Modelling the impact of social mixing and behaviour on infectious disease transmission: application to SARS-CoV-2

In regard to infectious diseases socioeconomic determinants are strongly associated with differential exposure and susceptibility however they are seldom accounted for by standard compartmental infectious disease models. These associations are explored here with a novel compartmental infectious disease model which, stratified by deprivation and age, accounts for population-level behaviour including social mixing patterns. As an exemplar using a fully Bayesian approach our model is fitted, in real-time if required, to the UKHSA COVID-19 community testing case data from England. Metrics including reproduction number and forecasts of daily case incidence are estimated from the posterior samples. From this UKHSA dataset it is observed that during the initial period of the pandemic the most deprived groups reported the most cases however this trend reversed after the summer of 2021. Forward simulation experiments based on the fitted model demonstrate that this reversal can be accounted for by differential changes in population level behaviours including social mixing and testing behaviour, but it is not explained by the depletion of susceptible individuals. In future epidemics, with a focus on socioeconomic factors the approach outlined here provides the possibility of identifying those groups most at risk with a view to helping policy-makers better target their support.Comment: Main article: 25 pages, 6 figures. Appendix 2 pages, 1 figure. Supplementary Material: 15 pages, 14 figures. Version 2 - minor updates: fixed typos, updated mathematical notation and small quantity of descriptive text added. Version 3 - minor update: made colour coding consistent across all time series figure

Bayesian inference for high-dimensional discrete-time epidemic models: spatial dynamics of the UK COVID-19 outbreak

In the event of a disease outbreak emergency, such as COVID-19, the ability to construct detailed stochastic models of infection spread is key to determining crucial policy-relevant metrics such as the reproduction number, true prevalence of infection, and the contribution of population characteristics to transmission. In particular, the interaction between space and human mobility is key to prioritising outbreak control resources to appropriate areas of the country. Model-based epidemiological intelligence must therefore be provided in a timely fashion so that resources can be adapted to a changing disease landscape quickly. The utility of these models is reliant on fast and accurate parameter inference, with the ability to account for large amount of censored data to ensure estimation is unbiased. Yet methods to fit detailed spatial epidemic models to national-level population sizes currently do not exist due to the difficulty of marginalising over the censored data. In this paper we develop a Bayesian data-augmentation method which operates on a stochastic spatial metapopulation SEIR state-transition model, using model-constrained Metropolis-Hastings samplers to improve the efficiency of an MCMC algorithm. Coupling this method with state-of-the-art GPU acceleration enabled us to provide nightly analyses of the UK COVID-19 outbreak, with timely information made available for disease nowcasting and forecasting purposes

Visualising spatio-temporal health data: the importance of capturing the 4th dimension

Confronted by a rapidly evolving health threat, such as an infectious disease outbreak, it is essential that decision-makers are able to comprehend the complex dynamics not just in space but also in the 4th dimension, time. In this paper this is addressed by a novel visualisation tool, referred to as the Dynamic Health Atlas web app, which is designed specifically for displaying the spatial evolution of data over time while simultaneously acknowledging its uncertainty. It is an interactive and open-source web app, coded predominantly in JavaScript, in which the geospatial and temporal data are displayed side-by-side. The first of two case studies of this visualisation tool relates to an outbreak of canine gastroenteric disease in the United Kingdom, where many veterinary practices experienced an unusually high case incidence. The second study concerns the predicted COVID-19 reproduction number along with incidence and prevalence forecasts in each local authority district in the United Kingdom. These studies demonstrate the effectiveness of the Dynamic Health Atlas web app at conveying geospatial and temporal dynamics along with their corresponding uncertainties.Comment: 4 Figures, 27 page

Recent advances in understanding pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is an intractable cancer and a leading cause of cancer deaths worldwide. Over 90% of patients die within 1 year of diagnosis. Deaths from PDAC are increasing and it remains a cancer of substantial unmet need. A number of factors contribute to its poor prognosis: namely, late presentation, early metastases and limited systemic therapy options because of chemoresistance. A variety of research approaches underway are aimed at improving patient survival. Here, we review high-risk groups and efforts for early detection. We examine recent developments in the understanding of complex molecular and metabolic alterations which accompany PDAC. We explore artificial intelligence and biological targets for therapy and examine the role of tumour stroma and the immune microenvironment. We also review recent developments with respect to the PDAC microbiome. It is hoped that current research efforts will translate into earlier diagnosis, improvements in treatment and better outcomes for patients

Know The Star, Know the Planet. IV. A Stellar Companion to the Host star of the Eccentric Exoplanet HD 8673b

HD 8673 hosts a massive exoplanet in a highly eccentric orbit (e=0.723). Based on two epochs of speckle interferometry a previous publication identified a candidate stellar companion. We observed HD 8673 multiple times with the 10 m Keck II telescope, the 5 m Hale telescope, the 3.63 m AEOS telescope and the 1.5m Palomar telescope in a variety of filters with the aim of confirming and characterizing the stellar companion. We did not detect the candidate companion, which we now conclude was a false detection, but we did detect a fainter companion. We collected astrometry and photometry of the companion on six epochs in a variety of filters. The measured differential photometry enabled us to determine that the companion is an early M dwarf with a mass estimate of 0.33-0.45 M?. The companion has a projected separation of 10 AU, which is one of the smallest projected separations of an exoplanet host binary system. Based on the limited astrometry collected, we are able to constrain the orbit of the stellar companion to a semi-major axis of 35{60 AU, an eccentricity ? 0.5 and an inclination of 75{85?. The stellar companion has likely strongly in uenced the orbit of the exoplanet and quite possibly explains its high eccentricity.Comment: Accepted to the Astronomical Journal, 6 Pages, 5 Figure

Evidence for an FU Orionis-like Outburst from a Classical T Tauri Star

We present pre- and post-outburst observations of the new FU Orionis-like young stellar object PTF 10qpf (also known as LkHa 188-G4 and HBC 722). Prior to this outburst, LkHa 188-G4 was classified as a classical T Tauri star on the basis of its optical emission-line spectrum superposed on a K8-type photosphere, and its photometric variability. The mid-infrared spectral index of LkHa 188-G4 indicates a Class II-type object. LkHa 188-G4 exhibited a steady rise by ~1 mag over ~11 months starting in Aug. 2009, before a subsequent more abrupt rise of > 3 mag on a time scale of ~2 months. Observations taken during the eruption exhibit the defining characteristics of FU Orionis variables: (i) an increase in brightness by > 4 mag, (ii) a bright optical/near-infrared reflection nebula appeared, (iii) optical spectra are consistent with a G supergiant and dominated by absorption lines, the only exception being Halpha which is characterized by a P Cygni profile, (iv) near-infrared spectra resemble those of late K--M giants/supergiants with enhanced absorption seen in the molecular bands of CO and H_2O, and (v) outflow signatures in H and He are seen in the form of blueshifted absorption profiles. LkHa 188-G4 is the first member of the FU Orionis-like class with a well-sampled optical to mid-infrared spectral energy distribution in the pre-outburst phase. The association of the PTF 10qpf outburst with the previously identified classical T Tauri star LkHa 188-G4 (HBC 722) provides strong evidence that FU Orionis-like eruptions represent periods of enhanced disk accretion and outflow, likely triggered by instabilities in the disk. The early identification of PTF 10qpf as an FU Orionis-like variable will enable detailed photometric and spectroscopic observations during its post-outburst evolution for comparison with other known outbursting objects.Comment: 14 pages, 11 figures, ApJ accepte

Mannosidase 2, alpha 1 deficiency is associated with ricin resistance in embryonic stem (ES) cells.

Host gene products required for mediating the action of toxins are potential targets for reversing or controlling their pathogenic impact following exposure. To identify such targets libraries of insertional gene-trap mutations generated with a PiggyBac transposon in Blm-deficient embryonic stem cells were exposed to the plant toxin, ricin. Resistant clones were isolated and genetically characterised and one was found to be a homozygous mutant of the mannosidase 2, alpha 1 (Man2α1) locus with a matching defect in the homologous allele. The causality of the molecular lesion was confirmed by removal of the transposon following expression of PB-transposase. Comparative glycomic and lectin binding analysis of the Man2α1 (-/-) ricin resistant cells revealed an increase in the levels of hybrid glycan structures and a reduction in terminal β-galactose moieties, potential target receptors for ricin. Furthermore, naïve ES cells treated with inhibitors of the N-linked glycosylation pathway at the mannosidase 2, alpha 1 step exhibited either full or partial resistance to ricin. Therefore, we conclusively identified mannosidase 2, alpha 1 deficiency to be associated with ricin resistance

Short Sleep Is Associated With Low Bone Mineral Density and Osteoporosis in the Women’s Health Initiative

Short sleep duration, recognized as a public health epidemic, is associated with adverse health conditions, yet little is known about the association between sleep and bone health. We tested the associations of usual sleep behavior and bone mineral density (BMD) and osteoporosis. In a sample of 11,084 postmenopausal women from the Women’s Health Initiative (WHI; mean age 63.3â years, SD = 7.4), we performed a crossâ sectional study of the association of selfâ reported usual hours of sleep and sleep quality (WHI Insomnia Rating Score) with whole body, total hip, femoral neck, and spine BMD using linear regression models. We also studied the association of sleep duration and quality with dualâ energy Xâ ray absorptiometry (DXA)â defined low bone mass (Tâ scoreâ <â â 2.5 to <â 1) and osteoporosis (Tâ scoreâ â ¤â â 2.5) using multinomial regression models. We adjusted for age, DXA machine, race, menopausal symptoms, education, smoking, physical activity, body mass index, alcohol use, physical function, and sleep medication use. In adjusted linear regression models, women who reported sleeping 5â hours or less per night had on average 0.012 to 0.018â g/cm2 significantly lower BMD at all four sites compared with women who reported sleeping 7â hours per night (reference). In adjusted multinomial models, women reporting 5â hours or less per night had higher odds of low bone mass and osteoporosis of the hip (odds ratio [OR] =â 1.22; 95% confidence interval [CI] 1.03â 1.45, and 1.63; 1.15â 2.31, respectively). We observed a similar pattern for spine BMD, where women with 5â hours or less per night had higher odds of osteoporosis (adjusted OR = 1.28; 95% CI 1.02â 1.60). Associations of sleep quality and DXA BMD failed to reach statistical significance. Short sleep duration was associated with lower BMD and higher risk of osteoporosis. Longitudinal studies are needed to confirm the crossâ sectional effects of sleep duration on bone health and explore associated mechanisms. © 2019 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154418/1/jbmr3879_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154418/2/jbmr3879.pd

Microbial functional diversity covaries with permafrost thaw-induced environmental heterogeneity in tundra soil.

Permafrost soil in high latitude tundra is one of the largest terrestrial carbon (C) stocks and is highly sensitive to climate warming. Understanding microbial responses to warming-induced environmental changes is critical to evaluating their influences on soil biogeochemical cycles. In this study, a functional gene array (i.e., geochip 4.2) was used to analyze the functional capacities of soil microbial communities collected from a naturally degrading permafrost region in Central Alaska. Varied thaw history was reported to be the main driver of soil and plant differences across a gradient of minimally, moderately, and extensively thawed sites. Compared with the minimally thawed site, the number of detected functional gene probes across the 15-65&nbsp;cm depth profile at the moderately and extensively thawed sites decreased by 25% and 5%, while the community functional gene β-diversity increased by 34% and 45%, respectively, revealing decreased functional gene richness but increased community heterogeneity along the thaw progression. Particularly, the moderately thawed site contained microbial communities with the highest abundances of many genes involved in prokaryotic C degradation, ammonification, and nitrification processes, but lower abundances of fungal C decomposition and anaerobic-related genes. Significant correlations were observed between functional gene abundance and vascular plant primary productivity, suggesting that plant growth and species composition could be co-evolving traits together with microbial community composition. Altogether, this study reveals the complex responses of microbial functional potentials to thaw-related soil and plant changes and provides information on potential microbially mediated biogeochemical cycles in tundra ecosystems

PTF10nvg: An Outbursting Class I Protostar in the Pelican/North American Nebula

During a synoptic survey of the North American Nebula region, the Palomar Transient Factory (PTF) detected an optical outburst (dubbed PTF10nvg) associated with the previously unstudied flat or rising spectrum infrared source IRAS 20496+4354. The PTF R-band light curve reveals that PTF10nvg brightened by more than 5 mag during the current outburst, rising to a peak magnitude of R~13.5 in 2010 Sep. Follow-up observations indicate PTF10nvg has undergone a similar ~5 mag brightening in the K band, and possesses a rich emission-line spectrum, including numerous lines commonly assumed to trace mass accretion and outflows. Many of these lines are blueshifted by ~175 km/s from the North American Nebula's rest velocity, suggesting that PTF10nvg is driving an outflow. Optical spectra of PTF10nvg show several TiO/VO bandheads fully in emission, indicating the presence of an unusual amount of dense (> 10^10 cm^-3), warm (1500-4000 K) circumstellar material. Near-infrared spectra of PTF10nvg appear quite similar to a spectrum of McNeil's Nebula/V1647 Ori, a young star which has undergone several brightenings in recent decades, and 06297+1021W, a Class I protostar with a similarly rich near--infrared emission line spectrum. While further monitoring is required to fully understand this event, we conclude that the brightening of PTF10nvg is indicative of enhanced accretion and outflow in this Class-I-type protostellar object, similar to the behavior of V1647 Ori in 2004-2005.Comment: Accepted to the Astronomical Journal; 21 pages, 11 figures, 6 tables in emulateapj format; v2 fixes typo in abstract; v3 updates status to accepted, adjusts affiliations, adds acknowledgmen