Ioannis Manardi ... epistolarum medicinalium libri duodeuiginti / hi partim infinitis in locis [et] ab ipso autore iam recens castigati sunt, partim iam primum in lucem aeduntur ; eiusdem annotationes & censura in medicanina simplicia & composita Mesue.

Indice a tres col.

El impacto de la crisis en la industria cinematográfica en Europa

Este trabajo analiza el impacto que ha generado la crisis económica y financiera más reciente en las industrias cinematográficas de siete países miembros de la Unión Europea. Las conclusiones señalan que, en efecto, la crisis ha impactado negativamente en las industrias de España e Italia, y muy gravemente en la de Portugal, pero en el lado contrario, la del Reino Unido ha experimentado un crecimiento apreciable y las de Francia y Alemania también lo han hecho, aunque en menor medida. Y en segundo lugar, es muy notable la escasa colaboración alcanzada entre los agentes europeos.

Sobre Κρῆτες de Sófocles

En este artículo se estudia una obra atribuida a Sófocles titulada Κρῆτες (Los cretenses), una tragedia sólo conocida por dos dudosos testimonios de Hesiquio y Ateneo de Náucratis. A finales del siglo xviii una nueva lectura de ambos los adscribía a otra tragedia, con lo que se negaba la existencia de Κρῆτες. A pesar de esto, este título se sigue manteniendo en las ediciones de la obra sofoclea, ahora relacionado con nuevos hallazgos de fragmentos papiráceos del autor. Nuestro objetivo es el de analizar los testimonios en profundidad para concluir si la obra pudo o no haberse escrito.

Synthetic Lethal Targeting of ARID1A-Mutant Ovarian Clear Cell Tumors with Dasatinib

New targeted approaches to ovarian clear cell carcinomas (OCCC) are needed, given the limited treatment options in this disease and the poor response to standard chemotherapy. Using a series of high-throughput cell-based drug screens in OCCC tumor cell models, we have identified a synthetic lethal (SL) interaction between the kinase inhibitor dasatinib and a key driver in OCCC, ARID1A mutation. Imposing ARID1A deficiency upon a variety of human or mouse cells induced dasatinib sensitivity, both in vitro and in vivo, suggesting that this is a robust synthetic lethal interaction. The sensitivity of ARID1A-deficient cells to dasatinib was associated with G₁ -S cell-cycle arrest and was dependent upon both p21 and Rb. Using focused siRNA screens and kinase profiling, we showed that ARID1A-mutant OCCC tumor cells are addicted to the dasatinib target YES1. This suggests that dasatinib merits investigation for the treatment of patients with ARID1Amutant OCCC. Mol Cancer Ther; 15(7); 1472-84. Ó2016 AACR.

FLIP: a targetable mediator of resistance to radiation in non-small cell lung cancer

Resistance to radiotherapy due to insufficient cancer cell death is a significant cause of treatment failure in non-small cell lung cancer (NSCLC). The endogenous caspase-8 inhibitor, FLIP, is a critical regulator of cell death that is frequently overexpressed in NSCLC and is an established inhibitor of apoptotic cell death induced via the extrinsic death receptor pathway. Apoptosis induced by ionizing radiation (IR) has been considered to be mediated predominantly via the intrinsic apoptotic pathway; however, we found that IR-induced apoptosis was significantly attenuated in NSCLC cells when caspase-8 was depleted using RNA interference (RNAi), suggesting involvement of the extrinsic apoptosis pathway. Moreover, overexpression of wild-type FLIP, but not a mutant form that cannot bind the critical death receptor adaptor protein FADD, also attenuated IR-induced apoptosis, confirming the importance of the extrinsic apoptotic pathway as a determinant of response to IR in NSCLC. Importantly, when FLIP protein levels were down-regulated by RNAi, IR-induced cell death was significantly enhanced. The clinically relevant histone deacetylase (HDAC) inhibitors vorinostat and entinostat were subsequently found to sensitize a subset of NSCLC cell lines to IR in a manner that was dependent on their ability to suppress FLIP expression and promote activation of caspase-8. Entinostat also enhanced the anti-tumor activity of IR in vivo. Therefore, FLIP down-regulation induced by HDAC inhibitors is a potential clinical strategy to radio-sensitize NSCLC and thereby improve response to radiotherapy. Overall, this study provides the first evidence that pharmacological inhibition of FLIP may improve response of NCSLC to IR.

A Phase II Biomarker-Embedded Study of Lapatinib plus Capecitabine as First-line Therapy in Patients with Advanced or Metastatic Gastric Cancer

An exploratory phase II biomarker-embedded trial (LPT109747; NCT00526669) designed to determine the association of lapatinib-induced fluoropyrimidine gene changes with efficacy of lapatinib plus capecitabine as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma independent of tumor HER2 status. Tumor biopsies obtained before and after 7-day lapatinib (1,250 mg) to analyze changes in gene expression, followed by a 14-day course of capecitabine (1,000 mg/m(2) twice daily, 14/21 days) plus lapatinib 1,250 mg daily. Blood samples were acquired for pharmacokinetic analysis. Primary clinical objectives were response rate (RR) and 5-month progression-free survival (PFS). Secondary objectives were overall survival (OS), PFS, time to response, duration of response, toxicity, and identification of associations between lapatinib pharmacokinetics and biomarker endpoints. Primary biomarker objectives were modulation of 5-FU-pathway genes by lapatinib, effects of germline SNPs on treatment outcome, and trough steady-state plasma lapatinib concentrations. Sixty-eight patients were enrolled; (75% gastric cancer, 25% gastroesophageal junction). Twelve patients (17.9%) had confirmed partial response, 31 (46.3%) had stable disease, and 16 (23.9%) had progressive disease. Median PFS and OS were 3.3 and 6.3 months, respectively. Frequent adverse events included diarrhea (45%), decreased appetite (39%), nausea (36%), and fatigue (36%). Lapatinib induced no changes in gene expression from baseline and no significant associations were found for SNPs analyzed. Elevated baseline HER3 mRNA expression was associated with a higher RR (33% vs. 0%; P = 0.008). Lapatinib plus capecitabine was well tolerated, demonstrating modest antitumor activity in patients with advanced gastric cancer. The association of elevated HER3 and RR warrants further investigation as an important player for HER-targeted regimens in combination with capecitabine

Ioannis Driedonis a Turnhout ..., De libertate Christiana lib[er].

Sign.: []2, A-Z4, 2A-2K4, A-R4, S6

The Accuracy and Reliability of Traditional Surface Flow Type Mapping: Is It Time for A New Method of Characterising Physical River Habitat?

Surface flow types (SFT) are advocated as ecologically relevant hydraulic units, often mapped visually from the bankside to characterise rapidly the physical habitat of rivers. SFT mapping is simple, non-invasive and cost-efficient. However, it is also qualitative, subjective and plagued by difficulties in recording accurately the spatial extent of SFT units. Quantitative validation of the underlying physical habitat parameters is often lacking, and does not consistently differentiate between SFTs. Here, we investigate explicitly the accuracy, reliability and statistical separability of traditionally mapped SFTs as indicators of physical habitat, using independent, hydraulic and topographic data collected during three surveys of a c. 50m reach of the River Arrow, Warwickshire, England. We also explore the potential of a novel remote sensing approach, comprising a small unmanned aerial system (sUAS) and Structure-from-Motion photogrammetry (SfM), as an alternative method of physical habitat characterisation. Our key findings indicate that SFT mapping accuracy is highly variable, with overall mapping accuracy not exceeding 74%. Results from analysis of similarity (ANOSIM) tests found that strong differences did not exist between all SFT pairs. This leads us to question the suitability of SFTs for characterising physical habitat for river science and management applications. In contrast, the sUAS-SfM approach provided high resolution, spatially continuous, spatially explicit, quantitative measurements of water depth and point cloud roughness at the microscale (spatial scales ≤1m). Such data are acquired rapidly, inexpensively, and provide new opportunities for examining the heterogeneity of physical habitat over a range of spatial and temporal scales. Whilst continued refinement of the sUAS-SfM approach is required, we propose that this method offers an opportunity to move away from broad, mesoscale classifications of physical habitat (spatial scales 10-100m), and towards continuous, quantitative measurements of the continuum of hydraulic and geomorphic conditions which actually exists at the microscale.

Validation of Electronic Health Record Phenotyping of Bipolar Disorder Cases and Controls

Objective: The study was designed to validate use of elec-tronic health records (EHRs) for diagnosing bipolar disorder and classifying control subjects. Method: EHR data were obtained from a health care system of more than 4.6 million patients spanning more than 20 years. Experienced clinicians reviewed charts to identify text features and coded data consistent or inconsistent with a diagnosis of bipolar disorder. Natural language processing was used to train a diagnostic algorithm with 95% specificity for classifying bipolar disorder. Filtered coded data were used to derive three additional classification rules for case subjects and one for control subjects. The positive predictive value (PPV) of EHR-based bipolar disorder and subphenotype di- agnoses was calculated against diagnoses from direct semi- structured interviews of 190 patients by trained clinicians blind to EHR diagnosis. Results: The PPV of bipolar disorder defined by natural language processing was 0.85. Coded classification based on strict filtering achieved a value of 0.79, but classifications based on less stringent criteria performed less well. No EHR- classified control subject received a diagnosis of bipolar dis- order on the basis of direct interview (PPV=1.0). For most subphenotypes, values exceeded 0.80. The EHR-based clas- sifications were used to accrue 4,500 bipolar disorder cases and 5,000 controls for genetic analyses. Conclusions: Semiautomated mining of EHRs can be used to ascertain bipolar disorder patients and control subjects with high specificity and predictive value compared with diagnostic interviews. EHRs provide a powerful resource for high-throughput phenotyping for genetic and clinical research.

The Askaryan radio array

The Askar'yan Radio Array (ARA), a neutrino detector to be situated at the South Pole next to the IceCube detector, will be sensitive to ultrahigh-energy cosmic neutrinos above 0.1 EeV and will have the greatest sensitivity within the favored energy range from 0.1 EeV up to 10 EeV. Neutrinos of this energy are guaranteed by current observations of the GZK-cutoff by the HiRes and Pierre Auger Observatories. The detection method is based on Cherenkov emission by a neutrino induced cascade in the ice, coherent at radio wavelengths, which was predicted by Askar'yan in 1962 and verified in beam tests at SLAC in 2006. The detector is planned to consist of 37 stations with 16 antennas each, deployed at depths of up to 200 m under the ice surface. During the last two polar seasons (2010-2011, 2011-2012), a prototype station and a first detector station were successfully deployed and are taking data. These data have been and are currently being analyzed to study the ambient noise background and the radio frequency properties of the South Pole ice sheet. A worldwide collaboration is working on the planning, construction and data analysis of the detector array. This article will give a short report on the status of the ARA detector and show recent results from the recorded data. © 2013 AIP Publishing LLC.

LA TÉCNICA EN LA ECONOMÍA Y LA INVESTIGACIÓN

La metodología ha sido una temática manejada y aplicada generalmente por técnicos que se arro-gaban o se les atribuía autoridad para determinar lo que era correcto o indebido en los procesos investigativos y de evaluación de las acciones en el medio social. En el presente se comienza a cuestionar de manera sistemática y cada vez en mayor medida la importancia otorgada a las metodologías o técnicas que se emplean en la investigación y en la evaluación. Esta vertiente crítica, no se puede decir, en sentido estricto, que es totalmente nueva, por el contrario es la continuidad de perspectivas que ya se habían planteado en el pasado.Lo nuevo son las circunstancias que promueven que esos cuestionamientos se aprecien como evidentes y pertinentes en el actual desarrollo científico. La revaloración de posiciones ha implicado también relativos cambios en la concepción de la ciencia y la labor científica, así como también en las aplicaciones de la producción tecnológica. De una idea que suponía que la ciencia proporcionaba los conocimientos absolutos de la realidad y nos daba las fórmulas y recetas de cómo hacer las cosas para obtener determinado resultado, se ha pasado a postular que los conocimientos científicos son relativos, no absolutos, inmutables ni universales. Relatividad fundada en que los conocimientos científicos son históricos, esto es, condicionados por los conocimientos, prejuicios y necesidades sociales existentes en un momento determinado a los que el investigador no se puede abstraer y por lo tanto presentes en sus descubrimientos.Esta modificación ha implicado también una transformación en la concepción de la realidad, de una visión cotidiana de la existencia de leyes universales aplicables a los cuerpos celestes y la sociedad, se ha pasado a postular que las pretendidas leyes, también deberán ser cuestionadas, dado que no existen en el mundo de lo real fenómenos que puedan ser idénticos a otros. La peculiaridad de las realidades sociales, individuales, tecnológicas y naturales, ha dado una dimensión adicional a la relatividad de los conocimientos científicos.

Promptvarivm morale svper Evangelia dominicalia totivs anni:. Ad instructionem concionatorum. Reformationem peccatorum consolationem piorum. /

Title vignette; initials, head-piece.