Envelope determinants of equine lentiviral vaccine protection

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection

CONNECT for quality: protocol of a cluster randomized controlled trial to improve fall prevention in nursing homes

<p>Abstract</p> <p>Background</p> <p>Quality improvement (QI) programs focused on mastery of content by individual staff members are the current standard to improve resident outcomes in nursing homes. However, complexity science suggests that learning is a social process that occurs within the context of relationships and interactions among individuals. Thus, QI programs will not result in optimal changes in staff behavior unless the context for social learning is present. Accordingly, we developed CONNECT, an intervention to foster systematic use of management practices, which we propose will enhance effectiveness of a nursing home Falls QI program by strengthening the staff-to-staff interactions necessary for clinical problem-solving about complex problems such as falls. The study aims are to compare the impact of the CONNECT intervention, plus a falls reduction QI intervention (CONNECT + FALLS), to the falls reduction QI intervention alone (FALLS), on fall-related process measures, fall rates, and staff interaction measures.</p> <p>Methods/design</p> <p>Sixteen nursing homes will be randomized to one of two study arms, CONNECT + FALLS or FALLS alone. Subjects (staff and residents) are clustered within nursing homes because the intervention addresses social processes and thus must be delivered within the social context, rather than to individuals. Nursing homes randomized to CONNECT + FALLS will receive three months of CONNECT first, followed by three months of FALLS. Nursing homes randomized to FALLS alone receive three months of FALLs QI and are offered CONNECT after data collection is completed. Complexity science measures, which reflect staff perceptions of communication, safety climate, and care quality, will be collected from staff at baseline, three months after, and six months after baseline to evaluate immediate and sustained impacts. FALLS measures including quality indicators (process measures) and fall rates will be collected for the six months prior to baseline and the six months after the end of the intervention. Analysis will use a three-level mixed model.</p> <p>Discussion</p> <p>By focusing on improving local interactions, CONNECT is expected to maximize staff's ability to implement content learned in a falls QI program and integrate it into knowledge and action. Our previous pilot work shows that CONNECT is feasible, acceptable and appropriate.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00636675">NCT00636675</a></p

Biogeography and genetic diversity of the atlantid heteropods.

The atlantid heteropods are regularly encountered, but rarely studied marine planktonic gastropods. Relying on a small (<14 mm), delicate aragonite shell and living in the upper ocean means that, in common with pteropods, atlantids are likely to be affected by imminent ocean changes. Variable shell morphology and widespread distributions indicate that the family is more diverse than the 23 currently known species. Uncovering this diversity is fundamental to determining the distribution of atlantids and to understanding their environmental tolerances. Here we present phylogenetic analyses of all described species of the family Atlantidae using 437 new and 52 previously published cytochrome c oxidase subunit 1 mitochondrial DNA (mtCO1) sequences. Specimens and published sequences were gathered from 32 Atlantic Ocean stations, 14 Indian Ocean stations and 21 Pacific Ocean stations between 35°N and 43°S. DNA barcoding and Automatic Barcode Gap Discovery (ABGD) proved to be valuable tools for the identification of described atlantid species, and also revealed ten additional distinct clades, suggesting that the diversity within this family has been underestimated. Only two of these clades displayed obvious morphological characteristics, demonstrating that much of the newly discovered diversity is hidden from morphology-based identification techniques. Investigation of six large atlantid collections demonstrated that 61% of previously described (morpho) species have a circumglobal distribution. Of the remaining 39%, two species were restricted to the Atlantic Ocean, five occurred in the Indian and Pacific oceans, one species was only found in the northeast Pacific Ocean, and one occurred only in the Southern Subtropical Convergence Zone. Molecular analysis showed that seven of the species with wide distributions were comprised of two or more clades that occupied distinct oceanographic regions. These distributions may suggest narrower environmental tolerances than the described morphospecies. Results provide an updated biogeography and mtCO1 reference dataset of the Atlantidae that may be used to identify atlantid species and provide a first step in understanding their evolutionary history and accurate distribution, encouraging the inclusion of this family in future plankton research

Modifikation des Systems 'Oelsaugteppich' zur Entfernung dickerer Oele von der Meeresoberflaeche und Erprobung mit verschiedenen Traegern auf See Schlussbericht

SIGLETIB: FR 3728+a-b / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Weiterentwicklung, Adaption an moegliche Traeger und Erprobung des Prinzips 'Oelsaugteppich' auf See zur Entfernung von Oel von der Meeresoberflaeche im Flachwasser- und Wattgebiet Schlussbericht

With 27 figs.SIGLETIB: FR 2950 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Ueberwachungssystem fuer Nachweis und Ortung von Undichtigkeiten an Deponien wassergefaehrdender Stoffe Abschlussbericht

With 54 refs.TIB Hannover: FR 1382 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Entwicklung eines Messgeraetes fuer Gase und Daempfe mit automatischer Eichung und Selbstueberwachung Schlussbericht

With 41 refs.Available from TIB Hannover: FR 5851 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Prospective study of progeny of inapparent equine carriers of equine infectious anemia virus.

Progeny of a band of horses, positive by the agar-gel immunodiffusion (AGID) test for equine infectious anemia (EIA) antibody, were observed through their weaning over a 4-year period. Sentinels (AGID test-negative) were allowed to mingle with EIA-infected mares and their foals in pasture situations in an area with high populations of potential vectors. Of 27 adult sentinels, 8 (30%) seroconverted in annual rates ranging from 0% to 75%. In contrast, only 2 of 31 (6%) foals weaned became infected. Difference in infection rates between adult sentinels and foals was significant (chi 2, P less than 0.05). Possible explanations for differences included protective value of colostral immunity and differences in attractiveness to blood feeding vectors. Detectable colostral immunity to EIA virus in the AGID test persisted for 25 to 195 days, with a mean of 124 days