62 research outputs found

    Priming Immunization with DNA Augments Immunogenicity of Recombinant Adenoviral Vectors for Both HIV-1 Specific Antibody and T-Cell Responses

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    Induction of HIV-1-specific T-cell responses relevant to diverse subtypes is a major goal of HIV vaccine development. Prime-boost regimens using heterologous gene-based vaccine vectors have induced potent, polyfunctional T cell responses in preclinical studies.The first opportunity to evaluate the immunogenicity of DNA priming followed by recombinant adenovirus serotype 5 (rAd5) boosting was as open-label rollover trials in subjects who had been enrolled in prior studies of HIV-1 specific DNA vaccines. All subjects underwent apheresis before and after rAd5 boosting to characterize in depth the T cell and antibody response induced by the heterologous DNA/rAd5 prime-boost combination.rAd5 boosting was well-tolerated with no serious adverse events. Compared to DNA or rAd5 vaccine alone, sequential DNA/rAd5 administration induced 7-fold higher magnitude Env-biased HIV-1-specific CD8(+) T-cell responses and 100-fold greater antibody titers measured by ELISA. There was no significant neutralizing antibody activity against primary isolates. Vaccine-elicited CD4(+) and CD8(+) T-cells expressed multiple functions and were predominantly long-term (CD127(+)) central or effector memory T cells and that persisted in blood for >6 months. Epitopes mapped in Gag and Env demonstrated partial cross-clade recognition.Heterologous prime-boost using vector-based gene delivery of vaccine antigens is a potent immunization strategy for inducing both antibody and T-cell responses.ClinicalTrials.gov NCT00102089, NCT00108654

    First Resolved Scattered-light Images of Four Debris Disks in Scorpius-Centaurus with the Gemini Planet Imager

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    We present the first spatially resolved scattered-light images of four debris disks around members of the Scorpius-Centaurus (Sco-Cen) OB association with high-contrast imaging and polarimetry using the Gemini Planet Imager (GPI). All four disks are resolved for the first time in polarized light, and one disk is also detected in total intensity. The three disks imaged around HD 111161, HD 143675, and HD 145560 are symmetric in both morphology and brightness distribution. The three systems span a range of inclinations and radial extents. The disk imaged around HD 98363 shows indications of asymmetries in morphology and brightness distribution, with some structural similarities to the HD 106906 planet–disk system. Uniquely, HD 98363 has a wide comoving stellar companion, Wray 15-788, with a recently resolved disk with very different morphological properties. HD 98363 A/B is the first binary debris disk system with two spatially resolved disks. All four targets have been observed with ALMA, and their continuum fluxes range from one nondetection to one of the brightest disks in the region. With the new results, a total of 15 A/F stars in Sco-Cen have resolved scattered-light debris disks, and approximately half of these systems exhibit some form of asymmetry. Combining the GPI disk structure results with information from the literature on millimeter fluxes and imaged planets reveals a diversity of disk properties in this young population. Overall, the four newly resolved disks contribute to the census of disk structures measured around A/F stars at this important stage in the development of planetary systems

    Comparative Genomics of Gardnerella vaginalis Strains Reveals Substantial Differences in Metabolic and Virulence Potential

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    Gardnerella vaginalis is described as a common vaginal bacterial species whose presence correlates strongly with bacterial vaginosis (BV). Here we report the genome sequencing and comparative analyses of three strains of G. vaginalis. Strains 317 (ATCC 14019) and 594 (ATCC 14018) were isolated from the vaginal tracts of women with symptomatic BV, while Strain 409-05 was isolated from a healthy, asymptomatic individual with a Nugent score of 9.Substantial genomic rearrangement and heterogeneity were observed that appeared to have resulted from both mobile elements and substantial lateral gene transfer. These genomic differences translated to differences in metabolic potential. All strains are equipped with significant virulence potential, including genes encoding the previously described vaginolysin, pili for cytoadhesion, EPS biosynthetic genes for biofilm formation, and antimicrobial resistance systems, We also observed systems promoting multi-drug and lantibiotic extrusion. All G. vaginalis strains possess a large number of genes that may enhance their ability to compete with and exclude other vaginal colonists. These include up to six toxin-antitoxin systems and up to nine additional antitoxins lacking cognate toxins, several of which are clustered within each genome. All strains encode bacteriocidal toxins, including two lysozyme-like toxins produced uniquely by strain 409-05. Interestingly, the BV isolates encode numerous proteins not found in strain 409-05 that likely increase their pathogenic potential. These include enzymes enabling mucin degradation, a trait previously described to strongly correlate with BV, although commonly attributed to non-G. vaginalis species.Collectively, our results indicate that all three strains are able to thrive in vaginal environments, and therein the BV isolates are capable of occupying a niche that is unique from 409-05. Each strain has significant virulence potential, although genomic and metabolic differences, such as the ability to degrade mucin, indicate that the detection of G. vaginalis in the vaginal tract provides only partial information on the physiological potential of the organism

    The Science Performance of JWST as Characterized in Commissioning

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    This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

    Swimways: Protecting Paddlefish through Movement-centered Management

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    Attempts to mitigate lack of formal interjurisdictional paddlefish management have been made in the United States through the Mississippi River Interstate Cooperative Resource Association (MICRA). We used 1988–2009 data from the MICRA paddlefish (Polyodon spathula) stock assessment database—a database containing mark–recapture and biometric information on more than 30,000 individually marked wild paddlefish and more than 2 million hatchery-origin paddlefish—to estimate survival and movement across large and potentially biologically relevant spatial scales. Paddlefish frequently moved between political jurisdictions with differing conservation strategies and harvest regulations and showed differences in survival parameter estimates throughout their range. We argue that the degree of interjursidictional movements, spatially variant survival rates, and conservation concerns associated with paddlefish necessitate more cohesive interjurisdictional management. Based on criteria used to establish flyways for migratory bird management, we offer swimways as a potential spatial configuration for biologically relevant management units. Corredores de nado: protección del pez espátula mediante manejo centrado en su movimiento Resumen: La Asociación Interestatal de Recursos Cooperativos del Río Mississippi (AIRCRM) ha hecho intentos para mitigar la falta de manejo inter-jurisdiccional del pez espátula en los EEUU. Se utilizó información sobre evaluación de los stocks de pez espátula (Polyodon spathula) contenida en la base de datos de AIRCRM para el periodo 1995-2009, la cual contiene información biométrica y de marca-recaptura de \u3e30,000 peces espátula marcados individualmente y de \u3e2 milliones de especímenes provenientes de cultivo, con el fin de estimar la supervivencia y movimiento a escalas espaciales amplias y con potencial biológico relevante. El pez espátula frecuentemente se mueve entre jurisdicciones políticas que difieren en cuanto a sus estrategias de conservación y regulaciones de captura, y muestra diferencias en sus parámetros de supervivencia a lo largo de su ámbito geográfico. Se argumenta que el grado de movimiento inter-jurisdiccional, el cambio espacial en las tasas de supervivencia y las preocupaciones de conservación asociadas a esta especie, demandan de un manejo interjurisdiccional con mayor cohesión. Sobre la base de criterios usados para establecer corredores de vuelo para el manejo de aves migratorias, aquí se muestra un corredor de nado como una potencial configuración espacial para unidades de manejo biológicamente-relevantes

    Interpreting Arterial Blood Gases Successfully

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    Arterial blood gas (ABG) analysis is a crucial skill for perioperative nurses, in particular the RN circulator. This article provides the physiological basis for assessing ABGs perioperatively and presents a systematic approach to blood gas analysis using the Romanski method. Blood gas sample data allow the reader to practice ABG interpretation. In addition, four case studies are presented that give the reader the opportunity to analyze ABGs within the context of surgical patient scenarios. The ability to accurately assess ABGs allows the perioperative nurse to assist surgical team members in restoring a patient\u27s acid-base balance

    COVID-19 response unites perioperative teams at a recently merged health care system

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    Advocate Aurora Health, located in the north-central United States, is the result of a merger between two large health care organizations in April 2018. The health care system comprises 26 hospitals, offers more than 500 sites of care, and employs 75,000 team members. This article discusses the effects that coronavirus disease 2019 had on the perioperative services departments while directors and site leaders were still managing the complexities of the merger. Included are strategies used to address the challenges created by the pandemic, special considerations based on level-of-care capacity, the effect that the hold on elective surgeries had on staffing assignments, the reactivation process when elective surgery resumed, and the importance of keeping the perioperative team members informed and safe. It also illustrates how facing the challenges caused by the pandemic helped to solidify the merger of the two health care organizations

    Outcomes in residential treatment for youth: The role of early engagement

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    Client engagement is commonly believed to be an important condition for the attainment of positive outcomes in human services. This paper addresses client engagement in the context of residential treatment centers (RTCs) for youth. Three waves of data from interviews with adolescents in two RTCs are used to test hypotheses reflecting competing explanations for whether and how engagement may relate to self-view, school, and family outcomes. Findings suggest that youths who are more engaged early in treatment tend to have more positive outcomes, lesser engaged youths show the greatest degree of positive change, and that a relationship between early engagement and certain outcomes, but not others, may be mediated by certain treatment interventions.Child welfare Outcomes Engagement
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