Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents and young adults (BREATHER): Extended follow-up results of a randomised, open-label, non-inferiority trial

BACKGROUND: Weekends off antiretroviral therapy (ART) may help engage HIV-1-infected young people facing lifelong treatment. BREATHER showed short cycle therapy (SCT; 5 days on, 2 days off ART) was non-inferior to continuous therapy (CT) over 48 weeks. Planned follow-up was extended to 144 weeks, maintaining original randomisation. METHODS: BREATHER was an open-label, non-inferiority trial. Participants aged 8-24yrs with virological suppression on efavirenz-based first-line ART were randomised 1:1, stratified by age and African/non-African sites, to remain on CT or change to SCT. The Kaplan-Meier method was used to estimate the proportion of participants with viral rebound (confirmed VL≥50 copies/mL) under intent-to-treat at 48 weeks (primary outcome), and in extended follow-up at 96, 144, and 192 weeks. SCT participants returned to CT following viral rebound, 3 VL blips or discontinuation of efavirenz. FINDINGS: Of 199 participants (99 SCT, 100 CT), 97 per arm consented to extended follow-up. Median follow-up was 185.3 weeks (IQR 160.9-216.1). 69 (70%) SCT participants remained on SCT at last follow-up. 105 (53%) were male, baseline median age 14 years (IQR 12-18), median CD4 count 735 cells/μL (IQR 576-968). 16 SCT and 16 CT participants had confirmed VL≥50 copies/mL by the end of extended follow-up (HR 1.00, 95% CI 0.50-2.00). Estimated difference in percentage with viral rebound (SCT minus CT) by week 144 was 1.9% (90% CI -6.6-10.4; p = 0.72) and was similar in a per-protocol analysis. There were no significant differences between arms in proportions of participants with grade 3/4 adverse events (18 SCT vs 16 CT participants; p = 0.71) or ART-related adverse events (10 vs 12; p = 0.82). 20 versus 8 serious adverse events (SAEs) were reported in 16 SCT versus 4 CT participants, respectively (p = 0.005 comparing proportions between groups; incidence rate ratio 2.49, 95%CI 0.71-8.66, p = 0.15). 75% of SAEs (15 SCT, 6 CT) were hospitalisations for a wide range of conditions. 3 SCT and 6 CT participants switched to second-line ART following viral failure (p = 0.50). CONCLUSIONS: Sustainable non-inferiority of virological suppression in young people was shown for SCT versus CT over median 3.6 years. Standard-dose efavirenz-based SCT is a viable option for virologically suppressed HIV-1 infected young people on first-line ART with 3-monthly VL monitoring. TRIAL REGISTRATION: EudraCT 2009-012947-40 ISRCTN 97755073 ClinicalTrials.gov NCT01641016

Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologiainfo:eu-repo/semantics/publishedVersio

Oceanic influence on southernmost South American precipitation

The potential oceanic influence on southernmost South American precipitation since 1930 is analyzed in this study. The aim is to define oceanic characteristics that can produce wetter or drier conditions over the mentioned region on different time scales. Results suggest important precipitation-oceanic links in decadal and interdecadal oscillations. The eastern and central subtropical Indian, western tropical Pacific and western and central subtropical Pacific could be forcing the precipitation on decadal time scale. Moreover, the eastern tropical and western subtropical Indian and western and central subtropical Pacific could be forcing the variability of precipitation on interdecadal time scale. Although the research was focused in forcing of precipitation, relations among different regions of the Indian and Pacific oceans on decadal and interdecadal time scales have also been detected. Therefore, results presented here can be useful in describing new aspects of the remote influence of both oceans on regional climate.En este trabajo se analiza la posible influencia oceánica en la variabilidad de la precipitación sobre el extremo sur de Sudamérica desde 1930. El objetivo es definir características oceánicas que pueden producir condiciones de más o menos lluvia en diferentes escalas de tiempo en la mencionada región. Los resultados sugieren importantes relaciones entre los océanos y la precipitación en oscilaciones decadales e interdecadales. El este y centro del índico subtropical, el oeste del Pacífico tropical y el oeste y centro del Pacífico subtropical podrían estar influenciando la precipitación en escala decadal. Por otra parte, la región este tropical y oeste subtropical del índico, y el oeste y centro del Pacífico subtropical podrían influenciar la variabilidad de la precipitación en escala interdecadal. Si bien el estudio se enfocó en la variabilidad de la precipitación, relaciones entre diferentes regiones de los océanos Índico y Pacífico en escalas decadal e interdecadal han sido también detectadas. Por lo tanto, los resultados aquí presentados pueden también ser útiles para describir nuevos aspectos de la influencia remota de ambos océanos en el clima regional

A systematic literature review on IoT-aware business process modeling views, requirements and notations

The Internet of things has been adopted in several sectors both influencing how people work and enhancing organizations' business processes. This resulted in the rise of relevant research topics such as IoT-aware business processes. The modeling of these processes makes it possible to better understand working scenarios and to support the adoption of model-driven development approaches for IoT-aware and process-oriented software systems. Since much research has been performed on this topic, a better awareness of the current status is needed. This paper reports a systematic literature review to develop a map on modeling notations for IoT-aware business processes. The survey mainly adopts an academic point of view, resulting in the detailed analysis of 84 research works from the leading computer science digital libraries. The output of the review is in the form of schemes and reflections. In particular, our research aims to shed light on (1) the relevant modeling views referring to different types of IoT-aware business processes; (2) the IoT requirements supported by the modeling notations; and (3) the modeling notations proposed and/or adopted to model IoT-aware business processes. Finally, our research work highlights possible future research lines needing further investigations

Simulación de la Pequeña Edad de Hielo usando el modelo EdGCM

La Pequeña Edad de Hielo fue un período frío que abarcó desde mediados del siglo XIV hasta mediados del siglo XIX. Durante ese tiempo ocurrieron tres pulsos de temperaturas extremadamente bajas. En el presente trabajo se analiza el segundo de ellos denominado Mínimo de Maunder (MM) que ocurrió entre 1645 y 1715. La disminución de la actividad solar, el aumento de la actividad volcánica y el cambio en las concentraciones de Dióxido de Carbono fueron sus principales forzantes. Mediante el Modelo de Circulación General EdGCM se realizan distintas simulaciones de las condiciones climáticas, con el fin de obtener escenarios de respuesta de la temperatura y la circulación atmosférica a los cambios producidos en la irradiancia y los gases invernadero, en especial del CO2. A su vez, son calculadas por medio de los re-análisis del NCEP/NCAR, las diferencias climáticas entre años de máxima y mínima irradiancia a fin de compararlas con las diferencias ocurridas entre las condiciones actuales y del MM dadas por el modelo. Las anomalías anuales de temperatura, entre el MM y las condiciones de fines del siglo XX, son negativas para ambos hemisferios y las anomalías de temperatura resultan más intensas para el semestre frío. Además, sobre Sudamérica, se observa un centro más intenso en latitudes subtropicales y desde el centro hasta el sur de Patagonia. El patrón de enfriamiento simulado por el modelo concuerda, en algunos casos aún en magnitud, con la información de proxy datos de algunas regiones de Sudamérica. La componente zonal del oeste se muestra desplazada hacia menores latitudes durante el MM. Los campos de anomalías de circulación atmosférica simulados para el MM, muestran un patrón, en latitudes medias y altas, en que alternan tres ó cuatro centros positivos con negativos, el cual concuerda con una mayor componente meridional del flujo. Ambos resultan patrones parecidos con los que ocurren actualmente durante eventos El Niño.The Little Ice Age (LIA) was a cold period that ranged from taken part of the century XIV until taken part of the century XIX. In the period occurred three pulses of minimum values of temperature and will study the second of them comprised between 1645-1715 designated Maunder Minimum (MM). The decrease of the solar activity, the increase of the volcanic activity and the change in the Carbon Dioxide concentrations were the main forcings during these periods. In present work we realize distinct simulations of the climatic conditions for the South Hemisphere, by means of the General Circulation Model EdGCM, with the end to obtain stages of answer to the changes of irradiance and CO2 for the MM. At the same time, the climatic differences between years of maxima and minimum values of sunshine during the century XX determined by means of the results of the re-analysis of the NCEP/NCAR, compare with the differences between the current conditions and the ones of the MM, simulated by the model. The anomalies between the XX century and the MM obtained with the EdGCM are in agree qualitatively, and also quantitatively in some locations, with the proxy data information for various regions of the Hemisphere South. The annual temperature anomalies, between the MM and the 20th century ending conditions, are negative for both hemispheres and the temperature anomalies result more intense on semester November-April. Furthermore, over South America, shows a more intense centre in subtropical latitude and central and south Patagonia. The cold pattern obtained by the model is in agreement, on magnitude too, with proxy information obtained in some South America regions. The westerly wind component undergoes a shift to lower latitudes during the MM. The atmospheric circulation anomalies obtained in the simulations, show a pattern, over middle and high latitudes, where alternate three or four positive and negative anomaly centres, which is in agreement with a greater meridional component of the flux. Both patterns are similar to those present during El Niño events.Asociación Argentina de Geofísicos y Geodesta

Series de precipitación de la región centro oeste y sus variaciones

Se analizan las series de precipitaciones estivales de 8 estaciones meteorológicas de la región Centro Oeste de la Argentina mediante la aplicación de filtros de baja y alta frecuencias. Se establecen las matrices de correlación de las series originales y filtradas y se efectúa un análisis de enlace (linkage). Los resultados muestran que la región presenta igual variabilidad,1as ondas lar gas que la componen se encuentran en fase, con un período de 18 años aproximadamente por lo que están altamente correlacionadas. Las ondas cortas, más representativas del microclima de cada estación, no se correlacionan.The records of summer rainfall from 8 meteorological stations in the Central West region of Argentina has been analyzed by means of low-pass and high-pass filters. Linkage analysis has also been applied to the correlation matrix of filtered and unfiltered data. The results show that the region has equal variabllity, the long waves components are in face with a period of 18 years aproximately and high correlation coefficients. The short waves are more representatives of the microclima of each station. They are not correlated.Asociación Argentina de Geofísicos y Geodesta

Series de precipitación de la región centro oeste y sus variaciones

Se analizan las series de precipitaciones estivales de 8 estaciones meteorológicas de la región Centro Oeste de la Argentina mediante la aplicación de filtros de baja y alta frecuencias. Se establecen las matrices de correlación de las series originales y filtradas y se efectúa un análisis de enlace (linkage). Los resultados muestran que la región presenta igual variabilidad,1as ondas lar gas que la componen se encuentran en fase, con un período de 18 años aproximadamente por lo que están altamente correlacionadas. Las ondas cortas, más representativas del microclima de cada estación, no se correlacionan.The records of summer rainfall from 8 meteorological stations in the Central West region of Argentina has been analyzed by means of low-pass and high-pass filters. Linkage analysis has also been applied to the correlation matrix of filtered and unfiltered data. The results show that the region has equal variabllity, the long waves components are in face with a period of 18 years aproximately and high correlation coefficients. The short waves are more representatives of the microclima of each station. They are not correlated.Asociación Argentina de Geofísicos y Geodesta

Contribution à l’étude de l’hépatite contagieuse du chien. Ill. - Essai de «diagnostic enzymatique » de l'infection expérimentale du chien

Compagnucci M., Pilet Ch., Chevet A., Goret Pierre. Contribution à l’étude de l’hépatite contagieuse du Chien. III. Essai de «diagnostic enzymatique» de l’infection expérimentale du Chien. In: Bulletin de l'Académie Vétérinaire de France tome 116 n°1, 1963. pp. 35-39

Ethical perspectives on surgical video recording for patients, surgeons and society: systematic review

Background Operating-room audiovisual recording is increasingly proposed, although its ethical implications need elucidation. The aim of this systematic review was to examine the published literature on ethical aspects regarding operating-room recording. Methods MEDLINE (via PubMed), Embase, and Cochrane databases were systematically searched for articles describing ethical aspects regarding surgical (both intracorporeal and operating room) recording from database inception to the present (the last search was undertaken in July 2022). Medical subject headings used in the search included ‘operating room’, ‘surgery’, ‘video recording’, ‘black box’, ‘ethics’, ‘consent’, ‘confidentiality’, ‘privacy’, and more. Title, abstract, and full-text screening determined relevance. The quality of studies was assessed using Centre for Evidence-Based Medicine grading and no formal assessment of risk of bias was attempted given the theoretical nature of the data collected. Results From 1048 citations, 22 publications met the inclusion criteria, with three more added from their references. There was evident geographical (21 were from North America/Europe) and recency (all published since 2010) bias and an exclusive patient/clinician perspective (25 of 25). The varied methodology (including ten descriptive reviews, seven opinion pieces, five surveys, two case reports, and one RCT) and evidence level (14 level V and 10 level III/IV) prevented meaningful systematic grading/meta-analysis. Publications were narratively analysed for ethical thematic content (mainly education, performance, privacy, consent, and ownership) that was then grouped by the four principles of biomedical ethics of Beauchamp and Childress, accounting for 63 distinct considerations concerning beneficence (22 of 63; 35 per cent), non-maleficence (17 of 63; 27 per cent), justice (14 of 63; 22 per cent), and autonomy (10 of 63; 16 per cent). From this, a set of proposed guidelines on the use of operative data is presented. Conclusion For a surgical video to be a truly valuable resource, its potential benefits must be more fully weighed against its potential disadvantages, so that any derived instruments have a solid ethical foundation. Universal, ethical, best-practice guidelines are needed to protect clinicians, patients, and society