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

Resonant radiation pressure on neutral particles in a waveguide

A theoretical analysis of electromagnetic forces on neutral particles in an hollow waveguide is presented. We show that the effective scattering cross section of a very small (Rayleigh) particle can be strongly modified inside a waveguide. The coupling of the scattered dipolar field with the waveguide modes induce a resonant enhanced backscattering state of the scatterer-guide system close to the onset of new modes. The particle effective cross section can then be as large as the wavelength even far from any transition resonance. As we will show, a small particle can be strongly accelerated along the guide axis while being highly confined in a narrow zone of the cross section of the guide.Comment: RevTeX,4 pages,3 PS figure

Effect of thermal processing on the profile of bioactive compounds and antioxidant capacity of fermented orange juice

Previously, we reported that alcoholic fermentation enhanced flavanones and carotenoids content of orange juice. The aim of this work was to evaluate the influence of pasteurization on the qualitative and quantitative profile of bioactive compounds and the antioxidant capacity of fermented orange juice. Ascorbic acid (203 mg/L), total flavanones (647 mg/L), total carotenoids (7.07 mg/L) and provitamin A (90.06 RAEs/L) values of pasteurized orange beverage were lower than those of fermented juice. Total phenolic remained unchanged (585 mg/L) and was similar to that of original juice. The flavanones naringenin-7-O-glucoside, naringenin-7-O-rutinoside, hesperetin-7-O-rutinoside, hesperetin-7-O-glucoside and isosakuranetin-7-O-rutinoside, and the carotenoids karpoxanthin and isomer, neochrome, lutein, ζ-carotene, zeaxanthin, mutatoxanthin epimers, β-cryptoxanthin and auroxanthin epimers were the major compounds. Pasteurization produced a decrease in antioxidant capacity of fermented juice. However, TEAC (5.45 mM) and ORAC (6353 μM) values of orange beverage were similar to those of original orange juice. The novel orange beverage could be a valuable source of bioactive compounds with antioxidant capacity and exert potential beneficial effects.We are grateful for the support of Junta de Andalucía (Projects P09-AGR4814M, P08-AGR-03477 and Grupo PAI BIO311), and of National Funding Agencies (Projects AGL2010-14850/ALI, AGL2011-23690, CSD007-0063 and CSIC 201170E041). We are also grateful to Fundación Séneca - CARM “Group of Excellence in Research” 04486/GERM/06. The research project grant of B.E.-L. is supported by Junta de Andalucía. A.G.-I., F.F. and S.M. are members of the CORNUCOPIA Network 112RT0460 and D.H.-M. of the IBERCAROT Network 112RT0445 financed by CYTED. We are also grateful to Grupo Hespérides Biotech S.L. for providing the samples.Peer Reviewe

Dynamic equivalence between atomic and colloidal liquids

We show that the kinetic-theoretical self-diffusion coefficient of an atomic fluid plays the same role as the short-time self-diffusion coefficient D_S in a colloidal liquid, in the sense that the dynamic properties of the former, at times much longer than the mean free time, and properly scaled with D_S, will indistinguishable from those of a colloidal liquid with the same interaction potential. One important consequence of such dynamic equivalence is that the ratio D_L/ D_S of the long-time to the short-time self-diffusion coefficients must then be the same for both, an atomic and a colloidal system characterized by the same inter-particle interactions. This naturally extends to atomic fluids a well-known dynamic criterion for freezing of colloidal liquids[Phys. Rev. Lett. 70, 1557 (1993)]. We corroborate these predictions by comparing molecular and Brownian dynamics simulations on (soft- and hard-sphere) model systems, representative of what we may refer to as the "hard-sphere" dynamic universality class

Identification of the Immunological Changes Appearing in the CSF During the Early Immunosenescence Process Occurring in Multiple Sclerosis

Patients with multiple sclerosis (MS) suffer with age an early immunosenescence process, which influence the treatment response and increase the risk of infections. We explored whether lipid-specific oligoclonal IgM bands (LS-OCMB) associated with highly inflammatory MS modify the immunological profile induced by age in MS. This cross-sectional study included 263 MS patients who were classified according to the presence (M+, n=72) and absence (M-, n=191) of LS-OCMB. CSF cellular subsets and molecules implicated in immunosenescence were explored. In M- patients, aging induced remarkable decreases in absolute CSF counts of CD4+ and CD8+ T lymphocytes, including Th1 and Th17 cells, and of B cells, including those secreting TNF-alpha. It also increased serum anti-CMV IgG antibody titers (indicative of immunosenescence) and CSF CHI3L1 levels (related to astrocyte activation). In contrast, M+ patients showed an age-associated increase of TIM-3 (a biomarker of T cell exhaustion) and increased values of CHI3L1, independently of age. Finally, in both groups, age induced an increase in CSF levels of PD-L1 (an inductor of T cell tolerance) and activin A (part of the senescence-associated secretome and related to inflammaging). These changes were independent of the disease duration. Finally, this resulted in augmented disability. In summary, all MS patients experience with age a modest induction of T-cell tolerance and an activation of the innate immunity, resulting in increased disability. Additionally, M- patients show clear decreases in CSF lymphocyte numbers, which could increase the risk of infections. Thus, age and immunological status are important for tailoring effective therapies in MS.This work was supported by grants FIS-PI15/00513, FIS-PI18/00572 and RD16/0015/0001 from the Instituto de Salud Carlos III. Ministerio de Ciencia e Innovación, Spain and FEDER: "Una manera de hacer Europa"

Implementation of a multidisciplinary psychoeducational intervention for Parkinson's disease patients and carers in the community: study protocol

Background: Parkinson’s disease progressively limits patients at different levels and as a result family members play a key role in their care. However, studies show lack of an integrative approach in Primary Care to respond to the difficulties and psychosocial changes experienced by them. The aim of this study is to evaluate the effects of a multidisciplinary psychoeducational intervention focusing on improving coping skills, the psychosocial adjustment to Parkinson’s disease and the quality of life in patients and family carers in a Primary Care setting. Methods: This quasi-experimental study with control group and mixed methods was designed to evaluate a multidisciplinary psychoeducational intervention. Based on the study power calculations, 100 people with Parkinson’s disease and 100 family carers will be recruited and assigned to two groups. The intervention group will receive the ReNACE psychoeducational intervention. The control group will be given a general educational programme. The study will be carried out in six community-based health centres. The results obtained from the two groups will be collected for evaluation at three time points: at baseline, immediately after the intervention and at 6 months post-intervention. The results will be measured with these instruments: the Quality of Life Scale PDQ39 for patients and the Scale of Quality of Life of Care-givers SQLC for family carers, and for all participants the Psychosocial Adjustment to Illness scale and the Brief COPE Inventory. Focus groups will be organised with some patients and family carers who will have received the ReNACE psychoeducational intervention and also with the healthcare professionals involved in its development. Discussion: An important gap exists in the knowledge and application of interventions with a psychosocial approach for people with PD and family carers as a whole. This study will promote this comprehensive approach in Primary Care, which will clearly contribute in the existing knowledge and could reduce the burden of PD for patients and family carers, and also in other long-term conditions

¿Qué sabemos de los peces óseos marinos del neógeno en Chile? Diversidad e implicaciones biogeográficas

Durante el Neógeno ocurren intensos eventos, oceanográficos y climáticos, que influyeron sobre la fauna marina de Chile desde el pasado hasta la actualidad. Estudios enfocados en la evaluación del efecto de estos eventos sobre la diversidad de mamíferos, aves y tiburones han sido previamente abordados. Sin embargo, las interacciones de estos eventos con los peces óseos como grupo de estudio no han sido analizados en detalle. Este trabajo compara la diversidad de peces óseos del Neógeno con la actualidad y da a conocer lo que sabemos de su diversidad. Se procesaron los datos disponibles de la presencia de peces óseos marinos en formaciones neógenas de Chile y la actualidad. Se comparó la composición del registro fósil de peces neógenos con el registro de peces actuales a 3 niveles taxonómicos distintos (familia, género y especie). Finalmente, se analizaron los rangos de distribución de los taxa fósiles que sobrevivieron con el objetivo de realizar aproximaciones de las dinámicas paleobiogeográficas. Nuestros resultados muestran que la diversidad actual de peces óseos marinos en Chile es de 624 géneros (1.196 especies), mientras que para el Neógeno se han reportado 65 géneros (46 especies). Comparado con la diversidad actual, el registro fósil de peces es representado por un 3,9% a nivel de especie, 10,4% a nivel de género y 23,4% a nivel de familias, lo que puede ser relacionado con la baja cantidad de estudios enfocados en fósiles de este grupo. Del total de 46 especies fósiles reportadas, sólo una se encuentra actualmente presente en las costas de Chile. A nivel genérico, un 38,5% se encuentra actualmente ausente en la región y un 61,5% sobrevive. En relación a los géneros ausentes actualmente, un 20% corresponde a extinción global y un 80% a extinción regional. Estos cambios en las dinámicas biogeográficas de peces óseos del pasado al reciente, podrían estar relacionadas con los intensos eventos climáticos y oceanográficos que han ocurrido en los últimos 23 millones de años. Los análisis de rarefacción y de extrapolación de especies confirman que a pesar de que han aumentado los trabajos sobre peces óseos en los últimos años, todavía se podrían encontrar un mayor número de taxa si se aplica un mayor esfuerzo de muestreo. Estudios futuros podrían ayudarnos a comprender de mejor manera el efecto de los cambios climáticos y oceanográficos sobre los peces del Neógeno de Chile.Durant el Neogen ocorren intensos esdeveniments, oceanogràfics, i climàtics, que van influir sobre la fauna marina de Xile des del passat fins a l’actualitat. Estudis enfocats en l’avaluació de l’efecte d’aquests esdeveniments sobre la diversitat de mamífers, ocells i taurons han sigut prèviament abordats. No obstant això, les interaccions d’aquests esdeveniments amb els peixos ossis com a grup d’estudi no han sigut analitzats detalladament. Aquest treball analitza la diversitat de peixos ossis del Neogen comparat amb l’actualitat i dona a conéixer que sabem de la seua diversitat. Es van analizar les dades disponibles de la presència de peixos ossis marins en formacions neógenas de Xile i l’actualitat. Es va comparar la composició del registre fòssil de peixos neògens amb el registre de peixos actuals a 3 nivells taxonòmics diferents (família, gènere i espècie). Finalment, es van analizar els rangs de distribució dels taxa fòssils que van sobreviure amb la finalitat de realitzar aproximacions de les dinàmiques paleobiogeográficas. Els nostres resultats mostren que la diversitat actual de peixos ossis marins a Xile és de 624 gèneres (1.196 espècies), mentre que per al Neogen s’han reportat 65 gèneres (46 espècies). Comparat amb la diversitat actual, el registre fòssil de peixos és representat per un 3,9% a nivell d’espècie, 10,4% a nivell de gènere i 23,4% a nivell de famílies, la qual cosa pot ser relacionat amb la baixa quantitat d’estudis enfocats en fòssils d’aquest grup. Del total de 46 espècies fòssils reportades, només un 4% es troba actualment present en les costes de Xile. A nivell genèric, un 38.5% es troba actualment absent a la regió i un 61.5% sobreviu. En relació als gèneres absents actualment, un 20% correspon a extinció global i un 80% a extinció regional. Aquests canvis en les dinàmiques biogeogràfiques de peixos ossis del passat al recent, podrien estar relacionades amb els intensos esdeveniments climàtics i oceanogràfics que han ocorregut en els últims 23 milions d’anys. Les anàlisis de rarefacció i d’extrapolació d’espècies confirmen que a pesar que han augmentat els treballs sobre el grup en els últims anys, encara es podrien trobar un major número de taxa si s’aplica un major esforç de mostreig. Estudis futurs podrien ajudar-nos a comprendre de millor manera l’efecte dels canvis climàtics i oceanogràfics sobre els peixos del Neogen de Xile.During the Neogene occurred intense oceanographic and climatic events which had an effect on the marine fauna from the past to the present. Studies focused on the evaluation of the effect of these events on the diversity of mammals, birds and sharks have been previously addressed. However, the interactions of these events with bony fishes as a study group have not been analyzed in detail. This work analyzes the diversity of bony fishes from the Neogene compared to today and reveals what we know about their diversity. We analyzed the available data on the presence of marine bony fishes from Neogene formations in Chile and today. The composition of the fossil record of Neogene fishes was compared to the current fish record at 3 different taxonomic levels (family, genus, and species). Lastly, the distribution ranges of the surviving fossil taxa were analyzed in order to make approximations of the paleobiogeographic dynamics. Our results show that the current diversity of marine bony fish in Chile is composed of 624 genera (1,196 species), whereas from the Neogene 65 genera (46 species) have been reported. Compared to the current diversity, the fossil record of fishes is represented by 3.9% at the species level, 10.4% at the genus level and 23.4% at the family level, which can be related to the low number of studies focused on fossils of this group. Of the total of 46 fossil species reported, only 4% is currently present along the coast of Chile. At a generic level, 38.5% are currently absent in the region whereas 61.5% survived. In relation to the genera currently absent in the region, 20% are globally extinct and 80% regional extinct. These changes in the biogeographic dynamics of bony fishes from the past to the recent could be related to the intense climatic and oceanographic events that have occurred in the last 23 million years. The rarefaction and extrapolation analyses confirm that although the studies focused on the group have increased in the last years, a higher number of taxa could still be found if the sampling effort is increased. Future studies could help us to a better understanding of the effects of climatic and oceanographic changes on the group during the Neogene of Chile

Peabody Picture Vocabulary Test-III: Normative data for Spanish-speaking pediatric population

OBJECTIVE: To generate normative data for the Peabody Picture Vocabulary Test-III (PPVT-III) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Honduras, Guatemala, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the PPVT-III as part of a larger neuropsychological battery. PPVT-III scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age in all countries, such that scores increased linearly as a function of age. In addition, age2 had a significant effect in all countries, except Guatemala and Paraguay. Models showed that children whose parent(s) had a MLPE >12 years obtained higher scores compared to children whose parent(s) had a MLPE ≤12 years in all countries, except for Cuba, Peru, and Puerto Rico. Sex affected scores for Chile, Ecuador, Guatemala, Mexico, and Spain. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate interpretation of the PPVT-III when used in pediatric populations

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO