Vaccination against Foot-and-mouth disease : do initial conditions affect its benefit?

When facing incursion of a major livestock infectious disease, the decision to implement a vaccination programme is made at the national level. To make this decision, governments must consider whether the benefits of vaccination are sufficient to outweigh potential additional costs, including further trade restrictions that may be imposed due to the implementation of vaccination. However, little consensus exists on the factors triggering its implementation on the field. This work explores the effect of several triggers in the implementation of a reactive vaccination-to-live policy when facing epidemics of foot-and-mouth disease. In particular, we tested whether changes in the location of the incursion and the delay of implementation would affect the epidemiological benefit of such a policy in the context of Scotland. To reach this goal, we used a spatial, premises-based model that has been extensively used to investigate the effectiveness of mitigation procedures in Great Britain. The results show that the decision to vaccinate, or not, is not straightforward and strongly depends on the underlying local structure of the population-at-risk. With regards to disease incursion preparedness, simply identifying areas of highest population density may not capture all complexities that may influence the spread of disease as well as the benefit of implementing vaccination. However, if a decision to vaccinate is made, we show that delaying its implementation in the field may markedly reduce its benefit. This work provides guidelines to support policy makers in their decision to implement, or not, a vaccination-to-live policy when facing epidemics of infectious livestock disease

Misspecification of at-risk periods and distributional assumptions in estimating COPD exacerbation rates: The resultant bias in treatment effect estimation.

In trials comparing the rate of chronic obstructive pulmonary disease exacerbation between treatment arms, the rate is typically calculated on the basis of the whole of each patient's follow-up period. However, the true time a patient is at risk should exclude periods in which an exacerbation episode is occurring, because a patient cannot be at risk of another exacerbation episode until recovered. We used data from two chronic obstructive pulmonary disease randomized controlled trials and compared treatment effect estimates and confidence intervals when using two different definitions of the at-risk period. Using a simulation study we examined the bias in the estimated treatment effect and the coverage of the confidence interval, using these two definitions of the at-risk period. We investigated how the sample size required for a given power changes on the basis of the definition of at-risk period used. Our results showed that treatment efficacy is underestimated when the at-risk period does not take account of exacerbation duration, and the power to detect a statistically significant result is slightly diminished. Correspondingly, using the correct at-risk period, some modest savings in required sample size can be achieved. Using the proposed at-risk period that excludes recovery times requires formal definitions of the beginning and end of an exacerbation episode, and we recommend these be always predefined in a trial protocol.Martin Law is used by the UK Medical Research Council (Funding, NIHR grant RP-PG-0109-10056)

The impact of the COVID-19 pandemic on the relationship between physical activity levels and mental health in UK university students

Aim: Physical activity (PA) is widely acknowledged as a cost-effective strategy to support mental health in students. However, the COVID-19 pandemic’s disruptive influence raises questions about how the relationship between PA and student mental health may have evolved. Therefore, the present study explored this relationship before, during and after the pandemic. Methods: A repeated cross-sectional design was employed with survey data collected annually (2019–2022) in term one (October) at an English university. Mental well-being was evaluated using the Short Warwick-Edinburgh Mental Well-being Scale and weekly moderate to vigorous physical activity (MVPA) measured in 6,250 students. Pearson’s Product Moment Correlation tests were used to assess the correlation between mental well-being and MVPA for each year. Results: There was a weak (r = 0.14–0.19, p < 0.001) positive correlation between mental well-being and MVPA for each year. This relationship was stronger for males compared to females in 2020 (Z = 1.02, p < 0.01) and 2022 (Z = 3.56, p < 0.001). Conclusion: The consistent correlation between mental well-being and MVPA suggests that the pandemic did not alter the discernible link between the two variables, emphasising the importance of PA for student mental health even during unprecedented circumstances

Determining factors of physical activity and sedentary behaviour in university students during the COVID-19 pandemic: a longitudinal study

Introduction: Historically, university students demonstrate poor movement behaviours that could negatively impact current and future health. Recent literature has focused on identifying determinants of physical activity (PA) and sedentary behaviour (SB) in this population to inform the development of intervention strategies. However, the COVID-19 pandemic substantially restricted movement behaviours in this population, meaning findings of previous research may no longer be applicable within the current societal context. The present study explored the longitudinal relationships between pre-pandemic psychological, behavioural and anthropometric factors, and the movement behaviours of UK university students nine months following the outbreak of COVID-19. Methods: Mental wellbeing (MWB), perceived stress (PS), body mass index (BMI), SB, and PA were assessed using an online self-report survey in 255 students prior to (October 2019) and nine months following (October 2020) the first confirmed case of COVID-19 in the UK. Path analysis was utilised to test relationships between pre-COVID mental wellbeing, perceived stress and BMI, and movement behaviours during the pandemic. Results: The fit of the path analysis model was good (χ2 = 0.01; CMIN = 0.10, CFI = 1.00, RMSEA = 0.00). Pre-covid MWB and PS positively influenced PA (β = 0.29; β = 0.24; P < 0.01) but not SB (β = -0.10; β = 0.00; P = 0.79) during the pandemic. Additionally, pre-pandemic SB and PA positively influenced SB and PA during the pandemic respectively (SB: β = 0.26; P < 0.01) (PA: β = 0.55; P < 0.01). Pre-pandemic BMI did not influence any measured variable during the pandemic (PA: β = 0.03 and P = 0.29; SB: β = 0.06 and P = 0.56), and there was no mediating effect of PA on SB during the pandemic (β = -0.26; P = 0.14). Conclusion: These findings indicate that pre-covid mental health and movement behaviours had a direct positive influence on PA during the pandemic, but not SB. This longitudinal study demonstrates the influence that prior psychological and behavioural factors have in determining university students’ response to periods of elevated stress and uncertainty, furthering our understanding of determinants of health-related behaviours in students

Effects of different antibiotic classes on airway bacteria in stable COPD using culture and molecular techniques: a randomised controlled trial

Long-term antibiotic therapy is used to prevent exacerbations of COPD but there is uncertainty over whether this reduces airway bacteria. The optimum antibiotic choice remains unknown. We conducted an exploratory trial in stable patients with COPD comparing three antibiotic regimens against placebo

Quantifying the Risk of Localised Animal Movement Bans for Foot-and-Mouth Disease

The maintenance of disease-free status from Foot-and-Mouth Disease is of significant socio-economic importance to countries such as the UK. The imposition of bans on the movement of susceptible livestock following the discovery of an outbreak is deemed necessary to prevent the spread of what is a highly contagious disease, but has a significant economic impact on the agricultural community in itself. Here we consider the risk of applying movement restrictions only in localised zones around outbreaks in order to help evaluate how quickly nation-wide restrictions could be lifted after notification. We show, with reference to the 2001 and 2007 UK outbreaks, that it would be practical to implement such a policy provided the basic reproduction ratio of known infected premises can be estimated. It is ultimately up to policy makers and stakeholders to determine the acceptable level of risk, involving a cost benefit analysis of the potential outcomes, but quantifying the risk of spread from different sized zones is a prerequisite for this. The approach outlined is relevant to the determination of control zones and vaccination policies and has the potential to be applied to future outbreaks of other diseases

Dynamic changes in the epigenomic landscape regulate human organogenesis and link to developmental disorders

How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark the fidelity of stem cell differentiation or cell programming, or interpret the pathogenicity of noncoding variation. Here, we study histone modifications across thirteen tissues during human organogenesis. We integrate the data with transcription to build an overview of how the human genome differentially regulates alternative organ fates including by repression. Promoters from nearly 20,000 genes partition into discrete states. Key developmental gene sets are actively repressed outside of the appropriate organ without obvious bivalency. Candidate enhancers, functional in zebrafish, allow imputation of tissue-specific and shared patterns of transcription factor binding. Overlaying more than 700 noncoding mutations from patients with developmental disorders allows correlation to unanticipated target genes. Taken together, the data provide a comprehensive genomic framework for investigating normal and abnormal human development

Conditional Facilitation of an Aphid Vector, Acyrthosiphon pisum, by the Plant Pathogen, Pea Enation Mosaic Virus

Plant pathogens can induce symptoms that affect the performance of insect herbivores utilizing the same host plant. Previous studies examining the effects of infection of tic bean, Vicia faba L. (Fabales: Fabaceae), by pea enation mosaic virus (PEMV), an important disease of legume crops, indicated there were no changes in the growth and reproductive rate of its primary vector the pea aphid, Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae). Here, we report the results of laboratory experiments investigating how A. pisum responded to PEMV infection of a different host plant, Pisum sativum L., at different stages of symptom development. Aphid growth rate was negatively related to the age of the host plant, but when they were introduced onto older plants with well-developed PEMV symptoms they exhibited a higher growth rate compared to those developing on uninfected plants of the same age. In choice tests using leaf discs A. pisum showed a strong preference for discs from PEMV-infected peas, probably in response to visual cues from the yellowed and mottled infected leaves. When adults were crowded onto leaves using clip-cages they produced more winged progeny on PEMV-infected plants. The results indicate that PEMV produces symptoms in the host plant that can enhance the performance of A. pisum as a vector, modify the production of winged progeny and affect their spatial distribution. The findings provide further evidence that some insect vector/plant pathogen interactions could be regarded as mutualistic rather than commensal when certain conditions regarding the age, stage of infection and species of host plant are met

Method for Quantitative Study of Airway Functional Microanatomy Using Micro-Optical Coherence Tomography

We demonstrate the use of a high resolution form of optical coherence tomography, termed micro-OCT (μOCT), for investigating the functional microanatomy of airway epithelia. μOCT captures several key parameters governing the function of the airway surface (airway surface liquid depth, periciliary liquid depth, ciliary function including beat frequency, and mucociliary transport rate) from the same series of images and without exogenous particles or labels, enabling non-invasive study of dynamic phenomena. Additionally, the high resolution of μOCT reveals distinguishable phases of the ciliary stroke pattern and glandular extrusion. Images and functional measurements from primary human bronchial epithelial cell cultures and excised tissue are presented and compared with measurements using existing gold standard methods. Active secretion from mucus glands in tissue, a key parameter of epithelial function, was also observed and quantified

ruvA Mutants that resolve Holliday junctions but do not reverse replication forks

RuvAB and RuvABC complexes catalyze branch migration and resolution of Holliday junctions (HJs) respectively. In addition to their action in the last steps of homologous recombination, they process HJs made by replication fork reversal, a reaction which occurs at inactivated replication forks by the annealing of blocked leading and lagging strand ends. RuvAB was recently proposed to bind replication forks and directly catalyze their conversion into HJs. We report here the isolation and characterization of two separation-of-function ruvA mutants that resolve HJs, based on their capacity to promote conjugational recombination and recombinational repair of UV and mitomycin C lesions, but have lost the capacity to reverse forks. In vivo and in vitro evidence indicate that the ruvA mutations affect DNA binding and the stimulation of RuvB helicase activity. This work shows that RuvA's actions at forks and at HJs can be genetically separated, and that RuvA mutants compromised for fork reversal remain fully capable of homologous recombination