A monovalent chimpanzee adenovirus Ebola vaccine boosted with MVA

BACKGROUND The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. The development of an effective Ebola vaccine is a priority for control of a future outbreak. METHODS In this phase 1 study, we administered a single dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) to 60 healthy adult volunteers in Oxford, United Kingdom. The vaccine was administered in three dose levels — 1×1010 viral particles, 2.5×1010 viral particles, and 5×1010 viral particles — with 20 participants in each group. We then assessed the effect of adding a booster dose of a modified vaccinia Ankara (MVA) strain, encoding the same Ebola virus glyco- protein, in 30 of the 60 participants and evaluated a reduced prime–boost interval in another 16 participants. We also compared antibody responses to inactivated whole Ebola virus virions and neutralizing antibody activity with those observed in phase 1 studies of a recombinant vesicular stomatitis virus–based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) to determine relative potency and assess durability. RESULTS No safety concerns were identified at any of the dose levels studied. Four weeks after immunization with the ChAd3 vaccine, ZEBOV-specific antibody responses were similar to those induced by rVSV-ZEBOV vaccination, with a geometric mean titer of 752 and 921, respectively. ZEBOV neutralization activity was also similar with the two vaccines (geo- metric mean titer, 14.9 and 22.2, respectively). Boosting with the MVA vector increased virus-specific antibodies by a factor of 12 (geometric mean titer, 9007) and increased glycoprotein-specific CD8+ T cells by a factor of 5. Significant increases in neutralizing antibodies were seen after boosting in all 30 participants (geometric mean titer, 139; P<0.001). Virus-specific antibody responses in participants primed with ChAd3 remained positive 6 months after vaccination (geometric mean titer, 758) but were significantly higher in those who had received the MVA booster (geometric mean titer, 1750; P<0.001). CONCLUSIONS The ChAd3 vaccine boosted with MVA elicited B-cell and T-cell immune responses to ZEBOV that were superior to those induced by the ChAd3 vaccine alone. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT02240875.)

Las edades de Hitler. De Satán a un ser de carne y hueso, y su representación en clave paródica

Adolf Hitler suscitó desde su entrada en la escena política alemana una fascinación perversa, un sentimiento que, con el tiempo, ha dado lugar a numerosas representaciones culturales sobre el Führer. La muestra, rica y variada tanto en el fondo como en la forma, nos permitirá trazar tres estadios en lo referente al proceso de construcción historiográfica del hitlerismo, iniciado con la caída del Tercer Reich. Estos responden en buena medida al devenir sociopolítico y cultural de la sociedad a escala global desde el final de la guerra y hasta nuestros días y pueden resumirse en tres: primero, la satanización; segundo, la humanización; tercero, el retrato caricaturesco. Proponemos un recorrido histórico por diversos productos culturales del dictador alemán cuyo propósito es desentrañar el retrato psicológico poliédrico que se ha construido en torno a la figura de Hitler.

The Kepler-454 system: a small, not-rocky inner planet, a Jovian world, and a distant companion

Kepler-454 (KOI-273) is a relatively bright (V = 11.69 mag), Sun-like star that hosts a transiting planet candidate in a 10.6 day orbit. From spectroscopy, we estimate the stellar temperature to be 5687 ± 50 K, its metallicity to be [m/H] = 0.32 ± 0.08, and the projected rotational velocity to be v sin i <2.4 km s^-1. We combine these values with a study of the asteroseismic frequencies from short cadence Kepler data to estimate the stellar mass to be , the radius to be 1.066 ± 0.012 R_o, and the age to be Gyr. We estimate the radius of the 10.6 day planet as 2.37 ± 0.13 R_⊕. Using 63 radial velocity observations obtained with the HARPS-N spectrograph on the Telescopio Nazionale Galileo and 36 observations made with the HIRES spectrograph at the Keck Observatory, we measure the mass of this planet to be 6.8 ± 1.4 M_⊕. We also detect two additional non-transiting companions, a planet with a minimum mass of 4.46 ± 0.12 M_J in a nearly circular 524 day orbit and a massive companion with a period >10 years and mass >12.1 M_J. The 12 exoplanets with radii ⊕ and precise mass measurements appear to fall into two populations, with those ⊕ following an Earth-like composition curve and larger planets requiring a significant fraction of volatiles. With a density of 2.76 ± 0.73 g cm^-3, Kepler-454b lies near the mass transition between these two populations and requires the presence of volatiles and/or H/He gas.

Prior knowledge transfer across transcriptional data sets and technologies using compositional statistics yields new mislabelled ovarian cell line

Here, we describe gene expression compositional assignment (GECA), a powerful, yet simple method based on compositional statistics that can validate the transfer of prior knowledge, such as gene lists, into independent data sets, platforms and technologies. Transcriptional profiling has been used to derive gene lists that stratify patients into prognostic molecular subgroups and assess biomarker performance in the pre-clinical setting. Archived public data sets are an invaluable resource for subsequent in silico validation, though their use can lead to data integration issues. We show that GECA can be used without the need for normalising expression levels between data sets and can outperform rank-based correlation methods. To validate GECA, we demonstrate its success in the cross-platform transfer of gene lists in different domains including: bladder cancer staging, tumour site of origin and mislabelled cell lines. We also show its effectiveness in transferring an epithelial ovarian cancer prognostic gene signature across technologies, from a microarray to a next-generation sequencing setting. In a final case study, we predict the tumour site of origin and histopathology of epithelial ovarian cancer cell lines. In particular, we identify and validate the commonly-used cell line OVCAR-5 as non-ovarian, being gastrointestinal in origin. GECA is available as an open-source R package.

Specific JAK2 mutation (JAK2R683) and multiple gene deletions in Down syndrome acute lymphoblastic leukemia

Children with Down syndrome (DS) have a greatly increased risk of acute megakaryoblastic leukemia (AMKL) and acute lymphoblastic leukemia (ALL). Both DS-AMKL and the related transient myeloproliferative disorder (TMD) have GATA1 mutations as obligatory, early events. To identify mutations contributing to leukemogenesis in DS-ALL, we undertook sequencing of candidate genes, including FLT3, RAS, PTPN11, BRAF, and JAK2. Sequencing of the JAK2 pseudokinase domain identified a specific, acquired mutation, JAK2R683, in 12 (28%) of 42 DS-ALL cases. Functional studies of the common JAK2R683G mutation in murine Ba/F3 cells showed growth factor independence and constitutive activation of the JAK/STAT signaling pathway. High-resolution SNP array analysis of 9 DS-ALL cases identified additional submicroscopic deletions in key genes, including ETV6, CDKN2A, and PAX5. These results infer a complex molecular pathogenesis for DS-ALL leukemogenesis, with trisomy 21 as an initiating or first hit and with chromosome aneuploidy, gene deletions, and activating JAK2 mutations as complementary genetic events. (Blood. 2009; 113: 646-648)

Positive narratives: the stories young people with Social, Emotional and Behavioural Difficulties (SEBD) tell about their futures

This research drew on positive psychology in order to offer an optimistic way of conceptualising the lives of young people who are often described as having ‘SEBD’ (Social, emotional, behaviour difficulties), now SEMH (Social, emotional, mental health) in the new SEND Code of Practice (2014). Positive psychology places emphasis on: the future, strengths, resources and potential, and suggests that negative experiences can build positive qualities. A life path tool was used in order to hear the stories that eight young people tell about themselves in the future. Narrative Oriented Inquiry (NOI) was used to analyse the themes of potential and growth in their stories. The young people in this research identified a range of strengths and resources in their lives that they had built as a result of earlier negative experiences. Their stories reveal their hopes and aspirations for the future. By giving these young people the opportunity to tell their stories this research permitted them to focus on where they were going, rather than where they had been.

Ruthenibacterium lactatiformans gen. nov., sp.nov., an anaerobic, lactate-producing member of the family Ruminococcaceae isolated from human faeces

Two novel strains of Gram-stain-negative, rod-shaped, obligately anaerobic, non-spore-forming, non-motile bacteria were isolated from the faeces of healthy human subjects. The strains, designated as 585-1T and 668, were characterized by mesophilic fermentative metabolism, production of d-lactic acid, succinic acid and acetic acid as end products of d-glucose fermentation, prevalence of C18 : 1 ω9, C18 : 1 ω9 aldehyde, C16 : 0 and C16 : 1 ω7c fatty acids, presence of glycine, glutamic acid, lysine, alanine and aspartic acid in the petidoglycan peptide moiety and lack of respiratory quinones. Whole genome sequencing revealed the DNA G+C content was 56.4–56.6 mol%. The complete 16S rRNA gene sequences of the two strains shared 91.7/91.6 % similarity with Anaerofilum pentosovorans FaeT, 91.3/91.2 % with Gemmiger formicilis ATCC 27749T and 88.9/88.8 % with Faecalibacterium prausnitzii ATCC 27768T. On the basis of chemotaxonomic and genomic properties it was concluded that the strains represent a novel species in a new genus within the family Ruminococcaceae , for which the name Ruthenibacterium lactatiformans gen. nov., sp. nov. is proposed. The type strain of Ruthenibacterium lactatiformans is 585-1T (=DSM 100348T=VKM B-2901T).

Concussion: Examining the Effect of Neuronal Oxidative Stress on the Pathophysiology of Brain and Blood Brain Barrier Cells

Neuronal stretching during concussion alters glucose transport and reduces neuronal viability, also affecting other cells in the brain and the Blood Brain Barrier (BBB). Our hypothesis is that oxidative stress (OS) generated in neurons during concussions contributes to this outcome. To validate this, we investigated: (1) whether OS independently causes alterations in brain and BBB cells, namely human neuron-like, neuroblastoma cells (NCs), astrocyte cells (ACs) and brain microvascular endothelial cells (ECs), and (2) whether OS originated in NCs (as in concussion) is responsible for causing the subsequent alterations observed in ACs and ECs. We used H2O2 treatment to mimic OS, validated by examining the resulting reactive oxygen species, and evaluated alterations in cell morphology, expression and localization of the glucose transporter GLUT1, and the overall cell viability. Our results showed that OS, either directly affecting each cell type or originally affecting NCs, caused changes in several morphological parameters (surface area, Feret diameter, circularity, inter-cellular distance), slightly varied GLUT1 expression and lowered the overall cell viability of all NCs, ACs, and ECs. Therefore, we can conclude that oxidative stress, which is known to be generated during concussion, caused alterations in NCs, ACs, and ECs whether independently originated in each cell or when originated in the NCs and could further propagate the ACs and ECs.

O uso de filme como recurso pedagógico no estudo das epidemias: possibilidades na aprendizagem significativa

Acompanha: Epidemias na escola? Só em filmes: possibilidades de contaminação na aprendizagem significativa

Disseminated Cerebral and Intradural Extramedullary Spinal Nocardiosis in an Immunocompetent Patient

Disseminated nocardiosis of the central nervous system (CNS) has been rarely reported, especially in the immunocompetent patient. We report a case of cerebral and cervical intradural extramedullary nocardiosis likely to have been the result of disseminated spread from a pulmonary infective focus. Attempts at tissue biopsy and culture of the initial cerebral and pulmonary lesions both failed to yield the diagnosis. Interval development of a symptomatic intradural extramedullary cervical lesion resulted in open biopsy and an eventual diagnosis of nocardiosis was made. We highlight the diagnostic dilemma and rarity of spinal nocardial dissemination in an immunocompetent individual.

CATARINA 2012-Leg 1 - CTD-O2 Data report

The CATARINA Leg1 cruise was carried out from June 22 to July 24 2012 on board the B/O Sarmiento de Gamboa, under the scientific supervision of Aida Rios (CSIC-IIM). It included the occurrence of the OVIDE hydrological section that was performed in June 2002, 2004, 2006, 2008 and 2010, as part of the CLIVAR program (name A25) ), and under the supervision of Herlé Mercier (CNRSLPO). This section begins near Lisbon (Portugal), runs through the West European Basin and the Iceland Basin, crosses the Reykjanes Ridge (300 miles north of Charlie-Gibbs Fracture Zone, and ends at Cape Hoppe (southeast tip of Greenland). The objective of this repeated hydrological section is to monitor the variability of water mass properties and main current transports in the basin, complementing the international observation array relevant for climate studies. In addition, the Labrador Sea was partly sampled (stations 101-108) between Greenland and Newfoundland, but heavy weather conditions prevented the achievement of the section south of 53°40’N. The quality of CTD data is essential to reach the first objective of the CATARINA project, i.e. to quantify the Meridional Overturning Circulation and water mass ventilation changes and their effect on the changes in the anthropogenic carbon ocean uptake and storage capacity. The CATARINA project was mainly funded by the Spanish Ministry of Sciences and Innovation and co-funded by the Fondo Europeo de Desarrollo Regional. The hydrological OVIDE section includes 95 surface-bottom stations from coast to coast, collecting profiles of temperature, salinity, oxygen and currents, spaced by 2 to 25 Nm depending on the steepness of the topography. The position of the stations closely follows that of OVIDE 2002. In addition, 8 stations were carried out in the Labrador Sea. From the 24 bottles closed at various depth at each stations, samples of sea water are used for salinity and oxygen calibration, and for measurements of biogeochemical components that are not reported here. The data were acquired with a Seabird CTD (SBE911+) and an SBE43 for the dissolved oxygen, belonging to the Spanish UTM group. The software SBE data processing was used after decoding and cleaning the raw data. Then, the LPO matlab toolbox was used to calibrate and bin the data as it was done for the previous OVIDE cruises, using on the one hand pre and post-cruise calibration results for the pressure and temperature sensors (done at Ifremer) and on the other hand the water samples of the 24 bottles of the rosette at each station for the salinity and dissolved oxygen data. A final accuracy of 0.002°C, 0.002 psu and 0.04 ml/l (2.3 umol/kg) was obtained on final profiles of temperature, salinity and dissolved oxygen, compatible with international requirements issued from the WOCE program.

New worlds and new churches: The Orthodox Church(es) and the European Union

The Orthodox church(es) share a common commitment to the unity of dogma and spirituality. There is, however, no doctrinal formulation that comes close to a form of political theology at a pan-Orthodox level. This means that the Orthodox churches’ attitude towards the European Union (EU) is driven by their ecclesial diversity and by complex inter-ecclesial relations. More fundamentally they share a fragmented and plural, theological objection to the very ideas of Europe and the West. This has been further complicated by the emergence of a substantial Orthodox diaspora from Eastern Europe, Russia, and the Middle East living across the breadth of the European continent. Consequently the ecclesial identity and self-perception of the autocephalous Orthodox churches is changing. These churches are becoming increasingly transnational and extra-territorial. With this, their perception of Europe and the West, as seen through the eyes of their diaspora communities, is altering from “threat” to “home” (Makrides and Uffelmann, 2003). The growing diaspora will not only impact the Christian demographics of Europe but will also transform the Eastern Churches’ view of Europe and the EU (Leustean, 2009; 2011; 2013; 2014a; 2014b).

"A beleza é o grau mais elevado da verdade", "Os Memoráveis", de Lídia Jorge

Foi um prazer ler o último romance de Lídia Jorge, editado em março último, pela Dom Quixote. E as razões foram muitas. Porque fala de um dia da nossa história que me diz bastante: o 25 de abril de 1974. Apesar de ter dele apenas uma vaga ideia, foi sendo sempre falado na minha família e faz parte do meu presente. Porque reconheço grande parte da história ali contada, fazendo-me sentir cúmplice, quer do texto, quer dos acontecimentos. Porque o romance é um género que faz falta para contar a História. É um modo de chegar a muito mais gente que, depois de o ler (ou enquanto o vai lendo), vai ter vontade de ir procurar os outros livros – os de História não romanceada – para aprender sobre as horas daquela noite de 24 para 25 e sobre os seus protagonistas. Apesar da «transfiguração literária », como se lê na nota de edição, quem sabe se não os reconhecerá? E saltando muitas outras razões, porque é um livro muito bem escrito. As pontas que vão sendo soltas ao longo da narrativa juntam-se em outros momentos, completando quadros de sentido. Ana Maria Machada, a narradora, como participante da história, sabe tanto como nós sobre o que pensam as outras personagens, mas sabe um bocadinho mais do que, em certos momentos, conta. Por exemplo, quando a equipa de reportagem entrevista a viúva de um dos capitães de Abril (que percebemos ser Salgueiro Maia, apesar de apenas ser referido pela sua «alcunha doméstica», isto é, pelo nome que a mãe de Ana Maria lhe dera: Charlie 8) e tenta conseguir que esta diga quem queria mal ao marido, perante a relutância em acusar alguém, a «Machadinha» afirma «Nós sabíamos, mas não tão bem como ela, que as vinganças de que foram vítimas ele e os outros como ele, tinham tido autores concretos, nomeáveis, intérpretes e responsáveis, colocados no topo das estruturas criadas num país onde passara a haver liberdade para legitimar tudo e o seu contrário» (p. 249).

Composition of objectively measured physical activity and sedentary behaviour participation across the school-day, influence of gender and weight status: cross-sectional analyses among disadvantaged Victorian school children

BACKGROUND: The after-school period has been described as the 'critical window' for physical activity (PA) participation. However, little is known about the importance of this window compared with the before and during-school period among socioeconomically disadvantaged children, and influence of gender and weight status.

METHODS: 39 out of 156 (RR=25%) invited primary schools across 26 local government areas in Victoria, Australia, consented to participate with 856 children (RR=36%) participating in the wider study. The analysis sample included 298 Grade 4 and Grade 6 children (mean age: 11.2±1.1; 44% male) whom met minimum accelerometry wear-time criteria and had complete height, weight and health-behaviours questionnaire data. Accelerometry measured duration in daily light-intensity PA (LPA), moderate-to-vigorous PA (MVPA) and sedentary time (ST) was calculated for before-school=8-8:59, during-school=9:00-15:29 and after-school=15:30-18:00. Bivariate and multivariable linear regression analyses were conducted.

RESULTS: During-school represented the greatest accumulation of LPA and MVPA compared with the before and after-school periods. Boys engaged in 102 min/day of LPA (95% CI 98.5 to 104.9) and 62 min/day of MVPA (95% CI 58.9 to 64.7) during-school; girls engaged in 103 min/day of LPA (95% CI 99.7 to 106.5) and 45 min/day of MVPA (95% CI 42.9 to 47.4). Linear regression models indicated that girls with overweight or obesity engaged in significantly less LPA, MVPA and more time in ST during-school.

CONCLUSIONS: This study highlights the importance of in-school PA compared with after-school PA among socioeconomically disadvantage children whom may have fewer resources to participate in after-school PA.

The Amplifier - v. 12, no. 4

In this issue...Butte Symphony, Dr. Adam Smith, NASA, Petroleum Engineering Scholarship, Charlie Brown, Peanuts Cartoon, Glee club, Library-Museum Building