Storage stability of bevacizumab in polycarbonate and polypropylene syringes

Purpose To compare and examine the storage stability of compounded bevacizumab in polycarbonate (PC) and polypropylene (PP) syringes over a 6-month period. PC syringes have been used in a recent clinical study and bevacizumab stability has not been reported for this type of syringe. Methods Repackaged bevacizumab was obtained from Moorfields Pharmaceuticals in polycarbonate (PC) and polypropylene (PP) syringes. Bevacizumab from the stored syringes was analysed at monthly time points for a 6-month period and compared with bevacizumab from a freshly opened vial at each time point. SDS-PAGE electrophoresis and size-exclusion chromatography (SEC) was used to observe aggregation and degradation. Dynamic light scattering (DLS) provided information about the hydrodynamic size and particle size distribution of bevacizumab in solution. VEGF binding and the active concentration of bevacizumab was determined by surface plasmon resonance (SPR) using Biacore. Results SDS-PAGE and SEC analysis did not show any changes in the presence of higher molecular species (HMWS) or degradation products in PC and PP syringes from T0 to T6 compared to bevacizumab sampled from a freshly opened vial. The hydrodynamic diameter of bevacizumab in the PC syringe after six months of storage was not significantly different to bevacizumab taken from a freshly opened vial. Using SPR, the VEGF binding activity of bevacizumab in the PC syringe was comparable with bevacizumab taken from a freshly opened vial. Conclusion No significant difference over a 6-month period was observed in the quality of bevacizumab repackaged into prefilled PC polycarbonate and PP polypropylene syringes when compared to bevacizumab that is supplied from the vial.

Novel strategies for targeting innate immune responses to influenza.

NlmCategory="UNASSIGNED">We previously reported that TLR4(-/-) mice are refractory to mouse-adapted A/PR/8/34 (PR8) influenza-induced lethality and that therapeutic administration of the TLR4 antagonist Eritoran blocked PR8-induced lethality and acute lung injury (ALI) when given starting 2 days post infection. Herein we extend these findings: anti-TLR4- or -TLR2-specific IgG therapy also conferred significant protection of wild-type (WT) mice from lethal PR8 infection. If treatment is initiated 3 h before PR8 infection and continued daily for 4 days, Eritoran failed to protect WT and TLR4(-/-) mice, implying that Eritoran must block a virus-induced, non-TLR4 signal that is required for protection. Mechanistically, we determined that (i) Eritoran blocks high-mobility group B1 (HMGB1)-mediated, TLR4-dependent signaling in vitro and circulating HMGB1 in vivo, and an HMGB1 inhibitor protects against PR8; (ii) Eritoran inhibits pulmonary lung edema associated with ALI; (iii) interleukin (IL)-1β contributes significantly to PR8-induced lethality, as evidenced by partial protection by IL-1 receptor antagonist (IL-1Ra) therapy. Synergistic protection against PR8-induced lethality was achieved when Eritoran and the antiviral drug oseltamivir were administered starting 4 days post infection. Eritoran treatment does not prevent development of an adaptive immune response to subsequent PR8 challenge. Overall, our data support the potential of a host-targeted therapeutic approach to influenza infection.Mucosal Immunology advance online publication 27 January 2016; doi:10.1038/mi.2015.141.

Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance

International audience

Do hatchery-reared sea urchins pose a threat to genetic diversity in wild populations?

In salmonids, the release of hatchery-reared fish has been shown to cause irreversible genetic impacts on wild populations. However, although responsible practices for producing and releasing genetically diverse, hatchery-reared juveniles have been published widely, they are rarely implemented. Here, we investigated genetic differences between wild and early-generation hatchery-reared populations of the purple sea urchin Paracentrotus lividus (a commercially important species in Europe) to assess whether hatcheries were able to maintain natural levels of genetic diversity. To test the hypothesis that hatchery rearing would cause bottleneck effects (that is, a substantial reduction in genetic diversity and differentiation from wild populations), we compared the levels and patterns of genetic variation between two hatcheries and four nearby wild populations, using samples from both Spain and Ireland. We found that hatchery-reared populations were less diverse and had diverged significantly from the wild populations, with a very small effective population size and a high degree of relatedness between individuals. These results raise a number of concerns about the genetic impacts of their release into wild populations, particularly when such a degree of differentiation can occur in a single generation of hatchery rearing. Consequently, we suggest that caution should be taken when using hatchery-reared individuals to augment fisheries, even for marine species with high dispersal capacity, and we provide some recommendations to improve hatchery rearing and release practices. Our results further highlight the need to consider the genetic risks of releasing hatchery-reared juveniles into the wild during the establishment of restocking, stock enhancement and sea ranching programs.

An updated evolutionary classification of CRISPR–Cas systems

The evolution of CRISPR–cas loci, which encode adaptive immune systems in archaea and bacteria, involves rapid changes, in particular numerous rearrangements of the locus architecture and horizontal transfer of complete loci or individual modules. These dynamics complicate straightforward phylogenetic classification, but here we present an approach combining the analysis of signature protein families and features of the architecture of cas loci that unambiguously partitions most CRISPR–cas loci into distinct classes, types and subtypes. The new classification retains the overall structure of the previous version but is expanded to now encompass two classes, five types and 16 subtypes. The relative stability of the classification suggests that the most prevalent variants of CRISPR–Cas systems are already known. However, the existence of rare, currently unclassifiable variants implies that additional types and subtypes remain to be characterized.

Nuevas tendencias del Estado Civil en Colombia

34 p.

Identificación de Peligros, Evaluación y valoración de riesgos y determinación de controles en seguridad y salud en el trabajo en la Corporación Tecnológica de Bogotá

101 p.

Normative reference values for the 20-meter shuttlerun test in a population-based sample of schoolchildren in Bogota, Colombia: The FUPRECOL Study

Our aim was to determine the normative reference values of cardiorespiratory fitness (CRF) and to establish the proportion of subjects with low CRF suggestive of future cardio-metabolic risk.

Efectos jurídicos de prohibir minería en ecosistemas de páramos con títulos mineros preexistentes

A raíz del impacto ambiental que produce la actividad minera sobre la biodiversidad y los recursos naturales, el sistema jurídico colombiano sustrajo de esta actividad, zonas de especial importancia ecológica y ambiental, que podrían llegar a deteriorarse en su totalidad. Sin embargo, si bien es clara la importancia de proteger estas zonas de la actividad extractiva, lo cierto es que en la actualidad se presenta un alto porcentaje de estas zonas que se superponen con títulos mineros. Circunstancia que conlleva a que entren en tensión intereses constitucionales protegidos. Por un lado, el interés general de proteger el medio ambiente y los recursos naturales y por el otro, el interés público de desarrollar la actividad minera. De acuerdo a lo anterior, a través de este trabajo de investigación, se busca describir y analizar las consecuencias en el ámbito jurídico, que se generan, al prohibir la actividad minera en zonas sobre las cuales el Estado había autorizado la realización de actividades de exploración y /o explotación minera con anterioridad al cambio regulatorio. En consecuencia, se expondrán los escenarios en que se puede encontrar un contrato de concesión, con la prohibición legal de desarrollar actividades mineras en ecosistemas de páramos. Específicamente, se analizará la situación de los títulos mineros que cuenten con licencia ambiental, títulos mineros que se encuentren en etapa de exploración y los títulos que habiendo terminado la etapa de exploración su licencia ambiental se encuentre en trámite.

La exploración y producción de hidrocarburos en yacimientos no convencionales, frente a los principios de prevención, precaución y desarrollo sostenible

El presente trabajo de grado busca exponer el panorama actual de la exploración y producción de hidrocarburos en Yacimientos No Convencionales, realizada utilizando el fracturamiento hidráulico – Fracking – cómo método para lograr mejores condiciones físicas en el reservorio que permitan la extracción del recurso. El método mencionado es estudiado a la luz de los principios de prevención, precaución y desarrollo sostenible, que rigen la política ambiental en Colombia, con el objetivo de analizar los posibles impactos ambientales y sociales que se puedan generar por el desarrollo de la actividad extractiva de hidrocarburos en Yacimientos No Convencionales. Para finalmente mostrar que el Fracking como actividad está legalmente permitida en Colombia, y la legislación vigente responde a los principios mencionados previamente.

Constituição da República Federativa do Brasil [gravação de som] : texto constitucional promulgado em 5 de outubro de 1988, com as alterações adotadas pelas Emendas Constitucionais números 1/1992 a 90/2015, pelo Decreto-Legislativo número 186 de 2008 e pelas Emendas Constitucionais de Revisão números 1 a 6/1994

Áudio gravado com o aplicativo Balabolka com o uso da voz Microsoft Heloísa.

Decreto nº 8.456/2015 : Decreto de contingenciamento - 22/05/2015 - e sua repercussão sobre as emendas individuais da LOA 2015

Tem como objetivo apresentar os limites orçamentários e financeiros estabelecidos pelo Decreto nº 8.456/2015 e, especialmente, as implicações sobre as emendas parlamentares individuais, sujeitas ao regime do “orçamento impositivo” (classificadas, na lei orçamentária, sob o código de identificador de resultado primário RP6.

Análise do Anexo I do Decreto nº 8.456/2015 relativa às despesas da área temática IV – MCTI, MEC, MinC e ME

Analisa e detalha as ações orçamentárias das dotações iniciais constantes da Lei Orçamentária para 2015 – LOA 2015 dos órgãos integrantes da Área Temática IV (Ministério da Ciência, Tecnologia e Inovação – MCTI, Ministério da Educação – MEC, Ministério da Cultura – MinC e Ministério do Esporte – ME) que foram objeto de limitação de movimentação e empenho em face do Decreto nº 8.456, de 22 de maio de 2015.

Decreto Rectoral No. 1038 : Por el cual se establece el Procedimiento para entrega de trabajos de grado, tesis y disertaciones

Decreto rectoral No. 1038 (28 de octubre de 2008) Este decreto establece el procedimiento de entrega de documentos, considerando que desde el año 2008 la Universidad del Rosario, a través de su biblioteca se unió a las iniciativas internacionales de depósito de trabajos de grado, tesis y disertaciones de sus estudiantes en los Repositorios Institucionales y creó la herramienta e.doc. El objetivo de la herramienta e.doc es facilitar el acceso y maximizar la visibilidad de la producción científica, académica e institucional de la Universidad del Rosario garantizando su preservación. Que gracias a la utilización de los estándares y protocolos internacionales, el e.doc formará parte de las redes de Repositorio Institucional en el mundo, lo que significa para los estudiantes potencializar la divulgación de sus trabajos y aumentar la presencia en las comunidades científicas internacionales. Igualmente se deberá garantizar la calidad adecuada de los contenidos divulgados para lograr la visibilidad exterior pretendida por la Universidad del Rosario.