Search

Airborne transmission is predicted to be a prevalent route of human exposure with SARS-CoV-2. Aside from African green monkeys, nonhuman primate models that replicate airborne transmission of SARS-CoV-2 have not been investigated. A comparative evaluation of COVID-19 in African green monkeys, rhesus macaques, and cynomolgus macaques following airborne exposure to SARS-CoV-2 was performed to determine critical disease parameters associated with disease progression, and establish correlations between primate and human COVID-19. Respiratory abnormalities and viral shedding were noted for all animals, indicating successful infection. Cynomolgus macaques developed fever, and thrombocytopenia was measured for African green monkeys and rhesus macaques. Type II pneumocyte hyperplasia and alveolar fibrosis were more frequently observed in lung tissue from cynomolgus macaques and African green monkeys. The data indicate that, in addition to African green monkeys, macaques can be successfully infected by airborne SARS-CoV-2, providing viable macaque natural transmission models for medical countermeasure evaluation.

Airborne transmission is predicted to be a prevalent route of human exposure with SARS-CoV-2. Aside from African green monkeys, nonhuman primate models that replicate airborne transmission of SARS-CoV-2 have not been investigated. A comprehensive and comparative evaluation of COVID-19 in African green monkeys, rhesus macaques, and cynomolgus macaques following airborne exposure to SARS-CoV-2 was performed to define parameters critical to disease progression and the extent to which they correlate with human COVID-19. Respiratory abnormalities and viral shedding were noted for all animals, indicating successful infection. Cynomolgus macaques developed fever, and thrombocytopenia was measured for African green monkeys and rhesus macaques. Type II pneumocyte hyperplasia and alveolar fibrosis were more frequently observed in lung tissue from cynomolgus macaques and African green monkeys. The data indicate that, in addition to African green monkeys, macaques can be successfully infected by airborne SARS-CoV-2, providing viable macaque natural transmission models for medical countermeasure evaluation.One Sentence SummaryNonhuman primates develop COVID-19 following airborne virus exposure.

Background In 1980, smallpox disease was eradicated from nature and Variola virus, the etiological agent of smallpox, was confined to two laboratories, one located in Russia (Moscow) later moved to VECTOR (Novosibirsk, Siberia) and one in the United States (CDC Atlanta). Vaccinations among the general public ceased shortly after the successful eradication campaign, resulting in an increasingly immunologically susceptible population. Because of the possibility of intentional reintroduction of Variola virus and the emergence of other pathogenic poxviruses, there is a great need for the development of medical countermeasures to treat poxvirus disease. It is highly likely that the U.S. FDA “animal rule” will be necessary for regulatory approval of these interventions. Therefore, relevant animal models and the associated supporting assays will require development to stand up to regulatory scrutiny. Methods An optimized real time PCR assay for the detection of orthopoxviruses has been developed by researchers at the United States Army Research Institute of Infectious Diseases (USAMRIID). To support animal studies that will be used to support approval of medical countermeasures by the U.S. FDA, the assay was designed to quantitate poxvirus genomic DNA in a nonhuman primate (cynomolgus macaque) blood matrix as a measurement of viremia. This manuscript describes the validation of the process, including DNA extraction from whole blood anticoagulated with EDTA, for obtaining and quantitating monkeypox genomes by evaluating precision, accuracy, the standard curve, specificity, robustness and stability of the assay and/or components of the assay. Results The assay had a lower limit of quantitation of 50 genome copies/5 uL sample, upper limit of quantitation of 5 × 107 GC/5uL sample and a limit of detection of 2.5 genome copies /5uL sample. The assay was specific for orthopoxvirus. Matrix effects were detected and suggest the presence of PCR inhibitor(s) that was co-extracted with the target DNA. Conclusions The assay has been validated for the purpose of quantitating monkeypox viral load in blood from cynomolgus macaques. This assay has and will continue to support submissions to the FDA for approval of antiviral therapeutics for smallpox. Electronic supplementary material The online version of this article (10.1186/s12985-017-0880-8) contains supplementary material, which is available to authorized users.

In this article we discuss the experiences of academics who occupy middle-level leadership roles in higher education. We use the term middle management to describe personnel occupying positions below the level of dean and often referred to as associate deans or heads of school. Practitioners rarely turn their attention to their own organizations, and in this study we focus on Australian universities, including our own, and international university experiences. Our study was designed to gather qualitative data via semi-structured interviews, after which our data were crafted into narrative accounts. In answering our research questions, we found that these middle managers perceive their role as overwhelming, with a sense of huge responsibility and little power. They describe their role as reactive, they feel isolated and they enjoy making a difference in others’ lives. Participants acknowledge the importance of developing support structures by building relationships with colleagues.

Publisher Summary Avoiding problems with clinical computing systems involves smart decisions to select software that works, to build and install it carefully, have good relationships with users and vendors, listen to their comments, monitor carefully to detect impending problems before they hit, expect and plan for downtimes, minimizing impact, and strive for best possible availability and reliability. Avoiding problems in the project phase requires attention to team structure and development as well as determining a project management approach. The life of a clinical computing system is divided into three parts: system acquisition, project, and operations. This chapter focuses on the operations phase. The operations phase is the ongoing use, maintenance, and support of the clinical computing system and its users. This phase is strongly influenced by system acquisition and project management. There are strong bodies of knowledge in areas such as system selection, contract negotiation, development and retention of talented staff, project management, and implementation methodologies which can lend guidance, strengthen knowledge, and contribute to success. Success in the phases from initial planning to the preconversion training prepares an organization for a smoother conversion and move to operations.

Publisher Summary The success of a system conversion and the transition to operations involves careful planning of rollouts and their impact, attention to the details which support a smoothly running production system, and understanding and preparing for impact to business during times when the system is unavailable. Conversion is the process of bringing the fully configured software live and available for use. The operations phase entails the day-to-day running, maintenance, enhancement, and safeguarding of the system to meet the availability and reliability requirements. As with the project phases, the conversion and operations phases can be carefully managed with clear, well-thought-out strategies that help the users, the system, and the organization avoid problems. Information technology (IT) systems are a necessary tool and resource for delivery of care in many organizations; as healthcare moves persistently to clinical computing, this primary dependency only increases. How and when to convert to new software depends on several factors, including number of users to be trained and who will be impacted, current state, and organizational tolerance for change. Careful thought must be given to staging of applications. It is likely that along with personnel and facilities, IT will be viewed as a fundamental piece of the organizational infrastructure and must be managed as such.

Background To plan an appropriate public health response to the hepatitis C virus (HCV) epidemic requires that estimates of HCV incidence and prevalence, and projections of the long-term sequelae of infection, are as accurate as possible. In this paper, mathematical models are used to synthesize data on the epidemiology and natural history of HCV in Australia to estimate HCV incidence and prevalence in Australia to end 2001, and project future trends in the long-term sequelae of HCV infection. Methods Mathematical models of the HCV epidemic in Australia were developed based on estimates of the pattern of injecting drug use. Estimates of HCV infections due to injecting drug use were then adjusted to allow for HCV infections resulting from other transmission routes. Projections of the long-term sequelae of HCV infection were obtained by combining modelled HCV incidence with estimates of the progression rates to these outcomes. Results It was estimated that there were 210 000 (lower and upper limits of 157 000 and 252 000) people in Australia living with HCV antibodies at the end of 2001, with HCV incidence in 2001 estimated to be 16 000 (11 000‐19 000). It was estimated that 6500 (5000‐8000) people were living with HCV-related cirrhosis in 2001, that 175 (130‐210) people developed HCV-associated liver failure, and that there were 50 (40‐60) incident cases of HCV-related hepatocellular carcinoma (HCC). It was estimated that in 2001 22 500 quality adjusted life years were lost to chronic HCV infection, the majority (77%) in people with early (stage 0/1) liver disease. Discussion Model-based estimates were broadly consistent with other sources of information on the HCV epidemic in Australia. These models suggest that the prevalence of HCV-related cirrhosis and the incidence of HCV-related liver failure and HCC will more than triple in Australia by 2020.