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. © 2013 Craigo et al

Sea level changes during the last and present interglacials in Sal Island (Cape Verde archipelago)

Last interglacial and Holocene deposits are particularly well developed in the southern parts of Sal Island (Cape Verde Archipelago). They primarily consist of low-elevation (≤2 m above sea level [a.s.l.]) marine deposits made of a basal conglomerate embedded in carbonate mud, passing upwards to calcarenites. All deposits contain an abundant fauna with corals, algae and molluscs with Strombus latus Gmelin and accompanying warm water species of the “Senegalese” fauna. Small scale geomorphological mapping with detailed morphosedimentary analysis revealed lateral facies changes and imbricate (offlapping) structures that suggest small-scale oscillations of paleo-sealevels during high sea stand intervals. U-series measurements (in coral fragments) allowed unequivocal identification of Marine Isotope Substage (MIS) 5.5 units, but were not precise enough to date the sea level oscillations of the interval. However, geomorphological data and sedimentary facies analysis suggest a double sea level highstand during the peak of the last interglacial. MIS 5.5 age deposits occur at Sal and the Canary Islands at low topographic elevations, between 1 and 2 masl. However, these values are lower than the elevations measured for the correlative terraces outcropping at the western tropical Atlantic islands, widely considered to be tectonically stable. Combining the results in this paper with earlier investigations of the “Senegalese” fauna distribution as far north as the Mediterranean basin, it is suggested that the last-interglacial oceanic temperatures in this basin, as well as the temperatures in other islands of the Eastern Atlantic and the coasts of Morocco, were warmer than modern temperatures

Sea level and climate changes during OIS 5e in the Western Mediterranean

Palaeontological, geomorphological and sedimentological data supported by isotopic dating on Oxygen Isotopic Stage (OIS) 5e deposits from the Spanish Mediterranean coast, are interpreted with the aim of reconstructing climatic instability in the Northern Hemisphere. Data point to marked climatic instability during the Last Interglacial (OIS 5e), with a change in meteorological conditions and, consequently, in the sedimentary environment. The oolitic facies generated during the first part of OIS 5e (ca. 135 kyr) shift into reddish conglomeratic facies during the second part (ca. 117 kyr). Sea surface Temperature (SST) and salinity are interpreted mainly on the basis of warm Senegalese fauna, which show chronological and spatial differential distribution throughout the Western Mediterranean. Present hydrological and meteorological conditions are used also as modern analogues to reconstruct climatic variability throughout the Last Interglacial, and this variability is interpreted within the wider framework of the North Atlantic record. All the available data indicate an increase in storminess induced by an increase in the influence of northwesterlies, a slight drop of SST in the northern Western Mediterranean, and an important change in meteorological conditions at the end of OIS 5e (117 kyr). These changes correlate well with the decrease in summer insolation and with the climatic instability recorded in North Atlantic high latitudes

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

Late Quaternary sea-level change and early human societies in the central and eastern Mediterranean Basin : an interdisciplinary review

This article reviews key data and debates focused on relative sea-level changes since the Last Interglacial (approximately the last 132,000 years) in the Mediterranean Basin, and their implications for past human populations. Geological and geomorphological landscape studies are critical to archaeology. Coastal regions provide a wide range of resources to the populations that inhabit them. Coastal landscapes are increasingly the focus of scholarly discussions from the earliest exploitation of littoral resources and early hominin cognition, to the inundation of the earliest permanently settled fishing villages and eventually, formative centres of urbanisation. In the Mediterranean, these would become hubs of maritime transportation that gave rise to the roots of modern seaborne trade. As such, this article represents an original review of both the geo-scientific and archaeological data that specifically relate to sea-level changes and resulting impacts on both physical and cultural landscapes from the Palaeolithic until the emergence of the Classical periods. Our review highlights that the interdisciplinary links between coastal archaeology, geomorphology and sea-level changes are important to explain environmental impacts on coastal human societies and human migration. We review geological indicators of sea level and outline how archaeological features are commonly used as proxies for measuring past sea levels, both gradual changes and catastrophic events. We argue that coastal archaeologists should, as a part of their analyses, incorporate important sea-level concepts, such as indicative meaning. The interpretation of the indicative meaning of Roman fishtanks, for example, plays a critical role in reconstructions of late Holocene Mediterranean sea levels. We identify avenues for future work, which include the consideration of glacial isostatic adjustment (GIA) in addition to coastal tectonics to explain vertical movements of coastlines, more research on Palaeolithic island colonisation, broadening of Palaeolithic studies to include materials from the entire coastal landscape and not just coastal resources, a focus on rescue of archaeological sites under threat by coastal change, and expansion of underwater archaeological explorations in combination with submarine geomorphology. This article presents a collaborative synthesis of data, some of which have been collected and analysed by the authors, as the MEDFLOOD (MEDiterranean sea-level change and projection for future FLOODing) community, and highlights key sites, data, concepts and ongoing debates

Stability of equine infectious anemia virus in Aedes aegypti (Diptera: Culicidae), Stomoxys calcitrans (Diptera: Muscidae), and Tabanus fuscicostatus (Diptera: Tabanidae) stored at -70°C

Equine infectious anemia virus (EIAV) was injected intrathoracically into Aedes aegypti, Stomoxys calcitrans, and Tabanus fuscicostatus, and fed to Ae. aegypti in suspensions of either artificial blood or Eagle\u27s Minimum Essential Medium. Insects were stored at -70°C for up to 9 months before testing for the presence of EIAV. The viral tissue culture titers detected from stored insects were similar to those from insects tested at time 0