Switching from natalizumab to fingolimod: an observational study

Background – Multiple sclerosis patients who discontinue using natalizumab are at risk of a rebound in disease activity. However, the optimal alternative therapy is not currently known. Aims of the study – We report on clinical and MRI data and patient safety in a group of relapsing–remitting multiple sclerosis patients who tested seropositive for the JC virus and who have switched from natalizumab to fingolimod because of concerns regarding PML risks. Methods – The test for JC virus antibodies was performed in 18 relapsing–remitting multiple sclerosis patients who were being treated with natalizumab for more than 1 year. Eight seropositive patients switched to fingolimod while the seronegative patients continued with natalizumab. Results – After switching to fingolimod, five of eight patients (63%) experienced clinical relapses, and MRI activity was detected in six of eight patients (75%). Neither clinical relapses nor MRI activity was observed in the patients who continued with natalizumab. No serious adverse effects were detected. Conclusions – Natalizumab is an effective treatment for relapsing–remitting multiple sclerosis, but its discontinuation continues to be a complex problem. All of the therapies tried thus far, including fingolimod, have been unable to control the reactivation of the disease. Further studies addressing alternative therapies after natalizumab discontinuation are necessary

A semantic interoperability approach to support integration of gene expression and clinical data in breast cancer

[Abstract] Introduction. The introduction of omics data and advances in technologies involved in clinical treatment has led to a broad range of approaches to represent clinical information. Within this context, patient stratification across health institutions due to omic profiling presents a complex scenario to carry out multi-center clinical trials. Methods. This paper presents a standards-based approach to ensure semantic integration required to facilitate the analysis of clinico-genomic clinical trials. To ensure interoperability across different institutions, we have developed a Semantic Interoperability Layer (SIL) to facilitate homogeneous access to clinical and genetic information, based on different well-established biomedical standards and following International Health (IHE) recommendations. Results. The SIL has shown suitability for integrating biomedical knowledge and technologies to match the latest clinical advances in healthcare and the use of genomic information. This genomic data integration in the SIL has been tested with a diagnostic classifier tool that takes advantage of harmonized multi-center clinico-genomic data for training statistical predictive models. Conclusions. The SIL has been adopted in national and international research initiatives, such as the EURECA-EU research project and the CIMED collaborative Spanish project, where the proposed solution has been applied and evaluated by clinical experts focused on clinico-genomic studies.Instituto de Salud Carlos III, PI13/02020Instituto de Salud Carlos III, PI13/0028

GATE : a simulation toolkit for PET and SPECT

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols, and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at the address http://www-lphe.epfl.ch/GATE/

Increased glycolipid storage produced by the inheritance of a complex intronic haplotype in the α-galactosidase A (GLA) gene

BACKGROUND: Accumulation of galactosphingolipids is a general characteristic of Fabry disease, a lysosomal storage disorder caused by the deficient activity of α-galactosidase A encoded by the GLA gene. Although many polymorphic GLA haplotypes have been described, it is still unclear whether some of these variants are causative of disease symptoms. We report the study of an inheritance of a complex intronic haplotype (CIH) (c.-10C > T, c.369 + 990C > A, c.370-81_370-77delCAGCC, c.640-16A > G, c.1000-22C > T) within the GLA gene associated with Fabry-like symptoms and galactosphingolipid accumulation. We analysed α-Gal A activity in plasma, leukocytes and skin fibroblasts in patients, and measured accumulation of galactosphingolipids by enzymatic methods and immunofluorescence techniques. Additionally, we evaluated GLA expression using quantitative PCR, EMSA, and cDNA cloning. RESULTS: CIH carriers had an altered GLA expression pattern, although most of the carriers had high residual enzyme activity in plasma, leukocytes and in skin fibroblasts. Nonetheless, CIH carriers had significant galactosphingolipid accumulation in fibroblasts in comparison with controls, and also glycolipid deposits in renal tubules and glomeruli. EMSA assays indicated that the c.-10C > T variant in the promoter affected a nuclear protein binding site. CONCLUSIONS: Thus, inheritance of the CIH caused an mRNA deregulation altering the GLA expression pattern, producing a tissue glycolipid storage

The ANTARES Optical Beacon System

ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented.Comment: 21 pages, 18 figures, submitted to Nucl. Instr. and Meth. Phys. Res.

Correspondence: Strongly-driven Re + CO2 redox reaction at high-pressure and high-temperature

Santamaría-Perez, D.; Mcguire, C.; Makhluf, A.; Kavner, A.; Chulia-Jordan, R.; Jorda Moret, JL.; Rey Garcia, F.... (2016). Correspondence: Strongly-driven Re + CO2 redox reaction at high-pressure and high-temperature. Nature Communications. 7:1-3. doi:10.1038/ncomms13647S137Yoo, C. S. et al. Crystal structure of carbon dioxide at high pressure: “superhard” polymeric carbon dioxide. Phys. Rev. Lett. 83, 5527–5530 (1999).Santoro, M. et al. Partially collapsed cristobalite structure in the non molecular phase V in CO2 . Proc. Natl Acad. Sci. 109, 5176–5179 (2012).Datchi, F., Mallick, B., Salamat, A. & Ninet, S. Structure of polymeric carbon dioxide CO2-V. Phys. Rev. Lett. 108, 125701 (2012).Santoro, M. et al. Silicon carbonate phase formed from carbon dioxide and silica under pressure. Proc. Natl Acad. Sci. 108, 7689–7692 (2011).Santoro, M. et al. Carbon enters silica forming a cristobalite-type CO2.SiO2 solid solution. Nat. Commun. 5, 3761 (2014).Corma, A., Rey, F., Rius, J., Sabater, M. J. & Valencia, S. Supramolecular self-assembled molecules as organic directing agent for synthesis of zeolites. Nature 431, 287–290 (2004).Guth, J.-L., Kessler, H. & Wey, R. in Studies in Surface Science and Catalysis Vol. 28 (eds Murakami, Y., Iijima, A. & Ward, J. W.) 121 (Kodansha-Elsevier, 1986).Santamaria-Perez, D. et al. Exploring the chemical reactivity between carbon dioxide and three transition metals (Au, Pt, and Re) at high-pressure high-temperature conditions. Inorg. Chem. 55, 10793–10799 (2016).Magneli, A. Studies on rhenium oxides. Acta Chem. Scand. 11, 28–33 (1957)

Critical pathways for the management of preeclampsia and severe preeclampsia in institutionalised health care settings

BACKGROUND: Preeclampsia is a complex disease in which several providers should interact continuously and in a coordinated manner to provide proper health care. However, standardizing criteria to treat patients with preeclampsia is problematical and severe flaws have been observed in the management of the disease. This paper describes a set of critical pathways (CPs) designed to provide uniform criteria for clinical decision-making at different levels of care of pregnant patients with preeclampsia or severe preeclampsia. METHODS: Clinicians and researchers from different countries participated in the construction of the CPs. The CPs were developed using the following steps: a) Definition of the conceptual framework; b) Identification of potential users: primary care physicians and maternal and child health nurses in ambulatory settings; ob/gyn and intensive care physicians in secondary and tertiary care levels. c) Structural development. RESULTS: The CPs address the following care processes: 1. Screening for preeclampsia, risk assessment and classification according to the level of risk. 2. Management of preeclampsia at primary care clinics. 3. Evaluation and management of preeclampsia at secondary and tertiary care hospitals: 4. Criteria for clinical decision-making between conservative management and expedited delivery of patients with severe preeclampsia. CONCLUSION: Since preeclampsia continues to be one of the primary causes of maternal deaths and morbidity worldwide, the expected impact of these CPs is the contribution to improving health care quality in both developed and developing countries. The CPs are designed to be applied in a complex health care system, where different physicians and health providers at different levels of care should interact continuously and in a coordinated manner to provide care to all preeclamptic women. Although the CPs were developed using evidence-based criteria, they could require careful evaluation and remodelling according to each system's demands. Additionally, the CPs need to be tested in large-scale, multi-level studies in order to thoroughly examine and evaluate their efficacy and effectiveness