First investigation of a novel 2D position-sensitive semiconductor detector concept

This paper presents a first study of the performance of a novel 2D position-sensitive microstrip detector, where the resistive charge division method was implemented by replacing the metallic electrodes with resistive electrodes made of polycrystalline silicon. A characterization of two proof-of-concept prototypes with different values of the electrode resistivity was carried out using a pulsed Near Infra-Red laser. The experimental data were compared with the electrical simulation of the sensor equivalent circuit coupled to simple electronics readout circuits. The good agreement between experimental and simulation results establishes the soundness of resistive charge division method in silicon microstrip sensors and validates the developed simulation as a tool for the optimization of future sensor prototypes. Spatial resolution in the strip length direction depends on the ionizing event position. The average value obtained from the protype analysis is close to 1.2% of the strip length for a 6 MIP signal.Comment: 14 pages, 12 figure

Texture analysis in gel electrophoresis images using an integrative kernel-based approach

[Abstract] Texture information could be used in proteomics to improve the quality of the image analysis of proteins separated on a gel. In order to evaluate the best technique to identify relevant textures, we use several different kernel-based machine learning techniques to classify proteins in 2-DE images into spot and noise. We evaluate the classification accuracy of each of these techniques with proteins extracted from ten 2-DE images of different types of tissues and different experimental conditions. We found that the best classification model was FSMKL, a data integration method using multiple kernel learning, which achieved AUROC values above 95% while using a reduced number of features. This technique allows us to increment the interpretability of the complex combinations of textures and to weight the importance of each particular feature in the final model. In particular the Inverse Difference Moment exhibited the highest discriminating power. A higher value can be associated with an homogeneous structure as this feature describes the homogeneity; the larger the value, the more symmetric. The final model is performed by the combination of different groups of textural features. Here we demonstrated the feasibility of combining different groups of textures in 2-DE image analysis for spot detection.Instituto de Salud Carlos III; PI13/00280United Kingdom. Medical Research Council; G10000427, MC_UU_12013/8Galicia. Consellería de Economía e Industria; 10SIN105004P

Functional and molecular characterization of inherited platelet disorders in the Iberian Peninsula: results from a collaborative study

BACKGROUND: The diagnostic evaluation of inherited platelet disorders (IPDs) is complicated and time-consuming, resulting in a relevant number of undiagnosed and incorrectly classified patients. In order to evaluate the spectrum of IPDs in individuals with clinical suspicion of these disorders, and to provide a diagnostic tool to centers not having access to specific platelets studies, we established the project "Functional and Molecular Characterization of Patients with Inherited Platelet Disorders" under the scientific sponsorship of the Spanish Society of Thrombosis and Haemostasis. PATIENTS/METHODS: Subjects were patients from a prospective cohort of individuals referred for clinical suspicion of IPDs as well as healthy controls. Functional studies included light transmission aggregation, flow cytometry, and when indicated, Western-blot analysis of platelet glycoproteins, and clot retraction analysis. Genetic analysis was mainly performed by sequencing of coding regions and proximal regulatory regions of the genes of interest. RESULTS: Of the 70 cases referred for study, we functionally and molecularly characterized 12 patients with Glanzmann Thrombasthenia, 8 patients with Bernard Soulier syndrome, and 8 with other forms of IPDs. Twelve novel mutations were identified among these patients. The systematic study of patients revealed that almost one-third of patients had been previously misdiagnosed. CONCLUSIONS: Our study provides a global picture of the current limitations and access to the diagnosis of IPDs, identifies and confirms new genetic variants that cause these disorders, and emphasizes the need of creating reference centers that can help health care providers in the recognition of these defects

Actividad física y acelerometría: orientaciones metodológicas, recomendaciones y patrones de movimiento en escolares

Introducción: En los últimos años, ha cobrado especial importancia el empleo de acelerómetros para valorar la actividad física de niños y jóvenes. La metodología utilizada en el uso de la acelerometría determina los resultados obtenidos y condiciona la posibilidad de comparar diferentes estudios. Objetivo: El objetivo de esta revisión, se centra en aspectos metodológicos relacionados con la evaluación de la actividad física en escolares utilizando la acelerometría. Metodología: Se realizó una revisión de la literatura de los artículos incluidos en las bases de datos Medline/ Pubmed y Scielo que utilizaran acelerómetros con participantes en edad escolar entre Enero de 2002 y Agosto de 2013, seleccionándose 133 artículos científicos. Resultados: Parece existir un cierto consenso respecto a la elección del lugar de colocación, el tiempo de registro y el empleo de epochs cada vez más reducidos; sin embargo, se encuentra una gran variabilidad respecto al modelo de acelerómetro empleado y los puntos de corte seleccionados. Discusión y Conclusiones: Los diferentes criterios empleados, dificultan la comparación en la metodología empleada entre estudios a pesar de que existan ciertos puntos en común entre ellos. Introduction: Over the last years, the use of accelerometers has become relevant to quantify physical activity among youth. Methods used with accelerometers might modify the results and the possibility to compare different papers. These devices have been proved to be effective and valid quantifying long periods of physical activity compared to other methods. Objective: To show methodological criteria regarding physical activity assessed by accelerometry with schoolars. Methodology: It was conducted a review of the literature related to accelerometers and scholar-aged subjects at PubMed from January 2002 to August 2013, selecting 133 papers. Results: As far as it is shown, it appears to be some tendencies related to the choice of attachment of the device, wearing time and a shorter epoch-length; however, it has been found a wide variability regarding the model of accelerometer and cutoff points used. Discussion and Conclusions: The different criterion used makes it difficult to compare methodological aspects among studies in spite of some papers carried out similar methods

Ess target performance for different beam pulses

Last trends in the design of linear accelerators for high power spallation sources point to the use of ion beams of larger energies and shorter pulse lengths in order to enhance the reliability of the system. In this sense the recommendations for ESS are to increase the energy of the proton beam from 1.3GeV to 2-2.5GeV and to reduce the length of the beam pulse from 2ms to 1-1.5ms, keeping the source average power at 5MW. Different values for the repetition rate are also being discussed (16 2/3, 20, 25 Hz). ESS Bilbao is analyzing the impact of these modifications on the design of the target system. In this paper the effects of the different beam energies on the target disc thermohydraulics and the neutron performance of the source are discussed. Initial calculations were performed for a rotating target with ESS 2002 parameters. During the development of the work –that are being performed in collaboration with SNS– the decision was made to use the SNS-STS Target-Moderator-Reflector Assembly (TMRA) –slightly modified to accommodate the target design being studied for ESS– which presents a state of the art design with a cylindrical liquid para-hydrogen moderator in wing configuration aimed to enhance cold neutron productio

Heterogenous presence of neutrophil extracellular traps in human solid tumours is partially dependent on IL-8

Neutrophil extracellular traps (NETs) are webs of extracellular nuclear DNA extruded by dying neutrophils infiltrating tissue. NETs constitute a defence mechanism to entrap and kill fungi and bacteria. Tumours induce the formation of NETs to the advantage of the malignancy via a variety of mechanisms shown in mouse models. Here, we investigated the presence of NETs in a variety of human solid tumours and their association with IL-8 (CXCL8) protein expression and CD8+ T-cell density in the tumour microenvironment. Multiplex immunofluorescence panels were developed to identify NETs in human cancer tissues by co-staining with the granulocyte marker CD15, the neutrophil marker myeloperoxidase and citrullinated histone H3 (H3Cit), as well as IL-8 protein and CD8+ T cells. Three ELISA methods to detect and quantify circulating NETs in serum were optimised and utilised. Whole tumour sections and tissue microarrays from patients with non-small cell lung cancer (NSCLC; n = 14), bladder cancer (n = 14), melanoma (n = 11), breast cancer (n = 31), colorectal cancer (n = 20) and mesothelioma (n = 61) were studied. Also, serum samples collected retrospectively from patients with metastatic melanoma (n = 12) and NSCLC (n = 34) were ELISA assayed to quantify circulating NETs and IL-8. NETs were detected in six different human cancer types with wide individual variation in terms of tissue density and distribution. At least in NSCLC, bladder cancer and metastatic melanoma, NET density positively correlated with IL-8 protein expression and inversely correlated with CD8+ T-cell densities. In a series of serum samples from melanoma and NSCLC patients, a positive correlation between circulating NETs and IL-8 was found. In conclusion, NETs are detectable in formalin-fixed human biopsy samples from solid tumours and in the circulation of cancer patients with a considerable degree of individual variation. NETs show a positive association with IL-8 and a trend towards a negative association with CD8+ tumour-infiltrating lymphocytes

Present Status and Future Programs of the n_TOF Experiment

This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial License 3.0, which permits unrestricted use, distribution, and reproduction in any noncommercial medium, provided the original work is properly citedThe neutron time-of-flight facility n_TOF at CERN, Switzerland, operational since 2001, delivers neutrons using the Proton Synchrotron (PS) 20 GeV/c proton beam impinging on a lead spallation target. The facility combines a very high instantaneous neutron flux, an excellent time of flight resolution due to the distance between the experimental area and the production target (185 meters), a low intrinsic background and a wide range of neutron energies, from thermal to GeV neutrons. These characteristics provide a unique possibility to perform neutron-induced capture and fission cross-section measurements for applications in nuclear astrophysics and in nuclear reactor technology.The most relevant measurements performed up to now and foreseen for the future will be presented in this contribution. The overall efficiency of the experimental program and the range of possible measurements achievable with the construction of a second experimental area (EAR-2), vertically located 20 m on top of the n_TOF spallation target, might offer a substantial improvement in measurement sensitivities. A feasibility study of the possible realisation of the installation extension will be also presented

Phase II Trial of Neoadjuvant Sitravatinib Plus Nivolumab in Patients Undergoing Nephrectomy for Locally Advanced Clear Cell Renal Cell Carcinoma

Sitravatinib is an immunomodulatory tyrosine kinase inhibitor that can augment responses when combined with programmed death-1 inhibitors such as nivolumab. We report a single-arm, interventional, phase 2 study of neoadjuvant sitravatinib in combination with nivolumab in patients with locally advanced clear cell renal cell carcinoma (ccRCC) prior to curative nephrectomy (NCT03680521). The primary endpoint was objective response rate (ORR) prior to surgery with a null hypothesis ORR = 5% and the alternative hypothesis set at ORR = 30%. Secondary endpoints were safety; pharmacokinetics (PK) of sitravatinib; immune effects, including changes in programmed cell death-ligand 1 expression; time-to-surgery; and disease-free survival (DFS). Twenty patients were evaluable for safety and 17 for efficacy. The ORR was 11.8%, and 24-month DFS probability was 88·0% (95% CI 61.0 to 97.0). There were no grade 4/5 treatment-related adverse events. Sitravatinib PK did not change following the addition of nivolumab. Correlative blood and tissue analyses showed changes in the tumour microenvironment resulting in an immunologically active tumour by the time of surgery (median time-to-surgery: 50 days). The primary endpoint of this study was not met as short-term neoadjuvant sitravatinib and nivolumab did not substantially increase ORR