Glasgow Psychosis Screening tool for use in adults with Intellectual Disabilities (GPS-ID): development and psychometric properties

Background: Prevalence of psychosis is known to be higher in adults with intellectual disabilities (ID) than in the general adult population. However, there have been no attempts to develop a psychosis screening tool specifically for the adult ID population. The present study describes the development and preliminary evaluation of a new measure, the Glasgow Psychosis Screening tool for use in Adults with Intellectual Disabilities (GPS-ID). Method: An item pool was generated following: 1) focus groups with adults with ID and psychosis, and their carers and/or workers; 2) expert input from clinicians. A draft scale was compiled and refined following expert feedback. The new scale, along with the Psychotic Symptom Rating Scales was administered to 20 adults with ID (10 with and 10 without psychosis) and their relative or carers. Results: The GPS-ID total score, self-report subscale and informant rating-subscale differentiated psychosis and non-psychosis groups. The tool had good internal consistency (Cronbach’s α=0.91), and a cut-off score ≥4 yielded high sensitivity (90%) and specificity (100%). The method of tool development supports face and content validity. Criterion validity was not supported. Conclusions: Preliminary investigation of the tool’s psychometric properties is positive, although further investigation is required. The tool is accessible to adults with mild to moderate ID and can be completed in 15-30 minutes. The GPS-ID is not a diagnostic tool, therefore any adult exceeding the cut-off score of ≥4 should receive further assessment.

Quantifying uplift and denudation of a thermally heterogeneous crust: a detailed multi-thermochronometeric study of central west Britain

Topography is often thought as exclusively linked to mountain ranges formed by plates collision. It is now, however, known that apart from compression, uplift and denudation of rocks may be triggered by rifting, like it happens at elevated passive margins, and away from plate boundaries by both intra-plate stress causing reactivation of older structures, and by epeirogenic movements driven by mantle dynamics and initiating long-wavelength uplift. In the Cenozoic, central west Britain and other parts of the North Atlantic margins experienced multiple episodes of rock uplift and denudation that have been variable both at spatial and temporal scales. The origin of topography in central west Britain is enigmatic, and because of its location, it may be related to any of the processes mentioned above. In this study, three low temperature thermochronometers, the apatite fission track (AFT) and apatite and zircon (U-Th-Sm)/He (AHe and ZHe, respectively) methods were used to establish the rock cooling history from 200◦C to 30◦C. The samples were collected from the intrusive rocks in the high elevation, high relief regions of the Lake District (NW England), southern Scotland and northern Wales. AFT ages from the region are youngest (55–70 Ma) in the Lake District and increase northwards into southern Scotland and southwards in north Wales (>200 Ma). AHe and ZHe ages show no systematic pattern; the former range from 50 to 80 Ma and the latter tend to record the post-emplacement cooling of the intrusions (200–400 Ma). The complex, multi-thermochronometric inverse modelling suggests a ubiquitous, rapid Late Cretaceous/early Palaeogene cooling event that is particularly marked in Lake District and Criffell. The timing and rate of cooling in southern Scotland and in northern Wales is poorly resolved as the amount of cooling was less than 60◦C. The Lake District plutons were at >110◦C prior to the early Palaeogene; cooling due to a combined effect of high heat flow, from the heat producing granite batholith, and the blanketing effect of the overlying low conductivity Late Mesozoic limestones and mudstones. Modelling of the heat transfer suggests that this combination produced an elevated geothermal gradient within the sedimentary rocks (50–70◦C/km) that was about two times higher than at the present day. Inverse modelling of the AFT and AHe data taking the crustal structure into consideration suggests that denudation was the highest, 2.0–2.5 km, in the coastal areas of the Lake District and southern Scotland, gradually decreasing to less than 1 km in the northern Southern Uplands and northern Wales. Both the rift-related uplift and the intra-plate compression poorly correlate with the timing, location and spatial distribution of the early Palaeogene denudation. The pattern of early Palaeogene denudation correlates with the thickness of magmatic underplating, if the changes of mean topography, Late Cretaceous water depth and eroded rock density are taken into consideration. However, the uplift due to underplating alone cannot fully justify the total early Palaeogene denudation. The amount that is not ex- plained by underplating is, however, roughly spatially constant across the study area and can be referred to the transient thermal uplift induced by the mantle plume arrival. No other mechanisms are required to explain the observed pattern of denudation. The onset of denudation across the region is not uniform. Denudation started at 70–75 Ma in the central part of the Lake District whereas the coastal areas the rapid erosion appears to have initiated later (65–60 Ma). This is ~10 Ma earlier than the first vol- canic manifestation of the proto-Iceland plume and favours the hypothesis of the short period of plume incubation below the lithosphere before the volcanism. In most of the localities, the rocks had cooled to temperatures lower than 30◦C by the end of the Palaeogene, suggesting that the total Neogene denudation was, at a maximum, several hundreds of metres. Rapid cooling in the last 3 million years is resolved in some places in southern Scotland, where it could be explained by glacial erosion and post-glacial isostatic uplift.

Lifestyle factors, adiposity and cardiometabolic risk factors in South Asian women living in Scotland

South Asians migrating to the Western world have a 3 to 5-fold higher risk of developing type 2 diabetes and double the risk of cardiovascular disease (CVD) than the background population of White European descent, without exhibiting a proportional higher prevalence of conventional cardiometabolic risk factors. Notably, women of South Asian descent are more likely to be diagnosed with type 2 diabetes as they grow older compared with South Asian men and, in addition, they have lost the cardio-protective effects of being females. Despite South Asian women in Western countries being a high risk group for developing future type 2 diabetes and CVD, they have been largely overlooked. The aims of this thesis were to compare lifestyle factors, body composition and cardiometabolic risk factors in healthy South Asian and European women who reside in Scotland, to examine whether ethnicity modifies the associations between modifiable environmental factors and cardiometabolic risks and to assess whether vascular reactivity is altered by ethnicity or other conventional and novel CVD risks. I conducted a cross-sectional study and recruited 92 women of South Asian and 87 women of White European descent without diagnosed diabetes or CVD. Women on hormone replacement therapy or hormonal contraceptives were excluded too. Age and body mass index (BMI) did not differ between the two ethnic groups. Physical activity was assessed and with self-reported questionnaires and objectively with the use of accelerometers. Cardiorespiratory fitness was quantified with the predicted maximal oxygen uptake (VO2 max) during a submaximal test (Chester step test). Body composition was assessed with skinfolds measured at seven body sites, five body circumferences, measurement of abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) with the use of magnetic resonance imaging (MRI) and liver fat with the use MR spectroscopy. Dietary density was assessed with food frequency questionnaires. Vascular response was assessed by measuring the response to acetylcholine and sodium nitroprusside with the use of Laser Doppler Imaging with Iontophoresis (LDI-ION) and the response to shear stress with the use of Peripheral Arterial Tonometry (EndoPAT). The South Asian women exhibited a metabolic profile consistent with the insulin resistant phenotype, characterised by greater levels of fasting insulin, lower levels of high density lipoprotein (HDL) and higher levels of triglycerides (TG) compared with their European counterparts. In addition, the South Asians had greater levels of glycated haemoglobin (HbA1c) for any given level of fasting glucose. The South Asian women engaged less time weekly with moderate to vigorous physical activity (MVPA) and had lower levels of cardiorespiratory fitness for any given level of physical activity than the women of White descent. In addition, they accumulated more fat centrally for any given BMI. Notably, the South Asians had equivalent SAT with the European women but greater VAT and hepatic fat for any given BMI. Dietary density did not differ among the groups. Increasing central adiposity had the largest effect on insulin resistance in both ethic groups compared with physical inactivity or decreased cardiorespiratory fitness. Interestingly, ethnicity modified the association between central adiposity and insulin resistance index with a similar increase in central adiposity having a substantially larger effect on insulin resistance index in the South Asian women than in the Europeans. I subsequently examined whether ethnic specific thresholds are required for lifestyle modifications and demonstrated that South Asian women need to engage with MVPA for around 195 min.week-1 in order to equate their cardiometabolic risk with that of the Europeans exercising 150 min.week-1. In addition, lower thresholds of abdominal adiposity and BMI should apply for the South Asians compared with the conventional thresholds. Although the South Asians displayed an adverse metabolic profile, vascular reactivity measured with both methods did not differ among the two groups. An additional finding was that menopausal women with hot flushing of both ethnic groups showed a paradoxical vascular profile with enhanced skin perfusion (measured with LDI-ION) but decreased reactive hyperaemia index (measured with EndoPAT) compared with asymptomatic menopausal women. The latter association was independent of conventional CVD risk factors. To conclude, South Asian women without overt disease who live in Scotland display an adverse metabolic profile with steeper associations between lifestyle risk factors and adverse cardiometabolic outcomes compared with their White counterparts. Further work in exploring ethnic specific thresholds in lifestyle interventions or in disease diagnosis is warranted.

Phylodynamic modelling of foot-and-mouth disease virus sequence data

The under-reporting of cases of infectious diseases is a substantial impediment to the control and management of infectious diseases in both epidemic and endemic contexts. Information about infectious disease dynamics can be recovered from sequence data using time-varying coalescent approaches, and phylodynamic models have been developed in order to reconstruct demographic changes of the numbers of infected hosts through time. In this study I have demonstrated the general concordance between empirically observed epidemiological incidence data and viral demography inferred through analysis of foot-and-mouth disease virus VP1 coding sequences belonging to the CATHAY topotype over large temporal and spatial scales. However a more precise and robust relationship between the effective population size (