Q-switched mode locking noise-like pulse generation from a thulium-doped all-fiber laser based on nonlinear polarization rotation

Q-switched mode locking (QML) noise-like pulse (NLP) emission from an all-fiber thulium-doped laser based on the nonlinear polarization rotation effect is reported. The QML emission is obtained in a cavity with net anomalous dispersion in a pump power interval in between the CW laser threshold and the threshold of the NLP regime. Highest-energy QML pulses were observed with a repetition rate of 812 kHz with a pump power of 520 mW at the optical wavelength of 1881.09 nm. A maximum overall energy of 460 nJ at an average output power of 6.4 mW was reached, which corresponds to a burst of mode-locked noise-like sub-pulses with 8.7 ns of pulse duration within a QML envelope of 11 μs. These results demonstrate unconventional pulse operation regime of NLPs and provide insights into the dynamics of mode-locked fiber lasers

Variable order Mittag-Leffler fractional operators on isolated time scales and application to the calculus of variations

We introduce new fractional operators of variable order on isolated time scales with Mittag-Leffler kernels. This allows a general formulation of a class of fractional variational problems involving variable-order difference operators. Main results give fractional integration by parts formulas and necessary optimality conditions of Euler-Lagrange type.Comment: This is a preprint of a paper whose final and definite form is with Springe

Fasciola hepatica induces eosinophil apoptosis in the migratory and biliary stages of infection in sheep

The aim of the present work was to evaluate the number of apoptotic eosinophils in the livers of sheep experimentally infected with Fasciola hepatica during the migratory and biliary stages of infection. Four groups (n = 5) of sheep were used; groups 1–3 were orally infected with 200 metacercariae (mc) and sacrificed at 8 and 28 days post-infection (dpi), and 17 weeks post-infection (wpi), respectively. Group 4 was used as an uninfected control. Apoptosis was detected using immunohistochemistry with a polyclonal antibody against anti-active caspase-3, and transmission electron microscopy (TEM). Eosinophils were identified using the Hansel stain in serial sections for caspase-3, and by ultrastructural features using TEM. At 8 and 28 dpi, numerous caspase-3+ eosinophils were mainly found at the periphery of acute hepatic necrotic foci. The percentage of caspase -3+ apoptotic eosinophils in the periphery of necrotic foci was high (46.1–53.9) at 8 and 28 dpi, respectively, and decreased in granulomas found at 28 dpi (6%). Transmission electron microscopy confirmed the presence of apoptotic eosinophils in hepatic lesions at 8 and 28 dpi. At 17 wpi, apoptotic eosinophils were detected in the infiltrate surrounding some enlarged bile ducts containing adult flukes. This is the first report of apoptosis induced by F. hepatica in sheep and the first study reporting apoptosis in eosinophils in hepatic inflammatory infiltrates in vivo. The high number of apoptotic eosinophils in acute necrotic tracts during the migratory and biliary stages of infection suggests that eosinophil apoptosis may play a role in F. hepatica survival during different stages of infection.This work was supported by EU grants (FPVII-265862-PARAVAC, H2020-635408-PARAGONE) and the Spanish Ministry of Science grant AGL2009-08726. TEM studies were carried out by the Central Services for Research of the University of Córdoba (SCAI)Veterinari

Apoptosis of peritoneal leucocytes during early stages of Fasciola hepatica infections in sheep

Several immunomodulatory properties have been described in Fasciola hepatica infections. Apoptosis has been shown to be an effective mechanism to avoid the immune response in helminth infections. The aim of the present work was to study apoptosis in peritoneal leucocytes of sheep experimentally infected with F. hepatica during the early stages of infection. Five groups (n = 5) of sheep were used. Groups 2–5 were orally infected with 200 metacercariae (mc) and sacrificed at 1, 3, 9 and 18 days post-infection (dpi), respectively. Group 1 was used as the uninfected control (UC). Apoptosis was detected using three different methods 1) immunocytochemistry (ICC) with a polyclonal antibody anti-active caspase-3; 2) an annexin V flow cytometry assay using the Annexin V-FITC/propidium iodide (PI); and 3) transmission electron microscopy (TEM). The differential leucocyte count revealed that the majority of peritoneal granulocytes were eosinophils, which increased significantly at 9 and 18 dpi with respect to the uninfected controls. The ICC study revealed that the percentage of caspase-3+ apoptotic peritoneal leucocytes increased significantly from 3 dpi onwards with respect to the uninfected controls. The flow cytometry annexin V assay detected a very significant (P < 0.001) increase of apoptotic peritoneal macrophages, lymphocytes and granulocytes, which remained higher than in the UC until 18 dpi. Transmission electron microscopy studies also confirmed the presence of apoptosis in peritoneal eosinophils at 18 dpi. This is the first report of apoptosis induced by F. hepatica in the peritoneal leucocytes of sheep in vivo. The results of this work suggest the importance of apoptosis induction for the survival of the juvenile parasites in the peritoneal migratory stages of infection.This work was supported by EU grants (H2020-635408-PARAGONE) and the Spanish Ministry of Science grant AGL2015-67023-C2-1-R. The TEM studies were carried out by the Central Research Services (SCAI) of the University of CórdobaAccepted manuscriptVeterinari

Percepción de los formadores colegiales sobre el futuro profesional de esta nueva figura laboral en la farmacia comunitaria

Objetivo: Explorar la percepción de Formadores Colegiales con experiencia previa sobre su formación y sus funciones futurasen la implantación y sostenibilidad del servicio de Seguimiento Farmacoterapéutico en el ámbito de la farmacia comunitariaespañola. Método: Estudio cualitativo mediante la técnica del grupo focal. El coordinador de la reunión focal utilizó un guión temáticopreviamente elaborado que permitía explorar la opinión de los Formadores Colegiales sobre sus experiencias y percepciones acercadel futuro de esta nueva figura profesional. El contenido de la conversación fue registrado en una grabadora, transcrito en su totalidady posteriormente analizado mediante análisis de contenido. Resultados: La reunión grupal celebrada en la sede del Consejo General de Colegios Oficiales de Farmacéuticos, en Madrid, tuvo unaduración de 95 minutos. Participaron seis Formadores Colegiales. En función de los temas tratados se identificaron dos dimensiones;una primera que abarca las funciones que debe desempeñar un Formador Colegial (resaltando la función de motivador, facilitadorde la comunicación y formador metodológico y clínico) y una segunda en las que se describen las características que ese profesionaldebe tener para poder realizar su papel facilitador (entre las que destacan que debe ser un profesional contratado por el Colegio deFarmacéuticos correspondiente, con lugar físico de trabajo dentro del mismo, y con jornada laboral completa y flexible, entre otrascaracterísticas). Conclusiones: El presente artículo aporta información relevante sobre la figura innovadora del Formador Colegial, describiendo lascaracterísticas intrínsecas necesarias para desarrollar su labor y las funciones a desempeñar. Dicha información debería ser utilizadapor aquellos Colegios Oficiales de Farmacéuticos provinciales que deseen implantar Servicios Profesionales Farmacéuticos, talescomo el servicio de Seguimiento Farmacoterapéutico

Percepción de los formadores colegiales sobre el futuro profesional de esta nueva figura laboral en la farmacia comunitaria

Objetivo: Explorar la percepción de Formadores Colegiales con experiencia previa sobre su formación y sus funciones futurasen la implantación y sostenibilidad del servicio de Seguimiento Farmacoterapéutico en el ámbito de la farmacia comunitariaespañola. Método: Estudio cualitativo mediante la técnica del grupo focal. El coordinador de la reunión focal utilizó un guión temáticopreviamente elaborado que permitía explorar la opinión de los Formadores Colegiales sobre sus experiencias y percepciones acercadel futuro de esta nueva figura profesional. El contenido de la conversación fue registrado en una grabadora, transcrito en su totalidady posteriormente analizado mediante análisis de contenido. Resultados: La reunión grupal celebrada en la sede del Consejo General de Colegios Oficiales de Farmacéuticos, en Madrid, tuvo unaduración de 95 minutos. Participaron seis Formadores Colegiales. En función de los temas tratados se identificaron dos dimensiones;una primera que abarca las funciones que debe desempeñar un Formador Colegial (resaltando la función de motivador, facilitadorde la comunicación y formador metodológico y clínico) y una segunda en las que se describen las características que ese profesionaldebe tener para poder realizar su papel facilitador (entre las que destacan que debe ser un profesional contratado por el Colegio deFarmacéuticos correspondiente, con lugar físico de trabajo dentro del mismo, y con jornada laboral completa y flexible, entre otrascaracterísticas). Conclusiones: El presente artículo aporta información relevante sobre la figura innovadora del Formador Colegial, describiendo lascaracterísticas intrínsecas necesarias para desarrollar su labor y las funciones a desempeñar. Dicha información debería ser utilizadapor aquellos Colegios Oficiales de Farmacéuticos provinciales que deseen implantar Servicios Profesionales Farmacéuticos, talescomo el servicio de Seguimiento Farmacoterapéutico

Present and Future of Parkinson’s Disease in Spain: PARKINSON-2030 Delphi Project

Parkinson's disease (PD) is a chronic progressive and irreversible disease and the second most common neurodegenerative disease worldwide. In Spain, it affects around 120.000-150.000 individuals, and its prevalence is estimated to increase in the future. PD has a great impact on patients' and caregivers' lives and also entails a substantial socioeconomic burden. The aim of the present study was to examine the current situation and the 10-year PD forecast for Spain in order to optimize and design future management strategies. This study was performed using the modified Delphi method to try to obtain a consensus among a panel of movement disorders experts. According to the panel, future PD management will improve diagnostic capacity and follow-up, it will include multidisciplinary teams, and innovative treatments will be developed. The expansion of new technologies and studies on biomarkers will have an impact on future PD management, leading to more accurate diagnoses, prognoses, and individualized therapies. However, the socio-economic impact of the disease will continue to be significant by 2030, especially for patients in advanced stages. This study highlighted the unmet needs in diagnosis and treatment and how crucial it is to establish recommendations for future diagnostic and therapeutic management of PD

Ruxolitinib in refractory acute and chronic graft-versus-host disease : a multicenter survey study

Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients