The application of statistical network models in disease research

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Host social structure is fundamental to how infections spread and persist, and so the statistical modelling of static and dynamic social networks provides an invaluable tool to parameterise realistic epidemiological models. We present a practical guide to the application of network modelling frameworks for hypothesis testing related to social interactions and epidemiology, illustrating some approaches with worked examples using data from a population of wild European badgers Meles meles naturally infected with bovine tuberculosis. Different empirical network datasets generate particular statistical issues related to non-independence and sampling constraints. We therefore discuss the strengths and weaknesses of modelling approaches for different types of network data and for answering different questions relating to disease transmission. We argue that statistical modelling frameworks designed specifically for network analysis offer great potential in directly relating network structure to infection. They have the potential to be powerful tools in analysing empirical contact data used in epidemiological studies, but remain untested for use in networks of spatio-temporal associations. As a result, we argue that developments in the statistical analysis of empirical contact data are critical given the ready availability of dynamic network data from bio-logging studies. Furthermore, we encourage improved integration of statistical network approaches into epidemiological research to facilitate the generation of novel modelling frameworks and help extend our understanding of disease transmission in natural populations.M.J.S. is funded by a NERC standard grant (NE/M004546/1) awarded to R.A.M., D.P.C., D.J.H. and M.B., with the APHA team at Woodchester Park, UK (lead scientist is R.J.D.) as project partners

Validity of two simple measures for estimating life-course socio-economic position in cross-sectional postal survey data in an older population: results from the North Staffordshire Osteoarthritis Project (NorStOP)

BACKGROUND: Since few cohorts encompass the whole life-course, many studies that measure socio-economic position (SEP) across the life-course rely on participant recall of SEP measures from cross-sectional postal or interview surveys. It is also particularly important that SEP measures should be appropriate for the age of the population studied, as the level of missing data has been shown to increase in older people. The aim of this study was to investigate the accuracy of recall of two SEP measures in older adults, age left school and longest job, by examining their validity in a general population postal survey in North Staffordshire, UK. METHODS: Sets of questions on education and longest job were included in a questionnaire at different stages of the study. All patients aged 50+ registered with three general practices were sent a baseline Health Questionnaire. 6 years later, 3410 responders were mailed a follow-up Health Questionnaire; a sub-sample of these participants took part in independent qualitative interviews. Validity was assessed by: percentage completion; internal percentage agreement within each set of questions; percentage agreement of qualitative and quantitative data for age left school and longest job; comparing recall of age left school with historical change in legal school leaving age; comparing frequency of pottery job titles with those in 1981 Census data for Stoke-on-Trent. RESULTS: The adjusted response to different stages of the study was 71-85%. Completion of questions was 83-98%. Internal agreement was 84-97% (education) and 95-100% (longest job). Comparison of survey and interview data showed 86% agreement (± 1 year) for age left school and 91% agreement for longest job. The change in age left school data concurred with the historical shift in legal school leaving age. 11% of job titles were pottery in NorStOP data and 15% in Stoke-on-Trent Census data. CONCLUSIONS: The results from this study provide evidence for the accuracy of recall of two simple measures of SEP (age left school and longest job) in a postal survey of older adults. Consistency with evidence from external datasets indicated the potential validity of these measures for studying life-course SEP in population surveys

Does attrition during follow-up of a population cohort study inevitably lead to biased estimates of health status?

Attrition is a potential source of bias in cohort studies. Although attrition may be inevitable in cohort studies of older people, there is little empirical evidence as to whether bias due to such attrition is also inevitable. Anonymised primary care data, routinely collected in clinical practice and independent of any cohort research study, represents an ideal unselected comparison dataset with which to compare primary care data from consenting responders to a cohort study. Our objective was to use this method as a novel means to assess if (i) responders at follow-up stages in a cohort study remain representative of responders at baseline and (ii) attrition biases estimates of longitudinal associations. We compared primary care consultation morbidities and prescription prevalences among circa 32,000 patients aged 50+ who contribute to an anonymised general practice database (Consultations in Primary Care Archive (CiPCA)) with those from patients aged 50+ in the North Staffordshire Osteoarthritis Project (NorStOP) cohort, United Kingdom (2002-2008; n=16,159). 8,197 (51%) persons responded to the NorStOP baseline survey and consented to medical record review. 5,121 and 3,311 responded at 3- and 6-year follow-ups. Differences in consulting prevalence of non-musculoskeletal morbidities between NorStOP responders and CiPCA comparison population did not increase over the two follow-up points except for ischaemic heart disease. Differences observed at baseline for osteoarthritis-related consultations were generally unchanged at the two follow-ups (standardised prevalence ratios for osteoarthritis (1.09-1.13) and joint pain (1.12-1.23)). Age and gender adjusted associations between baseline consultation for chronic morbidity and future new osteoarthritis and related consultations were similar in CiPCA (adjusted Hazard Ratio: 1.40; 95% Confidence Interval: 1.34,1.47) and NorStOP 6-year responders (1.32; 1.15,1.51). There was little evidence that responders at follow-ups represented any further selection bias to that present at baseline. Attrition in cohort studies of older people does not inevitably indicate bias

Line versus Flux Statistics -- Considerations for the Low Redshift Lyman-alpha Forest

The flux/transmission power spectrum has become a popular statistical tool in studies of the high redshift ($z > 2$) Lyman-alpha forest. At low redshifts, where the forest has thinned out into a series of well-isolated absorption lines, the motivation for flux statistics is less obvious. Here, we study the relative merits of flux versus line correlations, and derive a simple condition under which one is favored over the other on purely statistical grounds. Systematic errors probably play an important role in this discussion, and they are outlined as well.Comment: 6 pages, to appear in "The IGM/Galaxy Connection: The Distribution of Baryons at z=0", eds. J. L. Rosenberg and M. E. Putma

Seasonal variation in daily patterns of social contacts in the European badger Meles meles

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Social interactions among hosts influence the persistence and spread of infectious pathogens. Daily 20 and seasonal variation in the frequency and type of social interactions will play an important role in 21 disease epidemiology, and alongside other factors may have an influence on wider disease dynamics 22 by causing seasonal forcing of infection, especially if the seasonal variation experienced by a 23 population is considerable. We explored temporal variation in within-group contacts in a high-24 density population of European badgers Meles meles naturally-infected with bovine tuberculosis. 25 Summer contacts were more likely and of longer duration during the daytime, while the frequency 26 and duration of winter contacts did not differ between day and night. In spring and autumn within-27 group contacts peaked at dawn and dusk, corresponding with when they were of shortest duration 28 with reduced potential for aerosol transmission of pathogens. Summer and winter could be critical 29 for bovine tuberculosis transmission in badgers, due to the high frequency and duration of contacts 30 during resting periods, and we discuss the links between this result and empirical data. This study 31 reveals clear seasonality in daily patterns of contact frequency and duration in species living in stable 32 social groups, suggesting that changes in social contacts could drive seasonal forcing of infection in 33 wildlife populations even when the number of individuals interacting remains similar.MJS is funded by NERC grant NE/M004546/1 awarded to RAM, DPC, DJH and MB, with RJD and the 386 APHA team at Woodchester Park, UK as project partners. Data were collected for NW’s PhD, funded 387 by Defra. We thank Jared Wilson-Aggarwal and two anonymous reviewers for useful comments and 388 Keith Silk for providing the photograph for Figure 1

Social structure contains epidemics and regulates individual roles in disease transmission in a group-living mammal

This is the final version. Available from Wiley via the DOI in this record. Data accessibility: The original weighted adjacency matrix for the high‐density population of European badgers, as well as code used for simulating networks and disease simulations can be found online https://doi.org/10.5061/dryad.49n3878.Population structure is critical to infectious disease transmission. As a result, theoretical and empirical contact network models of infectious disease spread are increasingly providing valuable insights into wildlife epidemiology. Analyzing an exceptionally detailed dataset on contact structure within a high-density population of European badgers Meles meles, we show that a modular contact network produced by spatially structured stable social groups, lead to smaller epidemics, particularly for infections with intermediate transmissibility. The key advance is that we identify considerable variation among individuals in their role in disease spread, with these new insights made possible by the detail in the badger dataset. Furthermore, the important impacts on epidemiology are found even though the modularity of the Badger network is much lower than the threshold that previous work suggested was necessary. These findings reveal the importance of stable social group structure for disease dynamics with important management implications for socially structured populations.Natural Environment Research Council (NERC

Effects of ecstasy/polydrug use on memory for associative information

Rationale Associative learning underpins behaviours that are fundamental to the everyday functioning of the individual. Evidence pointing to learning deficits in recreational drug users merits further examination. Objectives A word pair learning task was administered to examine associative learning processes in ecstasy/polydrug users. Methods After assignment to either single or divided attention conditions, 44 ecstasy/polydrug users and 48 non-users were presented with 80 word pairs at encoding. Following this, four types of stimuli were presented at the recognition phase: the words as originally paired (old pairs), previously presented words in different pairings (conjunction pairs), old words paired with new words, and pairs of new words (not presented previously). The task was to identify which of the stimuli were intact old pairs. Results Ecstasy/ploydrug users produced significantly more false-positive responses overall compared to non-users. Increased long-term frequency of ecstasy use was positively associated with the propensity to produce false-positive responses. It was also associated with a more liberal signal detection theory decision criterion value. Measures of long term and recent cannabis use were also associated with these same word pair learning outcome measures. Conjunction word pairs, irrespective of drug use, generated the highest level of false-positive responses and significantly more false-positive responses were made in the divided attention condition compared to the single attention condition. Conclusions Overall, the results suggest that long-term ecstasy exposure may induce a deficit in associative learning and this may be in part a consequence of users adopting a more liberal decision criterion value

Emotional intelligence buffers the effect of physiological arousal on dishonesty

We studied the emotional processes that allow people to balance two competing desires: benefitting from dishonesty and keeping a positive self-image. We recorded physiological arousal (skin conductance and heart rate) during a computer card game in which participants could cheat and fail to report a certain card when presented on the screen to avoid losing their money. We found that higher skin conductance corresponded to lower cheating rates. Importantly, emotional intelligence regulated this effect; participants with high emotional intelligence were less affected by their physiological reactions than those with low emotional intelligence. As a result, they were more likely to profit from dishonesty. However, no interaction emerged between heart rate and emotional intelligence. We suggest that the ability to manage and control emotions can allow people to overcome the tension between doing right or wrong and license them to bend the rules

Therapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial.

Introduction: Chronic cannabis use has been associated with impaired cognition and elevated psychological symptoms, particularly psychotic-like experiences. While Δ9-tetrahydrocannabinol (THC) is thought to be primarily responsible for these deleterious effects, cannabidiol (CBD) is purported to have antipsychotic properties and to ameliorate cognitive, symptomatic, and brain harms in cannabis users. However, this has never been tested in a prolonged administration trial in otherwise healthy cannabis users. Here, we report the first study of prolonged CBD administration to a community sample of regular cannabis users in a pragmatic trial investigating potential restorative effects of CBD on psychological symptoms and cognition. Materials and Methods: Twenty frequent cannabis users (16 male, median age 25 years) underwent a 10-week open-label trial of 200 mg of daily oral CBD treatment, while continuing to use cannabis as usual. The majority of participants were daily cannabis users who had used cannabis for several years (median 5.5 years of regular use). Participants underwent psychological and cognitive assessments at baseline (BL) and post-treatment (PT) and were monitored weekly throughout the trial. Results: CBD was well tolerated with no reported side effects; however, participants retrospectively reported reduced euphoria when smoking cannabis. No impairments to cognition were found, nor were there deleterious effects on psychological function. Importantly, participants reported significantly fewer depressive and psychotic-like symptoms at PT relative to BL, and exhibited improvements in attentional switching, verbal learning, and memory. Increased plasma CBD concentrations were associated with improvements in attentional control and beneficial changes in psychological symptoms. Greater benefits were observed in dependent than in nondependent cannabis users. Conclusions: Prolonged CBD treatment appears to have promising therapeutic effects for improving psychological symptoms and cognition in regular cannabis users. Our findings require replication given the lack of a placebo control in this pragmatic trial, but suggest that CBD may be a useful adjunct treatment for cannabis dependence

Design considerations in a clinical trial of a cognitive behavioural intervention for the management of low back pain in primary care : Back Skills Training Trial

Background Low back pain (LBP) is a major public health problem. Risk factors for the development and persistence of LBP include physical and psychological factors. However, most research activity has focused on physical solutions including manipulation, exercise training and activity promotion. Methods/Design This randomised controlled trial will establish the clinical and cost-effectiveness of a group programme, based on cognitive behavioural principles, for the management of sub-acute and chronic LBP in primary care. Our primary outcomes are disease specific measures of pain and function. Secondary outcomes include back beliefs, generic health related quality of life and resource use. All outcomes are measured over 12 months. Participants randomised to the intervention arm are invited to attend up to six weekly sessions each of 90 minutes; each group has 6–8 participants. A parallel qualitative study will aid the evaluation of the intervention. Discussion In this paper we describe the rationale and design of a randomised evaluation of a group based cognitive behavioural intervention for low back pain