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.

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.

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.

Don Quijote y Hamlet

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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

Spaghetti Shakespeare: Johnny Hamlet and the Italian Western

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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.

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

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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.

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

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....

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

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.

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…

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,…

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...

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.

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...

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

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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.

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.

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...

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.

Shaw on Hamlet

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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)

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...

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...

Olivier's 'Essay on Hamlet'

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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.

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.

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.

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.

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.

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.

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.

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.

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

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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.

The Hamlet Project.

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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)

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

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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.

Can misfolded proteins be beneficial? The HAMLET case.

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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.

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.

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

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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)

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

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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.

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

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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.

"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

Ruin and Revolution in ``Hamlet."

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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.

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

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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

Irony in Tennyson's "Little Hamlet".

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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)

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

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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.

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

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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.

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

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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.

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.

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…

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

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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.

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

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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.

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

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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.

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.

Hamlet and psychoanalytic experience.

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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.

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

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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

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

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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…

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

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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.

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

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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.

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

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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.

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

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

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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.

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

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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.

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

"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)

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)

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)

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.

Os Simpsons em Hamlet: um petisco de Shakespeare

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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

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...

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

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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…

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.

Mason & Dixon and Hamlet

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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.

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

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.

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)

Apariencia y realidad en Hamlet y Las Meninas

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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.

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)

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,

Shakespearean Tragedy Revisited: Death in Othello and Hamlet

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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.

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

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.

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)

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...

«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...

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

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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.

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

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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.

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)

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

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 ...

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

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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.

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

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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.

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

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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.

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.

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

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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.

Hamlet on the Macintosh: An Experimental Seminar That Worked.

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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)

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

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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…

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

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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.

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

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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)

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

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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.

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

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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.

Lipids as tumoricidal components of human α-lactalbumin made lethal to tumor cells (HAMLET): unique and shared effects on signaling and death.

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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.

Harriot, Digges, and the Ghost in Hamlet.

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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

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

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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.

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

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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…

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.

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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

Tròpics de Shakespeare : orígens i originalitat del Hamlet català

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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...

HyperHamlet – Intricacies of Data Selection

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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.

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

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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,…

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

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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…

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.

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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.

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

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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…

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

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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

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

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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.

ANÁLISE DOS EFEITOS DE FALA DO CONSELHEIRO REAL EM HAMLET

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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.

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

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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.

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

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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.

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

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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)

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

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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…

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

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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

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

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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).

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

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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.

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...

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

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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.

"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

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

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)

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...

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....

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.

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.

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 ...

Manuel Tamayo y Baus’s Un Drama Nuevo (1867 and the Reception of Hamlet in 19th-Century Spain

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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.

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...

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.

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.

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.

"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…

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.

The Fifth Slovene Hamlet: Return to Tradition?

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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.

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…

The Genius of Shakespeare’s “Plagiarisms”. Case Studies: Hamlet, Othello, King Lear and Macbeth

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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.

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…

"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...

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.

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.

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)

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

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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

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

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.

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.

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…

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

The characters God and Hamlet by Jack Miles

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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.

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.

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

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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.

Questioning the ‘of’ in Performance-as-translation: Multimedia as a Subtext in the 2003 Pécs Performance ‘of’ Hamlet

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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.

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

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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.

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

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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.

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

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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.

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 ...

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

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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.

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

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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

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

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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.

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

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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.

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

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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.

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

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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.

A Novel Initiation Mechanism of Death in Streptococcus pneumoniae Induced by the Human Milk Protein-Lipid Complex HAMLET and Activated during Physiological Death*

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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

A novel initiation mechanism of death in Streptococcus pneumoniae induced by the human milk protein-lipid complex HAMLET and activated during physiological death.

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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.

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

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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.

Gender Identity and Gender Performativity in Shakespeare’s Selected Plays: Macbeth, Hamlet and Merry Wives of Windsor

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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.

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

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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.

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

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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

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.

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

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

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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.

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

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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

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

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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

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

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.

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

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

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.

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.

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.

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.

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...

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.

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.

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 ...

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.

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

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

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

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.

[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.

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

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...

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.  

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.

"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...

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

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

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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.

The Breach and the Observance : Theatre retranslation as a strategy of artistic differentiation, with special reference to retranslations of Shakespeare's Hamlet (1777-2001)

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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.

The Defence of Moratín’s «Hamlet» in the «Continuación del Semanario de Salamanca»

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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.

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

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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

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

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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.

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

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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

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

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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.

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

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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

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

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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.

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

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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.

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

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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.

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

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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.

Speech and Language Delay

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... 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 ...

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)

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

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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.

No need to be HAMLET or BAMLET to interact with histones: binding of monomeric alpha-lactalbumin to histones and basic poly-amino acids.

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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.

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

Oedipus the King and Hamlet: A Descent to the Fathers

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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.

REASONS FOR PATIENT DELAYS & HEALTH SYSTEM DELAYS FOR TUBERCULOSIS IN SOUTH INDIA

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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.

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

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

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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

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

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

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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.

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%.

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)

Analysis of Decadal-Scale Shoreline Change along the Hamlet of Paulatuk (Canadian Arctic), using Landsat Satellite Imagery and GIS techniques from 1984 to 2014.

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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.

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

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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

Hamlet no cinema: as adaptações fílmicas de Laurence Olivier (1948 e Franco Zeffirelli (1990

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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.

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

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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.

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...

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

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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

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

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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.

Transcultural Hamlet: Representations of Ophelia and Gertrud in 21st-century Iran

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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.

Implementación de la estrategia didáctica del desarrollo del pensamiento crítico-reflexivo en el análisis literario de Hamlet de Shakespeare

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Norman Marín-Calderón

2014-01-01

Full Text Available Este ensayo se concentra en el proceso de ejecución del desarrollo del pensamiento crítico- reflexivo como una estrategia didáctica universitaria en la enseñanza de una clase de literatura, más específicamente, de la obra de William Shakespeare, Hamlet (1603. Dicha estrategia se basó en una serie de actividades comunicativas que se propusieron observar el desarrollo de las habilidades cognitivas, el proceso de crítica y análisis, la reflexión personal a través de experiencias vivenciales, así como el desarrollo de técnicas de argumentación y pensamiento crítico de los estudiantes. El propósito en la implementación de la estrategia fue la de potenciar la calidad académica de las producciones críticas y argumentativas de los estudiantes, al momento de analizar Hamlet en tanto texto literario.

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

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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.

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

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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.

Delays in diagnosis and treatment of extrapulmonary tuberculosis in Guatemala.

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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.

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

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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.

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

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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.

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

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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…

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)

Structural characterization of more potent alternatives to HAMLET, a tumoricidal complex of α-lactalbumin and oleic acid.

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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.

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

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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.

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

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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

Immediate versus delayed treatment for recently symptomatic carotid artery stenosis

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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

Delayed orgasm and anorgasmia.

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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.

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...

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

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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.

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

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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.

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

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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

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

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...

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

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

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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.

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

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

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.

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...

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

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....

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

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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

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.

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

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

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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.

The Unbearable Lightness of Memory: From Hamlet, Prince of Denmark to Jorge Luis Borges’ Shakespeare’s Memory

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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.

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.

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

[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.

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.

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

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)

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

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

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

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.

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.

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

A Characeae Cells Plasma Membrane as a Model for Selection of Bioactive Compounds and Drugs: Interaction of HAMLET-Like Complexes with Ion Channels of Chara corallina Cells Plasmalemma.

Science.gov (United States)

Kataev, Anatoly; Zherelova, Olga; Grishchenko, Valery

2016-12-01

Interaction of a HAMLET-like La-OA cytotoxic complex (human α-lactalbumin-oleic acid) and its constituents with the excitable plasmalemma of giant Chara corallina cells was investigated. The voltage-clamp technique was used to study Ca 2+ and Cl - transient currents in the plasmalemma of intact cells. The action of the complex and OA on the target cell membrane has a dose-dependent character. It was found that the La-OA complex has an inhibiting effect on Ca 2+ current across the plasmalemma, while α-lactalbumin alone does not affect the electrophysiological characteristics of the cellular membrane. However, oleic acid blocks Ca 2+ current across the plasmalemma. This is accompanied by the induction of a non-selective conductivity in the cellular membrane, a decrease in the resting potential and plasma membrane resistance of algal cells. We propose that the cytotoxicity of La-OA and other HAMLET-like complexes is determined by oleic acid acting as a blocker of potential-dependent Ca 2+ channels in the plasma membrane of target cells. The presented results show that the study model of green algae C. corallina cells plasmalemma is a convenient tool for the investigation of ion channels in many animal cells.

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 ...

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

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

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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

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.

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.

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.

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

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

'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.

Choice between delayed food and immediate oxycodone in rats.

Science.gov (United States)

Secci, Maria E; Factor, Julie A; Schindler, Charles W; Panlilio, Leigh V

2016-12-01

The choice to seek immediate drug effects instead of more meaningful but delayed rewards is a defining feature of addiction. To develop a rodent model of this behavior, we allowed rats to choose between immediate intravenous delivery of the prescription opioid oxycodone (50 μg/kg) and delayed delivery of palatable food pellets. Rats preferred food at delays up to 30 s, but they chose oxycodone and food equally at 60-s delay and preferred oxycodone over food at 120-s delay. Comparison of food-drug choice, food-only, and drug-only conditions indicated that food availability decreased drug intake, but drug availability increased food intake. In the food-only condition, food was effective as a reinforcer even when delayed by 120 s. Pre-session feeding with chow slowed acquisition of food and drug self-administration, but did not affect choice. To establish procedures for testing potential anti-addiction medications, noncontingent pre-treatment with oxycodone or naltrexone (analogous to substitution and antagonist therapies, respectively) were tested on a baseline in which oxycodone was preferred over delayed food. Naltrexone pre-treatment decreased drug intake and increased food intake. Oxycodone pre-treatment decreased drug intake, but also produced extended periods with no food or drug responding. These findings show that the contingencies that induce preference for drugs over more meaningful but less immediate rewards in humans can be modeled in rodents, and they suggest that the model could be useful for assessing the therapeutic potential of treatments and exploring the underlying behavioral and neural mechanisms involved in addiction.

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.

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.

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.

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.

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.

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

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

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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

[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.

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…

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...

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

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

[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.

Neurodevelopmental delay in children exposed in utero to hyperemesis gravidarum.

Science.gov (United States)

Fejzo, Marlena S; Magtira, Aromalyn; Schoenberg, Frederic Paik; Macgibbon, Kimber; Mullin, Patrick M

2015-06-01

The purpose of this study is to determine the frequency of emotional, behavioral, and learning disorders in children exposed in utero to hyperemesis gravidarum (HG) and to identify prognostic factors for these disorders. Neurodevelopmental outcomes of 312 children from 203 mothers with HG were compared to neurodevelopmental outcomes from 169 children from 89 unaffected mothers. Then the clinical profiles of patients with HG and a normal child outcome were compared to the clinical profiles of patients with HG and a child with neurodevelopmental delay to identify prognostic factors. Binary responses were analyzed using either a Chi-square or Fisher Exact test and continuous responses were analyzed using a t-test. Children exposed in utero to HG have a 3.28-fold increase in odds of a neurodevelopmental diagnosis including attention disorders, learning delay, sensory disorders, and speech and language delay (Pneurodevelopmental delay. We found no evidence for increased risk of 13 emotional, behavioral, and learning disorders, including autism, intellectual impairment, and obsessive-compulsive disorder. However, the study was not sufficiently powered to detect rare conditions. Medications, treatments, and preterm birth were not associated with an increased risk for neurodevelopmental delay. Women with HG are at a significantly increased risk of having a child with neurodevelopmental delay. Common antiemetic treatments were not linked to neurodevelopmental delay, but early symptoms may play a role. There is an urgent need to address whether aggressive treatment that includes vitamin and nutrient supplementation in women with early symptoms of severe nausea of pregnancy decreases the risk of neurodevelopmental delay. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

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.

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.

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

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.

Patient and health system delay among patients with pulmonary tuberculosis in Beira city, Mozambique.

Science.gov (United States)

Saifodine, Abuchahama; Gudo, Paula Samo; Sidat, Mohsin; Black, James

2013-06-07

TB control is based on the rapid identification of cases and their effective treatment. However, many studies have shown that there are important delays in diagnosis and treatment of patients with TB. The purpose of this study was to assess the prevalence of and identify risk factors associated with patient delay and health system delay among newly diagnosed patients with pulmonary TB. A cross sectional study was carried out in Beira city, Mozambique between September 2009 and February 2010. Patients in the first month of treatment were consecutively selected to this study if they had a diagnosis of pulmonary TB, had no history of previous TB treatment, and were 18 years or older and provided informed consent. Data was obtained through a questionnaire administered to the patients and from patients' files. Among the 622 patients included in the study the median age was 32 years (interquartile range, 26-40) and 272 (43.7%) were females. The median total delay, patient delay and health system delay was 150 days (interquartile range, 91-240), 61 days (28-113) and 62 days (37-120), respectively. The contribution of patient delay and health system delay to total delay was similar. Farming, visiting first a traditional healer, low TB knowledge and coexistence of a chronic disease were associated with increased patient delay. More than two visits to a health facility, farming and coexistence of a chronic disease were associated with increased health system delay. This study revealed a long total delay with a similar contribution of patient delay and health system delay. To reduce the total delay in this setting we need a combination of interventions to encourage patients to seek appropriate health care earlier and to expedite TB diagnosis within the health care system.

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

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.

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.)

Epidemiology, diagnostic delay and outcome of tuberculosis in North Jutland, Denmark

DEFF Research Database (Denmark)

Andersen, Rosa M Ø; Bjørn-Præst, Simon O; Oren Gradel, Kim

2011-01-01

The objective of this study was to evaluate the clinical outcome of tuberculosis (TB) with regards to epidemiology, symptoms, delay, diagnostics, use of HIV-test, treatment, treatment outcome and mortality in the North Jutland Region from 2000 through 2008.......The objective of this study was to evaluate the clinical outcome of tuberculosis (TB) with regards to epidemiology, symptoms, delay, diagnostics, use of HIV-test, treatment, treatment outcome and mortality in the North Jutland Region from 2000 through 2008....

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.

The delaying effect of stigma on mental health help-seeking in Sri Lanka.

Science.gov (United States)

Fernando, Sunera M; Deane, Frank P; McLeod, Hamish J

2017-03-01

Mental health stigma has been associated with delays in seeking treatment. To describe perceived stigma experienced by patients and carers in Sri Lanka and to determine the effects of stigma on help-seeking delay. Survey of outpatients and family carers (n = 118 dyads) attending two psychiatric hospitals in Sri Lanka, using the Disclosure and Discrimination subscales of the Stigma Scale. Stigma was positively related to help-seeking delay for carers but not patients. Public stigma experienced by carers accounted for 23% of the variance in help-seeking delay. Reducing stigma may reduce help-seeking delays during the course of treatment. © 2016 John Wiley & Sons Australia, Ltd.

Factors influencing diagnosis delay of advanced breast cancer in Moroccan women.

Science.gov (United States)

Maghous, A; Rais, F; Ahid, S; Benhmidou, N; Bellahamou, K; Loughlimi, H; Marnouche, E; Elmajjaoui, S; Elkacemi, H; Kebdani, T; Benjaafar, N

2016-06-07

Delay in the diagnosis of breast cancer in symptomatic women of 3 months or more is associated with advanced stage and low survival. We conducted this study to learn more about the extent and reasons behind diagnosis delay of advanced breast cancer in Moroccan women. A group of patients with advanced breast cancer were interviewed at the National Institute of Oncology in Rabat during the period from February to December 2014. Diagnosis delay was devised into patient delay and system delay. Patient delay was defined as time from first symptoms until first medical consultation. System delay was defined as time from first presentation to a health care provider until definite diagnosis or treatment. Prospective information and clinical data were collected on a form during an interview with each patient and from medical records. In all, 137 patients were interviewed. The mean age of women was 48.3 ± 10.4 years. The median of consultation time was 6[4,12] months and the median of diagnosis time was 1[1,3] months. Diagnosis delay was associated to a personal reason in 96 (70.1 %) patients and to a medical reason in 19 (13.9 %) patients. A number of factors predicted diagnosis delay: symptoms were not considered serious in 66 (55.9 %) patients; traditional therapy was applied in 15 (12.7 %) patients and fear of cancer diagnosis and/or treatment in 14 (11.9 %) patients. A use of traditional methods was significantly associated with rural residence and far away from basic health center (p = 0.000). Paradoxically, a family history of breast cancer was significantly higher in who report a fear of cancer diagnosis and/or treatment to diagnosis delay (p Diagnosis delay is very serious problem in Morocco. Diagnosis delay was associated with complex interactions between several factors and with advanced stages. There is a need for improving breast cancer information in our populations and training of general practitioners to reduce advanced breast cancer by

Using Video to Bridge the Gap Between Problem Behavior and a Delayed Time-out Procedure.

Science.gov (United States)

Coppage, Sara; Meindl, James N

2017-09-01

Treatment plans focused on problem behavior often include punishment contingencies to decrease problem behavior. Immediate punishers are typically more effective than delayed punishers, but immediate delivery of a punisher is not always possible. Strategies need to be developed to increase the suppressive effects of delayed punishers. This study demonstrated the effectiveness of a treatment package involving replaying a video recording of problem behavior immediately before delivering a 15 min delayed time-out. This treatment package may prove to be an accessible and inexpensive strategy when using delayed punishers.

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

[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.

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.

Assessment of Confounding in Studies of Delay and Survival

DEFF Research Database (Denmark)

Tørring, Marie Louise; Vedsted, Peter; Frydenberg, Morten

BACKGROUND: Whether longer time to diagnosis (diagnostic delay) in patients with cancer symptoms is directly and independently associated with poor prognosis cannot be determined in randomised controlled trials. Analysis of observational data is therefore necessary. Many previous studies of the i......BACKGROUND: Whether longer time to diagnosis (diagnostic delay) in patients with cancer symptoms is directly and independently associated with poor prognosis cannot be determined in randomised controlled trials. Analysis of observational data is therefore necessary. Many previous studies......) Clarify which factors are considered confounders or intermediate variables in the literature. 2) Assess how and to what extent these factors bias survival estimates. CONSIDERATIONS: As illustrated in Figure 1, symptoms of cancer may alert patients, GP's, and hospital doctors differently and influence both...... delay and survival time in different ways. We therefore assume that the impact of confounding factors depends on the type of delay studied (e.g., patient delay, GP delay, referral delay, or treatment delay). MATERIALS & METHODS: The project includes systematic review and methodological developments...

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.

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.

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

Disparities in breast cancer surgery delay: the lingering effect of race.

Science.gov (United States)

Sheppard, Vanessa B; Oppong, Bridget A; Hampton, Regina; Snead, Felicia; Horton, Sara; Hirpa, Fikru; Brathwaite, Echo J; Makambi, Kepher; Onyewu, S; Boisvert, Marc; Willey, Shawna

2015-09-01

Delays to surgical breast cancer treatment of 90 days or more may be associated with greater stage migration. We investigated racial disparities in time to receiving first surgical treatment in breast cancer patients. Insured black (56 %) and white (44 %) women with primary breast cancer completed telephone interviews regarding psychosocial (e.g., self-efficacy) and health care factors (e.g., communication). Clinical data were extracted from medical charts. Time to surgery was measured as the days between diagnosis and definitive surgical treatment. We also examined delays of more than 90 days. Unadjusted hazard ratios (HRs) examined univariate relationships between delay outcomes and covariates. Cox proportional hazard models were used for multivariate analyses. Mean time to surgery was higher in blacks (mean 47 days) than whites (mean 33 days; p = .001). Black women were less likely to receive therapy before 90 days compared to white women after adjustment for covariates (HR .58; 95 % confidence interval .44, .78). Health care process factors were nonsignificant in multivariate models. Women with shorter delay reported Internet use (vs. not) and underwent breast-conserving surgery (vs. mastectomy) (p interventions to address delay are needed.

Is immediate adjunctive CBT more beneficial than delayed CBT in treating depression?: A Pilot Study.

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Rizvi, Sakina J; Zaretsky, Ari; Schaffer, Ayal; Levitt, Anthony

2015-03-01

Cognitive-behavioral therapy (CBT) is an efficacious first-line therapy for patients with major depressive disorder (MDD). Due to the limited accessibility of CBT, long wait lists result in delayed treatment, which may affect treatment outcomes. The goal of this pilot study was to obtain preliminary data from a randomized controlled trial to determine whether delayed CBT reduces the effectiveness of the therapy compared to immediate CBT in patients with MDD receiving pharmacotherapy. Patients were randomized to receive immediate CBT (n=18) or to begin CBT after 6 months (n=20) and received 14 weekly sessions, followed by two additional booster sessions. During the active treatment months, patients in the immediate group demonstrated reductions in scores on the Beck Depression Inventory II (BDI-II) that were similar to those in the delayed CBT group. However, when the analysis was performed using only data from patients in the delayed group who were still in a depressive episode, there was an overall greater decrease in BDI-II scores in the immediate group vs. the delayed group over the active treatment months, but not specifically at the 6-month endpoint. These findings suggest delays in depression treatment, similar to what occurs with real-world wait list times, may not have a significant impact on the effectiveness of CBT in patients who are already receiving treatment as usual. However, such delays may affect the effectiveness of CBT in those patients who remain depressed during the time delay. A larger trial is necessary to confirm these findings. (Journal of Psychiatric Practice 2015;21:107-113).

Delayed encephalopathy after acute carbon monoxide poisoning

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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.

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

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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.

Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children

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Sijuade Abayomi

2010-02-01

Full Text Available Abstract Background Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children. Methods The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008. Results 1,237 of 2,752 children (45% had delay in parasite clearance. Overall 211 children (17% with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P 50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P 20000/μl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P Conclusion Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa.

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...

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

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

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

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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.

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...

Stability of formation control using a consensus protocol under directed communications with two time delays and delay scheduling

Science.gov (United States)

Cepeda-Gomez, Rudy; Olgac, Nejat

2016-01-01

We consider a linear algorithm to achieve formation control in a group of agents which are driven by second-order dynamics and affected by two rationally independent delays. One of the delays is in the position and the other in the velocity information channels. These delays are taken as constant and uniform throughout the system. The communication topology is assumed to be directed and fixed. The formation is attained by adding a supplementary control term to the stabilising consensus protocol. In preparation for the formation control logic, we first study the stability of the consensus, using the recent cluster treatment of characteristic roots (CTCR) paradigm. This effort results in a unique depiction of the non-conservative stability boundaries in the domain of the delays. However, CTCR requires the knowledge of the potential stability switching loci exhaustively within this domain. The creation of these loci is done in a new surrogate coordinate system, called the 'spectral delay space (SDS)'. The relative stability is also investigated, which has to do with the speed of reaching consensus. This step leads to a paradoxical control design concept, called the 'delay scheduling', which highlights the fact that the group behaviour may be enhanced by increasing the delays. These steps lead to a control strategy to establish a desired group formation that guarantees spacing among the agents. Example case studies are presented to validate the underlying analytical derivations.

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

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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

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

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.

Health system delay and its effect on clinical stage of breast cancer: Multicenter study.

Science.gov (United States)

Unger-Saldaña, Karla; Miranda, Alfonso; Zarco-Espinosa, Gelasio; Mainero-Ratchelous, Fernando; Bargalló-Rocha, Enrique; Miguel Lázaro-León, Jesús

2015-07-01

The objective of this study was to determine the correlation between health system delay and clinical disease stage in patients with breast cancer. This was a cross-sectional study of 886 patients who were referred to 4 of the largest public cancer hospitals in Mexico City for the evaluation of a probable breast cancer. Data on time intervals, sociodemographic factors, and clinical stage at diagnosis were retrieved. A logistic regression model was used to estimate the average marginal effects of delay on the probability of being diagnosed with advanced breast cancer (stages III and IV). The median time between problem identification and the beginning of treatment was 7 months. The subinterval with the largest delay was that between the first medical consultation and diagnosis (median, 4 months). Only 15% of the patients who had cancer were diagnosed with stage 0 and I disease, and 48% were diagnosed with stage III and IV disease. Multivariate analyses confirmed independent correlations for the means of problem identification, patient delay, health system delay, and age with a higher probability that patients would begin cancer treatment in an advanced stage. In the sample studied, the majority of patients with breast cancer began treatment after a delay. Both patient delays and provider delays were associated with advanced disease. Research aimed at identifying specific access barriers to medical services is much needed to guide the design of tailored health policies that go beyond the promotion of breast care awareness and screening participation to include improvements in health services that facilitate access to timely diagnosis and treatment. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Delayed-Start Analyses in the Phase 3 Solanezumab EXPEDITION3 Study in Mild Alzheimer's Disease.

Science.gov (United States)

Liu-Seifert, H; Case, M G; Andersen, S W; Holdridge, K C; Aisen, P S; Kollack-Walker, S; Siemers, E

2018-01-01

A delayed-start design has been proposed to assess a potential disease-modifying effect in investigational drugs for Alzheimer's disease that target the underlying disease process. We extended this methodology to recently obtained data from the EXPEDITION3. EXPEDITION3 was a Phase 3, double-blind study with participants randomized to solanezumab (400 mg) or placebo every 4 weeks for 80 weeks, with an optional extension of active treatment. The delayed-start analysis was designed to determine if a statistically significant treatment difference established during the placebo-controlled period is maintained (at predefined level) during the delayed-start period, which would suggest the active drug has a disease-modifying effect. The delayed-start analysis was assessed across multiple efficacy measures, and includes data from baseline in the placebo-controlled period and up to 9 months in the delayed-start period. No significant difference was observed between the placebo and solanezumab treatment groups at the end of the placebo-controlled period for the Alzheimer's Disease Assessment Scale-Cognitive 14-item subscale. A significant treatment difference was observed at the end of the placebo-controlled period for the Alzheimer's Disease Cooperative Study-Activities of Daily Living instrumental items, an effect also seen at 6 months in the delayed-start period, and the noninferiority criterion was met. No other efficacy measures met these criteria. Delayed-start statistical methodology was used to understand the longitudinal outcomes in EXPEDITION3 and its extension. The small treatment differences observed at the end of the placebo-controlled phase prevented adequate assessment of any putative disease modifying effect.

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.

Delayed diagnosis of sarcoidosis is common in Brazil

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Mauri Monteiro Rodrigues

2013-09-01

Full Text Available OBJECTIVE: To determine the frequency of and the factors related to delayed diagnosis of sarcoidosis in Brazil. METHODS: We evaluated patients with a biopsy-proven diagnosis of sarcoidosis, using a questionnaire that addressed the following: time since symptom onset and since the first medical visit; and the number and specialty of the physicians visited. We divided the patients by the timeliness of the diagnosis-timely (< 6 months and delayed (≥ 6 months-comparing the two groups in terms of systemic and pulmonary symptoms; extrathoracic involvement; spirometric data; radiological staging; level of education; income; and tuberculosis (diagnosis and treatment. RESULTS: We evaluated 100 patients. The median number of physicians consulted was 3 (range, 1-14. In 11 cases, sarcoidosis was diagnosed at the first visit. In 54, the first physician seen was a general practitioner. The diagnosis of sarcoidosis was timely in 41 patients and delayed in 59. The groups did not differ in terms of gender; race; type of health insurance; level of education; income; respiratory/systemic symptoms; extrathoracic involvement; and radiological staging. In the delayed diagnosis group, FVC was lower (80.3 ± 20.4% vs. 90.5 ± 17.1%; p = 0.010, as was FEV1 (77.3 ± 19.9% vs. 86.4 ± 19.5%; p = 0.024, misdiagnosis with and treatment for tuberculosis (≥ 3 months also being more common (24% vs. 7%, p = 0.032, and 20% vs. 0%; p = 0.002, respectively. CONCLUSIONS: The diagnosis of sarcoidosis is often delayed, even when the imaging is suggestive of sarcoidosis. Delayed diagnosis is associated with impaired lung function at the time of diagnosis. Many sarcoidosis patients are misdiagnosed with and treated for tuberculosis.

Thalidomide for control delayed vomiting in cancer patients receiving chemotherapy

International Nuclear Information System (INIS)

Han, Z.; Sun, X.; Du, X.

2016-01-01

To explore the efficacy and safety of thalidomide for the treatment of delayed vomiting, induced by chemotherapy in cancer patients. Study Design: Randomized, double-blind controlled study. Place and Duration of Study: The Oncology Department of Affiliated Hospital of Xuzhou Medical University, Jiangsu Xuzhou, China, from January 2012 to January 2014. Methodology: A total of 78 cancer patients, who had delayed vomiting observed from 24 hours to 1 week after chemotherapy, were included in the study. Patients were divided in a treatment group (40 patients, 51.28%) and a control group (38 patients, 48.71%). The treatment group received thalidomide at an oral dose of 100 mg per night; 50 mg was added daily up to a dose of 200 mg per night, if the curative effect was suboptimal and the medicine was tolerated. Both the treatment and the control groups received a drip of 10 mg azasetron 30 minutes before chemotherapy. The control group only proportions of antiemetic effects and adverse reactions were compared using the ?2 test. Antiemetic effects and adverse reactions were assessed from Odds Ratios (OR) with 95% Confidence Intervals(95% CI). Results: The effective control rate of delayed vomiting in the treatment group was significantly higher than that in the control group (?2=5.174, p=0.023). No significant difference was found between the two groups in other adverse effects of chemotherapy. Karnofsky scores or the overall self-evaluation of the patients (p>0.05). Conclusion: Thalidomide can effectively control the delayed vomiting of cancer patients receiving chemotherapy and the adverse reactions of the agent can be tolerated.

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.

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...

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.

A simple model of carcinogenic mutations with time delay and diffusion.

Science.gov (United States)

Piotrowska, Monika Joanna; Foryś, Urszula; Bodnar, Marek; Poleszczuk, Jan

2013-06-01

In the paper we consider a system of delay differential equations (DDEs) of Lotka-Volterra type with diffusion reflecting mutations from normal to malignant cells. The model essentially follows the idea of Ahangar and Lin (2003) where mutations in three different environmental conditions, namely favorable, competitive and unfavorable, were considered. We focus on the unfavorable conditions that can result from a given treatment, e.g. chemotherapy. Included delay stands for the interactions between benign and other cells. We compare the dynamics of ODEs system, the system with delay and the system with delay and diffusion. We mainly focus on the dynamics when a positive steady state exists. The system which is globally stable in the case without the delay and diffusion is destabilized by increasing delay, and therefore the underlying kinetic dynamics becomes oscillatory due to a Hopf bifurcation for appropriate values of the delay. This suggests the occurrence of spatially non-homogeneous periodic solutions for the system with the delay and diffusion.

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.

Introduction to Focus Issue: Time-delay dynamics

Science.gov (United States)

Erneux, Thomas; Javaloyes, Julien; Wolfrum, Matthias; Yanchuk, Serhiy

2017-11-01

The field of dynamical systems with time delay is an active research area that connects practically all scientific disciplines including mathematics, physics, engineering, biology, neuroscience, physiology, economics, and many others. This Focus Issue brings together contributions from both experimental and theoretical groups and emphasizes a large variety of applications. In particular, lasers and optoelectronic oscillators subject to time-delayed feedbacks have been explored by several authors for their specific dynamical output, but also because they are ideal test-beds for experimental studies of delay induced phenomena. Topics include the control of cavity solitons, as light spots in spatially extended systems, new devices for chaos communication or random number generation, higher order locking phenomena between delay and laser oscillation period, and systematic bifurcation studies of mode-locked laser systems. Moreover, two original theoretical approaches are explored for the so-called Low Frequency Fluctuations, a particular chaotical regime in laser output which has attracted a lot of interest for more than 30 years. Current hot problems such as the synchronization properties of networks of delay-coupled units, novel stabilization techniques, and the large delay limit of a delay differential equation are also addressed in this special issue. In addition, analytical and numerical tools for bifurcation problems with or without noise and two reviews on concrete questions are proposed. The first review deals with the rich dynamics of simple delay climate models for El Nino Southern Oscillations, and the second review concentrates on neuromorphic photonic circuits where optical elements are used to emulate spiking neurons. Finally, two interesting biological problems are considered in this Focus Issue, namely, multi-strain epidemic models and the interaction of glucose and insulin for more effective treatment.

Magnetic Resonance Imaging (MRI) Evaluation of Developmental Delay in Pediatric Patients

OpenAIRE

Ali, Althaf S.; Syed, Naziya P.; Murthy, G.S.N.; Nori, Madhavi; Abkari, Anand; Pooja, B.K.; Venkateswarlu, J.

2015-01-01

Introduction: Developmental delay is defined as significant delay in one or more developmental domains. Magnetic Resonance Imaging (MRI) is the best modality to investigate such patients. Evaluation of a child with developmental delay is important not only because it allows early diagnosis and treatment but also helpful for parental counseling regarding the outcome of their child and to identify any possible risk of recurrence in the siblings. Thus this study was undertaken to evaluate the de...

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.

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.

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.

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

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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

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...

Prevalence and determinants of delay in diagnosis of pulmonary tuberculosis in Darjeeling district of West Bengal

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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.

Relation between delay and survival in 596 patients with breast cancer.

Science.gov (United States)

Machiavelli, M; Leone, B; Romero, A; Perez, J; Vallejo, C; Bianco, A; Rodriguez, R; Estevez, R; Chacon, R; Dansky, C

1989-01-01

To evaluate the influence of delay between first symptom and first treatment upon survival the medical records of 596 patients with breast cancer were reviewed. The following intervals were considered: less than 3 months; 3-6 months and greater than 6 months. Patients in the less than 3 months delay group had a better distribution by clinical stages and a 10-year survival rate higher than those in the longer delay groups (p = 0.034). However, within each stage no statistically significant difference in survival according to delay was observed. A Cox multivariate analysis revealed that performance status and stage of disease were independent predictors of survival, but not delay. Assuming the best prognosis for patients with clinical stages I and II and less than 3 months delay, the group with longer delay times had 15 deaths over what would have been predicted. This adverse effect was observed almost exclusively among patients over age 50 (14/15).

Recurrent meningitis and frontal encephalocele as delayed complications of craniofacial trauma.

Science.gov (United States)

Gumussoy, Murat; Ugur, Omer; Cukurova, Ibrahim; Uluyol, Sinan

2014-03-01

Frontal sinus back table fractures are seen rarely; also, typical presentation of frontal sinus encephalocele as a delayed complication of frontal sinus fracture is seen more rarely. We present a case of frontal encephalocele and recurrent meningitis as delayed complications of craniofacial trauma. Diagnosis, management, and treatment approaches of these complications are discussed.

Methyl bromide fumigation and delayed mortality: safe trade of live pests?

Science.gov (United States)

Phillips, C B; Iline, I I; Novoselov, M; McNeill, M R; Richards, N K; van Koten, C; Stephenson, B P

Live organisms intercepted from treated commodities during phytosanitary inspections usually arouse suspicions of treatment failure, sub-standard treatment application, or post-treatment infestation. The additional possibility that some treatments could kill slowly, meaning commodities might be inspected before pests have succumbed, is seldom considered for treatments other than irradiation. We used a novel biochemical viability assay to measure delays between methyl bromide fumigation and mortality of dipteran eggs, and evaluated the correspondence between egg viability and egg morphological features. Our experimental conditions simulated shipping of rock melons from Australia to New Zealand by sea and air. No eggs survived fumigation, but they took 3-20 days to die, whereas phytosanitary inspections of rock melons occur within 2-7 days. Delays were not influenced by methyl bromide concentration, but were significantly lengthened by cooler storage temperatures. Methyl bromide's preservative effects delayed degradation of egg morphology, so the biochemical assay detected mortality long before morphological signs of egg death appeared. The results show that commodities subjected to effective methyl bromide treatments are at risk of being inspected before all pests have either died, or started to exhibit morphological signs of death. This could cause commodities to be unnecessarily rejected by quarantine authorities. Better methods than inspection for live pests are needed to assist authorities to gain assurance that treated commodities have been effectively disinfested. These could be developed by exploiting biochemical responses of pests and commodities to treatments.

Speech and language delay in two children: an unusual presentation of hyperthyroidism.

Science.gov (United States)

Sohal, Aman P S; Dasarathi, Madhuri; Lodh, Rajib; Cheetham, Tim; Devlin, Anita M

2013-01-01

Hyperthyroidism is rare in pre-school children. Untreated, it can have a profound effect on normal growth and development, particularly in the first 2 years of life. Although neurological manifestations of dysthyroid states are well known, specific expressive speech and language disorder as a presentation of hyperthyroidism is rarely documented. Case reports of two children with hyperthyroidism presenting with speech and language delay. We report two pre-school children with hyperthyroidism, who presented with expressive speech and language delay, and demonstrated a significant improvement in their language skills following treatment with anti-thyroid medication. Hyperthyroidism must be considered in all children presenting with speech and language difficulties, particularly expressive speech delay. Prompt recognition and early treatment are likely to improve outcome.

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.

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)

Fuzzy delay model based fault simulator for crosstalk delay fault test ...

Indian Academy of Sciences (India)

In this paper, a fuzzy delay model based crosstalk delay fault simulator is proposed. As design trends move towards nanometer technologies, more number of new parameters affects the delay of the component. Fuzzy delay models are ideal for modelling the uncertainty found in the design and manufacturing steps.

How do patients access the private sector in Chennai, India? An evaluation of delays in tuberculosis diagnosis.

Science.gov (United States)

Bronner Murrison, L; Ananthakrishnan, R; Swaminathan, A; Auguesteen, S; Krishnan, N; Pai, M; Dowdy, D W

2016-04-01

The diagnosis and treatment of tuberculosis (TB) in India are characterized by heavy private-sector involvement. Delays in treatment remain poorly characterized among patients seeking care in the Indian private sector. To assess delays in TB diagnosis and treatment initiation among patients diagnosed in the private sector, and pathways to care in an urban setting. Cross-sectional survey of 289 consecutive patients diagnosed with TB in the private sector and referred for anti-tuberculosis treatment through a public-private mix program in Chennai from January 2014 to February 2015. Among 212 patients with pulmonary TB, 90% first contacted a formal private provider, and 78% were diagnosed by the first or second provider seen after a median of three visits per provider. Median total delay was 51 days (mean 68). Consulting an informal (rather than formally trained) provider first was associated with significant increases in total delay (absolute increase 22.8 days, 95%CI 6.2-39.5) and in the risk of prolonged delay >90 days (aRR 2.4, 95%CI 1.3-4.4). Even among patients seeking care in the formal (vs. informal) private sector in Chennai, diagnostic delays are substantial. Novel strategies are required to engage private providers, who often serve as the first point of contact.

On the cost/delay tradeoff of wireless delay tolerant geographic routing

OpenAIRE

Tasiopoulos, Argyrios; Tsiaras, Christos; Toumpis, Stavros

2012-01-01

In Delay Tolerant Networks (DTNs), there is a fundamental tradeoff between the aggregate transport cost of a packet and the delay in its delivery. We study this tradeoff in the context of geographical routing in wireless DTNs.We ?rst specify the optimal cost/delay tradeoff, i.e., the tradeoff under optimal network operation, using a dynamic network construction termed the Cost/Delay Evolving Graph (C/DEG) and the Optimal Cost/Delay Curve (OC/DC), a function that gives the minimum possible agg...

Comorbid depression, antisocial personality, and substance dependence: Relationship with delay discounting.

Science.gov (United States)

Moody, Lara; Franck, Christopher; Bickel, Warren K

2016-03-01

Within the field of addiction, as many as four-fifths of individuals in treatment for substance use disorder have co-existing lifetime psychopathology and as high as two-thirds have current psychopathology. Among substance-dependent individuals, excessive delay discounting is pervasive. Despite evidence of excessive discounting across substance use disorders, few studies have investigated the impact of co-occurring psychopathologies and SUD on delay discounting. We compared delay discounting in currently abstaining substance users with (a) SUD (n=166), (b) SUD and managed major depressive disorder (MDD; n=44), (c) SUD and antisocial personality disorder (APD; n=35), (d) SUD and managed MDD and APD (n=22) and (e) no SUD or co-occurring psychopathology (n=60). All groups with SUD discounted future delayed rewards significantly more than healthy controls (p<0.001 in each case, d=0.686, 0.835, 1.098 and 1.650, respective to groups a-d above). Individuals with both APD and SUD and individuals with MDD, APD, and SUD discounted future rewards significantly more than substance users without comorbid psychopathology (p=0.029, d=0.412 and p<0.001, d=0.964, respectively). Overall, individuals with multiple psychopathologies in addition to substance use have exacerbated deficits in discounting of the future, above and beyond that observed in substance use alone. Increased discounting in combined substance and psychopathology profiles suggest a greater chance of treatment failure and therefore may necessitate individualized treatment using adjunctive interventions to achieve better treatment outcomes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Leveraging delay discounting for health: Can time delays influence food choice?

Science.gov (United States)

Appelhans, Bradley M; French, Simone A; Olinger, Tamara; Bogucki, Michael; Janssen, Imke; Avery-Mamer, Elizabeth F; Powell, Lisa M

2018-03-15

Delay discounting, the tendency to choose smaller immediate rewards over larger delayed rewards, is theorized to promote consumption of immediately rewarding but unhealthy foods at the expense of long-term weight maintenance and nutritional health. An untested implication of delay discounting models of decision-making is that selectively delaying access to less healthy foods may promote selection of healthier (immediately available) alternatives, even if they may be less desirable. The current study tested this hypothesis by measuring healthy versus regular vending machine snack purchasing before and during the implementation of a 25-s time delay on the delivery of regular snacks. Purchasing was also examined under a $0.25 discount on healthy snacks, a $0.25 tax on regular snacks, and the combination of both pricing interventions with the 25-s time delay. Across 32,019 vending sales from three separate vending locations, the 25-s time delay increased healthy snack purchasing from 40.1% to 42.5%, which was comparable to the impact of a $0.25 discount (43.0%). Combining the delay and the discount had a roughly additive effect (46.0%). However, the strongest effects were seen under the $0.25 tax on regular snacks (53.7%) and the combination of the delay and the tax (50.2%). Intervention effects varied substantially between vending locations. Importantly, time delays did not harm overall vending sales or revenue, which is relevant to the real-world feasibility of this intervention. More investigation is needed to better understand how the impact of time delays on food choice varies across populations, evaluate the effects of time delays on beverage vending choices, and extend this approach to food choices in contexts other than vending machines. ClinicalTrials.gov, NCT02359916. Copyright © 2018 Elsevier Ltd. All rights reserved.

Teriparatide Induced Delayed Persistent Hypercalcemia

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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.

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.

Fiducial marker guided stereotactic liver radiotherapy: Is a time delay between marker implantation and planning CT needed?

DEFF Research Database (Denmark)

Worm, Esben S; Bertholet, Jenny; Høyer, Morten

2016-01-01

To minimize the risk of marker migration in fiducial marker guided liver SBRT it is common to add a delay of a week between marker implantation and planning CT. This study found that such a delay is unnecessary and could be avoided to minimize the treatment preparation time.......To minimize the risk of marker migration in fiducial marker guided liver SBRT it is common to add a delay of a week between marker implantation and planning CT. This study found that such a delay is unnecessary and could be avoided to minimize the treatment preparation time....

Monitoring delays in diagnosis of pulmonary tuberculosis in eight cities in Colombia

Directory of Open Access Journals (Sweden)

David A. Rodríguez

Full Text Available ABSTRACT Objective To measure time between onset of tuberculosis (TB symptoms and start of treatment, and to identify factors associated with delay in eight Colombian cities. Methods Operational research with a retrospective analytical cohort design was conducted in 2014 using routinely collected data about new smear-positive pulmonary TB patients from eight cities in Colombia (Barranquilla, Bogotá, Bucaramanga, Cali, Cúcuta, Medellín, Pereira, and Villavicencio. Date of symptom onset was sourced from TB surveillance databases. Data on all other variables came from National TB Program (NTP registers. Results There were 2 545 new cases of smear-positive pulmonary TB, but a plausible date of symptom onset was available for only 1 456 (57%. Median number of days between symptom onset and treatment start was 51 days (interquartile range: 27–101. A total of 72% of patients had a delay (> 30 days between symptom onset and treatment start, and 28% had a 3+ bacillary load at diagnosis. Based on multiple logistic regression, three factors were significantly associated with delay: being uninsured (odds ratio (OR: 1.30; 95% confidence interval (CI: 1.01–1.68 and having an unknown HIV status (OR: 1.81; CI: 1.04–3.17, which increased risk, and coming from a neighborhood with NTP-employed community health workers, which decreased risk (OR: 0.56; CI: 0.34–0.90. Conclusions Delays still prevent timely TB diagnosis and treatment in Colombia. As the country aims for TB elimination, delays must be reduced, especially in cities and vulnerable neighborhoods, to stop community transmission. The NTP should focus not only on the number of cases detected but also on how long it takes to detect them. To monitor interventions designed to reduce delays, additional dates in the process should be recorded routinely. In addition, reliability and completeness of data are crucial for monitoring.

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...

Representing delayed force feedback as a combination of current and delayed states.

Science.gov (United States)

Avraham, Guy; Mawase, Firas; Karniel, Amir; Shmuelof, Lior; Donchin, Opher; Mussa-Ivaldi, Ferdinando A; Nisky, Ilana

2017-10-01

To adapt to deterministic force perturbations that depend on the current state of the hand, internal representations are formed to capture the relationships between forces experienced and motion. However, information from multiple modalities travels at different rates, resulting in intermodal delays that require compensation for these internal representations to develop. To understand how these delays are represented by the brain, we presented participants with delayed velocity-dependent force fields, i.e., forces that depend on hand velocity either 70 or 100 ms beforehand. We probed the internal representation of these delayed forces by examining the forces the participants applied to cope with the perturbations. The findings showed that for both delayed forces, the best model of internal representation consisted of a delayed velocity and current position and velocity. We show that participants relied initially on the current state, but with adaptation, the contribution of the delayed representation to adaptation increased. After adaptation, when the participants were asked to make movements with a higher velocity for which they had not previously experienced with the delayed force field, they applied forces that were consistent with current position and velocity as well as delayed velocity representations. This suggests that the sensorimotor system represents delayed force feedback using current and delayed state information and that it uses this representation when generalizing to faster movements. NEW & NOTEWORTHY The brain compensates for forces in the body and the environment to control movements, but it is unclear how it does so given the inherent delays in information transmission and processing. We examined how participants cope with delayed forces that depend on their arm velocity 70 or 100 ms beforehand. After adaptation, participants applied opposing forces that revealed a partially correct representation of the perturbation using the current and the

Asymptotic Delay Analysis for Cross-Layer Delay-Based Routing in Ad Hoc Networks

Directory of Open Access Journals (Sweden)

Philippe Jacquet

2007-01-01

Full Text Available This paper addresses the problem of the evaluation of the delay distribution via analytical means in IEEE 802.11 wireless ad hoc networks. We show that the asymptotic delay distribution can be expressed as a power law. Based on the latter result, we present a cross-layer delay estimation protocol and we derive new delay-distribution-based routing algorithms, which are well adapted to the QoS requirements of real-time multimedia applications. In fact, multimedia services are not sensitive to average delays, but rather to the asymptotic delay distributions. Indeed, video streaming applications drop frames when they are received beyond a delay threshold, determined by the buffer size. Although delay-distribution-based routing is an NP-hard problem, we show that it can be solved in polynomial time when the delay threshold is large, because of the asymptotic power law distribution of the link delays.

A novel approach to delayed-start analyses for demonstrating disease-modifying effects in Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Hong Liu-Seifert

Full Text Available One method for demonstrating disease modification is a delayed-start design, consisting of a placebo-controlled period followed by a delayed-start period wherein all patients receive active treatment. To address methodological issues in previous delayed-start approaches, we propose a new method that is robust across conditions of drug effect, discontinuation rates, and missing data mechanisms. We propose a modeling approach and test procedure to test the hypothesis of noninferiority, comparing the treatment difference at the end of the delayed-start period with that at the end of the placebo-controlled period. We conducted simulations to identify the optimal noninferiority testing procedure to ensure the method was robust across scenarios and assumptions, and to evaluate the appropriate modeling approach for analyzing the delayed-start period. We then applied this methodology to Phase 3 solanezumab clinical trial data for mild Alzheimer's disease patients. Simulation results showed a testing procedure using a proportional noninferiority margin was robust for detecting disease-modifying effects; conditions of high and moderate discontinuations; and with various missing data mechanisms. Using all data from all randomized patients in a single model over both the placebo-controlled and delayed-start study periods demonstrated good statistical performance. In analysis of solanezumab data using this methodology, the noninferiority criterion was met, indicating the treatment difference at the end of the placebo-controlled studies was preserved at the end of the delayed-start period within a pre-defined margin. The proposed noninferiority method for delayed-start analysis controls Type I error rate well and addresses many challenges posed by previous approaches. Delayed-start studies employing the proposed analysis approach could be used to provide evidence of a disease-modifying effect. This method has been communicated with FDA and has been

Management Strategies to Facilitate Optimal Outcomes for Patients Treated with Delayed-release Dimethyl Fumarate.

Science.gov (United States)

Mayer, Lori; Fink, Mary Kay; Sammarco, Carrie; Laing, Lisa

2018-04-01

Delayed-release dimethyl fumarate is an oral disease-modifying therapy that has demonstrated significant efficacy in adults with relapsing-remitting multiple sclerosis. Incidences of flushing and gastrointestinal adverse events are common in the first month after delayed-release dimethyl fumarate initiation. Our objective was to propose mitigation strategies for adverse events related to initiation of delayed-release dimethyl fumarate in the treatment of patients with multiple sclerosis. Studies of individually developed mitigation strategies and chart reviews were evaluated. Those results, as well as mitigation protocols developed at multiple sclerosis care centers, are summarized. Key steps to optimize the effectiveness of delayed-release dimethyl fumarate treatment include education prior to and at the time of delayed-release dimethyl fumarate initiation, initiation dose protocol gradually increasing to maintenance dose, dietary suggestions for co-administration with food, gastrointestinal symptom management with over-the-counter medications, flushing symptom management with aspirin, and temporary dose reduction. Using the available evidence from clinical trials and evaluations of post-marketing studies, these strategies to manage gastrointestinal and flushing symptoms can be effective and helpful to the patient when initiating delayed-release dimethyl fumarate.

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

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

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)

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

Comment on ‘Time delays in molecular photoionization’

Science.gov (United States)

Baykusheva, Denitsa; Wörner, Hans Jakob

2017-04-01

In a recent article by Hockett et al (2016 J. Phys. B: At. Mol. Opt. Phys. 49 095602), time delays arising in the context of molecular single-photon ionization are investigated from a theoretical point of view. We argue that one of the central equations given in this article is incorrect and present a reformulation that is consistent with the established treatment of angle-dependent scattering delays (Eisenbud 1948 PhD Thesis Princeton University; Wigner 1955 Phys. Rev. 98 145-7 Smith 1960 Phys. Rev. 118 349-6 Nussenzveig 1972 Phys. Rev. D 6 1534-42).

[A case of proptosis by traumatic delayed meningo-encephalocele].

Science.gov (United States)

Shi, Ming; Gao, Xue; Zhao, Mei

2015-06-01

A case of traumatic delayed meningo-encephalocele suffered orbital fracture, but bony defects in frontal sinus had not been found on CT scanning. We treated the patient with surgery of intranasal endoscopy and repaired the skull base defect successfully during the first attempt. There was no recurrence in 10 months followed up. The leak site may not correlate with imaging in traumatic delayed meningo-encephalocele by comparing operative findings with the imaging estimate and endoscopy. Therefore, endoscopical approaching is effective in seeking and treatment.

Therapeutic endoscopy for dysphagia and delayed gastric emptying

NARCIS (Netherlands)

Hirdes, M.M.C.

2012-01-01

This PhD thesis focuses on the endoscopic treatment of benign and malignant dysphagia and delayed gastric emptying. Dysphagia due to a benign anastomotic stricture occurs in 40% of patients after esophagectomy and often requires ongoing endoscopic dilations. We evaluated whether corticosteroid

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

[Determinants of patient and health system delays for women with breast cancer in Morocco, 2013].

Science.gov (United States)

Benbakhta, B; Tazi, M; Benjaafar, N; Khattabi, A; Maaroufi, A

2015-06-01

In Morocco, breast cancer is the first most common cancer in women. It is diagnosed in most cases at an advanced stage. Delay in diagnosis and access to treatment for breast cancer increases morbidity and mortality. The objective of this study was to determine the consultation delay (patient delay), diagnosis delay and access to treatment delay (health system delays) of women with breast cancer admitted at the National Institute of Oncology in Rabat. Factors associated with these delays were analyzed. We conducted a cross-sectional study from December 2012 to May 2013 at the National Institute of Oncology in Rabat. Two hundred eligible and consenting women were interviewed using a structured and pre-tested questionnaire. Stages I and II were identified as "early stages" and III and IV as "advanced stages". In our population, 54% were diagnosed at an early stage of breast cancer and 46% at an advanced stage. The median total delay was 120 days (interquartile interval [IIQ]=81-202 days). The patient delay (median=65 days, IIQ=31-121) was longer than the health system delay (median=50 days, IIQ=29-77). High risk for a long total delay (more than 4 months) was observed for women who were aged over 65 years (OR=1.30, 95% CI 1.10-4.20), illiterate (OR=4.50, 95% CI 2.10-6.20), rural residents (OR=3.40, 95% CI 1.23-8.13), in a lower socioeconomic category (OR=4.75, 95% CI 1.45-15.60), without knowledge about breast self-examination (OR=5.67, 95% CI 2.65-12.15) and seen more than 2 times before diagnosis (OR=7.70, 95% CI 2.88-20.50). A long total delay increased the risk of being diagnosed at an advanced stage (OR=5.62, 95% CI 3.03-10.45). Efforts should be directed to providing good information to the population at risk, better access to screening and continuing medical training to enable diagnosis and early treatment. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

[Factors linked to delayed diagnosis of tuberculosis in Conakry (Guinea)].

Science.gov (United States)

Camara, A; Diallo, A; Camara, L M; Fielding, K; Sow, O Y; Chaperon, J

2006-03-01

Untreated smear-positive pulmonary tuberculosis constitutes a reservoir of infection which is highly contagious. The present study was conducted in Conakry, Guinea, to determine the different options which are available when seeking treatment or care, and to ascertain the average delay in diagnosis of pulmonary tuberculosis and the main factors linked to the delay in diagnosis after the initial onset of symptoms. Through a cross-sectional study, 113 consecutive patients with smear-positive pulmonary tuberculosis were interviewed through the use of a questionnaire. The median total delay from the onset of symptoms of pulmonary tuberculosis until the diagnosis was 11 weeks. This delay period exceeded 4 weeks for 90 of the patients (80%). The average delay linked to the conventional health care system was double that of the one at the fault of the patient (6 weeks versus 3 weeks, respectively). 54% of the patients had initially resorted to non-conventional care. To shorten this mean delay period, it is necessary to both strengthen the professional abilities and skills which train for one to better to detect tuberculosis and to sensitize the population to the subject matter and information on the illness and its symptoms.

Patient delay and associated factors among breast cancer patients

International Nuclear Information System (INIS)

Khan, M.A.; Khan, M.I.; Andleeb, U.

2015-01-01

Objectives: To stratify patients into various stages, calculate average patient delay and study various causes of delay to presentation. Methodology: This was a one year hospital based cross sectional study at Khyber Teaching Hospital, using non probability consecutive sampling. A simplified staging was used for this study; Early (Stage I), Intermediate (Stage II, III), and Late (Stage IV). A patient was labelled delay when >3 months had elapsed between first symptom perception and first doctor consultation. Results: 80 patients were included with age 21-80 years (mean 45.28+-13.15). 80% of the patients were married, 76.3% (n=61/80) were poor with annual income of <500 US $, 85% of patients were illiterate. The participants from Rural and Urban areas were similar (37 % vs 31%); 15% were from Afghanistan. 80% patients presented with a delay of >3 months. Most common cause of delay was false symptom interpretation in 25.3% (n=17) patients. Conclusion: Late clinical presentation is because of lack of health education, unawareness, misconceptions about treatment and strong belief in traditional medicine resulting in advanced disease. This is worsened by poverty and unavailability of health care services especially in rural areas. (author)

Fuzzy delay model based fault simulator for crosstalk delay fault test ...

Indian Academy of Sciences (India)

In this paper, a fuzzy delay model based crosstalk delay fault simulator is proposed. As design .... To find the quality of non-robust tests, a fuzzy delay ..... Dubois D and Prade H 1989 Processing Fuzzy temporal knowledge. IEEE Transactions ...

The delaying effect of stigma on mental health help‐seeking in Sri Lanka

OpenAIRE

Fernando, Sunera M.; Deane, Frank P.; McLeod, Hamish J.

2017-01-01

Background: Mental health stigma has been associated with delays in seeking treatment.\\ud Aims: To describe perceived stigma experienced by patients and carers in Sri Lanka and to determine the effects of stigma on help‐seeking delay.\\ud Methods: Survey of outpatients and family carers (n = 118 dyads) attending two psychiatric hospitals in Sri Lanka, using the Disclosure and Discrimination subscales of the Stigma Scale.\\ud Results: Stigma was positively related to help‐seeking delay for carer...

Reasons for delay in decision making and reaching health facility among obstetric fistula and pelvic organ prolapse patients in Gondar University hospital, Northwest Ethiopia.

Science.gov (United States)

Adefris, Mulat; Abebe, Solomon Mekonnen; Terefe, Kiros; Gelagay, Abebaw Addis; Adigo, Azmeraw; Amare, Selamawit; Lazaro, Dorothy; Berhe, Aster; Baye, Chernet

2017-08-22

Obstetric fistula and pelvic organ prolapse remain highly prevalent in sub-Saharan Africa, where women have poor access to modern health care. Women having these problems tend to stay at home for years before getting treatment. However, information regarding the reasons contributing to late presentation to treatment is scarce, especially at the study area. The objective of this study was to assess the reasons whywomen with obstetric fistula and pelvic organ prolapse at Gondar University Hospital delay treatment. A hospital based cross-sectional study was conducted among 384 women. Delay was evaluated by calculating symptom onset and time of arrival to get treatment at Gondar University Hospital. Regression analysis was conducted to elicit predictors of delay for treatment. Of the total 384 participants, 311 (80.9%) had pelvic organ prolapse and 73(19.1%) obstetric fistula. The proportion of women who delayed treatment of pelvic organ prolapse was 82.9% and that of obstetric fistula 60.9%. Fear of disclosing illness due to social stigma (AOR = 2; 1.03, 3.9) and lack of money (AOR = 1.97; 1.01, 3.86) were associated with the delay of treatment for pelvic organ prolapse,while increasing age (AOR =1.12; 1.01, 1.24) and divorce (AOR = 16.9; 1.75, 165.5) were were responsible for delaying treatment forobstetric fistula. A large numberof women with pelvic organ prolapse and obstetric fistula delayed treatment. Fear of disclosure due to social stigma and lack of moneywere the major factors that contributed to thedelay to seek treatment for pelvic organ prolapse,while increasing age and divorce were the predictors for delaying treatment for obstetric fistula.

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)

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.

An Examination of The Transdiagnostic Role of Delay Discounting in Psychological Inflexibility and Mental Health Problems

OpenAIRE

Levin, Michael; Haeger, Jack; Ong, Clarissa W.; Twohig, Michael P.

2018-01-01

Delay discounting is a basic behavioral process that has been found to predict addictive behaviors, and more recently, other mental health problems. Acceptance and Commitment Therapy (ACT), is a transdiagnostic treatment that appears to alter delay discounting, possibly through reducing psychological inflexibility. The current study sought to further bridge research on delay discounting and ACT by examining the relation of delay discounting to a broad range of selfreported mental health probl...

Hereditary angioedema with C1 inhibitor deficiency: delay in diagnosis in Europe.

Science.gov (United States)

Zanichelli, Andrea; Magerl, Markus; Longhurst, Hilary; Fabien, Vincent; Maurer, Marcus

2013-08-12

Hereditary angioedema (HAE) is a rare, debilitating, and potentially life-threatening disease characterized by recurrent edema attacks. Important advances in HAE treatment have been made, including the development of new therapies for treating or preventing attacks. Nevertheless, the disease is still frequently misdiagnosed and inappropriately treated, potentially exposing patients with laryngeal attacks to the risk of asphyxiation. The Icatibant Outcome Survey (IOS) is an international, observational study that documents the clinical outcome of HAE patients eligible for treatment with icatibant. Patient ages at first symptoms and at diagnosis were recorded at enrolment, and the delay between first symptoms and diagnosis was calculated. The median [range] diagnostic delay in HAE type I and II patients across eight countries was 8.5 years [0-62.0]. The median delay in diagnosis was longer for HAE type II versus type I (21 versus 8 years, respectively), although this did not quite reach statistical significance. Although it can be difficult to differentiate HAE symptoms from those of more common angioedema sub-types (e.g. idiopathic or acquired angioedema), our results show that HAE type I and II patients have an unacceptable delay in diagnosis, even those with a family history of the disease. Raising physician awareness of this disabling and potentially fatal disease may lead to a more accurate diagnosis and timely treatment.

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.

Percutaneous drainage of Morel-Lavallée lesions when the diagnosis is delayed.

Science.gov (United States)

Zhong, Biao; Zhang, Chi; Luo, Cong-feng

2014-10-01

Morel-Lavallée lesions are a closed internal degloving, and open débridement can damage the only remaining blood supply to the skin. We performed percutaneous draining and débridement to treat 8 patients in whom the diagnosis of Morel-Lavallée lesions was delayed more than 1 week. Here we discuss our treatment procedures and the outcomes in these 8 patients. We consider percutaneous drainage to be an effective treatment for patients with delayed diagnosis of Morel-Lavallée lesions.

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.

Magnetic resonance imaging (MRI) evaluation of developmental delay in pediatric patients.

Science.gov (United States)

Ali, Althaf S; Syed, Naziya P; Murthy, G S N; Nori, Madhavi; Abkari, Anand; Pooja, B K; Venkateswarlu, J

2015-01-01

Developmental delay is defined as significant delay in one or more developmental domains. Magnetic Resonance Imaging (MRI) is the best modality to investigate such patients. Evaluation of a child with developmental delay is important not only because it allows early diagnosis and treatment but also helpful for parental counseling regarding the outcome of their child and to identify any possible risk of recurrence in the siblings. Thus this study was undertaken to evaluate the developmental delay in Indian children which will help the clinicians in providing an estimation of the child's ultimate developmental potential and organize specific treatment requirement and also relieve parental apprehension. To study the prevalence of normal and abnormal MRI in pediatric patients presenting with developmental delay and further categorize the abnormal MRI based on its morphological features. It is a prospective, observational & descriptive study of MRI Brain in 81 paediatric patients (46 Males and 35 Females), aged between three months to 12 years; presenting with developmental delay in Deccan College of Medical Sciences, Hyderabad; over a period of three years (Sept 2011 to Sept 2014). MRI brain was done on 1.5T Siemens Magnetom Essenza & 0.35T Magnetom C with appropriate sequences and planes after making the child sleep/sedated/ anesthetized. Various anatomical structures like Ventricles, Corpus callosum, etc were systematically assessed. The MRI findings were divided into various aetiological subgroups. Normal MRI findings were seen in 32% cases and 68% had abnormal findings of which the proportion of Traumatic/ Neurovascular Diseases, Congenital & Developmental, Metabolic and Degenerative, neoplastic and non specific were 31%, 17%, 10%, 2.5% and 7.5% respectively. The ventricles and white matter mainly the corpus callosum were the most commonly affected anatomical structures. The diagnostic yield was found to be 68% and higher yield was seen in patients presenting with

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.

Using Video to Bridge the Gap Between Problem Behavior and a Delayed Time-out Procedure

OpenAIRE

Coppage, Sara; Meindl, James N.

2017-01-01

Treatment plans focused on problem behavior often include punishment contingencies to decrease problem behavior. Immediate punishers are typically more effective than delayed punishers, but immediate delivery of a punisher is not always possible. Strategies need to be developed to increase the suppressive effects of delayed punishers. This study demonstrated the effectiveness of a treatment package involving replaying a video recording of problem behavior immediately before delivering a 15 mi...

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.

Time to treatment as a quality metric in lung cancer: Staging studies, time to treatment, and patient survival

International Nuclear Information System (INIS)

Gomez, Daniel R.; Liao, Kai-Ping; Swisher, Stephen G.; Blumenschein, George R.; Erasmus, Jeremy J.; Buchholz, Thomas A.; Giordano, Sharon H.; Smith, Benjamin D.

2015-01-01

Purpose: Prompt staging and treatment are crucial for non-small cell lung cancer (NSCLC). We determined if predictors of treatment delay after diagnosis were associated with prognosis. Materials and methods: Medicare claims from 28,732 patients diagnosed with NSCLC in 2004–2007 were used to establish the diagnosis-to-treatment interval (ideally ⩽35 days) and identify staging studies during that interval. Factors associated with delay were identified with multivariate logistic regression, and associations between delay and survival by stage were tested with Cox proportional hazard regression. Results: Median diagnosis-to-treatment interval was 27 days. Receipt of PET was associated with delays (57.4% of patients with PET delayed [n = 6646/11,583] versus 22.8% of those without [n = 3908/17,149]; adjusted OR = 4.48, 95% CI 4.23–4.74, p < 0.001). Median diagnosis-to-PET interval was 15 days; PET-to-clinic, 5 days; and clinic-to-treatment, 12 days. Diagnosis-to-treatment intervals <35 days were associated with improved survival for patients with localized disease and those with distant disease surviving ⩾1 year but not for patients with distant disease surviving <1 year. Conclusion: Delays between diagnosing and treating NSCLC are common and associated with use of PET for staging. Reducing time to treatment may improve survival for patients with manageable disease at diagnosis

The Syntactic Theory of Belief and Knowledge.

Science.gov (United States)

1983-09-01

34 Hamlet " is if he knows that the author of " Hamlet " is Shakespeare . When we say that someone knows what X is, we mean that he knows that X is n, where n is...that a student knows who the author of " Hamlet " is if he knows that the author of " Hamlet " is n, where n is a personal name. We can represent this as...some n (know student (’- ’(author Hamlet ) n) & (IsPersonalName n) Since "Shakespearew is a personal name, the student knows who the author of

Delayed luminescence in a multiparameter approach to evaluation and reduction of radiobiological risks

Science.gov (United States)

Grasso, Rosaria; Cammarata, Francesco Paolo; Minafra, Luigi; Marchese, Valentina; Russo, Giorgio; Manti, Lorenzo; Musumeci, Francesco; Scordino, Agata

2017-07-01

In the framework of the research project ETHICS "Pre-clinical experimental and theoretical studies to improve treatment and protection by charged particles" funded by the National Nuclear Physics Institute, Italy, we studied the phenomenon called delayed luminescence emitted by non-tumorigenic breast epithelial MCF10A cell line after proton irradiation at different doses (0.5, 2, 6, 9 Gy). The aim is to found possible correlations between delayed luminescence and in vitro damaging induced by ion irradiation. The first results of this research show that the delayed luminescence kinetics is proton dose dependent. An interesting correlation between delayed luminescence and clonogenic potential was observed.

Synchronization of delayed systems in the presence of delay time modulation

International Nuclear Information System (INIS)

Kye, Won-Ho; Choi, Muhan; Kim, Myung-Woon; Lee, Soo-Young; Rim, Sunghwan; Kim, Chil-Min; Park, Young-Jai

2004-01-01

We investigate synchronization in the presence of delay time modulation for application to communication. We have observed that the robust synchronization is established by a common delay signal and its threshold is presented using Lyapunov exponents analysis. The influence of the delay time modulation in chaotic oscillators is also discussed

First treatment contact for ADHD: predictors of and gender differences in treatment seeking.

Science.gov (United States)

Dakwar, Elias; Levin, Frances R; Olfson, Mark; Wang, Shuai; Kerridge, Bradley; Blanco, Carlos

2014-12-01

For attention-deficit hyperactivity disorder (ADHD), treatment seeking is a critical first step in treatment initiation and remains insufficiently understood. The aims of this study were to estimate ADHD treatment-seeking probabilities over the lifetime and to identify predictors of treatment seeking for ADHD separately for males and females. Data were drawn from 2001 to 2005 as part of the National Epidemiologic Survey on Alcohol and Related Conditions, a two-wave face-to-face survey conducted by the National Institute on Alcohol Abuse and Alcoholism (N=34,653). The lifetime cumulative probability of ADHD treatment seeking was estimated at 55%. Males identifying as African American, with less than 12 years of education, or paranoid personality disorder or in an older cohort (>30 years old) at the time of interview were more likely to experience delays, whereas males with comorbid alcohol dependence, dysthymic disorder, borderline personality disorder, or histrionic personality disorder were less likely. Among females, older age (>44 years) was the only predictor of a delay to first treatment seeking, whereas bipolar disorder was associated with more rapid treatment seeking. Age of onset had opposite effects on treatment-seeking delays by gender; males but not females with early-onset ADHD were more likely to experience treatment-seeking delays. A large proportion of persons with ADHD do not seek treatment. Furthermore, treatment seeking by males was affected by a greater number of identifiable characteristics, suggesting that males might be more responsive to efforts directed toward expediting treatment entry. Future research should explore how to facilitate early access to treatment for individuals with ADHD.

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

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.

Chaos synchronization in time-delayed systems with parameter mismatches and variable delay times

International Nuclear Information System (INIS)

Shahverdiev, E.M.; Nuriev, R.A.; Hashimov, R.H.; Shore, K.A.

2004-06-01

We investigate synchronization between two undirectionally linearly coupled chaotic nonidentical time-delayed systems and show that parameter mismatches are of crucial importance to achieve synchronization. We establish that independent of the relation between the delay time in the coupled systems and the coupling delay time, only retarded synchronization with the coupling delay time is obtained. We show that with parameter mismatch or without it neither complete nor anticipating synchronization occurs. We derive existence and stability conditions for the retarded synchronization manifold. We demonstrate our approach using examples of the Ikeda and Mackey Glass models. Also for the first time we investigate chaos synchronization in time-delayed systems with variable delay time and find both existence and sufficient stability conditions for the retarded synchronization manifold with the coupling-delay lag time. (author)

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...

Effect of longer health service provider delays on stage at diagnosis and mortality in symptomatic breast cancer.

Science.gov (United States)

Murchie, P; Raja, E A; Lee, A J; Brewster, D H; Campbell, N C; Gray, N M; Ritchie, L D; Robertson, R; Samuel, L

2015-06-01

This study explored whether longer provider delays (between first presentation and treatment) were associated with later stage and poorer survival in women with symptomatic breast cancer. Data from 850 women with symptomatic breast cancer were linked with the Scottish Cancer Registry; Death Registry; and hospital discharge dataset. Logistic regression and Cox survival analyses with restricted cubic splines explored relationships between provider delays, stage and survival, with sequential adjustment for patient and tumour factors. Although confidence intervals were wide in both adjusted analyses, those with the shortest provider delays had more advanced breast cancer at diagnosis. Beyond approximately 20 weeks, the trend suggests longer delays are associated with more advanced stage, but is not statistically significant. Those with symptomatic breast cancer and the shortest presentation to treatment time (within 4 weeks) had the poorest survival. Longer time to treatment was not significantly associated with worsening mortality. Poor prognosis patients with breast cancer are being triaged for rapid treatment with limited effect on outcome. Prolonged time to treatment does not appear to be strongly associated with poorer outcomes for patients with breast cancer, but the power of this study to assess the effect of very long delays (>25 weeks) was limited. Efforts to reduce waiting times are important from a quality of life perspective, but tumour biology may often be a more important determinant of stage at diagnosis and survival outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

An approach to constitutional delay of growth and puberty

Directory of Open Access Journals (Sweden)

Ashraf T Soliman

2012-01-01

Full Text Available Constitutional delay of growth and puberty is a transient state of hypogonadotropic hypogonadism associated with prolongation of childhood phase of growth, delayed skeletal maturation, delayed and attenuated pubertal growth spurt, and relatively low insulin-like growth factor-1 secretion. In a considerable number of cases, the final adult height (Ht does not reach the mid-parental or the predicted adult Ht for the individual, with some degree of disproportionately short trunk. In the pre-pubertal male, testosterone (T replacement therapy can be used to induce pubertal development, accelerate growth and relieve the psychosocial complaints of the adolescents. However, some issues in the management are still unresolved. These include type, optimal timing, dose and duration of sex steroid treatment and the possible use of adjunctive or alternate therapy including: oxandrolone, aromatase inhibitors and human growth hormone.

Classic conditioning in aged rabbits: delay, trace, and long-delay conditioning.

Science.gov (United States)

Solomon, P R; Groccia-Ellison, M E

1996-06-01

Young (0.5 years) and aged (2+, 3+, and 4+ years) rabbits underwent acquisition of the classically conditioned nictitating membrane response in a delay (500-ms conditioned stimulus [CS], 400-ms interstimulus interval [ISI]), long-delay (1,000-ms CS, 900-ms ISI), or trace (500-ms CS, 400-ms stimulus-free period) paradigm. Collapsing across age groups, there is a general tendency for animals to acquire trace conditioning more slowly than delay conditioning. Collapsing across conditioning paradigms, there is a general tendency for aged animals to acquire more slowly than younger animals. Of greater significance, however, are the age differences in the different conditioning paradigms. In the delay and long-delay paradigms, significant conditioning deficits first appeared in the 4(+)-year-old group. In the trace conditioning paradigm, significant conditioning deficits became apparent in the 2(+)-year-old animals.

Delayed primary realignment of posterior urethral rupture | Shittu ...

African Journals Online (AJOL)

The treatment of acute posterior urethral rupture is controversial. Twelve patients who presented with acute posterior urethral rupture over a five--year period were treated by delayed primary realignment of the injury. The technique of this procedure and the outcome are the subject of this presentation. Eight patients had ...

Delayed Single Stage Perineal Posterior Urethroplasty.

Science.gov (United States)

Ali, Shahzad; Shahnawaz; Shahzad, Iqbal; Baloch, Muhammad Umar

2015-06-01

To determine the delayed single stage perineal posterior urethroplasty for treatment of posterior urethral stricture/distraction defect. Descriptive case series. Department of Urology, Jinnah Postgraduate Medical Centre, Karachi, from January 2009 to December 2011. Patients were selected for delayed single stage perineal posterior urethroplasty for treatment of posterior urethral stricture / distraction defect. All were initially suprapubically catheterized followed by definitive surgery after at least 3 months. Thirty male patients were analyzed with a mean follow-up of 10 months, 2 patients were excluded as they developed failure in first 3 months postoperatively. Mean patient's age was 26.25 ± 7.9 years. On follow-up, 7 patients (23.3%) experienced recurrent stricture during first 10 months. Five (16.6%) patients were treated successfully with single direct visual internal urethrotomy. Two patients (6.6%) had more than one direct visual internal urethrotomy and considered failed. Re-do perineal urethroplasty was eventually performed. The overall success rate was 93.3% with permissive criteria allowing single direct visual internal urethrotomy and 76.6% with strict criteria allowing no more procedures postoperatively. Posterior anastomotic urethroplasty offers excellent long-term results to patients with posterior urethral trauma and distraction defect even after multiple prior procedures.

Two weeks delayed bleeding in blunt liver injury: case report and review of the literature

Directory of Open Access Journals (Sweden)

Chulsky Alexander

2011-04-01

Full Text Available Abstract Most cases of blunt hepatic trauma are treated nowadays non-operatively. This type of conservative treatment has resulted in increased complication rate. Delayed complications occur in cases that didn't require surgical intervention during the first 24 hours. The most common late complication is hemorrhage. We report a case of two weeks delayed hemorrhage after blunt hepatic trauma in an adult. We describe the diagnostic procedures, the surgical treatment and review the relevant literature.

Global synchronization criteria with channel time-delay for chaotic time-delay system

International Nuclear Information System (INIS)

Sun Jitao

2004-01-01

Based on the Lyapunov stabilization theory, matrix measure, and linear matrix inequality (LMIs), this paper studies the chaos synchronization of time-delay system using the unidirectional linear error feedback coupling with time-delay. Some generic conditions of chaos synchronization with time-delay in the transmission channel is established. The chaotic Chua's circuit is used for illustration, where the coupling parameters are determined according to the criteria under which the global chaos synchronization of the time-delay coupled systems is achieved

Risk-factors for surgical delay following hip fracture.

Science.gov (United States)

Sanz-Reig, J; Salvador Marín, J; Ferrández Martínez, J; Orozco Beltrán, D; Martínez López, J F

To identify pre-operative risk factors for surgical delay of more than 2 days after admission in patients older than 65 years with a hip fracture. A prospective observational study was conducted on 180 hip fractures in patients older than 65 years of age admitted to our hospital from January 2015 to April 2016. The data recorded included, patient demographics, day of admission, pre-fracture comorbidities, mental state, level of mobility and physical function, type of fracture, antiaggregant and anticoagulant medication, pre-operative haemoglobin value, type of treatment, and surgical delay. The mean age of the patients was 83.7 years. The mean Charlson Index was 2.8. The pre-fracture baseline co-morbidities were equal or greater than 2 in 70% of cases. Mean timing of surgery was 3.1 days. At the time of admission, 122 (67.7%) patients were fit for surgery, of which 80 (44.4%) underwent surgery within 2 days. A Charlson index greater than 2, anticoagulant therapy, and admission on Thursday to Saturday, were independently associated with a surgical delay greater than 2 days. The rate of hip fracture patients undergoing surgery within 2 days is low. Risk factors associated to surgical delay are non-modifiable. However, their knowledge should allow the development of protocols that can reduce surgical delay in this group of patients. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Delayed minocycline but not delayed mild hypothermia protects against embolic stroke

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Noor Raza

2002-04-01

Full Text Available Abstract Background Inflammatory reactions occurring in the brain after ischemia may contribute to secondary damage. In the present study, effects of minocycline, an anti-inflammatory agent, alone or in combination with mild hypothermia on focal embolic cerebral ischemia have been examined. Methods Focal ischemic injury was induced by embolizing a preformed clot into the middle cerebral artery (MCA. Infarction volume was measured at 48 h after the injury. Mortality was also recorded. Results Delayed administration of minocycline alone or delayed minocycline plus delayed mild hypothermia reduced the infarction volume significantly. However, delayed mild hypothermia alone was not protective and delayed mild hypothermia in combination with minocycline did not show any additive effect. Conclusions These results suggest that minocycline is beneficial in focal ischemic brain injury, and the lack of the enhanced neuroprotection may be due to the brief exposure to hypothermia.

An experimental field study of delayed density dependence in natural populations of Aedes albopictus.

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