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

Equine infectious anemia : prevalence in working equids of livestock herds, in Minas Gerais, Brazil

Estimaram-se, no estado de Minas Gerais, a prevalência e a distribuição espacial da anemia infecciosa eqüina (AIE) em propriedades com eqüídeos de serviço. As amostras de sangue, de 6540 eqüídeos de 1940 rebanhos foram coletadas no período de setembro de 2003 a março de 2004, nos 853 municípios do estado. Utilizaram-se dois testes de laboratório em seqüência: ELISA, usando-se antígeno recombinante gp90, e imunodifusão em gel de ágar (IDGA). As prevalências foram de 5,3% [IC=4,3 a 6,3%] para rebanhos e de 3,1% [IC=2,2 a 3,9%] para animais. O estado de Minas Gerais foi considerado área endêmica para AIE. As mais altas prevalências para rebanhos e para animais foram encontradas na região Norte/Noroeste, seguida pela região Vale do Mucuri/Jequitinhonha. ___________________________________________________________________________________________________________ ABSTRACTThe prevalence and spatial distribution of equine infectious anemia (EIA) were estimated in livestock herds where equids were used as draft power and for transportation in the State of Minas Gerais, Brazil. Serum samples were collected from September/2003 to March/2004 in 853 municipalities of the state. The sample comprised 6,540 equids from 1,940 herds. Two laboratorial tests were performed in sequence: ELISA using a recombinant gp90 protein, following by the AGID. The prevalence in the herds was estimated in 5.3% [CI = 4.3 to 6.3%], and 3.1% [CI = 2.2 to 3.9%] of the animals tested were positive. Minas Gerais was considered an endemic region for EIA. The highest prevalence for herds and animals was found in North/Northwest region (strata) followed by Vale do Mucuri/Jequitinhonha region

Further evidence for a relatively high sea level during the penultimate interglacial: open-system U-series ages from La Marina (Alicante, East Spain)

The elevation and timing of high sea stands during Oxygen Isotope Stage (OIS) 7 are not as well constraíned as those of OIS 5e. Conflictíng values are reported from Medíterranean coastlines, and fossil dating is inaccurate because of ubiquitous open U-series systems. New morphostratigraphic data from La Marina (eastem Spain) supported by open-system U-series coral ages shed light on the maximum sea level duríng OIS 7. Fossil corals (Cladocora Caespitosa) underlying an OIS 5e marine unít yielded U-series ages from 178 ± (0 to 208 ± 1) ka (± 20σ n=7) with an outlier al 240 ± 18 ka. Mean open-system limit ages of 170 ± 10 (minimum age after correction for 234Th-230Th uptake) and 237 ± 20 ka (maximum ase after correction for 238U - 234U uptake) were calculated to have a probable age closer to the minimum value, for an assignment of OlS 7a or 7c. The occurrence of a warn-water "Senegalese" fauna (Strombus bubonius) in OIS5e and OIS 7 marine units confirms the arrival of tropical species to the Mediterranean before the last interglacial periodo Morpho-sedimentological and neotectonic studies suggest that the maximum paleo-sea level during OIS 7c or 7a was a few melers below that of OlS Se

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

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

Novel and dynamic evolution of equine infectious anemia virus genomic quasispecies associated with sequential disease cycles in an experimentally infected pony.

We have investigated the genetic evolution of three functionally distinct regions of the equine infectious anemia virus (EIAV) genome (env, rev, and long terminal repeat) during recurring febrile episodes in a pony experimentally infected with a well-characterized reference biological clone designated EIAV(PV). Viral populations present in the plasma of an EIAV(PV)-infected pony during sequential febrile episodes (18, 34, 80, 106, and 337 days postinfection) were amplified from viral RNA, analyzed, and compared to the inoculated strain. The comparison of the viral quasispecies showed that the inoculated EIAV(PV) quasispecies were all represented during the first febrile episode, but entirely replaced at the time of the second febrile episode, and that new predominant quasispecies were associated with each subsequent cycle of disease. One of the more surprising results was the in vivo generation of large deletion (up to 15 amino acids) in the principal neutralizing domain (PND) of gp90 during the third febrile episode. This deletion did not alter the competence for in vitro replication as shown by the analysis of a env chimeric clone with a partially deleted PND and did not altered the fitness of the virus in vivo, since this partially deleted envelope became the major population during the fourth febrile episode. Finally, we showed that the amino acid mutations were not randomly distributed but delineated eight variables regions, V1 to V8, with V3 containing the PND region. These studies provide the first detailed description of the evolution of EIAV genomic quasispecies during persistent infection and reveal new insights into the genetics and potential mechanisms of lentivirus genomic variation

Experience of Using Information Systems in Public Health Practice: Findings from a Qualitative Study

OBJECTIVE: Data collection and management by local health departments (LHDs) is a complex endeavor, complicated by system level and organizational factors. The purpose of this study was to describe the processes and use of information systems (IS) utilized for data collection, management, and sharing by LHD employees. METHODS: We interviewed a purposive sample of 12 staff working in the key public health practice areas of communicable disease control, immunizations, and vital records from three LHDs in different states. Our interview questions addressed job descriptions, daily activities, and the use and perceptions of both data and IS in support of their work. A content analytic approach was used to derive themes and categories common across programmatic areas. RESULTS: Local public health involves the use of mix of state-supplied and locally implemented IS supported by paper records. Additionally, each LHD in this study used at least one shadow system to maintain a duplicate set of information. Experiences with IS functionality and the extent to which it supported work varied by programmatic area, but inefficiencies, challenges in generating reports, limited data accessibility, and workarounds were commonly reported. CONCLUSIONS: Current approaches to data management and sharing do not always support efficient public health practice or allow data to be used for organizational and community decision making. Many of the challenges to effective and efficient public health work were not solely technological. These findings suggest the need for interorganizational collaboration, increasing organizational capacity, workflow redesign, and end user training