A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

Kast, Richard E. et al.To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma’s compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.Peer Reviewe

Modulation of coaxial modal interferometers based on long period gratings in double cladding fibers

This paper reports on the dynamic modulation of coaxial interferometers based on two cascaded long period gratings written in double cladding fibers. The interferometer is modulated by a piezoelectric ceramic which stretches one the gratings at tens of kHz, the output light is intensity modulated with an efficiency of 97 %. The device operates at 1530nm, has more than 50nm bandwidth, insertion loss of 0.4 dB and a temperature drift of 0.11 nm/ºC

Modifications in the distribution of met-enkephalin in the cat spinal cord after administration of clonidine. An immunocytochemical study

We have studied the modifications in the distribution of methionine-enkephalin in the cat spinal cord after intravenous or intrathecal administration of clonidine by using an immunocytochemical technique. In animals not treated with the substance, a very high density of immunoreactive fibers was found in layers I and 11; a high density in the dorso-lateral funiculus and in the reticular formation; a moderate density in layers 111, IV and V; and a low density in layer VI. However, after intravenous or intrathecal administration of clonidine a decrease in fibers containing met-enkephalin was observed in layers I and I1 (high or moderate density), the dorso-lateral funiculus, and the reticular formation (moderate or low density), and in layers IV and V (low or very low density). In all cases, the decrease in the immunoreactivity was more marked when clonidine was administered intrathecally. Our results suggest that clonidine induces the release of metenkephalin in the spinal cord. They further suggest that the opioid peptide released could be involved in the control of nociceptive transmission by inhibiting the release of neurotransmitters (e.g., substance P). In summary, our study shows that clonidine could be involved in antinociceptive mechanisms in the cat spinal cord

Fiber-Optic Aqueous Dipping Sensor Based on Coaxial-Michelson Modal Interferometers

Fiber-optic modal interferometers with a coaxial-Michelson configuration can be used to monitor aqueous solutions by simple dipping of few centimeters of a fiber tip. The fabrication of these sensors to work around 850 nm enables the use of compact, robust, and low-cost optical spectrum analyzers. The use of this type of portable sensor system to monitor sewage treatment plants is shown

The Toledo Mountains: A Resilient Landscape and a Landscape for Resilience? Hazards and Strategies in a Mid-Elevation Mountain Region in Central Spain

The Toledo Mountains are a mid-elevation mountain range that separates the Tagus and Guadiana basins in the central area of the Iberian Peninsula. The location of these mountains allows the development of typical Mediterranean vegetation with some Atlantic influence. Consequently, typical broadleaved evergreen Mediterranean vegetation currently dominates the regional landscape, with the remarkable presence of more mesophilous species in sheltered and more humid microsites such as gorges (e.g., Prunus lusitanica, Taxus baccata, Ilex aquifolium) and mires/bogs (e.g., Betula pendula susbp. fontqueri, Erica tetralix, Myrica gale). Palaeoecological studies in these mountains are essential to understand the long-term ecology and original distribution of these valuable communities and are key to assess their resilience. Understanding the hazards and opportunities faced in the past by the plant communities of the Toledo Mountains is necessary to enhance the management and protection of those species currently threatened. This study focuses on El Perro mire, a peatland on the southern Toledo Mountains (central Spain) where climatic variability has played a major role in landscape dynamics at multi-decadal to millennial timescales. Climatic events such as the 4.2 ka cal. Before Present (BP) or the Little Ice Age triggered relevant landscape changes such as the spread and latter decline of birch and hazel forests. Human communities also seemed to be affected by these events, as their resilience was apparently jeopardized by the new climatic conditions and they were forced to find new strategies to cope with the new scenarios.This research was funded the project REDISCO-HAR2017-88035-P (Plan Nacional I+D+I, Spanish Ministry of Economy and Competitiveness). Reyes Luelmo Lautenschlaeger is funded by a FPU contract (Spanish Ministry of Education, Culture and Sports)

Resumen de las actas y tareas de la Comisión de Monumentos Históricos y Artísticos de la Provincia de Burgos, y discursos leídos en la sesión....celebrada el 14 de setiembre [sic] de 1871 para inaugurar y abrir al público la Biblioteca y Museo Arqueológico y de Bellas Artes

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2013Contiene: Resumen de actas en la parte referente a Biblioteca y Museo Arqueológico y de Bellas Artes, leído por D. Luis Villanueva y Arribas. Discurso leído en la... inauguración de la Biblioteca Provincial de Burgos por el Dr. D. Anastasio Sáez Muñoz. Discurso leído en la inauguración del Museo Arqueológico y de Bellas Artes de Burgos por D. Juan M. Sánchez de la Camp

Mechanical Behaviour at Low Strains of LDPE Foams with Cell Sizes in the Microcellular Range: Advantages of Using these Materials in Structural Elements.

This paper presents the production method and the compressive mechanical response at low strains for a collection of polyethylene foams with high densities and cell sizes in the microcellular range. The materials were produced using a modified compression moulding technique that allows and independent control of density and cell size. The materials had a relative density between 0.27 and 0.92, an homogeneous and multi-structured cellular structure with dense skin and foamed core and cell sizes in the range 30 to 100 microns. The YoungŽs modulus was reduced when density did. For relative densities higher than 0.7, the reduced Young¿s modulus of the foams was higher than that of the solid. In addition, it has been proved that variations in the cell size at constant density did not influence the Young¿s modulus. The advantages of using these materials for the production of plastic pipes have been analysed. A reduction of the weight of pipes loaded in compression of up to 42 % can be reached by using these foams in spite of the solid material from which the foam was produced

Acción tutorial y competencias transversales: alcance de la contribución de los/as tutores/as de Filosofía y Letras, UA

La contribución que nos proponemos presentar atiende dos vertientes de la investigación que hemos llevado a cabo en este curso 2014/2015 en la red en investigación en docencia universitaria dedicada a la Acción tutorial de nuestro centro (Filosofía y Letras, UA). En un primer tiempo, daremos cuenta brevemente del análisis de los resultados obtenidos en las ediciones anteriores. Para ello expondremos cuestiones organizativas que han pretendido conseguir un mayor alcance de la labor de los tutores en colaboración con los tutores par, analizaremos y evaluaremos las medidas de mejora implementadas en el transcurso de las ediciones. En un segundo tiempo, analizaremos y evaluaremos el alcance del equipo de la Acción tutorial en su apoyo a los estudiantes en la adquisición de las competencias transversales. Nuestra investigación tiene como objetivo principal la medición de resultados obtenidos desde la implementación de la figura del tutor par en colaboración con el tutor docente así como la ideación de medidas de optimización para asegurar el espacio necesario para el funcionamiento correcto y pleno de la Acción Tutorial en todas sus dimensiones

Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low

Background: Although the Fat Mass and Obesity (FTO) and Melanocortin-4 Receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet). Methods: Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed. Results: Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern. Conclusions: These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition