A literature survey of clear air turbulence

Literature survey on clear air turbulenc

Ex vivo evaluation of mucosal responses to vaccination with ALVAC and AIDSVAX of non-human primates

Non-human primates (NHPs) remain the most relevant challenge model for the evaluation of HIV vaccine candidates; however, discrepancies with clinical trial results have emphasized the need to further refine the NHP model. Furthermore, classical evaluation of vaccine candidates is based on endpoints measured systemically. We assessed the mucosal responses elicited upon vaccination with ALVAC and AIDSVAX using ex vivo Rhesus macaque mucosal tissue explant models. Following booster immunization with ALVAC/AIDSVAX, anti-gp120 HIV-1CM244-specific IgG and IgA were detected in culture supernatant cervicovaginal and colorectal tissue explants, as well as systemically. Despite protection from ex vivo viral challenge, no neutralization was observed with tissue explant culture supernatants. Priming with ALVAC induced distinct cytokine profiles in cervical and rectal tissue. However, ALVAC/AIDSVAX boosts resulted in similar modulations in both mucosal tissues with a statistically significant decrease in cytokines linked to inflammatory responses and lymphocyte differentiation. With ALVAC/AIDSVAX boosts, significant correlations were observed between cytokine levels and specific IgA in cervical explants and specific IgG and IgA in rectal tissue. The cytokine secretome revealed differences between vaccination with ALVAC and ALVAC/AIDSVAX not previously observed in mucosal tissues and distinct from the systemic response, which could represent a biosignature of the vaccine combination

Cement waste-form development for ion-exchange resins at the Rocky Flats Plant

This report describes the development of a cement waste form to stabilize ion-exchange resins at Rocky Flats Environmental Technology Site (RFETS). These resins have an elevated potential for ignition due to inadequate wetness and contact with nitrates. The work focused on the preparation and performance evaluation of several Portland cement/resin formulations. The performance standards were chosen to address Waste Isolation Pilot Plant and Environmental Protection Agency Resource Conservation and Recovery Act requirements, compatibility with Rocky Flats equipment, and throughput efficiency. The work was performed with surrogate gel-type Dowex cation- and anion-exchange resins chosen to be representative of the resin inventory at RFETS. Work was initiated with nonactinide resins to establish formulation ranges that would meet performance standards. Results were then verified and refined with actinide-containing resins. The final recommended formulation that passed all performance standards was determined to be a cement/water/resin (C/W/R) wt % ratio of 63/27/10 at a pH of 9 to 12. The recommendations include the acceptable compositional ranges for each component of the C/W/R ratio. Also included in this report are a recommended procedure, an equipment list, and observations/suggestions for implementation at RFETS. In addition, information is included that explains why denitration of the resin is unnecessary for stabilizing its ignitability potential

Early Divergent Host Responses in SHIVsf162P3 and SIVmac251 Infected Macaques Correlate with Control of Viremia

We previously showed intravaginal inoculation with SHIVsf162p3 results in transient viremia followed by undetectable viremia in most macaques, and some displayed subsequent immunity to superinfection with pathogenic SIVmac251. Here we compare early T cell activation, proliferation, and plasma cytokine/chemokine responses in macaques intravaginally infected with either SHIVsf162p3 or SIVmac251 to determine whether distinct differences in host responses may be associated with early viral containment. The data show SIVmac251 infection results in significantly higher levels of T cell activation, proliferation, and a mixed cytokine/chemokine “storm” in plasma in primary infection, whereas infection with SHIVsf162p3 resulted in significantly lower levels of T cell activation, proliferation, and better preservation of memory CD4+ T cells in early infection which immediately preceded control of viremia. These results support the hypothesis that early systemic immune activation, T cell proliferation, and a more prominent and broader array of cytokine/chemokine responses facilitate SIV replication, and may play a key role in persistence of infection, and the progression to AIDS. In contrast, immune unresponsiveness may be associated with eventual clearance of virus, a concept that may have key significance for therapy and vaccine design

'Like building a plane and flying it all in one go': an interview study of infection prevention and control in Australian general practice during the first 2 years of the SARS-CoV-2 pandemic.

OBJECTIVES: General practitioners (GPs) and their staff have been at the frontline of the SARS-CoV-2 pandemic in Australia. However, their experiences of responding to and managing the risks of viral transmission within their facilities are poorly described. The aim of this study was to describe the experiences, and infection prevention and control (IPC) strategies adopted by general practices, including enablers of and challenges to implementation, to contribute to our understanding of the pandemic response in this critical sector. DESIGN: Semistructured interviews were conducted in person, by telephone or online video conferencing software, between November 2020 and August 2021. PARTICIPANTS: Twenty general practice personnel working in New South Wales, Australia, including nine GPs, one general practice registrar, four registered nurses, one nurse practitioner, two practice managers and two receptionists. RESULTS: Participants described implementing wide-ranging repertoires of IPC strategies-including telehealth, screening of patients and staff, altered clinic layouts and portable outdoor shelters, in addition to appropriate use of personal protective equipment (PPE)-to manage the demands of the SARS-CoV-2 pandemic. Strategies were proactive, influenced by the varied contexts of different practices and the needs and preferences of individual GPs as well as responsive to local, state and national requirements, which changed frequently as the pandemic evolved. CONCLUSIONS: Using the 'hierarchy of controls' as a framework for analysis, we found that the different strategies adopted in general practice often functioned in concert with one another. Most strategies, particularly administrative and PPE controls, were subjected to human variability and so were less reliable from a human factors perspective. However, our findings highlight the creativity, resilience and resourcefulness of general practice staff in developing, implementing and adapting their IPC strategies amidst constantly changing pandemic conditions

Early Regeneration of Thymic Progenitors in Rhesus Macaques Infected with Simian Immunodeficiency Virus

The thymus plays a critical role in the maturation and production of T lymphocytes and is a target of infection by human immunodeficiency virus (HIV) and the related simian immunodeficiency virus (SIV). Using the SIV/macaque model of AIDS, we examined the early effects of SIV on the thymus. We found that thymic infection by SIV resulted in increased apoptosis 7–14 d after infection, followed by depletion of thymocyte progenitors by day 21. A marked rebound in thymocyte progenitors occurred by day 50 and was accompanied by increased levels of cell proliferation in the thymus. Our results demonstrate a marked increase in thymic progenitor activity very early in the course of SIV infection, long before marked declines in peripheral CD4+ T cell counts

Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission

To gain insight into female-to-male HIV sexual transmission and how male circumcision protects against this mode of transmission, we visualized HIV-1 interactions with foreskin and penile tissues in ex vivo tissue culture and in vivo rhesus macaque models utilizing epifluorescent microscopy. 12 foreskin and 14 cadaveric penile specimens were cultured with R5-tropic photoactivatable (PA)-GFP HIV-1 for 4 or 24 hours. Tissue cryosections were immunofluorescently imaged for epithelial and immune cell markers. Images were analyzed for total virions, proportion of penetrators, depth of virion penetration, as well as immune cell counts and depths in the tissue. We visualized individual PA virions breaching penile epithelial surfaces in the explant and macaque model. Using kernel density estimated probabilities of localizing a virion or immune cell at certain tissue depths revealed that interactions between virions and cells were more likely to occur in the inner foreskin or glans penis (from local or cadaveric donors, respectively). Using statistical models to account for repeated measures and zero-inflated datasets, we found no difference in total virions visualized at 4 hours between inner and outer foreskins from local donors. At 24 hours, there were more virions in inner as compared to outer foreskin (0.0495 +/- 0.0154 and 0.0171 +/- 0.0038 virions/image, p = 0.001). In the cadaveric specimens, we observed more virions in inner foreskin (0.0507 +/- 0.0079 virions/image) than glans tissue (0.0167 +/- 0.0033 virions/image, p<0.001), but a greater proportion was seen penetrating uncircumcised glans tissue (0.0458 +/- 0.0188 vs. 0.0151 +/- 0.0100 virions/image, p = 0.099) and to significantly greater mean depths (29.162 +/- 3.908 vs. 12.466 +/- 2.985 μm). Our in vivo macaque model confirmed that virions can breach penile squamous epithelia in a living model. In summary, these results suggest that the inner foreskin and glans epithelia may be important sites for HIV transmission in uncircumcised men