Studies of the infections of wild bird populations in north west England

Little is known about the epidemiology of infection in wild birds. However, such infections can be zoonotic, transmitted to domestic livestock or both. Previous studies have resulted in conflicting evidence and views as to the role played by wild birds in the epidemiology of infectious diseases. This study aimed to determine the prevalence of a range of bacterial and viral pathogens in wild birds, over appropriate temporal and spatial scales, in order to begin to understand the (potential) role that birds play in the ecology of infectious diseases; in particular, to determine if wild birds act as sources and/or reservoirs of infection for human beings and/or domestic animals. This was achieved by carrying out a series of cross-sectional studies of wild bird populations in north-west England over a two year period. Samples collected from wild birds were examined for bacterial and viral agents including Campylobacter spp., verocytotoxigenic Escherichia coli, Salmonella spp., influenza A virus, avian paramyxovirus type-I, avian metapneumovirus, coronavirus and West Nile virus. Microorganisms were characterised using an array of microbiological and molecular techniques. Phylogenetic and epidemiological analyses were carried out to investigate host-pathogen ecology and evolution and to determine risk factors for the carriage of these agents by wild birds. Salmonellosis in wild passerines was found to be caused by a narrow range of possibly host-adapted S. Typhimurium strains, which were capable of invading and persisting in avian cells, susceptible to antimicrobials and contained a range of virulence genes, but lacked a gene that has been associated with some epidemic strains of S. Typhimurium in humans and livestock. It is suggested that S. Typhimurium infection in wild passerines is maintained within wild bird populations and it is unlikely that these strains represent a large zoonotic risk

Developing better information about the health and health care of people with developmental disabilities in Scotland

Introduction: Neurodevelopmental disorders are a group of disorders that manifest early in development, and include intellectual disabilities and autism, among others. Intellectual disabilities refer to impairments in intellectual functioning (an intelligence quotient <70), together with deficits in adaptive functioning (need for support for daily personal independence and social functioning), with onset during the developmental period. Autism is characterised by persistent deficits in social communication and social interactions across multiple contexts, and restricted, repetitive patterns of behaviour, interests or activities, with onset of these symptoms in the early developmental period. People with intellectual disabilities and people with autism are thought to experience high levels of physical and mental health problems and earlier mortality than other people on average. Yet, there is a dearth of empirical evidence about the health of people with intellectual disabilities and people with autism which presents a barrier to understanding the complex factors that produce differential health outcomes. Ensuring adults with intellectual disabilities or autism live not only longer but healthier lives is a priority for the World Health Organisation and the Scottish Government. Methods: The portfolio of publications (n=15) presented in this mixed methods PhD thesis, represents a selection of my peer reviewed publications in international scientific journals since 2015. I [Laura Hughes-McCormack] am the lead author on 4 of these publications and co-author on 11 publications (including being second author on 8 of these) which were prepared from research I undertook within the Scottish Learning Disabilities Observatory (SLDO) at the Institute of Health and Wellbeing, University of Glasgow. This research programme was funded by the Scottish Government in 2014 to provide evidence on the health of people with intellectual disabilities and autism in Scotland, and thus to inform the development of public policy. The research presented includes systematic reviews, quantitative research, data linkage research, and is presented in three themes throughout this thesis, as follows. Theme I. Health of people with intellectual disabilities and autism; seven of the nine quantitative studies presented under this theme/section analysed data from the Scottish Census, relating to people with intellectual disabilities or autism from 94% of the Scottish population (n=5,269,054) who responded to the Census in 2011. Two further studies (a quantitative study and a systematic review study) are reported, which investigated sedentary behaviour and oral health. Theme II. Health care of people with intellectual disabilities and Down syndrome; to quantify the management of long-term conditions, data for a population-based cohort of people with intellectual disabilities (n=721) was compared using an established evidence-based approach to measuring the quality of primary health care for all people without intellectual disabilities (n=764,672) in the largest health board in Scotland, throughout 2007-2010. A further systematic review study investigated hospital admissions for physical health conditions in adults with intellectual disabilities. Theme III. Survival/ death of people with intellectual disabilities and Down syndrome; two systematic reviews are reported, investigating deaths in people with intellectual disabilities and people with Down syndrome, and a further data linkage study which investigated birth and death rates and hospitalisations (throughout a 25-year period) among children/young people with Down syndrome in Scotland. Each theme includes a clear overview of the background/ rationale, methodology, results and impact of this body of work in relation to the development of better information on health and health care of people with intellectual disabilities and autism in Scotland. Results: Theme I: Health of people with intellectual disabilities and autism: Findings of the Scottish Census 2011 studies (I-VII), show that poor health was more common for people with intellectual disabilities (odds of 43 in statistically predicting poor general health) and they were seven times more likely to report a current mental health condition than people without intellectual disabilities. Autism had odds of 11.3 in predicting poor general health in children and young people, and odds of 7.5 in adults. Comorbidities were found to be common among people with autism. Other studies presented under this theme (VIII, IX) show adults with intellectual disabilities have higher levels, and different correlates, of sedentary behaviour and poorer oral health. Theme II: Health care of people with intellectual disabilities and Down syndrome: Findings from two studies (X, XI) show, people with intellectual disabilities were receiving lower quality health care compared to other people across all long‐term conditions investigated on 38/57 (66.7%) quality indicators. A follow up study, comparing baseline data to data in 2014 found adults with intellectual disabilities still had a lower proportion of indicators met than the general population; but by 2014, the healthcare inequality gap had reduced compared with 2007-10. A systematic review (XII), further investigating the quality of health care of people with intellectual disabilities, found people with intellectual disabilities were admitted to hospital more frequently than the general population for physical conditions which if managed effectively at the primary care level, should not lead to hospital admission, although evidence is limited. Theme III: Survival/ death of people with intellectual disabilities and Down syndrome: Findings from the two systematic reviews (XIII, XIV) found mortality rates are higher in (1) the intellectual disabilities population and (2) the Down syndrome population, compared with the general population. For the intellectual disabilities’ population, an average age of death of 20 years lower was found compared to the general population. For the Down syndrome population, compared with the general population, an average age of death of 28 years lower was found although survival rates have improved over time. Patterns of cause of death were different for people with intellectual disabilities and people with Down syndrome compared to the general population. The data linkage study (XV) found the incidence of Down syndrome live-births was 1.0/1,000 births over the last 25 years. More children and young people with Down syndrome died (n=92; 7.4%) over the 25-year period compared to controls (n=23; 0.4%); that is 18.5 times more. There was increased risk of hospitalisation as more of the Down syndrome group had at least one admission (1,105 [89.5%] versus 3,305 [53.5%]; adjusted HR=1.84 [1.68, 2.01]). Re-admissions, emergency admissions and length of stay were also higher for the Down syndrome group. Conclusions: This thesis has presented for each of the three inter-related themes, a range of my peer reviewed publications from international journals. A previous dearth of empirical evidence about the health and health care of people with intellectual disabilities and people with autism has presented barriers to understanding the complex factors that produce differential health outcomes. The research presented in this thesis has provided robust evidence on the extent of poor health, health care, and premature mortality among people with intellectual disabilities, and people with autism which has not previously been quantified in research. This evidence has led to shaping Scottish policy and practice to support the needs of people with intellectual disabilities, for example, the most recent learning disabilities strategy in Scotland, The Keys to Life, updated in 2019, includes input from my research

Culture Impacts the Neural Response to Perceiving Outgroups Among Black and White Faces

Outgroup members (e.g., individuals whose racial identity differs from perceivers’) are stigmatized in Eastern and Western cultures. However, it remains an open question how specific cultural influences affect stigmatization. In this study, we assessed whether cultural learning (i.e., social information acquired from the people in one’s environment) associated with Chinese individuals’ relocation to the United States differentiated the response to multiple outgroups. Two types of cultural learning predict diverging responses to outgroups – awareness of stereotypes about different racial outgroups is associated with increased negative affect and cognitive control toward the stereotyped outgroup. Conversely, intergroup contact attenuates those responses, and does so to a greater extent for individuals from Western cultures. As Chinese–Americans would have had more opportunities to have contact with both White and Black individuals (relative to the Chinese participants), we explored their responses to outgroups as well. Because the neural regions associated with stereotyping and intergroup contact have been well-characterized, we used neuroimaging to disentangle these possibilities. Eighteen White American, 18 Chinese–American, and 17 Chinese participants – who had relocated to the United States less than 1 year prior – viewed images of Black and White individuals while undergoing functional magnetic resonance imaging (fMRI). Participants also completed measures of awareness of cultural stereotypes in the United States about Black and White individuals, implicit bias, and experiences with White and Black individuals. Behaviorally, White American and Chinese–American participants had more intergroup contact with either race than did Chinese participants, but there was no effect of participant group on stereotype knowledge or implicit bias. When viewing faces of White (as compared to Black) individuals while undergoing fMRI, White American (relative to Chinese) participants had attenuated activation in regions of the brain associated with cognitive control, including the right dorsolateral prefrontal cortex, dorsal striatum, and ventrolateral prefrontal cortex. Chinese–Americans’ neural response to either race did not differ from White American or Chinese participants. Taken together, outgroup biases seemed to emerge in a culturally-dependent way based on variability in intergroup contact, but not necessarily awareness of stereotypes

A method for accurate detection of genomic microdeletions using real-time quantitative PCR

BACKGROUND: Quantitative Polymerase Chain Reaction (qPCR) is a well-established method for quantifying levels of gene expression, but has not been routinely applied to the detection of constitutional copy number alterations of human genomic DNA. Microdeletions or microduplications of the human genome are associated with a variety of genetic disorders. Although, clinical laboratories routinely use fluorescence in situ hybridization (FISH) to identify such cryptic genomic alterations, there remains a significant number of individuals in which constitutional genomic imbalance is suspected, based on clinical parameters, but cannot be readily detected using current cytogenetic techniques. RESULTS: In this study, a novel application for real-time qPCR is presented that can be used to reproducibly detect chromosomal microdeletions and microduplications. This approach was applied to DNA from a series of patient samples and controls to validate genomic copy number alteration at cytoband 22q11. The study group comprised 12 patients with clinical symptoms of chromosome 22q11 deletion syndrome (22q11DS), 1 patient trisomic for 22q11 and 4 normal controls. 6 of the patients (group 1) had known hemizygous deletions, as detected by standard diagnostic FISH, whilst the remaining 6 patients (group 2) were classified as 22q11DS negative using the clinical FISH assay. Screening of the patients and controls with a set of 10 real time qPCR primers, spanning the 22q11.2-deleted region and flanking sequence, confirmed the FISH assay results for all patients with 100% concordance. Moreover, this qPCR enabled a refinement of the region of deletion at 22q11. Analysis of DNA from chromosome 22 trisomic sample demonstrated genomic duplication within 22q11. CONCLUSION: In this paper we present a qPCR approach for the detection of chromosomal microdeletions and microduplications. The strategic use of in silico modelling for qPCR primer design to avoid regions of repetitive DNA, whilst providing a level of genomic resolution greater than standard cytogenetic assays. The implementation of qPCR detection in clinical laboratories will address the need to replace complex, expensive and time consuming FISH screening to detect genomic microdeletions or duplications of clinical importance

The relative influence of intellectual disabilities and autism on mental and general health in Scotland: a cross-sectional study of a whole country of 5.3 million children and adults

Objectives: To determine the relative extent that autism and intellectual disabilities are independently associated with poor mental and general health, in children and adults. Design: Cross-sectional study. For Scotland’s population, logistic regressions investigated odds of intellectual disabilities and autism predicting mental health conditions, and poor general health, adjusted for age and gender. Participants: 1 548 819 children/youth aged 0-24 years, and 3 746 584 adults aged more than 25 years, of whom 9396/1 548 819 children/youth had intellectual disabilities (0.6%), 25 063/1 548 819 children/youth had autism (1.6%); and 16 953/3 746 584 adults had intellectual disabilities (0.5%), 6649/3 746 584 adults had autism (0.2%). These figures are based on self-report. Main outcome measures: Self-reported general health status and mental health. Results: In children/youth, intellectual disabilities (OR 7.04, 95% CI 6.30 to 7.87) and autism (OR 25.08, 95% CI 23.08 to 27.32) both independently predicted mental health conditions. In adults, intellectual disabilities (OR 3.50, 95% CI 3.20 to 3.84) and autism (OR 5.30, 95% CI 4.80 to 5.85) both independently predicted mental health conditions. In children/youth, intellectual disabilities (OR 18.34, 95% CI 17.17 to 19.58) and autism (OR 8.40, 95% CI 8.02 to 8.80) both independently predicted poor general health. In adults, intellectual disabilities (OR 7.54, 95% CI 7.02 to 8.10) and autism (OR 4.46, 95% CI 4.06 to 4.89) both independently predicted poor general health. Conclusions: Both intellectual disabilities and autism independently predict poor health, intellectual disabilities more so for general health and autism more so for mental health. Intellectual disabilities and autism are not uncommon, and due to their associated poor health, sufficient services/supports are needed. This is not just due to coexistence of these conditions or just to having intellectual disabilities, as the population with autism is independently associated with substantial health inequalities compared with the general population, across the entire life course

Prevalence of long-term health conditions in adults with autism:Observational study of a whole country population

Objectives: To investigate the prevalence of comorbid mental health conditions and physical disabilities in a whole country population of adults aged 25+ with and without reported autism. Design: Secondary analysis of Scotland’s Census, 2011 data. Cross-sectional study. Setting: General population. Participants: 94% of Scotland’s population, including 6649/3 746 584 adults aged 25+ reported to have autism. Main outcome measures: Prevalence of six comorbidities: deafness or partial hearing loss, blindness or partial sight loss, intellectual disabilities, mental health conditions, physical disability and other condition; ORs (95% CI) of autism predicting these comorbidities, adjusted for age and gender; and OR for age and gender in predicting comorbidities within the population with reported autism. Results: Comorbidities were common: deafness/hearing loss—17.5%; blindness/sight loss—12.1%; intellectual disabilities—29.4%; mental health conditions—33.0%; physical disability—30.7%; other condition—34.1%. Autism statistically predicted all of the conditions: OR 3.3 (95% CI 3.1 to 3.6) for deafness or partial hearing loss, OR 8.5 (95% CI 7.9 to 9.2) for blindness or partial sight loss, OR 94.6 (95% CI 89.4 to 100.0) for intellectual disabilities, OR 8.6 (95% CI 8.2 to 9.0) for mental health conditions, OR 6.2 (95% CI 5.8 to 6.6) for physical disability and OR 2.6 (95% CI 2.5 to 2.8) for other condition. Contrary to findings within the general population, female gender predicted all conditions within the population with reported autism, including intellectual disabilities (OR=1.4). Conclusions: Clinicians need heightened awareness of comorbidities in adults with autism to improve detection and suitable care, especially given the added complexity of assessment in this population and the fact that hearing and visual impairments may cause additional difficulties with reciprocal communication which are also a feature of autism; hence posing further challenges in assessment

The impact of health behaviours on incident cardiovascular disease in Europeans and South Asians--a prospective analysis in the UK SABRE study.

BACKGROUND: There is consistent evidence on the impact of health behaviours on risk of cardiovascular disease (CVD) in European populations. As South Asians in the UK have an excess risk of CVD and coronary heart disease (CHD) compared to Europeans, we investigated whether a similar association between combined health behaviours and risk of CVD and CHD among this high-risk group exists, and estimated the population impact. METHODS AND FINDINGS: In a prospective cohort of 1090 Europeans and 1006 South Asians (40-69 y) without prevalent CVD at baseline (1988-1990), followed up for 21 years to 2011, there were 601 incident CVD events [Europeans n = 255; South Asians n = 346] of which 520 were CHD events [n = 207 and 313 respectively]. Participants scored between 0 to 4 points for a composite score including four baseline healthy behaviours (non-smoker, moderate alcohol intake, physically active, frequent fruit/vegetable intake). Adjusted hazard ratios (95% confidence intervals) for incident CHD in Europeans who had three, two, one, and zero compared to four health behaviours were 1.33 (0.78-2.29), 1.96 (1.15-3.33), 1.36 (0.74-2.48) and 2.45 (1.18-5.10), respectively, p-trend = 0.025. In South Asians, corresponding HRs were 2.88 (1.33-6.24), 2.28 (1.06-4.91), 3.36 (1.53-7.39) and 3.48 (1.38-8.81), p-trend = 0.022. The results were similar for incident CVD; Europeans HR 2.12 (1.14-3.94), p-trend = 0.014; South Asians HR 2.73 (1.20-6.21), p-trend = 0.018. The population attributable fraction in Europeans was 43% for CHD and 28% for CVD. In South Asians it was 63% and 51% respectively. CONCLUSIONS: Lack of adherence to four combined health behaviours was associated with 2 to 3-fold increased risk of incident CVD in Europeans and South Asians. A substantial population impact in the South Asian group indicates important potential for disease prevention in this high-risk group by adherence to healthy behaviours.The SABRE study was funded by the Wellcome Trust (082464/Z/07/Z) and British Heart Foundation (SP/07/001/23603). Support from NIHR Biomedical Research Centre funding scheme as well as the MRC Epidemiology Unit (MC_UU_12015/5 to NGF) is acknowledged.This is the final published version. It first appeared at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117364#ack

Cohort profile:Scotland’s record-linkage e-cohorts of people with intellectual disabilities, and autistic people (SCIDA)

Purpose: To investigate health, mortality and healthcare inequalities experienced by people with intellectual disabilities, and autistic people, and their determinants; an important step towards identifying and implementing solutions to reduce inequalities. This paper describes the cohorts, record-linkages and variables that will be used. Participants: Scotland’s Census, 2011 was used to identify Scotland’s citizens with intellectual disabilities, and autistic citizens, and representative general population samples with neither. Using Scotland’s community health index, the Census data (demography, household, employment, long-term conditions) were linked with routinely collected health, death and healthcare data: Scotland’s register of deaths, Scottish morbidity data 06 (SMR06: cancer incidence, mortality, treatments), Prescribing Information System (identifying asthma/chronic obstructive pulmonary disease; angina/congestive heart failure/hypertension; peptic ulcer/reflux; constipation; diabetes; thyroid disorder; depression; bipolar disorders; anxiety/sleep; psychosis; attention deficit hyperactivity disorder; epilepsy; glaucoma), SMR01 (general/acute hospital admissions and causes, ambulatory care sensitive admissions), SMR04 (mental health admissions and causes), Scottish Care Information–Diabetes Collaboration (diabetic care quality, diabetic outcomes), national bowel screening programme and cervical screening. Findings to date: Of the whole population, 0.5% had intellectual disabilities, and 0.6% were autistic. Linkage was successful for &gt;92%. The resultant e-cohorts include: (1) 22 538 people with intellectual disabilities (12 837 men and 9701 women), 4509 of whom are children &lt;16 years, (2) 27 741 autistic people (21 390 men and 6351 women), 15 387 of whom are children &lt;16 years and (3) representative general population samples with neither condition. Very good general health was reported for only 3389 (15.0%) people with intellectual disabilities, 10 510 (38.0%) autistic people, compared with 52.4% general population. Mental health conditions were reported for 4755 (21.1%) people with intellectual disabilities, 3998 (14.4%) autistic people, compared with 4.2% general population. Future plans: Analyses will determine the extent of premature mortality, causes of death, and avoidable deaths, profile of health conditions and cancers, healthcare quality and screening and determinants of mortality and healthcare

Rates, causes and predictors of all-cause and avoidable mortality in 163 686 children and young people with and without intellectual disabilities:A record linkage national cohort study

Objectives: To investigate mortality rates and associated factors, and avoidable mortality in children/young people with intellectual disabilities. Design: Retrospective cohort; individual record-linked data between Scotland’s 2011 Census and 9.5 years of National Records for Scotland death certification data. Setting: General community. Participants: Children and young people with intellectual disabilities living in Scotland aged 5–24 years, and an age-matched comparison group. Main outcome measures: Deaths up to 2020: age of death, age-standardised mortality ratios (age-SMRs); causes of death including cause-specific age-SMRs/sex-SMRs; and avoidable deaths. Results: Death occurred in 260/7247 (3.6%) children/young people with intellectual disabilities (crude mortality rate=388/100 000 person-years) and 528/156 439 (0.3%) children/young people without intellectual disabilities (crude mortality rate=36/100 000 person-years). SMRs for children/young people with versus those without intellectual disabilities were 10.7 for all causes (95% CI 9.47 to 12.1), 5.17 for avoidable death (95% CI 4.19 to 6.37), 2.3 for preventable death (95% CI 1.6 to 3.2) and 16.1 for treatable death (95% CI 12.5 to 20.8). SMRs were highest for children (27.4, 95% CI 20.6 to 36.3) aged 5–9 years, and lowest for young people (6.6, 95% CI 5.1 to 8.6) aged 20–24 years. SMRs were higher in more affluent neighbourhoods. Crude mortality incidences were higher for the children/young people with intellectual disabilities for most International Statistical Classification of Diseases and Related Health Problems, 10th Revision chapters. The most common underlying avoidable causes of mortality for children/young people with intellectual disabilities were epilepsy, aspiration/reflux/choking and respiratory infection, and for children/young people without intellectual disabilities were suicide, accidental drug-related deaths and car accidents. Conclusion: Children with intellectual disabilities had significantly higher rates of all-cause, avoidable, treatable and preventable mortality than their peers. The largest differences were for treatable mortality, particularly at ages 5–9 years. Interventions to improve healthcare to reduce treatable mortality should be a priority for children/young people with intellectual disabilities. Examples include improved epilepsy management and risk assessments, and coordinated multidisciplinary actions to reduce aspiration/reflux/choking and respiratory infection. This is necessary across all neighbourhoods

Birth incidence, deaths and hospitalisations of children and young people with Down syndrome, 1990–2015: birth cohort study

Objective: To investigate current Down syndrome live birth and death rates, and childhood hospitalisations, compared with peers.Setting: General community.Participants: All live births with Down syndrome, 1990–2015, identified via Scottish regional cytogenetic laboratories, each age–sex–neighbourhood deprivation matched with five non-Down syndrome controls. Record linkage to Scotland’s hospital admissions and death data.Primary outcome: HRs comparing risk of first hospitalisation (any and emergency), readmission for children with Down syndrome and matched controls were calculated using stratified Cox proportional hazards (PH) model, and length of hospital stay was calculated using a conditional log-linear regression model.Results: 689/1479 (46.6%) female and 769/1479 (51.9%) male children/young people with Down syndrome were identified (1.0/1000 births, with no reduction over time); 1235 were matched. 92/1235 (7.4%) died during the period, 18.5 times more than controls. More of the Down syndrome group had at least one admission (incidence rate ratio(IRR) 72.89 (68.72–77.32) vs 40.51 (39.15–41.92); adjusted HR=1.84 (1.68, 2.01)) and readmissions (IRR 54.85 (51.46–58.46) vs 15.06 (14.36–15.80); adjusted HR=2.56 (2.08, 3.14)). More of their admissions were emergencies (IRR 56.78 (53.13–60.72) vs 28.88 (27.73–30.07); first emergency admission adjusted HR=2.87 (2.61, 3.15)). Children with Down syndrome had 28% longer first admission after birth. Admission rate increased from 1990–2003 to 2004–2014 for the Down syndrome group (from 90.7% to 92.2%) and decreased for controls (from 63.3% to 44.8%).Conclusions: We provide contemporaneous statistics on the live birth rate of babies with Down syndrome, and their childhood death rate. They require more hospital admissions, readmissions emergency admissions and longer lengths of stays than their peers, which has received scant research attention in the past. This demonstrates the importance of statutory planning as well as informal support to families to avoid added problems in child development and family bonding over and above that brought by the intellectual disabilities associated with Down syndrome