Susceptibility to pattern glare following stroke

The aim of this work was to measure susceptibility to pattern glare within a stroke group, employing a direct method of assessment. Twenty stroke subjects, aged 38-85 years, were recruited, along with an age-matched control group (n = 20). Assessment of pattern glare susceptibility was undertaken using the pattern glare test. An abnormal degree of pattern glare is present when individuals score >1 on the mid-high spatial frequency difference variable, a relative score that allows for normalization of the subject, or >3 when viewing the mid spatial frequency grating. Stroke subjects demonstrate elevated levels of pattern glare compared to normative data values and a control population, as determined using the pattern glare test. This was most notable when considering the output measure for the mid-high difference variable. The mean score for the mid-high difference variable was 2.15 SD 1.27 for the stroke subjects versus 0.10 SD 1.12 for the control subjects. When considering the mid-high difference variable, 75% of the stroke group recorded an abnormal level of pattern glare compared to 5% in the control group. This study demonstrates an association between stroke subjects and elevated levels of pattern glare. Cortical hyperexcitability has been shown to present following stroke, and this has been proposed as a plausible explanation for the perceptual distortions experienced by individuals susceptible to pattern glare. Further work to assess the benefits of spectral filters in reducing perceptual distortions in stroke patients is currently underway.

Functional localisation of human sensory-motor cortex using magnetoencephalography

The 19 channel Neuromagnetometer system in the Clinical Neurophysiology Unit at Aston University is a multi-channel system, unique in the United Kingdom. A bite bar head localisation and MRI co-registration strategy which enabled accurate and reproducible localisation of MEG data into cortical space was developed. This afforded the opportunity to study magnetic fields of the human cortex generated by stimulation of peripheral nerve, by stimulation of visceral sensory receptors and by those evoked through voluntary finger movement. Initially, a study of sensory-motor evoked data was performed in a healthy control population. The techniques developed were then applied to patients who were to undergo neurosurgical intervention for the treatment of epilepsy and I or space occupying lesions. This enabled both validation of the effective accuracy of source localisation using MEG as well as to determine the clinical value of MEG in presurgical assessment of functional localisation in human cortex. The studies in this thesis have demonstrated that MEG can repeatedly and reliably locate sources contained within a single gyrus and thus potentially differentiate between disparate gyral activation. This ability is critical in the clinical application of any functional imaging technique; which is yet to be fully validated by any other 'non-invasive' functional imaging methodology. The technique was also applied to the study of visceral sensory representation in the cortex which yielded important data about the multiple cortical representation of visceral sensory function.

The relationship between parental perceptions of diabetes and glycaemic control

Aim: To measure the relationship between perceived child competence, parental self-efficacy, and children's glycaemic control. Methods: Cross-sectional outpatient based questionnaire survey of 78 parents of children aged 6-12 years with insulin dependent diabetes mellitus, diagnosed for at least one year. Parental perceptions of their child's competence were assessed, together with parental perceptions of their own self-efficacy in managing their child's diabetes. Glycaemic control was assessed by the average annual HbA 1C level. Results: The response rate was 64.5% (51 parents); 82% were mothers and the socioeconomic class and ethnicity spread was representative of the general population. The mean age of the children was 10 years and duration of diabetes 4.4 years. Poorer glycaemic control was associated with higher perceived child competence, together with lower perceived age of responsibility, lower perceived seriousness, and less frequent blood tests. Higher parental self-efficacy and higher perceived child competence predicted a higher level of normalisation, as did lower perceived seriousness, a lower perceived parental responsibility for management, and a less protective style of parenting. Conclusion: Parents' perceptions of their children's diabetes are significantly related to glycaemic control; however, those who appear more competent at managing diabetes may overestimate their child's capabilities, leading to poorer glycaemic control.

Ecological studies on river pollution control

This collection of papers records a series of studies, carried out over a period of some 50 years, on two aspects of river pollution control - the prevention of pollution by sewage biological filtration and the monitoring of river pollution by biological surveillance. The earlier studies were carried out to develop methods of controlling flies which bred in the filters and caused serious nuisance and possible public health hazard, when they dispersed to surrounding villages. Although the application of insecticides proved effective as an alleviate measure, because it resulted in only a temporary disturbance of the ecological balance, it was considered ecologically unsound as a long-term solution. Subsequent investigations showed that the fly populations in filters were largely determined by the amount of food available to the grazing larval stage in the form of filter film. It was also established that the winter deterioration in filter performance was due to the excessive accumulation of film. Subsequent investigations were therefore carried out to determine the factors responsible for the accumulation of film in different types of filter. Methods of filtration which were considered to control film accumulation by increasing the flushing action of the sewage, were found to control fungal film by creating nutrient limiting conditions. In some filters increasing the hydraulic flushing reduced the grazing fauna population in the surface layers and resulted in an increase in film. The results of these investigations were successfully applied in modifying filters and in the design of a Double Filtration process. These studies on biological filters lead to the conclusion that they should be designed and operated as ecological systems and not merely as hydraulic ones. Studies on the effects of sewage effluents on Birmingham streams confirmed the findings of earlier workers justifying their claim for using biological methods for detecting and assessing river pollution. Further ecological studies showed the sensitivity of benthic riffle communities to organic pollution. Using experimental channels and laboratory studies the different environmental conditions associated with organic pollution were investigated. The degree and duration of the oxygen depletion during the dark hours were found to be a critical factor. The relative tolerance of different taxa to other pollutants, such as ammonia, differed. Although colonisation samplers proved of value in sampling difficult sites, the invertebrate data generated were not suitable for processing as any of the commonly used biotic indexes. Several of the papers, which were written by request for presentation at conferences etc., presented the biological viewpoint on river pollution and water quality issues at the time and advocated the use of biological methods. The information and experiences gained in these investigations was used as the "domain expert" in the development of artificial intelligence systems for use in the biological surveillance of river water quality.

Sensing and control of adipocyte function

Obesity has become a global epidemic. Approximately 15% of the world population is either overweight or obese. This figure rises to 75% in many westernised countries including the United Kingdom. Health costs in the UK to treat obesity and associated disease are conservatively estimated at 6% of the National Health Service (NHS) budget equating to 3.33 billion Euros. Excess adiposity, especially in visceral depots, increases the risk of type 2 diabetes, cardiovascular disease, gall stones, hypertension and cancer. Type 2 diabetes mellitus accounts for >90% of all cases of diabetes of which the majority can be attributed to increased adiposity, and approximately 70% of cardiovascular disease has been attributed to obesity in the US. Weight loss reduces risk of these complications and in some cases can eliminate the condition. However, weight loss by conventional non-medicated methods is often unsuccessful or promptly followed by weight regain. This thesis has investigated adipocytes development and adipokine signalling with a view to enhance the understanding of tissue functionality and to identify possible targets or pathways for therapeutic intervention. Adipocyte isolation from human tissue samples was undertaken for these investigative studies, and the methodology was optimised. The resulting isolates of pre-adipocytes and mature adipocytes were characterised and evaluated. Major findings from these studies indicate that mature adipocytes undergo cell division post terminal differentiation. Gene studies indicated that subcutaneous adipose tissue exuded greater concentrations and fluctuations of adipokine levels than visceral adipose tissue, indicating an important adiposensing role of subcutaneous adipose tissue. It was subsequently postulated that the subcutaneous depot may provide the major focus for control of overall energy balance and by extension weight control. One potential therapeutic target, 11ß-hydrosteroid dehydrogenase (11ß-HSD1) was investigated, and prospective inhibitors of its action were considered (BVT1, BVT2 and AZ121). Selective reduction of adiposity of the visceral depot was desired due to its correlation with the detrimental effects of obesity. However, studies indicated that although the visceral depot tissue was not unaffected, the subcutaneous depot was more susceptible to therapeutic inhibition by these compounds. This was determined to be a potentially valuable therapeutic intervention in light of previous postulations regarding long-term energy control via the subcutaneous tissue depot.

What checkers actually check:an eye tracking study of inhibitory control and working memory

Background - Not only is compulsive checking the most common symptom in Obsessive Compulsive Disorder (OCD) with an estimated prevalence of 50–80% in patients, but approximately ~15% of the general population reveal subclinical checking tendencies that impact negatively on their performance in daily activities. Therefore, it is critical to understand how checking affects attention and memory in clinical as well as subclinical checkers. Eye fixations are commonly used as indicators for the distribution of attention but research in OCD has revealed mixed results at best. Methodology/Principal Finding - Here we report atypical eye movement patterns in subclinical checkers during an ecologically valid working memory (WM) manipulation. Our key manipulation was to present an intermediate probe during the delay period of the memory task, explicitly asking for the location of a letter, which, however, had not been part of the encoding set (i.e., misleading participants). Using eye movement measures we now provide evidence that high checkers’ inhibitory impairments for misleading information results in them checking the contents of WM in an atypical manner. Checkers fixate more often and for longer when misleading information is presented than non-checkers. Specifically, checkers spend more time checking stimulus locations as well as locations that had actually been empty during encoding. Conclusions/Significance - We conclude that these atypical eye movement patterns directly reflect internal checking of memory contents and we discuss the implications of our findings for the interpretation of behavioural and neuropsychological data. In addition our results highlight the importance of ecologically valid methodology for revealing the impact of detrimental attention and memory checking on eye movement patterns.

Common variants of the TCF7L2 gene are associated with increased risk of type 2 diabetes mellitus in a UK-resident South Asian population

Background - Recent studies have implicated variants of the transcription factor 7-like 2 (TCF7L2) gene in genetic susceptibility to type 2 diabetes mellitus in several different populations. The aim of this study was to determine whether variants of this gene are also risk factors for type 2 diabetes development in a UK-resident South Asian cohort of Punjabi ancestry. Methods - We genotyped four single nucleotide polymorphisms (SNPs) of TCF7L2 (rs7901695, rs7903146, rs11196205 and rs12255372) in 831 subjects with diabetes and 437 control subjects. Results - The minor allele of each variant was significantly associated with type 2 diabetes; the greatest risk of developing the disease was conferred by rs7903146, with an allelic odds ratio (OR) of 1.31 (95% CI: 1.11 – 1.56, p = 1.96 × 10-3). For each variant, disease risk associated with homozygosity for the minor allele was greater than that for heterozygotes, with the exception of rs12255372. To determine the effect on the observed associations of including young control subjects in our data set, we reanalysed the data using subsets of the control group defined by different minimum age thresholds. Increasing the minimum age of our control subjects resulted in a corresponding increase in OR for all variants of the gene (p ≤ 1.04 × 10-7). Conclusion - Our results support recent findings that TCF7L2 is an important genetic risk factor for the development of type 2 diabetes in multiple ethnic groups.

The continuum of psychotic symptoms in the general population:a cross-national study

OBJECTIVE: To identify the cross-national prevalence of psychotic symptoms in the general population and to analyze their impact on health status. METHOD: The sample was composed of 256,445 subjects (55.9% women), from nationally representative samples of 52 countries worldwide participating in the World Health Organization's World Health Survey. Standardized and weighted prevalence of psychotic symptoms were calculated in addition to the impact on health status as assessed by functioning in multiple domains. RESULTS: Overall prevalences for specific symptoms ranged from 4.80% (SE = 0.14) for delusions of control to 8.37% (SE = 0.20) for delusions of reference and persecution. Prevalence figures varied greatly across countries. All symptoms of psychosis produced a significant decline in health status after controlling for potential confounders. There was a clear change in health impact between subjects not reporting any symptom and those reporting at least one symptom (effect size of 0.55). CONCLUSIONS: The prevalence of the presence of at least one psychotic symptom has a wide range worldwide varying as much as from 0.8% to 31.4%. Psychotic symptoms signal a problem of potential public health concern, independent of the presence of a full diagnosis of psychosis, as they are common and are related to a significant decrement in health status. The presence of at least one psychotic symptom is related to a significant poorer health status, with a regular linear decrement in health depending on the number of symptoms.