plays within their own, or even reconstituted them completely. This paper discusses the manner in which Stoppard appropriates Shakespeare’s Hamlet and Macbeth – probably his best known and most frequently staged and adapted tragedies – in order to question the importance of both the author and his work within the context of contemporary culture and society.

  9. USING REMOTE SENSING AND GIS TECHNIQUES TO DETECT CHANGES TO THE PRINCE ALFRED HAMLET CONSERVATION AREA IN THE WESTERN CAPE, SOUTH AFRICA

    Directory of Open Access Journals (Sweden)

    P. Duncan

    2016-06-01

    Full Text Available Understanding and identifying the spatial-temporal changes in the natural environment is crucial for monitoring and evaluating conservation efforts, as well as understanding the impact of human activities on natural resources, informing responsible land management, and promoting better decision-making. Conservation areas are often under pressure from expanding farming and related industry, invasive alien vegetation, and an ever-increasing human settlement footprint. This study focuses on detecting changes to the Prince Alfred Hamlet commonage, near Ceres in the Cape Floral Kingdom. It was chosen for its high conservation value and significance as a critical water source area. The study area includes a fast-growing human settlement footprint in a highly productive farming landscape. There are conflicting development needs as well as risks to agricultural production, and both of these threaten the integrity of the ecosystems which supply underlying services to both demands on the land. Using a multi-disciplinary approach and high-resolution satellite imagery, land use and land cover changes can be detected and classified, and the results used to support the conservation of biodiversity and wildlife, and protect our natural resources. The aim of this research is to study the efficacy of using remote sensing and GIS techniques to detect changes to critical conservation areas where disturbances can be understood, and therefore better managed and mitigated before these areas are degraded beyond repair.

  10. Age and growth of the mutton hamlet Alphestes afer, with a review of the size and age of sex change among epinephelids.

    Science.gov (United States)

    Marques, S; Ferreira, B P

    2016-07-01

    This paper presents results on the age, growth and population structure of a small grouper, the mutton hamlet Alphestes afer, and discusses the observed size and age structure patterns in relation to reproductive strategies among the epinephelids. Ages were determined by examination of sectioned otoliths, which showed a distinct pattern of alternating translucent and opaque zones that formed annually, as validated with tetracycline labelling. The von Bertalanffy growth function was adjusted to the length-at-age data of the males and females, but no significant differences were observed between the resulting parameters. The females, however, were older at given sizes and attained larger sizes and ages, with a maximum observed longevity of 13 years and a total length (LT ) of 26 cm, while the males attained maximum longevities of only 10 years and a 22 cm maximum LT . The LT and age range for the sex change was 16-25 cm and 3-11 years. The total mortality rate (Z) was estimated to be 0·55 for females and 0·82 for males. With the males younger and smaller than the females, this species differed from the pattern commonly observed for protogynous epinephelids. Males had slower growth after maturation, probably due to energy allocation to sperm production during sexual development. This study shows that demography is an important tool to understand the pathways for reproductive strategies in grouper populations. © 2016 The Fisheries Society of the British Isles.

  11. Using Remote Sensing and GIS Techniques to Detect Changes to the Prince Alfred Hamlet Conservation Area in the Western Cape, South Africa

    Science.gov (United States)

    Duncan, P.; Lewarne, M.

    2016-06-01

    Understanding and identifying the spatial-temporal changes in the natural environment is crucial for monitoring and evaluating conservation efforts, as well as understanding the impact of human activities on natural resources, informing responsible land management, and promoting better decision-making. Conservation areas are often under pressure from expanding farming and related industry, invasive alien vegetation, and an ever-increasing human settlement footprint. This study focuses on detecting changes to the Prince Alfred Hamlet commonage, near Ceres in the Cape Floral Kingdom. It was chosen for its high conservation value and significance as a critical water source area. The study area includes a fast-growing human settlement footprint in a highly productive farming landscape. There are conflicting development needs as well as risks to agricultural production, and both of these threaten the integrity of the ecosystems which supply underlying services to both demands on the land. Using a multi-disciplinary approach and high-resolution satellite imagery, land use and land cover changes can be detected and classified, and the results used to support the conservation of biodiversity and wildlife, and protect our natural resources. The aim of this research is to study the efficacy of using remote sensing and GIS techniques to detect changes to critical conservation areas where disturbances can be understood, and therefore better managed and mitigated before these areas are degraded beyond repair.

  12. Perceived Discrimination and Reported Delay of Pharmacy Prescriptions and Medical Tests

    Science.gov (United States)

    Van Houtven, Courtney Harold; Voils, Corrine I; Oddone, Eugene Z; Weinfurt, Kevin P; Friedman, Joëlle Y; Schulman, Kevin A; Bosworth, Hayden B

    2005-01-01

    BACKGROUND Access to health care varies according to a person's race and ethnicity. Delaying treatment is one measure of access with important health consequences. OBJECTIVE Determine whether perceptions of unfair treatment because of race or ethnicity are associated with reported treatment delays, controlling for economic constraints, self-reported health, depression, and demographics. DESIGN Cross-sectional, observational study. PARTICIPANTS A randomly selected community sample of 181 blacks, 148 Latinos, and 193 whites in Durham County, NC. MEASUREMENTS A phone survey conducted in 2002 to assess discrimination, trust in medical care, quality of care, and access to care. Treatment delays were measured by whether or not a person reported delaying or forgoing filling a prescription and delaying or forgoing having a medical test/treatment in the past 12 months. Perceived discrimination was measured as unfair treatment in health care and as racism in local health care institutions. RESULTS The odds of delaying filling prescriptions were significantly higher (odds ratio (OR)=2.02) for persons who perceived unfair treatment, whereas the odds of delaying tests or treatments were significantly higher (OR=2.42) for persons who thought racism was a problem in health care locally. People with self-reported depression and people who reported not working had greater odds of delaying both types of care. CONCLUSIONS A prospective cohort study with both personal and macro measures of discrimination, as well as more refined measures of treatment delays, would help us better understand the relationship between perceived discrimination and treatment delays. PMID:16050850

  13. Stability and delay sensitivity of neutral fractional-delay systems.

    Science.gov (United States)

    Xu, Qi; Shi, Min; Wang, Zaihua

    2016-08-01

    This paper generalizes the stability test method via integral estimation for integer-order neutral time-delay systems to neutral fractional-delay systems. The key step in stability test is the calculation of the number of unstable characteristic roots that is described by a definite integral over an interval from zero to a sufficient large upper limit. Algorithms for correctly estimating the upper limits of the integral are given in two concise ways, parameter dependent or independent. A special feature of the proposed method is that it judges the stability of fractional-delay systems simply by using rough integral estimation. Meanwhile, the paper shows that for some neutral fractional-delay systems, the stability is extremely sensitive to the change of time delays. Examples are given for demonstrating the proposed method as well as the delay sensitivity.

  14. [Cost-effectiveness analysis of sofosbuvir, peginterferon and ribavirin in patients with chronic hepatitis C: Early treatment in the initial stage of fibrosis vs. delayed treatment in advanced fibrosis].

    Science.gov (United States)

    Buti, María; Domínguez-Hernández, Raquel; Oyagüez, Itziar; Casado, Miguel Ángel

    2016-01-01

    Cost-effectiveness analysis of sofosbuvir combined with peginterferon alpha-2a and ribavirin (SOF/Peg-IFN/RBV) in early versus advanced fibrosis in previously untreated patients with chronic hepatitis C genotype 1 (CHC-GT1), from the perspective of the Spanish National Health System (NHS). A Markov model was developed to compare lifetime costs and outcomes (life years gained [LYGs] and quality-adjusted life years [QALYs]) of 2 treatment strategies: SOF/Peg-IFN/RBV administered during early fibrosis (mild-moderate fibrosis; F2-F3) or advanced fibrosis (cirrhosis; F4). Efficacy (sustained virologic response), annual transition probabilities, disease management costs and utilities were obtained from the literature. Costs and outcomes were discounted annually at 3%. Direct costs were considered, expressed in Euros (€, 2014). Probabilistic sensitivity analysis (PSA) was also performed. SOF/Peg-IFN/RBV therapy at F2-F3 was more effective (19.12 LYGs and 14.14 QALYs) compared to F4. In a cohort of 1,000 patients, SOF/Peg-IFN/RBV prevented 66 cases of decompensated cirrhosis, 60 hepatocellular carcinomas and 4 liver transplantations compared with therapy in advanced fibrosis. The total lifetime cost of early therapy (€43,263) was less than the cost of treatment in the advanced stage (€49,018). Early therapy was a dominant strategy, more effective and less costly in all simulations. In the PSA analysis, administration of SOF/PEG-IFN/RBV at F2-F3 was dominant in all simulations. Starting SOF/Peg-IFN/RBV therapy at F2-F3, compared with therapy at F4, reduced the incidence of liver disease complications and was associated with cost savings for the Spanish NHS in CHC-GT1 patients. Copyright © 2016 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

  15. Delayed breast implant reconstruction

    DEFF Research Database (Denmark)

    Hvilsom, Gitte B.; Hölmich, Lisbet R.; Steding-Jessen, Marianne

    2012-01-01

    We evaluated the association between radiation therapy and severe capsular contracture or reoperation after 717 delayed breast implant reconstruction procedures (288 1- and 429 2-stage procedures) identified in the prospective database of the Danish Registry for Plastic Surgery of the Breast during...... of radiation therapy was associated with a non-significantly increased risk of reoperation after both 1-stage (HR = 1.4; 95% CI: 0.7-2.5) and 2-stage (HR = 1.6; 95% CI: 0.9-3.1) procedures. Reconstruction failure was highest (13.2%) in the 2-stage procedures with a history of radiation therapy. Breast...... reconstruction approaches other than implants should be seriously considered among women who have received radiation therapy....

  16. Delay tolerant networks

    CERN Document Server

    Gao, Longxiang; Luan, Tom H

    2015-01-01

    This brief presents emerging and promising communication methods for network reliability via delay tolerant networks (DTNs). Different from traditional networks, DTNs possess unique features, such as long latency and unstable network topology. As a result, DTNs can be widely applied to critical applications, such as space communications, disaster rescue, and battlefield communications. The brief provides a complete investigation of DTNs and their current applications, from an overview to the latest development in the area. The core issue of data forward in DTNs is tackled, including the importance of social characteristics, which is an essential feature if the mobile devices are used for human communication. Security and privacy issues in DTNs are discussed, and future work is also discussed.

  17. Observations on early and delayed colostomy closure.

    Science.gov (United States)

    Tade, A O; Salami, B A; Ayoade, B A

    2011-06-01

    Traditional treatment of a variety of colorectal pathologies had included a diverting colostomy that was closed eight or more weeks later during a readmission. The aim of this retrospective study was to determine the outcomes of early colostomy closure and delayed colostomy closure in patients with temporary colostomies following traumatic and non-traumatic colorectal pathologies. In this study early colostomy closure was the closure of a colostomy within three weeks of its construction, while delayed colostomy closure referred to closure after 3 weeks. Complete records of the 37 adult patients who had temporary colostomy constructed and closed between Jan. 1997 December 2003 for various colorectal pathologies were studied. Fourteen patients had early colostomy closure while 23 had delayed closure. In the early colostomy closure group there were 10 men and 4 women. The mean age of the patients was 28yr with a range of 18-65yr. Colostomies were closed 9-18 days after initial colostomy construction. There was no mortality. Morbidity rate 28.6% (4 out of 14). There were two faecal fistulas (14.3%). Twenty-three patients had delayed colostomy closure 8 weeks to 18 months after initial colostomy construction. These were patients unfit for early surgery after initial colostomy construction because of carcinoma, significant weight loss, or sepsis. There was no mortality. Morbidity rate was 26.1%. There were 3 faecal fistulas (13.2%). Outcomes following early colostomy closure and delayed closure were comparable. Patients fit for surgery should have early closure whilst patients who may have compromised health should have delayed closure.

  18. Atraso no amadurecimento de atemoia cv. African Pride após tratamento pós-colheita com 1-metilciclopropeno Delay in ripening of African Pride atemoya fruits after postharvest treatment with 1-methylcyclopropene

    Directory of Open Access Journals (Sweden)

    Maria Auxiliadora Coêlho de Lima

    2010-09-01

    Full Text Available Atemoias cv. African Pride foram colhidas na maturidade fisiológica com o objetivo de avaliar a influência da aplicação de 1-metilciclopropeno (1-MCP sobre a maturação pós-colheita. Foram testados: doses de 1-MCP (0, 100, 200 e 400 nL.L-1; e tempo de armazenamento (0, 8 e 15 dias sob refrigeração, a 14,5 ± 2,0 ºC e 60 ± 6% de UR, seguidos de 2, 4 e 5 dias a 23,8 ± 2,0 ºC e 65 ± 5% UR. O delineamento experimental foi inteiramente casualizado, em fatorial 4x 6 (dose de 1-MCPx tempo de armazenamento e quatro repetições. Apesar da interação estatisticamente significativa entre os fatores sobre a perda de massa, as diferenças entre tratamentos em cada avaliação não foram superiores a 1,3%. Os frutos tratados apresentaram-se mais firmes, com acidez titulável ligeiramente maior e atraso inicial no acúmulo de sólidos solúveis. A redução no conteúdo de pectina somente foi observada a partir do 15º dia, quando já havia ocorrido a maior taxa de amaciamento. A aparência também foi preservada pelo 1-MCP, verificando-se, nos frutos tratados, ausência de manchas e/ou microrganismos até o 17º dia. A dose de 200 nL.L-1 foi a mais eficiente, pois atrasou a perda de firmeza e manteve o teor de pectina ligeiramente maior.Atemoya fruits (cv. African Pride were harvested at physiological maturity stage with the objective of evaluating the influence of 1-methylcyclopropene (1-MCP application on postharvest maturation. The following parameters were analyzed: 1-MCP doses (0, 100, 200 and 400 nL.L-1 and time of storage (0, 8 and 15 days under refrigeration, at 14.5 ± 2.0 ºC and 60 ± 6% RH, followed by 2, 4, and 5 days at 23.8 ± 2.0 ºC and 65 ± 5% RH. The experimental design was completely randomized, in a 4x 5 (dose of 1-MCPx time of storage factorial with four replications. Besides the statistically significant interaction between the factors on weight loss, the differences among the treatments in each evaluation were not

  19. RETARDAMENTO DA MATURAÇÃO DE MAÇÃS 'FUJI' PELO TRATAMENTO COM 1-MCP E MANEJO DA TEMPERATURA DELAYING 'FUJI' APPLE RIPENING BY 1-MCP TREATMENT AND MANAGEMENT OF STORAGE TEMPERATURE

    Directory of Open Access Journals (Sweden)

    LUIZ CARLOS ARGENTA

    2001-08-01

    Full Text Available Maçãs cv. Fuji foram tratadas com 42 mimol·m-3 de 1-metilciclopropeno (1-MCP por 24 h a 20°C, um dia após a colheita, e então armazenadas a 0; 10 ou 20ºC por 70 dias. Tratamento com 1-MCP efetivamente retardou a maturação de maçãs 'Fuji'. 1-MCP reduziu a taxa respiratória dos frutos mantidos a 10 e 20ºC e inibiu a produção de etileno dos frutos mantidos nas três temperaturas de armazenagem. Frutos tratados com 1-MCP e armazenados a 20ºC exibiram taxas respiratórias similares ou inferiores àquelas de frutos-controle armazenados a 10ºC. Quando armazenados a 10 ou 20ºC, frutos tratados com 1-MCP preservaram mais a firmeza da polpa e a acidez titulável e exibiram menor amarelecimento da epiderme que frutos-controle. Entretanto, não houve benefícios significativos do tratamento 1-MCP sobre a conservação da qualidade dos frutos armazenados a 0ºC no período de 70 dias após a colheita. Os resultados indicam que o tratamento com 1-MCP pode ser uma estratégia para o aumento da conservação de maçãs cv. Fuji durante o transporte e a distribuição sob 10 ou 20ºC. O prolongamento da armazenagem a 20ºC por período superior a 40 dias pode ser limitado pelo murchamento dos frutos e desenvolvimento de podridões.'Fuji' apples were treated with 42 mumol·m-3 of 1-methylcyclopropene (1-MCP for 24 h at 20°C then stored at 0, 10 or 20 ºC for 70 days. MCP treatment reduced respiration on fruit held at 10 and 20 ºC and inhibited ethylene production regardless of storage temperature. Treated fruits held at 20ºC presented respiration rate similar to those of untreated fruits held at 10ºC. For fruit held at 10 or 20ºC, MCP treatment inhibited softening, loss of acidity and color changes on fruit surface. However, there was no considerable benefit of 1-MCP treatment on maintenance of fruit quality during short-term (70 days and storage at 0ºC. Results indicated that 1-MCP is an effective mean to delay ripening and to retain

  20. Location Estimation using Delayed Measurements

    DEFF Research Database (Denmark)

    Bak, Martin; Larsen, Thomas Dall; Nørgård, Peter Magnus

    1998-01-01

    When combining data from various sensors it is vital to acknowledge possible measurement delays. Furthermore, the sensor fusion algorithm, often a Kalman filter, should be modified in order to handle the delay. The paper examines different possibilities for handling delays and applies a new techn...... technique to a sensor fusion system for estimating the location of an autonomous guided vehicle. The system fuses encoder and vision measurements in an extended Kalman filter. Results from experiments in a real environment are reported...

  1. Delayed Complications After Transsphenoidal Surgery for Pituitary Adenomas.

    Science.gov (United States)

    Alzhrani, Gmaan; Sivakumar, Walavan; Park, Min S; Taussky, Philipp; Couldwell, William T

    2018-01-01

    Perioperative complications after transsphenoidal surgery for pituitary adenomas have been well documented in the literature; however, some complications can occur in a delayed fashion postoperatively, and reports are sparse about their occurrence, management, and outcome. Here, we describe delayed complications after transsphenoidal surgery and discuss the incidence, temporality from the surgery, and management of these complications based on the findings of studies that reported delayed postoperative epistaxis, delayed postoperative cavernous carotid pseudoaneurysm formation and rupture, vasospasm, delayed symptomatic hyponatremia, hypopituitarism, hydrocephalus, and sinonasal complications. Our findings from this review revealed an incidence of 0.6%-3.3% for delayed postoperative epistaxis at 1-3 weeks postoperatively, 18 reported cases of delayed carotid artery pseudoaneurysm formation at 2 days to 10 years postoperatively, 30 reported cases of postoperative vasospasm occurring 8 days postoperatively, a 3.6%-19.8% rate of delayed symptomatic hyponatremia at 4-7 days postoperatively, a 3.1% rate of new-onset hypopituitarism at 2 months postoperatively, and a 0.4%-5.8% rate of hydrocephalus within 2.2 months postoperatively. Sinonasal complications are commonly reported after transsphenoidal surgery, but spontaneous resolutions within 3-12 months have been reported. Although the incidence of some of these complications is low, providing preoperative counseling to patients with pituitary tumors regarding these delayed complications and proper postoperative follow-up planning is an important part of treatment planning. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Modeling delay in genetic networks: from delay birth-death processes to delay stochastic differential equations.

    Science.gov (United States)

    Gupta, Chinmaya; López, José Manuel; Azencott, Robert; Bennett, Matthew R; Josić, Krešimir; Ott, William

    2014-05-28

    Delay is an important and ubiquitous aspect of many biochemical processes. For example, delay plays a central role in the dynamics of genetic regulatory networks as it stems from the sequential assembly of first mRNA and then protein. Genetic regulatory networks are therefore frequently modeled as stochastic birth-death processes with delay. Here, we examine the relationship between delay birth-death processes and their appropriate approximating delay chemical Langevin equations. We prove a quantitative bound on the error between the pathwise realizations of these two processes. Our results hold for both fixed delay and distributed delay. Simulations demonstrate that the delay chemical Langevin approximation is accurate even at moderate system sizes. It captures dynamical features such as the oscillatory behavior in negative feedback circuits, cross-correlations between nodes in a network, and spatial and temporal information in two commonly studied motifs of metastability in biochemical systems. Overall, these results provide a foundation for using delay stochastic differential equations to approximate the dynamics of birth-death processes with delay.

  3. Modeling delay in genetic networks: From delay birth-death processes to delay stochastic differential equations

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Chinmaya; López, José Manuel; Azencott, Robert; Ott, William [Department of Mathematics, University of Houston, Houston, Texas 77004 (United States); Bennett, Matthew R. [Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77204, USA and Institute of Biosciences and Bioengineering, Rice University, Houston, Texas 77005 (United States); Josić, Krešimir [Department of Mathematics, University of Houston, Houston, Texas 77004 (United States); Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204 (United States)

    2014-05-28

    Delay is an important and ubiquitous aspect of many biochemical processes. For example, delay plays a central role in the dynamics of genetic regulatory networks as it stems from the sequential assembly of first mRNA and then protein. Genetic regulatory networks are therefore frequently modeled as stochastic birth-death processes with delay. Here, we examine the relationship between delay birth-death processes and their appropriate approximating delay chemical Langevin equations. We prove a quantitative bound on the error between the pathwise realizations of these two processes. Our results hold for both fixed delay and distributed delay. Simulations demonstrate that the delay chemical Langevin approximation is accurate even at moderate system sizes. It captures dynamical features such as the oscillatory behavior in negative feedback circuits, cross-correlations between nodes in a network, and spatial and temporal information in two commonly studied motifs of metastability in biochemical systems. Overall, these results provide a foundation for using delay stochastic differential equations to approximate the dynamics of birth-death processes with delay.

  4. Modeling delay in genetic networks: From delay birth-death processes to delay stochastic differential equations

    International Nuclear Information System (INIS)

    Gupta, Chinmaya; López, José Manuel; Azencott, Robert; Ott, William; Bennett, Matthew R.; Josić, Krešimir

    2014-01-01

    Delay is an important and ubiquitous aspect of many biochemical processes. For example, delay plays a central role in the dynamics of genetic regulatory networks as it stems from the sequential assembly of first mRNA and then protein. Genetic regulatory networks are therefore frequently modeled as stochastic birth-death processes with delay. Here, we examine the relationship between delay birth-death processes and their appropriate approximating delay chemical Langevin equations. We prove a quantitative bound on the error between the pathwise realizations of these two processes. Our results hold for both fixed delay and distributed delay. Simulations demonstrate that the delay chemical Langevin approximation is accurate even at moderate system sizes. It captures dynamical features such as the oscillatory behavior in negative feedback circuits, cross-correlations between nodes in a network, and spatial and temporal information in two commonly studied motifs of metastability in biochemical systems. Overall, these results provide a foundation for using delay stochastic differential equations to approximate the dynamics of birth-death processes with delay

  5. Systematic of delayed neutron parameters

    International Nuclear Information System (INIS)

    Isaev, S.G.; Piksaikin, V.M.

    2000-01-01

    The experimental studies of the energy dependence of the delayed neutron (DN) parameters for various fission systems has shown that the behaviour of a some combination of delayed neutron parameters has a similar features. On the basis of this findings the systematics of delayed neutron experimental data for thorium, uranium, plutonium and americium isotopes have been investigated with the purpose to find a correlation of DN parameters with characteristics of fissioning system as well as a correlation between the delayed neutron parameters themselves. It was presented the preliminary results which were obtained during study the physics interpretation of the results [ru

  6. Time Delay of CGM Sensors

    Science.gov (United States)

    Schmelzeisen-Redeker, Günther; Schoemaker, Michael; Kirchsteiger, Harald; Freckmann, Guido; Heinemann, Lutz; del Re, Luigi

    2015-01-01

    Background: Continuous glucose monitoring (CGM) is a powerful tool to support the optimization of glucose control of patients with diabetes. However, CGM systems measure glucose in interstitial fluid but not in blood. Rapid changes in one compartment are not accompanied by similar changes in the other, but follow with some delay. Such time delays hamper detection of, for example, hypoglycemic events. Our aim is to discuss the causes and extent of time delays and approaches to compensate for these. Methods: CGM data were obtained in a clinical study with 37 patients with a prototype glucose sensor. The study was divided into 5 phases over 2 years. In all, 8 patients participated in 2 phases separated by 8 months. A total number of 108 CGM data sets including raw signals were used for data analysis and were processed by statistical methods to obtain estimates of the time delay. Results: Overall mean (SD) time delay of the raw signals with respect to blood glucose was 9.5 (3.7) min, median was 9 min (interquartile range 4 min). Analysis of time delays observed in the same patients separated by 8 months suggests a patient dependent delay. No significant correlation was observed between delay and anamnestic or anthropometric data. The use of a prediction algorithm reduced the delay by 4 minutes on average. Conclusions: Prediction algorithms should be used to provide real-time CGM readings more consistent with simultaneous measurements by SMBG. Patient specificity may play an important role in improving prediction quality. PMID:26243773

  7. Diagnosis delay in Libyan female breast cancer.

    Science.gov (United States)

    Ermiah, Eramah; Abdalla, Fathi; Buhmeida, Abdelbaset; Larbesh, Entesar; Pyrhönen, Seppo; Collan, Yrjö

    2012-08-21

    To study the diagnosis delay and its impact on stage of disease among women with breast cancer on Libya. 200 women, aged 22 to 75 years with breast cancer diagnosed during 2008-2009 were interviewed about the period from the first symptoms to the final histological diagnosis of breast cancer. This period (diagnosis time) was categorized into 3 periods: 6 months. If diagnosis time was longer than 3 months, the diagnosis was considered delayed (diagnosis delay). Consultation time was the time taken to visit the general practitioner after the first symptoms. Retrospective preclinical and clinical data were collected on a form (questionnaire) during an interview with each patient and from medical records. The median of diagnosis time was 7.5 months. Only 30.0% of patients were diagnosed within 3 months after symptoms. 14% of patients were diagnosed within 3-6 months and 56% within a period longer than 6 months. A number of factors predicted diagnosis delay: Symptoms were not considered serious in 27% of patients. Alternative therapy (therapy not associated with cancer) was applied in 13.0% of the patients. Fear and shame prevented the visit to the doctor in 10% and 4.5% of patients, respectively. Inappropriate reassurance that the lump was benign was an important reason for prolongation of the diagnosis time. Diagnosis delay was associated with initial breast symptom(s) that did not include a lump (p diagnosis, the clinical stage distribution was as follows: 9.0% stage I, 25.5% stage II, 54.0% stage III and 11.5% stage IV.Diagnosis delay was associated with bigger tumour size (p Diagnosis delay is very serious problem in Libya. Diagnosis delay was associated with complex interactions between several factors and with advanced stages. There is a need for improving breast cancer awareness and training of general practitioners to reduce breast cancer mortality by promoting early detection. The treatment guidelines should pay more attention to the early phases of breast

  8. Prevalence and determinants of delay in diagnosis of pulmonary tuberculosis in Darjeeling district of West Bengal

    Directory of Open Access Journals (Sweden)

    Sibasis Das

    2017-01-01

    Full Text Available Background: Delayed diagnosis of tuberculosis (TB is a significant problem both in individual as well as community level. Different studies around globe revealed that these diagnostic delays are attributed to both patient delay and health system-related delay. Aims: This study aims to assess the magnitude of delay in diagnosis and the association with sociodemographic profile among new sputum-positive pulmonary TB patients in Darjeeling district. Materials and Methods: A cross-sectional study was conducted among 374 TB patients from October 2011 to March 2012 using a predesigned pretested schedule by face-to-face interview. Statistical Analysis: Logistic regression analysis, odds ratios (OR, adjusted ORs. Results: Patient delay, health system delay and total diagnostic delay were 27 days, 20.1 days, and 20.6 days; mean delays were 23.64, 5.71, and 29.46 days, and median delays were 25, 5, and 32 days, respectively. Risk factors associated with patient delay were female gender, rural residence, illiteracy, smoking, alcohol consumption, taking two, or more alternate treatments; for health system delay were female sex, rural residence, time to reach health facility, time spent per visit; and for total diagnostic delay were female sex, alcoholism, and seeking more than two alternate treatment. Conclusions: The risk factors for delay identified may be the subject of future interventions.

  9. Moments of the Wigner delay times

    International Nuclear Information System (INIS)

    Berkolaiko, Gregory; Kuipers, Jack

    2010-01-01

    The Wigner time delay is a measure of the time spent by a particle inside the scattering region of an open system. For chaotic systems, the statistics of the individual delay times (whose average is the Wigner time delay) are thought to be well described by random matrix theory. Here we present a semiclassical derivation showing the validity of random matrix results. In order to simplify the semiclassical treatment, we express the moments of the delay times in terms of correlation functions of scattering matrices at different energies. In the semiclassical approximation, the elements of the scattering matrix are given in terms of the classical scattering trajectories, requiring one to study correlations between sets of such trajectories. We describe the structure of correlated sets of trajectories and formulate the rules for their evaluation to the leading order in inverse channel number. This allows us to derive a polynomial equation satisfied by the generating function of the moments. Along with showing the agreement of our semiclassical results with the moments predicted by random matrix theory, we infer that the scattering matrix is unitary to all orders in the semiclassical approximation.

  10. [Vectorial transmission of malaria in a village along the Niger River and its fishing hamlet (Kéniéroba and Fourda, Mali)].

    Science.gov (United States)

    Keïta, M; Baber, I; Sogoba, N; Maïga, H M; Diallo, M'b; Doumbia, S; Traoré, S F

    2014-12-01

    A better understanding of malaria transmission dynamics is an essential element in the development of any targeted vector control strategy. The objective of this study was to better understand malaria transmission dynamics along the Niger River in Sudan savanna zone of Mali. Trough cross-sectional surveys, Anopheline larvae were collected by WHO standard dipping technique, and vector adults by Human Landing and pyrethrum spray catches methods. The vector population was composed of An. gambiae s.l. (> 99%) and An. funestus (hamlet Fourda) compared to farther inland Kéniéroba. The average infection rate of An. gambiae s.l. was 3.63% and 4.06% in Kéniéroba and Fourda respectively. The average entomological inoculation rate (EIR) during the study period was almost similar in Kéniéroba (0.70 infective bites/person/month) and Fourda (0.69 infective bites/person/month). The means EIRs over each of the rainy season 2006 and 2007 were always higher than the one of the dry season 2007 in both localities, with much smaller amplitude in Fourda than in Kéniéroba. However, the level of the transmission was 2.31 (0.37/0.16) times higher in Fourda than in Kéniéroba during the dry season.We conclude that in Sudan savanna zone of Mali, malaria transmission along the river is continuous throughout the year, but it is more intense in the immediate vicinity of the river during the dry season than during the rainy season in opposition to more distant localities to the river and vector control should not be focused only on the rainy in such setting.

  11. On the form of the forgetting function: the effects of arithmetic and logarithmic distributions of delays.

    Science.gov (United States)

    Sargisson, Rebecca J; White, K Geoffrey

    2003-11-01

    Forgetting functions with 18 delay intervals were generated for delayed matching-to-sample performance in pigeons. Delay interval variation was achieved by arranging five different sets of five delays across daily sessions. In different conditions, the delays were distributed in arithmetic or logarithmic series. There was no convincing evidence for different effects on discriminability of the distributions of different delays. The mean data were better fitted by some mathematical functions than by others, but the best-fitting functions depended on the distribution of delays. In further conditions with a fixed set of five delays, discriminability was higher with a logarithmic distribution of delays than with an arithmetic distribution. This result is consistent with the treatment of the forgetting function in terms of generalization decrement.

  12. Delay in the diagnosis of cancer

    DEFF Research Database (Denmark)

    Hansen, Rikke Pilegaard

    for a detailed description of the patients' diagnostic pathways, allowing the researchers to draw the time line from symptom onset to treatment start, and to describe the characteristics of the patients and the GPs. Existing scales were used whenever possible; otherwise, ad hoc questions were constructed....... Chaper 1 introduces the concept of delay in the diagnosis of cancer. The chapter aims to provide insight into the time interval from symptom to treatment and into the patient and GP characteristics that potentially influence this interval. In addition, the chapter gives a brief overview of cancer...

  13. Delayed Auditory Feedback and Movement

    Science.gov (United States)

    Pfordresher, Peter Q.; Dalla Bella, Simone

    2011-01-01

    It is well known that timing of rhythm production is disrupted by delayed auditory feedback (DAF), and that disruption varies with delay length. We tested the hypothesis that disruption depends on the state of the movement trajectory at the onset of DAF. Participants tapped isochronous rhythms at a rate specified by a metronome while hearing DAF…

  14. #FakeNobelDelayReasons

    CERN Multimedia

    2013-01-01

    Tuesday’s hour-long delay of the Nobel Prize in Physics announcement was (and still is) quite the cause for speculation. But on the Twittersphere, it was simply the catalyst for some fantastic puns, so-bad-they're-good physics jokes and other shenanigans. Here are some of our favourite #FakeNobelDelayReasons.    

  15. Picosecond resolution programmable delay line

    International Nuclear Information System (INIS)

    Suchenek, Mariusz

    2009-01-01

    The note presents implementation of a programmable delay line for digital signals. The tested circuit has a subnanosecond delay range programmable with a resolution of picoseconds. Implementation of the circuit was based on low-cost components, easily available on the market. (technical design note)

  16. Effect of caffeine on radiation-induced mitotic delay: delayed expression of G2 arrest

    International Nuclear Information System (INIS)

    Rowley, R.; Zorch, M.; Leeper, D.B.

    1984-01-01

    In the presence of 5 mM caffeine, irradiated (1.5 Gy) S and G 2 cells progressed to mitosis in register and without arrest in G 2 . Caffeine (5 mM) markedly reduced mitotic delay even after radiation doses up to 20 Gy. When caffeine was removed from irradiated (1.5 Gy) and caffeine-treated cells, a period of G 2 arrest followed, similar in length to that produced by radiation alone. The arrest expressed was independent of the duration of the caffeine treatment for exposures up to 3 hr. The similarity of the response to the cited effects of caffeine on S-phase delay suggests a common basis for delay induction in S and G 2 phases

  17. Project delay analysis of HRSG

    Science.gov (United States)

    Silvianita; Novega, A. S.; Rosyid, D. M.; Suntoyo

    2017-08-01

    Completion of HRSG (Heat Recovery Steam Generator) fabrication project sometimes is not sufficient with the targeted time written on the contract. The delay on fabrication process can cause some disadvantages for fabricator, including forfeit payment, delay on HRSG construction process up until HRSG trials delay. In this paper, the author is using semi quantitative on HRSG pressure part fabrication delay with configuration plant 1 GT (Gas Turbine) + 1 HRSG + 1 STG (Steam Turbine Generator) using bow-tie analysis method. Bow-tie analysis method is a combination from FTA (Fault tree analysis) and ETA (Event tree analysis) to develop the risk matrix of HRSG. The result from FTA analysis is use as a threat for preventive measure. The result from ETA analysis is use as impact from fabrication delay.

  18. A adaptação como procedimento técnico de tradução: uma leitura descritiva do Hamlet em quadrinhos brasileiro Adaptation as a technical procedure of translation: a descriptive reading of Hamlet in a Brazilian comic book

    Directory of Open Access Journals (Sweden)

    Marcel Alvaro de Amorim

    2013-03-01

    Full Text Available Os procedimentos técnicos da tradução foram identificados pela primeira vez no trabalho de Vinay e Darbelnet ([1958] 1977. Dentre esses procedimentos, o da adaptação foi então descrito, de forma local, como a adequação cultural ou situacional do texto da língua de partida no texto da língua de chegada. Na atualidade, mais que um procedimento local, teóricos como Bastin ([1998] 2011 consideram a prática da adaptação como um procedimento global, que envolve diversos outros procedimentos secundários de tradução. Sendo assim, os objetivos principais deste trabalho foram sistematizar uma categorização dos procedimentos secundários do processo de adaptação e aplicar tal categorização à análise de uma tradução/adaptação da peça Hamlet, de William Shakespeare, para o português brasileiro realizada por Bruno S. R. e ilustrada por Sam Hart, cotejando a com outras traduções estabelecidas da peça sempre que necessário.The technical procedures of translation were first identified in the work of Vinay and Darbelnet ([1958] 1977. Among these procedures, the adaptation was described, locally, as cultural or situational adequacy of the source text in the target culture and language. Currently, more than a local procedure, researchers as Bastin ([1998] 2011 have been considering adaptation as a global one that involves several other secondary procedures in the translation process. Therefore, the main objectives of this study were to categorize the secondary procedures of the adaptation process and apply this categorization to the analysis of a translation/adaptation of the play Hamlet, by William Shakespeare, written by Bruno S. R. and illustrated by Sam Hart, comparing it with other traditional translations of the play whenever necessary.

  19. Delayed radiation neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Nagashima, T.; Miyamoto, K.; Beppu, H.; Hirose, K.; Yamada, K. (Tokyo Metropolitan Neurological Hospital (Japan))

    1981-07-01

    A case of cervical plexus neuropathy was reported in association with chronic radio-dermatitis, myxedema with thyroid adenoma and epiglottic tumor. A 38-year-old man has noticed muscle weakness and wasting of the right shoulder girdle since age 33. A detailed history taking revealed a previous irradiation to the neck because of the cervical lymphadenopathy at age 10 (X-ray 3,000 rads), keroid skin change at age 19, obesity and edema since 26, and hoarseness at 34. Laryngoscopic examination revealed a tumor on the right vocal cord, diagnosed as benign papilloma by histological study. In addition, there were chronic radio-dermatitis around the neck, primary hypothyroidism with a benign functioning adenoma on the right lobe of the thyroid, the right phrenic nerve palsy and the right recurrent nerve palsy. All these lesions were considered to be the late sequellae of radiation to the neck in childhood. Other neurological signs were weakness and amyotrophy of the right shoulder girdle with patchy sensory loss, and areflexia of the right arm. Gross power was fairly well preserved in the right hand. EMG showed neurogenic changes in the tested muscles, suggesting a peripheral nerve lesion. Nerve conduction velocities were normal. No abnormal findings were revealed by myelography and spinal CT. The neurological findings of the patient were compatible with the diagnosis of middle cervical plexus palsy apparently due to late radiation effect. In the literature eight cases of post-radiation neuropathy with a long latency have been reported. The present case with the longest latency after the radiation should be included in the series of the reported cases of ''delayed radiation neuropathy.'' (author).

  20. Delayed radiation neuropathy

    International Nuclear Information System (INIS)

    Nagashima, Toshiko; Miyamoto, Kazuto; Beppu, Hirokuni; Hirose, Kazuhiko; Yamada, Katsuhiro

    1981-01-01

    A case of cervical plexus neuropathy was reported in association with chronic radio-dermatitis, myxedema with thyroid adenoma and epiglottic tumor. A 38-year-old man has noticed muscle weakness and wasting of the right shoulder girdle since age 33. A detailed history taking revealed a previous irradiation to the neck because of the cervical lymphadenopathy at age 10 (X-ray 3,000 rads), keroid skin change at age 19, obesity and edema since 26, and hoarseness at 34. Laryngoscopic examination revealed a tumor on the right vocal cord, diagnosed as benign papilloma by histological study. In addition, there were chronic radio-dermatitis around the neck, primary hypothyroidism with a benign functioning adenoma on the right lobe of the thyroid, the right phrenic nerve palsy and the right recurrent nerve palsy. All these lesions were considered to be the late sequellae of radiation to the neck in childhood. Other neurological signs were weakness and amyotrophy of the right shoulder girdle with patchy sensory loss, and areflexia of the right arm. Gross power was fairly well preserved in the right hand. EMG showed neurogenic changes in the tested muscles, suggesting a peripheral nerve lesion. Nerve conduction velocities were normal. No abnormal findings were revealed by myelography and spinal CT. The neurological findings of the patient were compatible with the diagnosis of middle cervical plexus palsy apparently due to late radiation effect. In the literature eight cases of post-radiation neuropathy with a long latency have been reported. The present case with the longest latency after the radiation should be included in the series of the reported cases of ''delayed radiation neuropathy.'' (author)