Clinical Experience of Edaravone in Amyotrophic Lateral Sclerosis

Objective: To describe clinical experience with edaravone in ALS over a period of 12 months Methods:The current study retrospectively investigated characteristics in a group of patients (n=31) with ALS who underwent edaravone treatment. Information including age, gender, race, and site of onset of symptoms were collected for all patients. Adverse events with edaravone therapy was documented where available. Results:The average age of the patients observed was 62.09 years, with 18 males and 13 females. 18 patients had limb onset, 12 bulbar onset, and 1 diaphragmatic onset. 7 of the 31 patients discontinued treatment at the end of one year. The average age of patients who discontinued edaravone was 65.71 years, of whom which 3 had limb onset, 3 bulbar onset, and 1 diaphragmatic onset. No perceived benefit, port complications, systemic bacteremia, and development of atrial fibrillation were documented as reasons for discontinuation of therapy.Conclusion: Edaravone is well tolerated in ALS patients at the end of one year. Lack of perceived benefit and port related complications are common reasons for discontinuation of treatmen

Efecto del tratamiento láser en la resistencia a la corrosión de los aceros dúplex en sales fundidas para componentes de almacenamiento de energía térmica

En aquest projecte s'estudien les capes d'òxid generades sobre la superfície de diferents mostres d'acer inoxidable dúplex DS2205, tractades i no tractades amb una texturització làser, mitjançant l'acció corrosiva de la sal fosa de carbonat LiNaK a 600 °C. D'aquesta manera, es simula el comportament dels materials en l'emmagatzematge d'energia per a centrals d'energia solar concentrada (CSP). L'objectiu és estudiar el comportament del tractament làser en la resistència a la corrosió d'aquests acers. Es preparen diferents mostres que es col·loquen amb la sal en diferents gresols d'alúmina, dins d'un forn durant 150, 300, 500 i 700 hores per a les mostres no tractades, i 150 i 500 hores per a les tractades mitjançant làser. La caracterització d'aquestes mostres es realitza mitjançant tècniques com la microscòpia òptica, microscòpia confocal, difracció de raigs X (XRD), espectroscòpia Raman, microscopi electrònic de rastreig (SEM) i espectroscòpia d'energia dispersiva de raigs X (EDX). Els resultats mostren una generació de doble capa d'òxid més densa, adherent i protectora per a les mostres tractades mitjançant làser.En este proyecto se estudian las capas de óxido generadas sobre la superficie de distintas muestras de acero inoxidable dúplex DS2205, tratadas y no tratadas con una texturización láser, mediante la acción corrosiva de la sal fundida de carbonato LiNaK a 600 ºC. De este modo, se simula el comportamiento de los materiales en el almacenamiento de energía para centrales de energía solar concentrada (CSP). El objetivo es estudiar el comportamiento del tratamiento láser en la resistencia a la corrosión de estos aceros. Se preparan distintas muestras que se colocan junto a la sal en distintos crisoles de alúmina, dentro de un horno durante 150, 300, 500 y 700 horas para las muestras no tratadas, y 150 y 500 horas para las tratadas mediante láser. La caracterización de estas muestras se realiza mediante técnicas como la microscopía óptica, microscopía confocal, difracción de rayos X (XRD), espectroscopia Raman, microscopio electrónico de barrido (SEM) y espectroscopia de energía dispersiva de rayos X (EDX). Los resultados muestran una generación de doble capa de óxido más densa, adherente y protectora para las muestras tratadas mediante láser.This project studies the oxide layers generated on the surface of different samples of duplex stainless steel DS2205, treated and untreated with laser texturization, by the corrosive action of molten LiNaK carbonate salt at 600 ºC. In this way, the behaviour of the materials in energy storage for concentrated solar power (CSP) plants is simulated. The objective is to study the behaviour of laser treatment on the corrosion resistance of these steels. Different samples are prepared and placed together with salt in different alumina crucibles in an oven for 150, 300, 500 and 700 hours for untreated samples, and 150 and 500 hours for laser-treated samples. The characterisation of these samples is carried out using techniques such as optical microscopy, confocal microscopy, X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). The results show a denser, more adherent and protective double oxide layer generation for the laser-treated samples

Evaluation of Two Triplex One-Step qRT-PCR Assays for the Quantification of Human Enteric Viruses in Environmental Samples

Articles not assigned to an issueInternational audienceHuman enteric viruses are responsible for waterborne and shellfish-associated disease outbreaks worldwide. Quantitative reverse transcription PCR (qRT-PCR) is often used to assess the health risks associated with shellfish and environmental water, but viral titres in sediments are less commonly investigated. In this study, we developed and validated two multiplex qRT-PCR assays for aquatic sediment and shellfish samples targeting viruses that are a common cause of gastroenteritis (norovirus GI, GII and hepatitis A virus), two emerging viruses (sapovirus and hepatitis E virus), along with mengovirus (MgV), which is often used as a sample process control for the assessment of RNA extraction efficiency. Singleplex and multiplex assays demonstrated comparable PCR efficiencies and gave reliable results over a wide concentration range. The multiplex assays showed remarkable sensitivity with a limit of detection of 1 RNA copy/µL nucleic acid extract for all target viruses and limits of quantification of 3-18 RNA copies/µL for the targeted human pathogenic viruses and 20-40 RNA copies/µL for MgV. The results demonstrated the veracity of multiplex qRT-PCR for the estimation of viral titres in sediment and shellfish, allowing the rapid assessment of viral infection risks associated with environments exposed to wastewater contamination

Conceptual Design of the Coronagraphic High Angular Resolution Imaging Spectrograph (CHARIS) for the Subaru Telescope

Recent developments in high-contrast imaging techniques now make possible both imaging and spectroscopy of planets around nearby stars. We present the conceptual design of the Coronagraphic High Angular Resolution Imaging Spectrograph (CHARIS), a lenslet-based, cryogenic integral field spectrograph (IFS) for imaging exoplanets on the Subaru telescope. The IFS will provide spectral information for 140x140 spatial elements over a 1.75 arcsecs x 1.75 arcsecs field of view (FOV). CHARIS will operate in the near infrared (lambda = 0.9 - 2.5 microns) and provide a spectral resolution of R = 14, 33, and 65 in three separate observing modes. Taking advantage of the adaptive optics systems and advanced coronagraphs (AO188 and SCExAO) on the Subaru telescope, CHARIS will provide sufficient contrast to obtain spectra of young self-luminous Jupiter-mass exoplanets. CHARIS is in the early design phases and is projected to have first light by the end of 2015. We report here on the current conceptual design of CHARIS and the design challenges

Ambient PM2.5 Exposure Up-regulates the Expression of Costimulatory Receptors on Circulating Monocytes in Diabetic Individuals

BACKGROUND: Exposure of humans to air pollutants such as ozone and particulate matter (PM) may result in airway and systemic inflammation and altered immune function. One putative mechanism may be through modification of cell-surface costimulatory molecules. OBJECTIVES: We examined whether changes in expression of costimulatory molecules on circulating cells are associated with ambient levels of fine PM [aerodynamic diameter ≤ 2.5 μm (PM2.5)] in a susceptible population of diabetic individuals. METHODS: Twenty subjects were studied for 4 consecutive days. Daily measurements of PM2.5 and meteorologic data were acquired on the rooftop of the exam site. Circulating cell-surface markers that mediate innate immune and inflammatory responses were assessed by flow cytometry on each day. Sensitivity analysis was conducted on glutathione S-transferase M1 (GSTM1) genotype, body mass index, and glycosylated hemoglobin A1c (HbA1c) levels to determine their role as effect modifiers. Data were analyzed using random effects models adjusting for season, weekday, and meteorology. RESULTS: We found significantly increased monocyte expression (mean fluorescent intensity) of CD80, CD40, CD86, HLA-DR, and CD23 per 10-μg/m3 increase in PM2.5 at 2- to 4-day lag times after exposure. These findings were significantly higher in obese individuals, in individuals with HbA1c > 7%, and in participants who were GSTM1 null. CONCLUSIONS: Exposure to PM2.5 can enhance antigen-presenting cell phenotypes on circulating cells, which may have consequences in the development of allergic or autoimmune diseases. These effects are amplified in diabetic individuals with characteristics that are associated with insulin resistance or with oxidative stress

Ash-flow sheets of early Miocene and early Pliocene age are present in the Castillo de Callalli, Arequipa Department, southern Perú

Two ash-flow sheets of markedly different age and petrography are exposed in the Castillo de Callalli. The lower, phenocryst-rich ash-flow sheet of low-silica rhyolite has a K-Ar age of 20.7 -+ 0.6 Ma. The overlying ash-flow sheet is composed of sanidine-bearing high-silica rhyolite. An 40Ar/39Ar age of 4.72 +- 0.02 Ma and petrographic characteristics show that the unit is almost certainly the lower ash-flow sheet of the Cailloma Tuff, which in adjacent quadrangles has been mapped variously as Fm. Sencca, Fm. Garza, Fm. Yauri, and Ignimbrita Acopata

Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves

peer-reviewedBackground There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine. Results There was a significant (P < 0.05) increase in BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group alone. Following administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (P < 0.05) rise over the period of study. However, the cell mediated immune response observed didn’t show any significant rise in any of the treatment groups. Conclusion Calves administered the intranasal nanoparticle vaccine induced significantly greater mucosal IgA responses, compared to the other treatment groups. This suggests an enhanced, sustained mucosal-based immunological response to the BPI3V nanoparticle vaccine in the face of pre-existing antibodies to BPI3V, which are encouraging and potentially useful characteristics of a candidate vaccine. However, ability of nanoparticle vaccine in eliciting cell mediated immune response needs further investigation. More sustained local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak

Network reconstruction for trans acting genetic loci using multi-omics data and prior information

BACKGROUND: Molecular measurements of the genome, the transcriptome, and the epigenome, often termed multi-omics data, provide an in-depth view on biological systems and their integration is crucial for gaining insights in complex regulatory processes. These data can be used to explain disease related genetic variants by linking them to intermediate molecular traits (quantitative trait loci, QTL). Molecular networks regulating cellular processes leave footprints in QTL results as so-called trans-QTL hotspots. Reconstructing these networks is a complex endeavor and use of biological prior information can improve network inference. However, previous efforts were limited in the types of priors used or have only been applied to model systems. In this study, we reconstruct the regulatory networks underlying trans-QTL hotspots using human cohort data and data-driven prior information. METHODS: We devised a new strategy to integrate QTL with human population scale multi-omics data. State-of-the art network inference methods including BDgraph and glasso were applied to these data. Comprehensive prior information to guide network inference was manually curated from large-scale biological databases. The inference approach was extensively benchmarked using simulated data and cross-cohort replication analyses. Best performing methods were subsequently applied to real-world human cohort data. RESULTS: Our benchmarks showed that prior-based strategies outperform methods without prior information in simulated data and show better replication across datasets. Application of our approach to human cohort data highlighted two novel regulatory networks related to schizophrenia and lean body mass for which we generated novel functional hypotheses. CONCLUSIONS: We demonstrate that existing biological knowledge can improve the integrative analysis of networks underlying trans associations and generate novel hypotheses about regulatory mechanisms