Thromboxane A2 receptor (TBXA2R) is a potent survival factor for triple negative breast cancers (TNBCs)

Triple Negative Breast Cancer (TNBC) is defined by the lack of ERα, PR expression and HER2 overexpression and is the breast cancer subtype with the poorest clinical outcomes. Our aim was to identify genes driving TNBC proliferation and/or survival which could represent novel therapeutic targets. We performed microarray profiling of primary TNBCs and generated differential genelists based on clinical outcomes following the chemotherapy regimen FEC (5-Fluorouracil/Epirubicin/Cyclophosphamide -‘good’ outcome no relapse > 3 years; ‘poor’ outcome relapse < 3 years). Elevated expression of thromboxane A2 receptor (TBXA2R) was observed in ‘good’ outcome TNBCs. TBXA2R expression was higher specifically in TNBC cell lines and TBXA2R knockdowns consistently showed dramatic cell killing in TNBC cells. TBXA2R mRNA and promoter activities were up-regulated following BRCA1 knockdown, with c-Myc being required for BRCA1-mediated transcriptional repression. We demonstrated that TBXA2R enhanced TNBC cell migration, invasion and activated Rho signalling, phenotypes which could be reversed using Rho-associated Kinase (ROCK) inhibitors. TBXA2R also protected TNBC cells from DNA damage by negatively regulating reactive oxygen species levels. In summary, TBXA2R is a novel breast cancer-associated gene required for the survival and migratory behaviour of a subset of TNBCs and could provide opportunities to develop novel, more effective treatments.

High resolution numerical simulation of triple point collision and origin of unburned gas pockets in turbulent detonations

A key issue in pulse detonation engine development is better understanding of the detonation structure and its propagation mechanism. Thus, in the present work the turbulent structure of an irregular detonation is studied through very high resolution numerical simulations of 600 points per half reaction length. The aim is to explore the nature of the transverse waves during the collision and reflection processes of the triple point with the channel walls. Consequently the formation and consumption mechanism of unreacted gas pockets is studied. Results show that the triple point and the transverse wave collide simultaneously with the wall. The strong transverse wave switches from a primary triple point before collision to a new one after reflection. Due to simultaneous interaction of the triple point and the transverse wave with the wall in the second half of the detonation cell, a larger high-pressurised region appears on the wall. During the reflection the reaction zone detaches from the shock front and produces a pocket of unburned gas. Three mechanisms found to be of significance in the re-initiation mechanism of detonation at the end of the detonation cell; i: energy resealed via consumption of unburned pockets by turbulent mixing ii: compression waves arise due to collision of the triple point on the wall which helps the shock to jump abruptly to an overdriven detonation iii: drastic growth of the Richtmyer–Meshkov instability causing a part of the front to accelerate with respect to the neighbouring portions.

Agricultura familiar y diferenciación social en la frontera de Misiones. Documento de trabajo PISPAD N° 10

En este trabajo nos ocuparemos de la frontera agraria de Misiones, considerándola desde el punto de vista de la política oficial y desde la perspectiva de los productores agrícolas allí asentados. En la primera parte consideraremos la frontera agraria de Misiones desde el punto de vista de la política oficial referida al tema. Los inicios de la década del setenta marcan la intensificación del control estatal sobre el espacio fronterizo y la mayor afluencia de población hacia el área. En la segunda parte describiremos el proceso de ocupación agrícola de uno de los departamentos del área Guaraní, centrándonos en el período 1970-1986.

Intercambios técnicos y economía del Don en la frontera agraria de Misiones. Documento de trabajo PISPAD N° 14

Esta investigación se propone contribuir al esclarecimiento del problema teórico abordado por el PISPAD "El estudio del comportamiento humano desde el punto de vista de la toma de decisiones bajo condiciones restrictivas". Los pequeños productores estudiados aquí son ocupantes fiscales de la frontera agraria de Misiones que han logrado la apropiación de tierra y madera fiscales mediante la gestiono de sus recursos domésticos.

Potential Therapeutic Targets in Triple Negative Breast Cancer

Triple negative breast cancers (TNBC) are often described as biologically aggressive tumors, with poorer survival compared to other breast cancer subtypes. The fact that TNBC lacks an obvious target like estrogen receptor and HER2 represents a major challenge in the management of these patients. Genomic analyses have revealed that TNBC comprises a diverse group of cancers, which have distinct molecular profiles and different prognosis. These studies also highlighted molecular aberrations that could serve as potential treatment targets. On the other hand, a high percentage of TNBCs express some important surface receptors that have been already exploited in the development of promising targeted therapies, which are currently tested in clinical trials. In this review, we will provide an overview on the molecular diversity of TNBC with special emphasis on the evolving role of some potential biomarkers that may be utilized in the near future.

A Triple-Isotope Approach to Predict the Breeding Origins of European Bats

Despite a commitment by the European Union to protect its migratory bat populations, conservation efforts are hindered by a poor understanding of bat migratory strategies and connectivity between breeding and wintering grounds. Traditional methods like mark-recapture are ineffective to study broad-scale bat migratory patterns. Stable hydrogen isotopes (delta D) have been proven useful in establishing spatial migratory connectivity of animal populations. Before applying this tool, the method was calibrated using bat samples of known origin. Here we established the potential of delta D as a robust geographical tracer of breeding origins of European bats by measuring delta D in hair of five sedentary bat species from 45 locations throughout Europe. The delta D of bat hair strongly correlated with well-established spatial isotopic patterns in mean annual precipitation in Europe, and therefore was highly correlated with latitude. We calculated a linear mixed-effects model, with species as random effect, linking delta D of bat hair to precipitation delta D of the areas of hair growth. This model can be used to predict breeding origins of European migrating bats. We used delta C-13 and delta N-15 to discriminate among potential origins of bats, and found that these isotopes can be used as variables to further refine origin predictions. A triple-isotope approach could thereby pinpoint populations or subpopulations that have distinct origins. Our results further corroborated stable isotope analysis as a powerful method to delineate animal migrations in Europe.

Is Australia ready for triple gene herbicide stack technology?

Integration of multiple herbicide-resistant genes (trait stacking) into crop plants would allow over the top application of herbicides that are otherwise fatal to crops. The US has just approved Bollgard II® XtendFlex™ cotton which has dicamba, glyphosate and glufosinate resistance traits stacked. The pace of glyphosate resistance evolution is expected to be slowed by this technology. In addition, over the top application of two more herbicides may help to manage hard to kill weeds in cotton such as flax leaf fleabane and milk thistle. However, there are some issues that need to be considered prior to the adoption of this technology. Wherever herbicide tolerant technology is adopted, volunteer crops can emerge as a weed problem, as can herbicide resistant weeds. For cotton, seed movement is the most likely way for resistant traits to move around. Management of multiple stack volunteers may add additional complexity to volunteer management in cotton fields and along roadsides. This paper attempts to evaluate the pros and cons of trait stacking technology by analysing the available literature in other crop growing regions across the world. The efficacy of dicamba and glufosinate on common weeds of the Australian cotton system, herbicide resistance evolution, synergy and antagonisms due to herbicide mixtures, drift hazards and the evolution of herbicide resistance to glyphosate, glufosinate and dicamba were analysed based on the available literature.

Construcción y evaluación de un portafolio estructural, para obligatorias retiro programado, utilizando la metodología de frontera eficiente de Markowitz y la Teoría de Momentum

Este proyecto de investigación construye y evalúa la asignación de activos para el portafolio de Pensión Obligatoria de Retiro Programado, el cual atiende los retiros a los que un pensionado tiene derecho a través de su mesada pensional, utilizando el modelo de Frontera Eficiente de Markowitz, en combinación con la teoría de Momentum -- Para la ejecución del modelo se determinaron los activos de inversión admisibles en el Régimen de Inversiones -- Posteriormente, se construyen las matrices de rentabilidades, de restricciones, de varianzas y covarianzas, las cuales constituyen los insumos para ejecutar el modelo de optimización de portafolios de Markowitz -- A continuación, se realiza la selección de los portafolios obtenidos, teniendo en cuenta el nivel de volatilidad que el portafolio de Obligatorias Retiro Programado debe presentar; lo anterior, con el fin de cumplir con el objetivo de preservación del capital en la cuenta individual del pensionado, de manera que se pueda atender, de acuerdo a su esperanza de vida y la de sus beneficiarios, el pago de las mesadas pensionales que le correspondan -- El resultado obtenido corresponde a una asignación, en gran parte, en activos de Renta Fija expedidos por el Gobierno Nacional (TES), tanto en tasa fija como en tasa indexada a la UVR -- Adicionalmente, el modelo de optimización sugiere participaciones en activos de renta variable y, particularmente, no asigna recursos representativos en títulos de deuda privada indexados al IPC -- Esta investigación puede ser útil al momento de diseñar un portafolio base para Obligatorias Retiro Programado que, bajo una administración pasiva, permita cumplir el objetivo de otorgar a los pensionados una mesada para satisfacer las necesidades básicas

Deformations of canonical triple covers

In this paper, we show that if X is a smooth variety of general type of dimension m≥3 for which the canonical map induces a triple cover onto Y, where Y is a projective bundle over P1 or onto a projective space or onto a quadric hypersurface, embedded by a complete linear series (except Q3 embedded in P4), then the general deformation of the canonical morphism of X is again canonical and induces a triple cover. The extremal case when Y is embedded as a variety of minimal degree is of interest, due to its appearance in numerous situations. For instance, by looking at threefolds Y of minimal degree we find components of the moduli of threefolds X of general type with KX3=3pg−9,KX3≠6, whose general members correspond to canonical triple covers. Our results are especially interesting as well because they have no lower dimensional analogues.

Eficacia del aceite de oliva en la prevención de úlceras por presión en pacientes inmovilizados en atención primaria. Ensayo clínico aleatorizado, multicéntrico, paralelo, triple ciego, de no inferioridad

Las úlceras por presión representan un importante problema de salud pública y tienen un importante impacto económico en los sistemas de salud. La mayoría de los estudios para prevenir las úlceras por presión se han llevado a cabo en contextos hospitalarios, usando ácidos grasos hiperoxigenados (AGHO) y hasta la fecha, no se ha realizado ningún estudio específico con aceite de oliva virgen extra (AOVE) en el entorno domiciliario. Material y método Objetivo principal: evaluar si la utilización de AOVE no es inferior a los AGHO en la prevención de úlceras por presión (UPP) en pacientes inmovilizados en el entorno domiciliario. Diseño: Ensayo clínico aleatorizado multicéntrico, paralelo, a triple ciego, de no inferioridad. Ámbito: Población consultante de centros de salud andaluces. Muestra: 831 pacientes inmovilizados en riesgo de padecer UPP. Resultados El período de seguimiento fue de 16 semanas. En el análisis por protocolo, ninguna de las zonas evaluadas presentó diferencias de riesgo de incidencia de las úlceras por presión que superasen el valor delta establecido (10%). Sacro: AOVE 8 (2,55%) vs AGHO 8 (3,08%), RAR 0,53 (-2,2 a 3,26). Talón derecho: AOVE 4 (1,27%) vs AGHO 5 (1,92)%, RAR 0,65 (-1,43 a 2,73). Talón izquierdo: AOVE 3 (0,96%) vs AGHO 3 (1,15%), RAR 0.2 (-1,49 a 1,88). Trocánter Derecho: AOVE 0 (0%) vs AGHO 4 (1,54%), RAR 1,54 (0,04-3,03). Trocánter izquierdo: AOVE 1 (0,32%) vs AGHO 1 (0,38%), RAR 0.07 (-0,91 a 1,04). Discusión Este ensayo clínico pretendía evaluar si la prevención de las UPP usando una fórmula de AOVE no era inferior a la prevención de UPP con el uso AGHO, en el entorno domiciliario y con pacientes inmovilizados de alto riesgo. Los resultados han mostrado esta no inferioridad al no observarse diferencias que hayan superado el límite inferior del intervalo de confianza y convierte al aceite de oliva en un producto eficaz para la prevención de UPP en este tipo de pacientes. Se necesitan más estudios para investigar el mecanismo de acción del AOVE en la prevención de las UPP y relacionarlo con la etiopatogenia de éstas. Bibliografía 1. Gorecki C, Brown JM, Nelson EA, Briggs M, Schoonhoven L, Dealey C, et al. Impact of pressure ulcers on quality of life in older patients: a systematic review. J Am Geriatr Soc. 2009 Jul;57(7):1175–83. 2. Yamamoto Y, Hayashino Y, Higashi T, Matsui M, Yamazaki S, Takegami M, et al. Keeping vulnerable elderly patients free from pressure ulcer is associated with high caregiver burden in informal caregivers. J Eval Clin Pract. 2010 Jun;16(3):585–9. 3. Hanson D, Langemo DK, Anderson J, Thompson P, Hunter S. Friction and shear considerations in pressure ulcer development. Adv Skin Wound Care. 2010 Jan;23(1):21–4. 4. Soldevilla Agreda JJ, Torra i Bou J-E, Verdú Soriano J, López Casanova P. 3.er Estudio Nacional de Prevalencia de Úlceras por Presión en España, 2009: Epidemiología y variables definitorias de las lesiones y pacientes. Gerokomos. 2011 Jun;22(2):77–90. 5. Kottner J, Lahmann N, Dassen T. [Pressure ulcer prevalence: comparison between nursing homes and hospitals]. Pflege Z. 2010 Apr;63(4):228–31. 6. Wilborn D, Halfens R, Dassen T, Tannen A. [Pressure ulcer prevalence in German nursing homes and hospitals: what role does the National Nursing Expert Standard Prevention of Pressure Ulcer play?]. Gesundheitswesen Bundesverb Ärzte Öffentl Gesundheitsdienstes Ger. 2010 Apr;72(4):240–5. 7. Tubaishat A, Anthony D, Saleh M. Pressure ulcers in Jordan: a point prevalence study. J Tissue Viability. 2011 Feb;20(1):14–9. 8. James J, Evans JA, Young T, Clark M. Pressure ulcer prevalence across Welsh orthopaedic units and community hospitals: surveys based on the European Pressure Ulcer Advisory Panel minimum data set. Int Wound J. 2010 Jun;7(3):147–52. 9. Defloor T, Schoonhoven L, Katrien V, Weststrate J, Myny D. Reliability of the European Pressure Ulcer Advisory Panel classification system. J Adv Nurs. 2006 Apr;54(2):189–98

A randomised controlled trial of triple antiplatelet therapy (Aspirin, Clopidogrel and Dipyridamole) in the secondary prevention of stroke: safety, tolerability and feasibility

Background: Aspirin, dipyridamole and clopidogrel are effective in secondary vascular prevention. Combination therapy with three antiplatelet agents might maximise the benefit of antiplatelet treatment in the secondary prevention of ischaemic stroke. Methodology/Principal Findings: A randomised, parallel group, observer-blinded phase II trial compared the combination of aspirin, clopidogrel and dipyridamole with aspirin alone. Adult patients with ischaemic stroke or transient ischaemic attack (TIA) within 5 years were included. The primary outcome was tolerability to treatment assessed as the number of patients completing randomised treatment. Recruitment was halted prematurely after publication of the ESPRIT trial (which confirmed that combined aspirin and dipyridamole is more effective than aspirin alone). 17 patients were enrolled: male 12 (71%), mean age 62 (SD 13) years, lacunar stroke syndrome 12 (71%), median stroke/TIA onset to randomisation 8 months. Treatment was discontinued in 4 of 9 (44%) patients receiving triple therapy vs. none of 8 taking aspirin (p = 0.08). One recurrent stroke occurred in a patient in the triple group who was noncompliant of all antiplatelet medications. The number of patients with adverse events and bleeding complications, and their severity, were significantly greater in the triple therapy group (p,0.01). Conclusions/Significance: Long term triple antiplatelet therapy was asociated with a significant increase in adverse events and bleeding rates, and their severity, and a trend to increased discontinuations. However, the patients had a low risk of recurrence and future trials should focus on short term therapy in high risk patients characterised by a very recent event or failure of dual antiplatelet therapy.