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The basic reproduction number, R0, is a well-known quantifier of epidemic spread. However, a class of existing methods for estimating R0 from incidence data early in the epidemic can lead to an over-estimation of this quantity. In particular, when fitting deterministic models to estimate the rate of spread, we do not account for the stochastic nature of epidemics and that, given the same system, some outbreaks may lead to epidemics and some may not. Typically, an observed epidemic that we wish to control is a major outbreak. This amounts to implicit selection for major outbreaks which leads to the over-estimation problem. We formally characterised the split between major and minor outbreaks by using Otsu's method which provides us with a working definition. We show that by conditioning a ‘deterministic’ model on major outbreaks, we can more reliably estimate the basic reproduction number from an observed epidemic trajectory.

Abstract Background From January to May 2021 the alpha variant (B.1.1.7) of SARS-CoV-2 was the most commonly detected variant in the UK. Following this, the Delta variant (B.1.617.2) then became the predominant variant. The UK COVID-19 vaccination programme started on 8th December 2020. Prior to the Delta variant, most vaccine effectiveness studies focused on the alpha variant. We therefore aimed to estimate the effectiveness of the BNT162b2 (Pfizer-BioNTech) and the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in preventing symptomatic and asymptomatic infection with respect to the Delta variant in a UK setting. Methods We used anonymised public health record data linked to infection data (PCR) using the Combined Intelligence for Population Health Action resource. We then constructed an SIR epidemic model to explain SARS-CoV-2 infection data across the Cheshire and Merseyside region of the UK. Vaccines were assumed to be effective after 21 days for 1 dose and 14 days for 2 doses. Results We determined that the effectiveness of the Oxford-AstraZeneca vaccine in reducing susceptibility to infection is 39% (95% credible interval [34, 43]) and 64% (95% credible interval [61, 67]) for a single dose and a double dose respectively. For the Pfizer-BioNTech vaccine, the effectiveness is 20% (95% credible interval [10, 28]) and 84% (95% credible interval [82, 86]) for a single-dose and a double dose respectively. Conclusion Vaccine effectiveness for reducing susceptibility to SARS-CoV-2 infection shows noticeable improvement after receiving two doses of either vaccine. Findings also suggest that a full course of the Pfizer-BioNTech provides the optimal protection against infection with the Delta variant. This reinforces the need to complete the full course programme to maximise individual protection and reduce transmission.

A more comprehensive map of viral host ranges can help identify and mitigate zoonotic and animal-disease risks. A divide-and-conquer approach which separates viral, mammalian and network features predicts over 20,000 unknown associations between known viruses and susceptible mammalian species.

Approximately a year into the COVID-19 pandemic caused by the SARS-CoV-2 virus, many countries have seen additional “waves” of infections, especially in the temperate northern hemisphere. Other vulnerable regions, such as South Africa and several parts of South America have also seen cases rise, further impacting local economies and livelihoods. Despite substantial research efforts to date, it remains unresolved as to whether COVID-19 transmission has the same sensitivity to climate observed for other common respiratory viruses such as seasonal influenza. Here, we look for empirical evidence of seasonality using a robust estimation framework. For 359 large cities across the world, we estimated the basic reproduction number (R0) using logistic growth curves fitted to cumulative case data. We then assess evidence for association with climatic variables through ordinary least squares (OLS) regression. We find evidence of seasonality, with lower R0 within cities experiencing greater surface radiation (coefficient = −0.005, p < 0.001), after adjusting for city-level variation in demographic and disease control factors. Additionally, we find association between R0 and temperature during the early phase of the epidemic in China. However, climatic variables had much weaker explanatory power compared to socioeconomic and disease control factors. Rates of transmission and health burden of the continuing pandemic will be ultimately determined by population factors and disease control policies.

Summary: Many xenobiotics can bind to off-target receptors and cause toxicity via the dysregulation of downstream transcription factors. Identification of subsequent off-target toxicity in these chemicals has often required extensive chemical testing in animal models. An alternative, integrated in vitro/in silico approach for predicting toxic off-target functional responses is presented to refine in vitro receptor identification and reduce the burden on in vivo testing. As part of the methodology, mathematical modeling is used to mechanistically describe processes that regulate transcriptional activity following receptor-ligand binding informed by transcription factor signaling assays. Critical reactions in the signaling cascade are identified to highlight potential perturbation points in the biochemical network that can guide and optimize additional in vitro testing. A physiologically based pharmacokinetic model provides information on the timing and localization of different levels of receptor activation informing whole-body toxic potential resulting from off-target binding. : Toxicology; Computational Toxicology; Systems Biology Subject Areas: Toxicology, Computational Toxicology, Systems Biology

Objectives To provide estimates for how different treatment pathways for the management of severe aortic stenosis (AS) may affect National Health Service (NHS) England waiting list duration and associated mortality.Design We constructed a mathematical model of the excess waiting list and found the closed-form analytic solution to that model. From published data, we calculated estimates for how the strategies listed under Interventions may affect the time to clear the backlog of patients waiting for treatment and the associated waiting list mortality.Setting The NHS in England.Participants Estimated patients with AS in England.Interventions (1) Increasing the capacity for the treatment of severe AS, (2) converting proportions of cases from surgery to transcatheter aortic valve implantation and (3) a combination of these two.Results In a capacitated system, clearing the backlog by returning to pre-COVID-19 capacity is not possible. A conversion rate of 50% would clear the backlog within 666 (533–848) days with 1419 (597–2189) deaths while waiting during this time. A 20% capacity increase would require 535 (434–666) days, with an associated mortality of 1172 (466–1859). A combination of converting 40% cases and increasing capacity by 20% would clear the backlog within a year (343 (281–410) days) with 784 (292–1324) deaths while awaiting treatment.Conclusion A strategy change to the management of severe AS is required to reduce the NHS backlog and waiting list deaths during the post-COVID-19 ‘recovery’ period. However, plausible adaptations will still incur a substantial wait to treatment and many hundreds dying while waiting.

River water temperature is a hydrological feature primarily controlled by topographical, meteorological, climatological, and anthropogenic factors. For Britain, the study of freshwater temperatures has focussed mainly on observations made in England and Wales; similar comprehensive data sets for Scotland are currently unavailable. Here we present a model for the whole of mainland Britain over three recent decades (1982-2011) that incorporates geographical extrapolation to Scotland. The model estimates daily mean freshwater temperature for every river segment and for any day in the studied period, based upon physico-geographical features, daily mean air and sea temperatures, and available freshwater temperature measurements. We also extrapolate the model temporally to predict future warming of Britain's rivers given current observed trends. Our results highlight the spatial and temporal diversity of British freshwater temperatures and warming rates. Over the studied period, Britain's rivers had a mean temperature of 9.84°C and experienced a mean warming of +0.22°C per decade, with lower rates for segments near lakes and in coastal regions. Model results indicate April as the fastest-warming month (+0.63°C per decade on average), and show that most rivers spend on average ever more days of the year at temperatures exceeding 10°C, a critical threshold for several fish pathogens. Our results also identify exceptional warming in parts of the Scottish Highlands (in April and September) and pervasive cooling episodes, in December throughout Britain and in July in the southwest of England (in Wales, Cornwall, Devon, and Dorset). This regional heterogeneity in rates of change has ramifications for current and future water quality, aquatic ecosystems, as well as for the spread of waterborne diseases.

Understanding models which represent the invasion of network-based systems by infectious agents can give important insights into many real-world situations, including the prevention and control of infectious diseases and computer viruses. Here we consider Markovian susceptible-infectious-susceptible (SIS) dynamics on finite strongly connected networks, applicable to several sexually transmitted diseases and computer viruses. In this context, a theoretical definition of endemic prevalence is easily obtained via the quasi-stationary distribution (QSD). By representing the model as a percolation process and utilising the property of duality, we also provide a theoretical definition of invasion probability. We then show that, for undirected networks, the probability of invasion from any given individual is equal to the (probabilistic) endemic prevalence, following successful invasion, at the individual (we also provide a relationship for the directed case). The total (fractional) endemic prevalence in the population is thus equal to the average invasion probability (across all individuals). Consequently, for such systems, the regions or individuals already supporting a high level of infection are likely to be the source of a successful invasion by another infectious agent. This could be used to inform targeted interventions when there is a threat from an emerging infectious disease.