Current developments in gene therapy for amyotrophic lateral sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating adult neurodegenerative disorder characterized by motor neuron degeneration and death around 3 years from onset. So far, riluzole is the only treatment available, although it only offers a slight increase in survival. The complex etiology of ALS, with several genes able to trigger the disease, makes its study difficult. Areas covered: RNA-mediated or protein-mediated toxic gain-of-function leading to motor neuron degeneration appears to be likely common pathogenic mechanisms in ALS. Consequently, gene therapy technologies to reduce toxic RNA and/or proteins and to protect motor neurons by modulating gene expression are at the forefront of the field. Here, we review the most promising scientific advances, paying special attention to the successful treatments tested in animal models as well as analyzing relevant gene therapy clinical trials. Expert opinion: Despite broad advances in target gene identification in ALS and advances in gene therapy technologies, a successful gene therapy for ALS continues to elude researchers. Multiple hurdles encompassing technical, biological, economical and clinical challenges must be overcome before a therapy for patients becomes available. Optimism remains due to positive results obtained in several in vivo studies demonstrating significant disease amelioration in animal models of ALS

Validación del monitor de medición de la grasa corporal por impedancia bioeléctrica OMRON BF 300

ObjetivosValorar la precisión del monitor de grasa corporal por impedancia bioeléctrica OMRON BF 300 y validar su medición del porcentaje de grasa corporal (%GC) frente a la ecuación de Siri. Diseño. Estudio descriptivo, transversal.EmplazamientoAtención primaria. Centros de Salud Coronel de Palma y San Fernando, Móstoles.ParticipantesEn la valoración de la precisión del monitor participaron 88 personas y 91 en la validación.Mediciones y resultados principalesLas determinaciones de %GC se realizaron por triplicado, anotándose la media. La precisión se evaluó mediante el coeficiente de correlación intraclase (CCI) y el coeficiente de variación (CV). La validez, mediante el error técnico, el CCI y el método de Bland-Altman. En la ecuación de Siri la densidad corporal se calculó con la ecuación de Durnin-Womersley. Precisión: el CCI fue de 0,999 y el CV de 0,4 ± 0,03. Validación: la diferencia de %GC monitor (26,6 ± 9,1%) – ecuación de Siri (27,8 ± 8,2%) fue de –1,27% (p < 0,01; IC del 95%, –1,97 a –0,57), el error técnico del monitor del 2,2% y el CCI de 0,956 (IC del 95%, 0,9335–0,9710), situándose un 80,2% de las diferencias monitor – ecuación por debajo del 5%, con un intervalo de concordancia por el método de Bland-Altman de +5,45 a –7,99%.ConclusionesEl monitor OMRON BF 300 satisface los criterios de precisión (CCI > 0,95 y CV bajo) y validación (error técnico excelente, CCI > 0,75 y diferencias clínicamente aceptables) y supone una alternativa válida a los pliegues cutáneos en la valoración nutricional del paciente.ObjectivesTo assess the accuracy of the OMRON BF 300 body fat monitor using bioelectric impedance and to validate its measurement of body fat percentage (BF%) against the Siri equation.DesignCross-sectional descriptive study.SettingPrimary care. Coronel de Palma and San Fernando Health Centres, Móstoles.Participants88 people took part in the assessment of the accuracy of the monitor, and 91 in the validation.Measurements and main resultsThe BF% were recorded in triplicate, with the mean being the figure noted. Precision was evaluated through the intra-class correlation coefficient (ICC) and the coefficient of variation (CV); validity, through technical error, the ICC and the Bland-Altman method. In the Siri equation, body density was calculated through the Durnin-Womersley equation. Precision: ICC was 0.999 and CV 0.4 ± 0.03. Validation: the difference between the BF% monitor (26.6 ± 9.1%) and the Siri equation (27.8 ± 8.2%) was –1.27% (p < 0.01; 95% CI –1.97 to –0.57); the technical error of the monitor was 2.2% and of the ICC 0.956 (95% CI, 0.9335–0.9710). Thus, 80.2% of the monitor-equation differences were below 5%, with a concordance interval under the Bland-Altman method of +5.45 to –7.99%.ConclusionsThe OMRON BF 300 monitor satisfies the precision criteria (ICC > 0.95 and low CV) and validation (excellent technical error, ICC > 0.75 and clinically acceptable differences) and is a valid alternative to cutaneous folds as a method of assessing nutrition of the patient

Survey explores active tectonics in Northeastern Caribbean

There is renewed interest in studying the active and complex northeastern Caribbean plate boundary to better understand subduction zone processes and for earthquake and tsunami hazard assessments [e.g., ten Brink and Lin, 2004; ten Brink et al., 2004; Grindlay et al, 2005]. To study the active tectonics of this plate boundary, the GEOPRICO-DO (Geological, Puerto Rico-Dominican) marine geophysical cruise, carried out between 28 March and 17 April 2005 (Figure 1), studied the active tectonics of this plate boundary. Initial findings from the cruise have revealed a large underwater landslide, and active faults on the seafloor (Figures 2a and 2c). These findings indicate that the islands within this region face a high risk from tsunami hazards, and that local governments should be alerted in order to develop and coordinate possible mitigation strategies. The cruise collected multibeam bathymetry, gravity, magnetic, high-resolution seismic, deep seismic sounding, and multichannel seismic reflection data, which are currently being processed and interpreted (Table 1). In early November 2005, 10 ocean-bottom seismometers (OBS) that had been deployed northeast of Puerto Rico and the Virgin Islands (Figure 1) during the cruise were recovered. These OBS recorded data during the cruise and the local seismicity between April and October 2005

A new scenario in metastatic renal cell carcinoma: a SOG‑GU consensus

[Abstract] Background This article describes and compares approved targeted therapies and the newer immunotherapy agents. Materials and methods This article especially performs an in-depth review of currently available data for tivozanib, explaining its mechanism of action, its safety profle and its role as an efcacy drug in the management of renal cancer. Results Despite the fact that the treatment of advanced RCC has been dramatically modifed in recent years, durable remissions are scarce and it remains a lethal disease. For frst- and second-line therapy, there is now growing evidence to guide the selection of the appropriate treatment. Conclusions Several TKIs are standard of care at diferent settings. Among those approved TKIs, tivozanib has similar efcacy than others with a better safety profle. The use of prognostic factors is critical to the selection of optimal therapy

Fermion-Boson Interactions and Quantum Algebras

Quantum Algebras (q-algebras) are used to describe interactions between fermions and bosons. Particularly, the concept of a su_q(2) dynamical symmetry is invoked in order to reproduce the ground state properties of systems of fermions and bosons interacting via schematic forces. The structure of the proposed su_q(2) Hamiltonians, and the meaning of the corresponding deformation parameters, are discussed.Comment: 20 pages, 10 figures. Physical Review C (in press

QUIJOTE scientific results - III. Microwave spectrum of intensity and polarization in the Taurus Molecular Cloud complex and L1527

ABSTRACT: We present new intensity and polarization observations of the Taurus Molecular Cloud (TMC) region in the frequency range 10–20 GHz with the multifrequency instrument (MFI) mounted on the first telescope of the Q-U-I-JOint TEnerife (QUIJOTE) experiment. From the combination of the QUIJOTE data with the WMAP 9-yr data release, the Planck second data release, the DIRBE maps, and ancillary data, we detect an anomalous microwave emission (AME) component with flux density SAME,peak = 43.0 ± 7.9 Jy in the TMC and SAME,peak = 10.7 ± 2.7 Jy in the dark cloud nebula L1527, which is part of the TMC. In the TMC the diffuse AME emission peaks around a frequency of 19 GHz, compared with an emission peak about a frequency of 25 GHz in L1527. In the TMC, the best constraint on the level of AME polarization is obtained at the Planck channel of 28.4 GHz, with an upper limit πAME < 4.2 per cent (95 per cent C.L.), which reduces to πAME < 3.8 per cent (95 per cent C.L.) if the intensity of all the free–free, synchrotron and thermal dust components are negligible at this frequency. The same analysis in L1527 leads to πAME < 5.3 per cent (95 per cent C.L.) or πAME < 4.5 per cent (95 per cent C.L.) under the same assumption. We find that in the TMC and L1527 on average about 80 per cent of the H II gas should be mixed with thermal dust. Our analysis shows how the QUIJOTE-MFI 10–20 GHz data provide key information to properly separate the synchrotron, free–free, and AME components.This work has been partially funded by the Spanish Ministry of Economy and Competitiveness (MINECO) under the projects AYA2007-68058-C03-01, AYA2010-21766-C03-02, AYA2012-39475-C02-01, AYA2014-60438-P: ESP2015- 70646.C2-1-R, AYA2015-64508-P and the Consolider-Ingenio project CSD2010-00064 (EPI: Exploring the Physics of Inflation)

The QUIJOTE experiment: project overview and first results

QUIJOTE (Q-U-I JOint TEnerife) is a new polarimeter aimed to characterize the polarization of the Cosmic Microwave Background and other Galactic and extragalactic signals at medium and large angular scales in the frequency range 10-40 GHz. The multi-frequency (10-20~GHz) instrument, mounted on the first QUIJOTE telescope, saw first light on November 2012 from the Teide Observatory (2400~m a.s.l). During 2014 the second telescope has been installed at this observatory. A second instrument at 30~GHz will be ready for commissioning at this telescope during summer 2015, and a third additional instrument at 40~GHz is now being developed. These instruments will have nominal sensitivities to detect the B-mode polarization due to the primordial gravitational-wave component if the tensor-to-scalar ratio is larger than r=0.05.Comment: To appear in "Highlights of Spanish Astrophysics VIII", Proceedings of the XI Scientific Meeting of the Spanish Astronomical Society, Teruel, Spain (2014

Planck intermediate results. XXXVI. Optical identification and redshifts of Planck SZ sources with telescopes at the Canary Islands observatories

Catalogs and data.-- et al.We present the results of approximately three years of observations of Planck Sunyaev-Zeldovich (SZ) sources with telescopes at the Canary Islands observatories as part of the general optical follow-up programme undertaken by the Planck Collaboration. In total, 78 SZ sources are discussed. Deep-imaging observations were obtained for most of these sources; spectroscopic observations in either in long-slit or multi-object modes were obtained for many. We effectively used 37.5 clear nights. We found optical counterparts for 73 of the 78 candidates. This sample includes 53 spectroscopic redshift determinations, 20 of them obtained with a multi-object spectroscopic mode. The sample contains new redshifts for 27 Planck clusters that were not included in the first Planck SZ source catalogue (PSZ1).The Planck Collaboration acknowledges the support of: ESA; CNES, and CNRS/INSU-IN2P3-INP (France); ASI, CNR, and INAF (Italy); NASA and DoE (USA); STFC and UKSA (UK); CSIC, MINECO, JA and RES (Spain); Tekes, AoF, and CSC (Finland); DLR and MPG (Germany); CSA (Canada); DTU Space (Denmark); SER/SSO (Switzerland); RCN (Norway); SFI (Ireland); FCT/MCTES (Portugal); ERC and PRACE (EU). A.S., R.B., H.L., and J.A.R.M. acknowledge financial support from the Spanish Ministry of Economy and Competitiveness (MINECO) under the 2011 Severo Ochoa Program MINECO SEV-2011-0187, and the Consolider-Ingenio project CSD2010-00064 (EPI: Exploring the Physics of Inflation).Peer Reviewe