Clinicopathologic features and long-term outcomes of NUT midline carcinoma

NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations.

Systematic review of the empirical evidence of study publication bias and outcome reporting bias

BACKGROUND: The increased use of meta-analysis in systematic reviews of healthcare interventions has highlighted several types of bias that can arise during the completion of a randomised controlled trial. Study publication bias has been recognised as a potential threat to the validity of meta-analysis and can make the readily available evidence unreliable for decision making. Until recently, outcome reporting bias has received less attention. METHODOLOGY/PRINCIPAL FINDINGS: We review and summarise the evidence from a series of cohort studies that have assessed study publication bias and outcome reporting bias in randomised controlled trials. Sixteen studies were eligible of which only two followed the cohort all the way through from protocol approval to information regarding publication of outcomes. Eleven of the studies investigated study publication bias and five investigated outcome reporting bias. Three studies have found that statistically significant outcomes had a higher odds of being fully reported compared to non-significant outcomes (range of odds ratios: 2.2 to 4.7). In comparing trial publications to protocols, we found that 40-62% of studies had at least one primary outcome that was changed, introduced, or omitted. We decided not to undertake meta-analysis due to the differences between studies. CONCLUSIONS: Recent work provides direct empirical evidence for the existence of study publication bias and outcome reporting bias. There is strong evidence of an association between significant results and publication; studies that report positive or significant results are more likely to be published and outcomes that are statistically significant have higher odds of being fully reported. Publications have been found to be inconsistent with their protocols. Researchers need to be aware of the problems of both types of bias and efforts should be concentrated on improving the reporting of trials.

Stem cell-related "self-renewal" signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma

PURPOSE: Glioblastomas are notorious for resistance to therapy, which has been attributed to DNA-repair proficiency, a multitude of deregulated molecular pathways, and, more recently, to the particular biologic behavior of tumor stem-like cells. Here, we aimed to identify molecular profiles specific for treatment resistance to the current standard of care of concomitant chemoradiotherapy with the alkylating agent temozolomide. PATIENTS AND METHODS: Gene expression profiles of 80 glioblastomas were interrogated for associations with resistance to therapy. Patients were treated within clinical trials testing the addition of concomitant and adjuvant temozolomide to radiotherapy. RESULTS: An expression signature dominated by HOX genes, which comprises Prominin-1 (CD133), emerged as a predictor for poor survival in patients treated with concomitant chemoradiotherapy (n = 42; hazard ratio = 2.69; 95% CI, 1.38 to 5.26; P = .004). This association could be validated in an independent data set. Provocatively, the HOX cluster was reminiscent of a "self-renewal" signature (P = .008; Gene Set Enrichment Analysis) recently characterized in a mouse leukemia model. The HOX signature and EGFR expression were independent prognostic factors in multivariate analysis, adjusted for the O-6-methylguanine-DNA methyltransferase (MGMT) methylation status, a known predictive factor for benefit from temozolomide, and age. Better outcome was associated with gene clusters characterizing features of tumor-host interaction including tumor vascularization and cell adhesion, and innate immune response. CONCLUSION: This study provides first clinical evidence for the implication of a "glioma stem cell" or "self-renewal" phenotype in treatment resistance of glioblastoma. Biologic mechanisms identified here to be relevant for resistance will guide future targeted therapies and respective marker development for individualized treatment and patient selection.

Interaction between effects of genes coding for dopamine and glutamate transmission on striatal and parahippocampal function

The genes for the dopamine transporter (DAT) and the D-Amino acid oxidase activator (DAOA or G72) have been independently implicated in the risk for schizophrenia and in bipolar disorder and/or their related intermediate phenotypes. DAT and G72 respectively modulate central dopamine and glutamate transmission, the two systems most robustly implicated in these disorders. Contemporary studies have demonstrated that elevated dopamine function is associated with glutamatergic dysfunction in psychotic disorders. Using functional magnetic resonance imaging we examined whether there was an interaction between the effects of genes that influence dopamine and glutamate transmission (DAT and G72) on regional brain activation during verbal fluency, which is known to be abnormal in psychosis, in 80 healthy volunteers. Significant interactions between the effects of G72 and DAT polymorphisms on activation were evident in the striatum, parahippocampal gyrus, and supramarginal/angular gyri bilaterally, the right insula, in the right pre-/postcentral and the left posterior cingulate/retrosplenial gyri (P < 0.05, FDR-corrected across the whole brain). This provides evidence that interactions between the dopamine and the glutamate system, thought to be altered in psychosis, have an impact in executive processing which can be modulated by common genetic variation.

Adenine nucleotide-dependent regulation of assembly of bacterial tubulin-like FtsZ by a hypermorph of bacterial actin-like FtsA.

Cytokinesis in bacteria depends upon the contractile Z ring, which is composed of dynamic polymers of the tubulin homolog FtsZ as well as other membrane-associated proteins such as FtsA, a homolog of actin that is required for membrane attachment of the Z ring and its subsequent constriction. Here we show that a previously characterized hypermorphic mutant FtsA (FtsA*) partially disassembled FtsZ polymers in vitro. This effect was strictly dependent on ATP or ADP binding to FtsA* and occurred at substoichiometric levels relative to FtsZ, similar to cellular levels. Nucleotide-bound FtsA* did not affect FtsZ GTPase activity or the critical concentration for FtsZ assembly but was able to disassemble preformed FtsZ polymers, suggesting that FtsA* acts on FtsZ polymers. Microscopic examination of the inhibited FtsZ polymers revealed a transition from long, straight polymers and polymer bundles to mainly short, curved protofilaments. These results indicate that a bacterial actin, when activated by adenine nucleotides, can modify the length distribution of bacterial tubulin polymers, analogous to the effects of actin-depolymerizing factor/cofilin on F-actin.

Cardiolipin membrane domains in prokaryotes and eukaryotes.

Cardiolipin (CL) plays a key role in dynamic organization of bacterial and mitochondrial membranes. CL forms membrane domains in bacterial cells, and these domains appear to participate in binding and functional regulation of multi-protein complexes involved in diverse cellular functions including cell division, energy metabolism, and membrane transport. Visualization of CL domains in bacterial cells by the fluorescent dye 10-N-nonyl acridine orange is critically reviewed. Possible mechanisms proposed for CL dynamic localization in bacterial cells are discussed. In the mitochondrial membrane CL is involved in organization of multi-subunit oxidative phosphorylation complexes and in their association into higher order supercomplexes. Evidence suggesting a possible role for CL in concert with ATP synthase oligomers in establishing mitochondrial cristae morphology is presented. Hypotheses on CL-dependent dynamic re-organization of the respiratory chain in response to changes in metabolic states and CL dynamic re-localization in mitochondria during the apoptotic response are briefly addressed.

Functional taxonomy of bacterial hyperstructures.

The levels of organization that exist in bacteria extend from macromolecules to populations. Evidence that there is also a level of organization intermediate between the macromolecule and the bacterial cell is accumulating. This is the level of hyperstructures. Here, we review a variety of spatially extended structures, complexes, and assemblies that might be termed hyperstructures. These include ribosomal or "nucleolar" hyperstructures; transertion hyperstructures; putative phosphotransferase system and glycolytic hyperstructures; chemosignaling and flagellar hyperstructures; DNA repair hyperstructures; cytoskeletal hyperstructures based on EF-Tu, FtsZ, and MreB; and cell cycle hyperstructures responsible for DNA replication, sequestration of newly replicated origins, segregation, compaction, and division. We propose principles for classifying these hyperstructures and finally illustrate how thinking in terms of hyperstructures may lead to a different vision of the bacterial cell.

Towards an SMS-based Social Network for Health Workers in Rural Areas in Myanmar

Seventy percent of the population in Myanmar lives in rural areas. Although health workers are adequately trained, they are overburdened due to understaffing and insufficient supplies. Literature confirms that information and communication technologies can extend the reach of healthcare. In this paper, we present an SMS-based social network that aims to help health workers to interact with other medical professionals through topic-based message delivery. Topics describe interests of users and the content of message. A message is delivered by matching message content with user interests. Users describe topics as ICD- 10 codes, a comprehensive medical taxonomy. In this ICD-10 coded SMS, a set of prearranged codes provides a common language for users to send structured information that fits inside an SMS.

Tracking the origins of Yakutian horses and the genetic basis for their fast adaptation to subarctic environments

Yakutia, Sakha Republic, in the Siberian Far East, represents one of the coldest places on Earth, with winter record temperatures dropping below -70 °C. Nevertheless, Yakutian horses survive all year round in the open air due to striking phenotypic adaptations, including compact body conformations, extremely hairy winter coats, and acute seasonal differences in metabolic activities. The evolutionary origins of Yakutian horses and the genetic basis of their adaptations remain, however, contentious. Here, we present the complete genomes of nine present-day Yakutian horses and two ancient specimens dating from the early 19th century and ∼5,200 y ago. By comparing these genomes with the genomes of two Late Pleistocene, 27 domesticated, and three wild Przewalski's horses, we find that contemporary Yakutian horses do not descend from the native horses that populated the region until the mid-Holocene, but were most likely introduced following the migration of the Yakut people a few centuries ago. Thus, they represent one of the fastest cases of adaptation to the extreme temperatures of the Arctic. We find cis-regulatory mutations to have contributed more than nonsynonymous changes to their adaptation, likely due to the comparatively limited standing variation within gene bodies at the time the population was founded. Genes involved in hair development, body size, and metabolic and hormone signaling pathways represent an essential part of the Yakutian horse adaptive genetic toolkit. Finally, we find evidence for convergent evolution with native human populations and woolly mammoths, suggesting that only a few evolutionary strategies are compatible with survival in extremely cold environments.

Discovery of Novel Adenosine Receptor Agonists That Exhibit Subtype Selectivity

A series of N6-bicyclic and N6-(2-hydroxy)cyclopentyl derivatives of adenosine were synthesized as novel A1R agonists and their A1R/A2R selectivity assessed using a simple yeast screening platform. We observed that the most selective, high potency ligands were achieved through N6-adamantyl substitution in combination with 5′-N-ethylcarboxamido or 5′-hydroxymethyl groups. In addition, we determined that 5′-(2-fluoro)thiophenyl derivatives all failed to generate a signaling response despite showing an interaction with the A1R. Some selected compounds were also tested on A1R and A3R in mammalian cells revealing that four of them are entirely A1R-selective agonists. By using in silico homology modeling and ligand docking, we provide insight into their mechanisms of recognition and activation of the A1R. We believe that given the broad tissue distribution, but contrasting signaling profiles, of adenosine receptor subtypes, these compounds might have therapeutic potential.

COMPARISON OF MEASUREMENTS OF ABSORBED DOSE TO WATER USING A WATER CALORIMETER AND IONIZATION CHAMBERS FOR CLINICAL RADIOTHERAPY PHOTON AND ELECTRON BEAMS

With the development of the water calorimeter direct measurement of absorbed dose in water becomes possible. This could lead to the establishment of an absorbed dose rather than an exposure related standard for ionization chambers for high energy electrons and photons. In changing to an absorbed dose standard it is necessary to investigate the effect of different parameters, among which are the energy dependence, the air volume, wall thickness and material of the chamber. The effect of these parameters is experimentally studied and presented for several commercially available chambers and one experimental chamber, for photons up to 25 MV and electrons up to 20 MeV, using a water calorimeter as the absorbed dose standard and the most recent formalism to calculate the absorbed dose with ion chambers.^ For electron beams, the dose measured with the calorimeter was 1% lower than the dose calculated with the chambers, independent of beam energy and chamber.^ For photon beams, the absorbed dose measured with the calorimeter was 3.8% higher than the absorbed dose calculated from the chamber readings. Such differences were found to be chamber and energy independent.^ The results for the photons were found to be statistically different from the results with the electron beams. Such difference could not be attributed to a difference in the calorimeter response. ^

La memoria literaria de la provincia de Misiones (2ª parte). 16H301

ASISTENCIA A CONGRESOS: 17 TRABAJOS PRESENTADOS. 1- I JORNADAS TEMÁTICAS DE LITERATURA ARGENTINA CONTEMPORÁNEA: EL HUMOR EN LA LITERATURA ARGENTINA. Mendoza, del 25 al 27 de agosto de 2011 Ponencias presentadas: A) El humor de María Elena: infancia, memoria y crítica, María de las Mercedes García Saraví- María Alejandra Viana. B) Una mirada humorística en Dormir al sol, Karina Lemes y Natalia Aldana. C) De los Cambios en tu hijo adolescente a la alienación del ser. Karina Lemes. D) Isidoro Blaisten; el Humor como coartada, elaborado por Marisa Renaut; 2 - II CONGRESO INTERNACIONAL DE LITERATURA Y CULTURA ESPAÑOLAS CONTEMPORÁNEAS. Diálogos transatlánticos 3, 4 y 5 de octubre de 2011. Presentadas las siguientes ponencias: A) Laberintos y zonas de densidad: Barcelona y La Plata en dos novelas policiales de Manuel Vázquez Montalbán y Néstor Ponce. Carolina Repetto Mercedes García Saraví. B) El asedio: eco del mundo novelesco de Arturo Pérez Reverte, Haydée Borowski – Mercedes García Saraví. C) De la metaficción y otros procedimientos en La loca de la casa, Karina Beatriz Lemes. 3– XVI CONGRESO NACIONAL DE LITERATURA ARGENTINA. Resistencia, 6, 7 y 8 de octubre de 2011. Presentadas las siguientes ponencias. A) “Ceviche: una nueva cocina del policial”, María Aurelia Escalada- Mercedes García Saraví. B) Entre Santa María y Ruvichá: mundos ficcionales de Latinoamérica. Jorge Hernando Otero. C) El titirimundi de Juan Enrique Acuña: resignificaciones de un arte menor. Ana Eugenia Kushidonchi - Carina Mabel Pereira. D) Gauna: el hallazgo de un manuscrito, Mara Rabbe. E) Filiaciones en el borde. Lorca y Acuña. Karina Lemes y Natalia Aldana. F) Un Amable trasgresor de los géneros, Gabriela Román. 4- IV JORNADAS NACIONALES DE MINIFICCIÓN: HORIZONTES DE LA BREVEDAD EN EL MUNDO IBEROAMERICANO. HOMENAJE A DAVID LAGMANOVICH (1927-2010) Mendoza. 2, 3 y 4 de noviembre de 2011. Presentadas las siguientes ponencias: A) Falsificaciones, de Marco Denevi: la traducción y el apócrifo, aportes al género microrrelato Gabriela Román y Mercedes García Saraví. B) Formas breves en la narrativa de Hugo Wenceslao Amable, por Gabriela Román. Aceptado para actas. 5- IV CONGRESO CELEHIS, Mar del Plata, 7, 8 y 9 de noviembre 2011. Presentadas las siguientes ponencias. A) De la crítica y otros procedimientos en la Loca de la casa, Karina B. Lemes; b) Trayectorias y fronteras en Cádiz: El asedio (2009) de Arturo Pérez Reverte. Haydée Borowski – Mercedes García Saraví. C) Algunos mundos ficcionales de América Latina. Por Jorge Hernando Otero.// Defensa de Tesinas: Jorge Hernando Otero. Relatos ruvichenses: un espacio misionero/latinoamericano. Directora: Mercedes García Saraví. Codirectora: Karina B. Lemes. Defendida 02/11/2011, Nota: 10 (diez).

Repositorios de tesis de posgrado: Capacidad del sistema académico NEA para la generación de depósitos de tesis de acceso libre. 16H315

Actividades realizadas durante el período: Exploración Teórica y Documental del Campo Investigativo; Búsqueda, localización y evaluación de bibliografía especializada; Búsqueda, selección y recuperación de documentos institucionales, nacionales e internacionales; Registro, interpretación y aplicación de la documentación descriptiva y explicativa, a la temática en estudio; Encuadre teórico-metodológico del proyecto

La calle y los niños: estrategias laborales en espacios públicos. En: Avá, nº 19

En la ciudad de La Plata el desarrollo de actividades laborales de niños y niñas en espacios públicos nos ha llevado en pensar en la especificidad que asume el trabajo infantil al ser desplegado en contextos de carácter público:¿de qué modos los niños trabajadores y sus familiares -que frecuentemente los acompañan- practican y representan el espacio laboral? ¿Qué repercusiones tiene ello en los sentidos que los sujetos le asignan a sus trabajos? Nuestras preguntas se orientan básicamente a pensar cómo se construye la experiencia de trabajar en un ámbito particular como el de la calle. A grandes rasgos identificamos que ese espacio no representa para ellos un puro sustrato material, la calle es segmentada y dotada de sentido por quienes allí trabajan. Los significados y modos que los niños y sus padres tienen de vincularse con el espacio laboral no son únicos, sino múltiples y a veces contrapuestos: tanto niños como adultos, aunque se hallan insertos en contextos limitantes, crean e inventan formas de practicar y regular los espacios de trabajo y a través de ello al trabajo mismo.