166,352 research outputs found
Epidemiological consequences of household-based antiviral prophylaxis for pandemic influenza
No full textAntiviral treatment offers a fast acting alternative to vaccination; as such it is viewed as a first-line of defence against pandemic influenza in protecting families and households once infection has been detected. In clinical trials, antiviral treatments have been shown to be efficacious in preventing infection, limiting disease and reducing transmission, yet their impact at containing the 2009 influenza A(H1N1)pdm outbreak was limited. To understand this seeming discrepancy, we develop a general and computationally efficient model for studying household-based interventions. This allows us to account for uncertainty in quantities relevant to the 2009 pandemic in a principled way, accounting for the heterogeneity and variability in each epidemiological process modelled. We find that the population-level effects of delayed antiviral treatment and prophylaxis mean that their limited overall impact is quantitatively consistent (at current levels of precision) with their reported clinical efficacy under ideal conditions. Hence, effective control of pandemic influenza with antivirals is critically dependent on early detection and delivery ideally within 24 h.Andrew J. Black, Thomas House, M. J. Keeling and J. V. Ros
Keeling, J, QX15108
No full textThis record was harvested from a previous catalogue system and will be withdrawn in 2025. Information in this record may be superseded or incomplete. Visit this record in UMA's new catalogue at: https://archives.library.unimelb.edu.au/nodes/view/396439Surname: KEELING. Given Name(s) or Initials: J. Military Service Number or Last Known Location: QX15108. Missing, Wounded and Prisoner of War Enquiry Card Index Number: 32606.232992
Item: [2016.0049.28732] "Keeling, J, QX15108
Serial block face scanning electron microscopy reveals novel organizational details of the retinal pigment epithelium
No full textAdvances in imaging have led to the development of several new types of microscopes such as serial block face scanning electron microscopy (SBF-SEM), lightsheet microscopy, as well as X-ray micro-computed tomography (micro-CT), which enables the study of samples in fundamentally different ways. Significantly, these are now commercially available, which facilitates their widespread use in research. With SBF-SEM, fixed and resin-embedded specimens can be serially sectioned and imaged to construct a 3D dataset of the ultrastructure of cells and tissues at high resolution. We used this technique on perfusion-fixed C57BL/6 mouse eyes to image the outer retina. Our findings revealed novel organizational details of the retinal pigment epithelium (RPE) (Keeling et al., 2020b); a specialized cell monolayer that maintains the overlying photoreceptors and also forms the outer blood-retinal-barrier. RPE cells were found to look after far more photoreceptors than was widely assumed. 3D-data enabled measurements of the RPE cytoplasmic and nuclear volumes, the length and angle of microvilli on the apical RPE surface, as well as sub-RPE spaces under the basolateral membrane. The study also compared between mono-nucleate vs. bi-nucleate RPE cells, whilst the use of computing microinstructions (macros) provided information on interactions between adjacent cells in the RPE monolayer. Analysis of SBF-SEM stacks showed several hundred mitochondria which were rendered in 3D, providing information on their volume and spatial distribution in healthy RPE. Mitochondria were found in varying shapes and sizes, and predominantly localized to the mid and basal-zones of cells. The capabilities of SBF-SEM alongside other imaging techniques are being increasingly harnessed by investigators to gain novel insights into the organization of cells and tissues in the eye. These findings also help improve the current understanding of pathology linked with common blinding conditions such as age-related macular degeneration (AMD), as well as rare forms of retinopathy which leads to irreversible sight-los
Data underpinning - Excitonic spectral features in strongly-coupled organic polaritons
No full textRealted article:
Cwik, J. A., Kirton, P., De Liberato, S., & Keeling, J. (2016). Excitonic spectral features in strongly-coupled organic polaritons. Physical Review A, 93(33840), 1-12. https://doi.org/10.1103/PhysRevA.93.033840</span
Draft genome sequence of the Daphnia pathogen Octosporea bayeri: insights into the gene content of a large microsporidian genome and a model for host-parasite interactions
No full textBackground: The highly compacted 2.9-Mb genome of Encephalitozoon cuniculi placed the microsporidia in the spotlight, encoding a mere 2,000 proteins and a highly reduced suite of biochemical pathways. This extreme level of reduction is not universal across the microsporidia, with genomes known to vary up to sixfold in size, suggesting that some genomes may harbor a gene content that is not as reduced as that of Enc. cuniculi. In this study, we present an in-depth survey of the large genome of Octosporea bayeri, a pathogen of Daphnia magna, with an estimated genome size of 24 Mb, in order to shed light on the organization and content of a large microsporidian genome. Results: Using Illumina sequencing, 898 Mb of O. bayeri genome sequence was generated, resulting in 13.3 Mb of unique sequence. We annotated a total of 2,174 genes, of which 893 encodes proteins with assigned function. The gene density of the O. bayeri genome is very low on average, but also highly uneven, so gene-dense regions also occur. The data presented here suggest that the O. bayeri proteome is well represented in this analysis and is more complex that that of Enc. cuniculi. Functional annotation of O. bayeri proteins suggests that this species might be less biochemically dependent on its host for its metabolism than its more reduced relatives. Conclusions: The combination of the data presented here, together with the imminent annotated genome of Daphnia magna, will provide a wealth of genetic and genomic tools to study host-parasite interactions in an interesting model for pathogenesis
[Report to Chief J. E. Curry, by an unknown author #1]
No full textReport to Chief J. E. Curry, by an unknown author. The report contains a list of officers who gave depositions to the United States Attorney
[Report to Chief J. E. Curry, by an unknown author #2]
No full textReport to Chief J. E. Curry, by an unknown author. The report contains a list of officers who gave depositions to the United States Attorney
Sigma-2 receptor modulators rescue POS trafficking deficits in RPE cell-based models of dry AMD
No full textPurpose : Toxic amyloid-beta oligomers (AβOs) and oxidative stress are hallmarks of dry age-related macular degeneration (dAMD) and can disrupt key homeostatic processes in retinal pigmented epithelium (RPE) cells (Rabin et al. 2013). AβOs disrupt RPE cell function in vivo (Ruozhou et al. 2013) and normal RPE-mediated photoreceptor outer segment (POS) phagocytosis in vitro (Lynn et al. 2021). Sigma-2 receptor (S2R) modulators prevent AβOs from binding to neurons and rescue deficits in neuronal functioning (Izzo et al. 2014). Based on dAMD-related deficits in RPE function and the role of the S2R as a key damage sensor, the hypothesis that S2R modulators could rescue AβO and oxidative stress-induced deficits in the ability of RPE cells to phagocytose POSs was tested.Methods : A human RPE cell line, ARPE-19 cells, were exposed to AβOs (0.5-2µM) over time (1-8 hr) and AβO binding was assessed via immunocytochemistry (ICC) and high content imaging (n=3-6 experiments). A trafficking assay was used to monitor internalization and degradation of POS over time. ARPE-19s were exposed to AβOs or H2O2 in the presence or absence of S2R modulators. The effects of S2R modulators on POS colocalization with lysosomal associated membrane protein 2 (LAMP2) and microtubule-associated proteins 1A/1B light chain 3B (LC3B) were quantified via confocal imaging and unbiased algorithm across time (12-48 hr; n=2 experiments). Statistical significance (p<0.05) was determined via Two-Way ANOVA and post hoc Tukey’s test.Results : ICC studies show that AβOs bind to ARPE-19s in time and concentration-dependent manners (EC50=1.86µM). Following exposure of cells to 1µM AβO, POS are retained in LAMP2 positive vesicles and trafficking is diminished to LC3B vesicles when compared to control. S2R modulators from three independent chemical series restored POS trafficking through LAMP2 positive vesicles at 36 and 48 hr (p<0.0001) and through LC3B vesicles at 48 hr (p<0.0001). The same S2R modulators restored POS trafficking after exposure to 100µM H2O2 through LAMP2 positive vesicles at 12 and 48 hr (p<0.001) and through LC3B vesicles at 12, 24, and 36 hr (p<0.001).Conclusions : Results point to a role of S2R modulators in rescuing AβO and oxidative stress-induced deficits in RPE cells by normalizing the homeostatic recycling of POSs in RPE cells. These data support S2R modulators as a promising potential therapy for dAMD
Social encounter networks : characterizing Great Britain
No full textA major goal of infectious disease epidemiology is to understand and predict the spread of infections within human populations, with the intention of better informing decisions regarding control and intervention. However, the development of fully mechanistic models of transmission requires a quantitative understanding of social interactions and collective properties of social networks. We performed a cross-sectional study of the social contacts on given days for more than 5000 respondents in England, Scotland and Wales, through postal and online survey methods. The survey was designed to elicit detailed and previously unreported measures of the immediate social network of participants relevant to infection spread. Here, we describe individual-level contact patterns, focusing on the range of heterogeneity observed and discuss the correlations between contact patterns and other socio-demographic factors. We find that the distribution of the number of contacts approximates a power-law distribution, but postulate that total contact time (which has a shorter-tailed distribution) is more epidemiologically relevant. We observe that children, public-sector and healthcare workers have the highest number of total contact hours and are therefore most likely to catch and transmit infectious disease. Our study also quantifies the transitive connections made between an individual's contacts (or clustering); this is a key structural characteristic of social networks with important implications for disease transmission and control efficacy. Respondents' networks exhibit high levels of clustering, which varies across social settings and increases with duration, frequency of contact and distance from home. Finally, we discuss the implications of these findings for the transmission and control of pathogens spread through close contact
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