Study of the Spanish Society of Medical Oncology (SEOM) on the access to oncology drugs and predictive biomarkers in Spain

Altres ajuts: This study was funded by SEOM.The Spanish Society of Medical Oncology (SEOM) has carried out a study to analyse the conditions of access to oncology drugs in clinical practice in Spain. For the first time, the access of predictive biomarkers has also been analyzed. A questionnaire was sent to 146 hospitals in Spain to collect information on the process of approval of 11 oncology drugs of an unquestionable clinical benefit and five predictive biomarkers of mandatory determination for specific treatments. Results highlight the still existing differences in the access of oncology drugs, as well as the newly identified differences in the access to predictive biomarkers between Autonomous Communities (AACC) in Spain, as well as between different hospitals within the same Autonomous Community. Conclusions The SEOM considers it necessary to reduce the differences identified, increase homogeneity, and improve conditions of access to oncology drugs and biomarkers, and makes proposals to address these issues

HD 173977: An ellipsoidal d Scuti star variable

Astronomy and Astrophysics, v. 426, p. 247-252, 2004. http://dx.doi.org/10.1051/0004-6361:20034068International audienc

A new L-dwarf member of the moderately metal-poor triple system HD 221356

We report on the discovery of a fourth component in the HD 221356 star system, previously known to be formed by an F8V, slightly metal-poor primary ([Fe/H]=-0.26), and a distant M8V+L3V pair. In our ongoing common proper motion search based on VISTA Hemisphere Survey (VHS) and 2MASS catalogues, we have detected a faint (J=13.76+/-0.04 mag) co-moving companion of the F8 star located at angular separation of 12.13+/-0.18 arcsec (position angle of 221.8+/-1.7), corresponding to a projected distance of ~312 AU at 26 pc. Near-infrared spectroscopy of the new companion, covering the 1.5-2.4 micron wavelength range with a resolving power of R~600, indicates an L1+/-1 spectral type. Using evolutionary models the mass of the new companion is estimated at ~0.08 solar masses, which places the object close to the stellar-substellar borderline. This multiple system provides an interesting example of objects with masses slightly above and below the hydrogen burning mass limit. The low mass companions of HD 221356 have slightly bluer colours than field dwarfs with similar spectral type, which is likely a consequence of the sub-solar metallicity of the system.Comment: 7 pages, 4 figures, accepted for publication in MNRA

A Photometric Study of the Light Variations of the Triple System DG Leonis

Multi-site and multi-year differential photometry of the triple star DG Leo reveals a complex frequency spectrum that can be modelled as the combination of at least three Delta Scuti type frequencies in the range 11.5-13 c/d (with semi-amplitudes of 2-7 mmag) and a superimposed slow variability of larger amplitude. The period of the slow variation fits very well with half the orbital period of the inner spectroscopic binary indicating the presence of ellipsoidal variations caused by the tidally deformed components in a close configuration. These findings, together with the results of a recent spectroscopic analysis (showing that the system consists of a pair of mild Am stars and one A-type component of normal solar composition), infer that DG Leo is an extremely interesting asteroseismic target. Identification of which component(s) of this multiple system is (or are) pulsating and determination of the excited pulsation modes will both contribute to a much better understanding of the non-trivial link between multiplicity, chemical composition, rotation, and pulsation in the lower part of the classical Cepheid instability strip.Comment: 10 pages, 5 Postscript figures, uses rotate.sty. Astronomy and Astrophysics, in press (2005

A chromosome-level genome assembly enables the identification of the follicule stimulating hormone receptor as the master sex determining gene in the flatfish Solea senegalensis

Sex determination (SD) shows huge variation among fish and a high evolutionary rate, as illustrated by the Pleuronectiformes (flatfishes). This order is characterized by its adaptation to demersal life, compact genomes and diversity of SD mechanisms. Here, we assembled the Solea senegalensis genome, a flatfish of great commercial value, into 82 contigs (614 Mb) combining long- and short-read sequencing, which were next scaffolded using a highly dense genetic map (28,838 markers, 21 linkage groups), representing 98.9% of the assembly. Further, we established the correspondence between the assembly and the 21 chromosomes by using BAC-FISH. Whole genome resequencing of six males and six females enabled the identification of 41 SNP variants in the follicle stimulating hormone receptor (fshr) consistent with an XX / XY SD system. The observed sex association was validated in a broader independent sample, providing a novel molecular sexing tool. Fshr displayed differential gene expression between male and female gonads from 86 days post-fertilization, when the gonad is still an undifferentiated primordium, concomitant with the activation of amh and cyp19a1a, testis and ovary marker genes, respectively, in males and females. The Y-linked fshr allele, which included 24 non-synonymous variants and showed a highly divergent 3D protein structure, was overexpressed in males compared to the X-linked allele at all stages of gonadal differentiation. We hypothesize a mechanism hampering the action of the follicle stimulating hormone driving the undifferentiated gonad toward testis.info:eu-repo/semantics/acceptedVersio

Causes of hOCT1-dependent cholangiocarcinoma resistance to sorafenib and sensitization by tumor-selective gene therapy

Although the multi-tyrosine kinase inhibitor sorafenib is useful in the treatment of several cancers, cholangiocarcinoma (CCA) is refractory to this drug. Among other mechanisms of chemoresistance, impaired uptake through human organic cation transporter type 1 (hOCT1) (gene SLC22A1) has been suggested. Here we have investigated the events accounting for this phenotypic characteristic and have evaluated the interest of selective gene therapy strategies to overcome this limitation. Gene expression and DNA methylation of SLC22A1 were analyzed using intrahepatic (iCCA) and extrahepatic (eCCA) biopsies (Copenhagen and Salamanca cohorts; n = 132) and The Cancer Genome Atlas (TCGA)-CHOL (n = 36). Decreased hOCT1 mRNA correlated with hypermethylation status of the SLC22A1 promoter. Treatment of CCA cells with decitabine (demethylating agent) or butyrate (histone deacetylase inhibitor) restored hOCT1 expression and increased sorafenib uptake. MicroRNAs able to induce hOCT1 mRNA decay were analyzed in paired samples of TCGA-CHOL (n = 9) and Copenhagen (n = 57) cohorts. Consistent up-regulation in tumor tissue was found for miR-141 and miR-330. High proportion of aberrant hOCT1 mRNA splicing in CCA was also seen. Lentiviral-mediated transduction of eCCA (EGI-1 and TFK-1) and iCCA (HuCCT1) cells with hOCT1 enhanced sorafenib uptake and cytotoxic effects. In chemically induced CCA in rats, reduced rOct1 expression was accompanied by impaired sorafenib uptake. In xenograft models of eCCA cells implanted in mouse liver, poor response to sorafenib was observed. However, tumor growth was markedly reduced by cotreatment with sorafenib and adenoviral vectors encoding hOCT1 under the control of the BIRC5 promoter, a gene highly up-regulated in CCA. Conclusion: The reason for impaired hOCT1-mediated sorafenib uptake by CCA is multifactorial. Gene therapy capable of selectively inducing hOCT1 in tumor cells can be considered a potentially useful chemosensitization strategy to improve the response of CCA to sorafenib

Str\"omgren photometry and spectroscopy of the Delta Scuti stars 7 Aql and 8 Aql

Photometric $(ubvy-\beta$) and spectroscopic observations of the $\delta$ Scuti variables \astrobj{7 Aql} and \astrobj{8 Aql} are described. The Str\"omgren standard indices and physical parameters of both stars are derived. Spectral types of F0V and F2III have been assigned to \astrobj{7 Aql} and \astrobj{8 Aql} respectively considering the results from both spectroscopy and photometry. Differential $uvby$ light curves were also analyzed. A attempt of multicolour mode identification is carried out.Comment: 6 pages, 7 figures, 4 tables, accepted for publication in New Astronom

Releyendo el fenómeno de la neolitización en el Bajo Aragón a la luz de la excavación del Cingle de Valmayor XI (Mequinenza, Zaragoza)

Este trabajo presenta los resultados preliminares obtenidos en la excavación del Cingle de Valmayor XI, desarrollada dentro del proyecto de investigación ‘Los caminos del Neolítico’. A través del análisis de las dataciones radiocarbónicas y de una detallada lectura estratigráfica se han podido establecer tres horizontes de ocupación diferentes con cronologías que corresponden a distintos momentos del vi milenio cal bc. Se ofrece una descripción general de los eventos arqueológicos documentados en cada una de estas fases, así como de gran parte del material recuperado –cerámica, lítica, industria ósea, elementos de adorno, fauna y restos carpológicos–. Por otra parte, a la luz de las nuevas dataciones presentadas, se propone una revisión del fenómeno de la neolitización en la región del Bajo Aragón y, por extensión, en todo el valle del Ebro; también se cuestiona la identificación de contextos como propios de economías productoras simplemente a través de la presencia de ciertos elementos materiales considerados tradicionalmente como ‘marcadores neolíticos’, sin que existan variaciones con respecto a las estrategias subsistenciales o de explotación del territorio

The influence of heart disease on characteristics, quality of life, use of health resources, and costs of COPD in primary care settings

<p>Abstract</p> <p>Background</p> <p>To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions.</p> <p>Methods</p> <p>Epidemiologic, observational, and descriptive study (EPIDEPOC study). Patients ≥ 40 years of age with stable COPD attending primary care settings were included. Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected. Results were compared between patients with or without associated heart disease.</p> <p>Results</p> <p>A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males. When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease. Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease. Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases. The annual total cost per patient was significantly higher in patients with heart disease; 2,937 ± 2,957 vs. 1,749 ± 2,120, p < 0.05. Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost.</p> <p>Conclusion</p> <p>Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease.</p