Differential mobility and local variation in infection attack rate.

Infectious disease transmission is an inherently spatial process in which a host's home location and their social mixing patterns are important, with the mixing of infectious individuals often different to that of susceptible individuals. Although incidence data for humans have traditionally been aggregated into low-resolution data sets, modern representative surveillance systems such as electronic hospital records generate high volume case data with precise home locations. Here, we use a gridded spatial transmission model of arbitrary resolution to investigate the theoretical relationship between population density, differential population movement and local variability in incidence. We show analytically that a uniform local attack rate is typically only possible for individual pixels in the grid if susceptible and infectious individuals move in the same way. Using a population in Guangdong, China, for which a robust quantitative description of movement is available (a travel kernel), and a natural history consistent with pandemic influenza; we show that local cumulative incidence is positively correlated with population density when susceptible individuals are more connected in space than infectious individuals. Conversely, under the less intuitively likely scenario, when infectious individuals are more connected, local cumulative incidence is negatively correlated with population density. The strength and direction of correlation changes sign for other kernel parameter values. We show that simulation models in which it is assumed implicitly that only infectious individuals move are assuming a slightly unusual specific correlation between population density and attack rate. However, we also show that this potential structural bias can be corrected by using the appropriate non-isotropic kernel that maps infectious-only code onto the isotropic dual-mobility kernel. These results describe a precise relationship between the spatio-social mixing of infectious and susceptible individuals and local variability in attack rates. More generally, these results suggest a genuine risk that mechanistic models of high-resolution attack rate data may reach spurious conclusions if the precise implications of spatial force-of-infection assumptions are not first fully characterized, prior to models being fit to data

The interaction of transmission intensity, mortality, and the economy: a retrospective analysis of the COVID-19 pandemic

The COVID-19 pandemic has caused over 6.4 million registered deaths to date, and has had a profound impact on economic activity. Here, we study the interaction of transmission, mortality, and the economy during the SARS-CoV-2 pandemic from January 2020 to December 2022 across 25 European countries. We adopt a Bayesian vector autoregressive model with both fixed and random effects. We find that increases in disease transmission intensity decreases Gross domestic product (GDP) and increases daily excess deaths, with a longer lasting impact on excess deaths in comparison to GDP, which recovers more rapidly. Broadly, our results reinforce the intuitive phenomenon that significant economic activity arises from diverse person-to-person interactions. We report on the effectiveness of non-pharmaceutical interventions (NPIs) on transmission intensity, excess deaths and changes in GDP, and resulting implications for policy makers. Our results highlight a complex cost-benefit trade off from individual NPIs. For example, banning international travel increases GDP however reduces excess deaths. We consider country random effects and their associations with excess changes in GDP and excess deaths. For example, more developed countries in Europe typically had more cautious approaches to the COVID-19 pandemic, prioritising healthcare and excess deaths over economic performance. Long term economic impairments are not fully captured by our model, as well as long term disease effects (Long Covid). Our results highlight that the impact of disease on a country is complex and multifaceted, and simple heuristic conclusions to extract the best outcome from the economy and disease burden are challenging

Impact of Scotland’s comprehensive, smoke-free legislation on stroke

<p>Background: Previous studies have reported a reduction in acute coronary events following smoke-free legislation. Evidence is lacking on whether stroke is also reduced. The aim was to determine whether the incidence of stroke, overalland by sub-type, fell following introduction of smoke-free legislation across Scotland on 26 March 2006.</p> <p>Methods and Findings: A negative binomial regression model was used to determine whether the introduction of smokefree legislation resulted in a step and/or slope change in stroke incidence. The model was adjusted for age-group, sex, socioeconomic deprivation quintile, urban/rural residence and month. Interaction tests were also performed. Routine hospital administrative data and death certificates were used to identify all hospital admissions and pre-hospital deaths due to stroke (ICD10 codes I61, I63 and I64) in Scotland between 2000 and 2010 inclusive. Prior to the legislation, rates of all stroke, intracerebral haemorrhage and unspecified stroke were decreasing, whilst cerebral infarction was increasing at 0.97% per annum. Following the legislation, there was a dramatic fall in cerebral infarctions that persisted for around 20 months. No visible effect was observed for other types of stroke. The model confirmed an 8.90% (95% CI 4.85, 12.77, p,0.001) stepwise reduction in cerebral infarction at the time the legislation was implemented, after adjustment for potential cofounders.</p> <p>Conclusions: Following introduction of national, comprehensive smoke-free legislation there was a selective reduction in cerebral infarction that was not apparent in other types of stroke.</p&gt

Association between exposure to environmental tobacco smoke and biomarkers of oxidative stress among patients hospitalised with acute myocardial infarction

Objective To determine whether exposure to environmental tobacco smoke was associated with oxidative stress among patients hospitalised for acute myocardial infarction.<p></p> Design An existing cohort study of 1,261 patients hospitalised for acute myocardial infarction.<p></p> Setting Nine acute hospitals in Scotland.<p></p> Participants Sixty never smokers who had been exposed to environmental tobacco smoke (admission serum cotinine ≥3.0 ng/mL) were compared with 60 never smokers who had not (admission serum cotinine ≤0.1 ng/mL).<p></p> Intervention None.<p></p> Main outcome measures Three biomarkers of oxidative stress (protein carbonyl, malondialdehyde (MDA) and oxidised low-density lipoprotein (ox-LDL)) were measured on admission blood samples and adjusted for potential confounders.<p></p> Results After adjusting for baseline differences in age, sex and socioeconomic status, exposure to environmental tobacco smoke was associated with serum concentrations of both protein carbonyl (beta coefficient 7.96, 95% CI 0.76, 15.17, p = 0.031) and MDA (beta coefficient 10.57, 95% CI 4.32, 16.81, p = 0.001) but not ox-LDL (beta coefficient 2.14, 95% CI −8.94, 13.21, p = 0.703).<p></p> Conclusions Exposure to environmental tobacco smoke was associated with increased oxidative stress. Further studies are requires to explore the role of oxidative stress in the association between environmental tobacco smoke and myocardial infarction.<p></p&gt

A novel multiplex assay combining autoantibodies plus PSA has potential implications for classification of prostate cancer from non-malignant cases

<p>Abstract</p> <p>Background</p> <p>The lack of sufficient specificity and sensitivity among conventional cancer biomarkers, such as prostate specific antigen (PSA) for prostate cancer has been widely recognized after several decades of clinical implications. Autoantibodies (autoAb) among others are being extensively investigated as potential substitute markers, but remain elusive. One major obstacle is the lack of a sensitive and multiplex approach for quantifying autoAb against a large panel of clinically relevant tumor-associated antigens (TAA).</p> <p>Methods</p> <p>To circumvent preparation of phage lysates and purification of recombinant proteins, we identified B cell epitopes from a number of previously defined prostate cancer-associated antigens (PCAA). Peptide epitopes from cancer/testis antigen NY-ESO-1, XAGE-1b, SSX-2,4, as well as prostate cancer overexpressed antigen AMACR, p90 autoantigen, and LEDGF were then conjugated with seroMAP microspheres to allow multiplex measurement of autoAb present in serum samples. Moreover, simultaneous quantification of autoAb plus total PSA was achieved in one reaction, and termed the "A+PSA" assay.</p> <p>Results</p> <p>Peptide epitopes from the above 6 PCAA were identified and confirmed that autoAb against these peptide epitopes reacted specifically with the full-length protein. A pilot study was conducted with the A+PSA assay using pre-surgery sera from 131 biopsy-confirmed prostate cancer patients and 121 benign prostatic hyperplasia and/or prostatitis patients. A logistic regression-based A+PSA index was found to enhance sensitivities and specificities over PSA alone in distinguishing prostate cancer from nonmalignant cases. The A+PSA index also reduced false positive rate and improved the area under a receiver operating characteristic curve.</p> <p>Conclusions</p> <p>The A+PSA assay represents a novel platform that integrates autoAb signatures with a conventional cancer biomarker, which may aid in the diagnosis and prognosis of prostate cancer and others.</p

Forecasting the combined effects of anticipated climate change and agricultural conservation practices on fish recruitment dynamics in Lake Erie

Many aquatic ecosystems are experiencing multiple anthropogenic stressors that threaten their ability to support ecologically and economically important fish species. Two of the most ubiquitous stressors are climate change and non- point source nutrient pollution.Agricultural conservation practices (ACPs, i.e. farming practices that reduce runoff, prevent erosion, and curb excessive nutrient loading) offer a potential means to mitigate the negative effects of non- point source pollution on fish populations. However, our understanding of how ACP implementation amidst a changing climate will affect fish production in large ecosystems that receive substantial upstream sediment and nutrient inputs remains incomplete.Towards this end, we explored how anticipated climate change and the implementation of realistic ACPs might alter the recruitment dynamics of three fish populations (native walleye Sander vitreus and yellow perch Perca flavescens and invasive white perch Morone americana) in the highly productive, dynamic west basin of Lake Erie. We projected future (2020- 2065) recruitment under different combinations of anticipated climate change (n = 2 levels) and ACP implementation (n = 4 levels) in the western Lake Erie catchment using predictive biological models driven by forecasted winter severity, spring warming rate, and Maumee River total phosphorus loads that were generated from linked climate, catchment- hydrology, and agricultural- practice- simulation models.In general, our models projected reduced walleye and yellow perch recruitment whereas invasive white perch recruitment was projected to remain stable or increase relative to the recent past. Our modelling also suggests the potential for trade- offs, as ACP implementation was projected to reduce yellow perch recruitment with anticipated climate change.Overall, our study presents a useful modelling framework to forecast fish recruitment in Lake Erie and elsewhere, as well as offering projections and new avenues of research that could help resource management agencies and policy- makers develop adaptive and resilient management strategies in the face of anticipated climate and land- management change.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156436/2/fwb13515.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156436/1/fwb13515_am.pd

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.The study was funded by the Department of Health and Social Care in England. Sequencing was provided through funding from the COVID-19 Genomics UK (COG-UK) Consortium. P.E. is Director of the Medical Research Council (MRC) Centre for Environment and Health (MR/L01341X/1, MR/S019669/1). P.E. acknowledges support from Health Data Research UK (HDR UK); the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre; NIHR Health Protection Research Units (HPRUs) in Chemical and Radiation Threats and Hazards, and Environmental Exposures and Health; the British Heart Foundation Centre for Research Excellence at Imperial College London (RE/18/4/34215); and the UK Dementia Research Institute at Imperial (MC_PC_17114). S.R., C.A.D. acknowledge support: MRC Centre for Global Infectious Disease Analysis, NIHR HPRU in Modelling and Health Economics, Wellcome Trust (200861/Z/16/Z, 200187/Z/15/Z), and Centres for Disease Control and Prevention (US, U01CK0005-01-02). G.C. is supported by an NIHR Professorship. H.War. acknowledges support from an NIHR Senior Investigator Award and the Wellcome Trust (205456/Z/16/Z). We thank The Huo Family Foundation for their support of our work on COVID-19. Quadram authors gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC); their research was funded by the BBSRC Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent project BBS/E/F/000PR10352. We thank members of the COVID-19 Genomics Consortium UK (COG-UK) for their contributions to generating the genomic data used in this study. COG-UK is supported by funding from the MRC, part of UK Research & Innovation (UKRI), NIHR and Genome Research Limited, operating as the Wellcome Sanger Institute

Patterns of Suicidal Ideation and Behavior in Northern Ireland and Associations with Conflict Related Trauma

In this study, data from the World Mental Health Survey's Northern Ireland (NI) Study of Health and Stress (NISHS) was used to assess the associations between conflict- and non-conflict-related traumatic events and suicidal behaviour, controlling for age and gender and the effects of mental disorders in NI. DSM mental disorders and suicidal ideation, plans and attempts were assessed using the Composite International Diagnostic Interview (CIDI) in a multi-stage, clustered area probability household sample (N = 4,340, response rate 68.4%). The traumatic event categories were based on event types listed in the PTSD section of the CIDI. Suicidal ideation and attempts were more common in women than men, however, rates of suicide plans were similar for both genders. People with mood, anxiety and substance disorders were significantly more likely than those without to endorse suicidal ideation, plan or attempt. The highest odds ratios for all suicidal behaviors were for people with any mental disorder. However, the odds of seriously considering suicide were significantly higher for people with conflict and non-conflict-related traumatic events compared with people who had not experienced a traumatic event. The odds of having a suicide plan remain significantly higher for people with conflict-related traumatic events compared to those with only non-conflict-related events and no traumatic events. Finally, the odds of suicide attempt were significantly higher for people who have only non-conflict-related traumatic events compared with the other two categories. The results suggest that traumatic events associated with the NI conflict may be associated with suicidal ideation and plans, and this effect appears to be in addition to that explained by the presence of mental disorders. The reduced rates of suicide attempts among people who have had a conflict-related traumatic event may reflect a higher rate of single, fatal suicide attempts in this population

Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity

The close correspondence between energy intake and expenditure over prolonged time periods, coupled with an apparent protection of the level of body adiposity in the face of perturbations of energy balance, has led to the idea that body fatness is regulated via mechanisms that control intake and energy expenditure. Two models have dominated the discussion of how this regulation might take place. The set point model is rooted in physiology, genetics and molecular biology, and suggests that there is an active feedback mechanism linking adipose tissue (stored energy) to intake and expenditure via a set point, presumably encoded in the brain. This model is consistent with many of the biological aspects of energy balance, but struggles to explain the many significant environmental and social influences on obesity, food intake and physical activity. More importantly, the set point model does not effectively explain the &lsquo;obesity epidemic' - the large increase in body weight and adiposity of a large proportion of individuals in many countries since the 1980s. An alternative model, called the settling point model, is based on the idea that there is passive feedback between the size of the body stores and aspects of expenditure. This model accommodates many of the social and environmental characteristics of energy balance, but struggles to explain some of the biological and genetic aspects. The shortcomings of these two models reflect their failure to address the gene-by-environment interactions that dominate the regulation of body weight. We discuss two additional models - the general intake model and the dual intervention point model - that address this issue and might offer better ways to understand how body fatness is controlled