The performance of interferon-gamma release assays in tuberculosis patients with type II diabetes

The sensitivity of Interferon-γ release assays for detection of Mycobacterium tuberculosis (MTB) infection or disease is affected by conditions that depress host immunity (such as HIV). It is critical to determine whether these assays are affected by diabetes and related conditions (i.e. hyperglycemia, chronic hyperglycemia, or being overweight/obese) given that immune impairment is thought to underline susceptibility to tuberculosis (TB) in people with diabetes. This is important for tuberculosis control due to the millions of type 2 diabetes patients at risk for tuberculosis worldwide.^ The objective of this study was to identify host characteristics, including diabetes, that may affect the sensitivity of two commercially available Interferon-γ (IFN-γ) release assays (IGRA), the QuantiFERON®-TB Gold (QFT-G) and the T-SPOT®.TB in active TB patients. We further explored whether IFN-γ secretion in response to MTB antigens (ESAT-6 and CFP-10) is associated with diabetes and its defining characteristics (high blood glucose, high HbA1c, high BMI). To achieve these objectives, the sensitivity of QFT-G and T-SPOT. TB assays were evaluated in newly diagnosed, tuberculosis confirmed (by positive smear for acid fast bacilli and/or positive culture for MTB) adults enrolled at Texas and Mexico study sites between March 2006 and April 2009. Univariate and multivariate models were constructed to identify host characteristics associated with IGRA result and level of IFN-γ secretion.^ QFT-G was positive in 68% of tuberculosis patients. Those with diabetes, chronic hyperglycemia or obesity were more likely to have a positive QFT-G result, and to secrete higher levels of IFN-γ in response to the mycobacterial antigens (p<0.05). Previous history of BCG vaccination was the only other host characteristic associated with QFT-G result, whereby a higher proportion of non-BCG vaccinated persons were QFT-G positive, in comparison to vaccinated persons. In a separate group of patients, the T-SPOT.TB was 94% sensitive, with similar performance in all tuberculosis patients, regardless of host characteristics.^ In summary, we have demonstrated the validity of QFT-G and T-SPOT. TB to support the diagnosis of TB in patients with a range of host characteristics, but most notably in patients with diabetes. We also confirmed that TB patients with diabetes and associated characteristics (chronic hyperglycemia or BMI) secreted higher titers of IFN-γ when stimulated with MTB specific antigens, in comparison to patients without these characteristics. Together, these findings suggest that the mechanism by which diabetes increases risk to TB may not be explained by the inability to secrete IFN-γ, a key cytokine for TB control.^

OS SENTIDOS DO FUTEBOL ESPETÁCULO PARA ESTUDANTES DE DISTINTAS CLASSES SOCIAIS

O presente estudo busca identificar em que medida o pertencimento de classe social interfere nos sentidos e perspectivas do jovem brasileiro frente ao futebol espetáculo, bem como compreender os mecanismos sociais que determinam a decisão de os sujeitos investirem na carreira profissional esportiva em detrimento da trajetória escolar longa. Começamos com uma abordagem sociológica, a análise crítica dos processos de difusão, massificação e profissionalização do futebol ocorridas no contexto da sociedade pós-industrial. Enfocamos a conflituosa mutação da modalidade, inicialmente elitizada com fins social-distintivos para esporte de massa ideal de ascensão social da classe popular , além da dependência com a mídia, das razões que levaram a caracterizar-se como produto da indústria cultural, culminando com a transformação do futebol em mercadoria submetida às leis e lógica da sociedade de consumo. Em seguida, entrelaçamos as relações de poder, aliança e concorrência dos agentes sociais que participam do complexo campo das práticas esportivas com os canais com que o público jovem estabelece contato com o esporte espetáculo. Neste aspecto, especial atenção foi dada à mídia, difusora da ideologia de uma sociedade capitalista aberta, que reforça a idéia do esporte como via de ascensão social para indivíduos de baixa renda, na mesma medida em que oculta em seu discurso as reais probabilidades de concretização do sucesso esportivo. A pesquisa de campo foi realizada em duas escolas do município de São Bernardo do Campo (SP), uma da rede pública estadual e outra da rede particular de ensino. Assim, constituímos dois grupos com alunos de distintas classes sociais, compostos por estudantes do 1º ano do Ensino Médio, sexo masculino, com 15 anos de idade e praticantes de futebol nas aulas de Educação Física. Metodologicamente, fizemos uso da observação participante e de entrevistas como instrumentos para a coleta de dados. Conjugadas aos objetivos do estudo, estruturamos a análise do material colhido em seis categorias, articulando questões sobre o prosseguimento nos estudos e o trabalho, as tendências para a pratica esportiva profissional, as representações sociais em torno do futebol, os usos e costumes no tempo livre e as expectativas da pratica esportiva implicadas pela herança cultural familiar. Como referencial teórico de análise, utilizamos de Pierre Bourdieu os conceitos de campo, habitus, estratégia, capital econômico, social e, principalmente, capital cultural, partindo da hipótese de que o nível cultural dos alunos e seus familiares interferem nos sentidos e formas de apropriação do esporte. Entre outras conclusões, obtivemos como resultado a configuração de uma trajetória esportiva profissional voltada para os alunos de baixa classe social, em oposição à trajetória escolar longa, estrategicamente adotada pelos alunos de classe social alta.(AU)

OS SENTIDOS DO FUTEBOL ESPETÁCULO PARA ESTUDANTES DE DISTINTAS CLASSES SOCIAIS

O presente estudo busca identificar em que medida o pertencimento de classe social interfere nos sentidos e perspectivas do jovem brasileiro frente ao futebol espetáculo, bem como compreender os mecanismos sociais que determinam a decisão de os sujeitos investirem na carreira profissional esportiva em detrimento da trajetória escolar longa. Começamos com uma abordagem sociológica, a análise crítica dos processos de difusão, massificação e profissionalização do futebol ocorridas no contexto da sociedade pós-industrial. Enfocamos a conflituosa mutação da modalidade, inicialmente elitizada com fins social-distintivos para esporte de massa ideal de ascensão social da classe popular , além da dependência com a mídia, das razões que levaram a caracterizar-se como produto da indústria cultural, culminando com a transformação do futebol em mercadoria submetida às leis e lógica da sociedade de consumo. Em seguida, entrelaçamos as relações de poder, aliança e concorrência dos agentes sociais que participam do complexo campo das práticas esportivas com os canais com que o público jovem estabelece contato com o esporte espetáculo. Neste aspecto, especial atenção foi dada à mídia, difusora da ideologia de uma sociedade capitalista aberta, que reforça a idéia do esporte como via de ascensão social para indivíduos de baixa renda, na mesma medida em que oculta em seu discurso as reais probabilidades de concretização do sucesso esportivo. A pesquisa de campo foi realizada em duas escolas do município de São Bernardo do Campo (SP), uma da rede pública estadual e outra da rede particular de ensino. Assim, constituímos dois grupos com alunos de distintas classes sociais, compostos por estudantes do 1º ano do Ensino Médio, sexo masculino, com 15 anos de idade e praticantes de futebol nas aulas de Educação Física. Metodologicamente, fizemos uso da observação participante e de entrevistas como instrumentos para a coleta de dados. Conjugadas aos objetivos do estudo, estruturamos a análise do material colhido em seis categorias, articulando questões sobre o prosseguimento nos estudos e o trabalho, as tendências para a pratica esportiva profissional, as representações sociais em torno do futebol, os usos e costumes no tempo livre e as expectativas da pratica esportiva implicadas pela herança cultural familiar. Como referencial teórico de análise, utilizamos de Pierre Bourdieu os conceitos de campo, habitus, estratégia, capital econômico, social e, principalmente, capital cultural, partindo da hipótese de que o nível cultural dos alunos e seus familiares interferem nos sentidos e formas de apropriação do esporte. Entre outras conclusões, obtivemos como resultado a configuração de uma trajetória esportiva profissional voltada para os alunos de baixa classe social, em oposição à trajetória escolar longa, estrategicamente adotada pelos alunos de classe social alta.(AU)

Effects of ocean warming and acidification on the early stages of marine fishes

Tese de doutoramento, Ciências do Mar, Universidade de Lisboa, Faculdade de Ciências, 2016

A report of a national mutation testing service for the MEN1 gene: clinical presentations and implications for mutation testing

Introduction: Mutation testing for the MEN1 gene is a useful method to diagnose and predict individuals who either have or will develop multiple endocrine neoplasia type 1 ( MEN 1). Clinical selection criteria to identify patients who should be tested are needed, as mutation analysis is costly and time consuming. This study is a report of an Australian national mutation testing service for the MEN1 gene from referred patients with classical MEN 1 and various MEN 1- like conditions. Results: All 55 MEN1 mutation positive patients had a family history of hyperparathyroidism, had hyperparathyroidism with one other MEN1 related tumour, or had hyperparathyroidism with multiglandular hyperplasia at a young age. We found 42 separate mutations and six recurring mutations from unrelated families, and evidence for a founder effect in five families with the same mutation. Discussion: Our results indicate that mutations in genes other than MEN1 may cause familial isolated hyperparathyroidism and familial isolated pituitary tumours. Conclusions: We therefore suggest that routine germline MEN1 mutation testing of all cases of classical'' MEN1, familial hyperparathyroidism, and sporadic hyperparathyroidism with one other MEN1 related condition is justified by national testing services. We do not recommend routine sequencing of the promoter region between nucleotides 1234 and 1758 ( Genbank accession no. U93237) as we could not detect any sequence variations within this region in any familial or sporadic cases of MEN1 related conditions lacking a MEN1 mutation. We also suggest that testing be considered for patients < 30 years old with sporadic hyperparathyroidism and multigland hyperplasia

Mapping the emergence of heart disease in a black, urban population in Africa: The Heart of Soweto Study

Background: There is increasing evidence that many populations in the developing world are in epidemiologic transition with the subsequent emergence of more affluent disease states. The Heart of Soweto Study will systematically investigate the emergence of heart disease (HD) in a large urban population in South Africa. Methods: Part of the conurbation of Johannesburg, South Africa, Soweto is a predominantly Black African community of I million individuals. During an initial two year period, all individuals presenting to the local Baragwanath Hospital (3500 beds) with any form of HD will be studied. Demographic and diagnostic coding data in those with pre-established HD will form an abbreviated clinical registry of > 12,000 prevalent cases. Similarly, socio-demographic, clinical and diagnostic data (e.g. echocardiography and ECG) in newly diagnosed patients will form a more detailed clinical registry of > 5000 incident cases. Sub-studies of the relationship between HIV status and H D and the optimal management of chronic heart failure will also be performed. Results: These data will provide a unique insight into the causes and consequences of a broad spectrum of HD-related conditions in a developing world community in epidemiologic transition. Initially documented Population rates, in addition to detailed examinations of the underlying risk factors and causes of HD-related morbidity/mortality will provide an important platform for future stages of the study: a community-based, population screening program and culturally specific primary and secondary programs of care. Conclusion: There is an urgent need to systematically track the emergence of HD in the developing world. Initially involving more than 15,000 individuals, the unique Heart of Soweto Study has the potential to provide a wealth of information in this regard. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

OS SENTIDOS DO FUTEBOL ESPETÁCULO PARA ESTUDANTES DE DISTINTAS CLASSES SOCIAIS

O presente estudo busca identificar em que medida o pertencimento de classe social interfere nos sentidos e perspectivas do jovem brasileiro frente ao futebol espetáculo, bem como compreender os mecanismos sociais que determinam a decisão de os sujeitos investirem na carreira profissional esportiva em detrimento da trajetória escolar longa. Começamos com uma abordagem sociológica, a análise crítica dos processos de difusão, massificação e profissionalização do futebol ocorridas no contexto da sociedade pós-industrial. Enfocamos a conflituosa mutação da modalidade, inicialmente elitizada com fins social-distintivos para esporte de massa ideal de ascensão social da classe popular , além da dependência com a mídia, das razões que levaram a caracterizar-se como produto da indústria cultural, culminando com a transformação do futebol em mercadoria submetida às leis e lógica da sociedade de consumo. Em seguida, entrelaçamos as relações de poder, aliança e concorrência dos agentes sociais que participam do complexo campo das práticas esportivas com os canais com que o público jovem estabelece contato com o esporte espetáculo. Neste aspecto, especial atenção foi dada à mídia, difusora da ideologia de uma sociedade capitalista aberta, que reforça a idéia do esporte como via de ascensão social para indivíduos de baixa renda, na mesma medida em que oculta em seu discurso as reais probabilidades de concretização do sucesso esportivo. A pesquisa de campo foi realizada em duas escolas do município de São Bernardo do Campo (SP), uma da rede pública estadual e outra da rede particular de ensino. Assim, constituímos dois grupos com alunos de distintas classes sociais, compostos por estudantes do 1º ano do Ensino Médio, sexo masculino, com 15 anos de idade e praticantes de futebol nas aulas de Educação Física. Metodologicamente, fizemos uso da observação participante e de entrevistas como instrumentos para a coleta de dados. Conjugadas aos objetivos do estudo, estruturamos a análise do material colhido em seis categorias, articulando questões sobre o prosseguimento nos estudos e o trabalho, as tendências para a pratica esportiva profissional, as representações sociais em torno do futebol, os usos e costumes no tempo livre e as expectativas da pratica esportiva implicadas pela herança cultural familiar. Como referencial teórico de análise, utilizamos de Pierre Bourdieu os conceitos de campo, habitus, estratégia, capital econômico, social e, principalmente, capital cultural, partindo da hipótese de que o nível cultural dos alunos e seus familiares interferem nos sentidos e formas de apropriação do esporte. Entre outras conclusões, obtivemos como resultado a configuração de uma trajetória esportiva profissional voltada para os alunos de baixa classe social, em oposição à trajetória escolar longa, estrategicamente adotada pelos alunos de classe social alta.(AU)

Carnosine:can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?

The dipeptide carnosine (β-alanyl-L-histidine) has contrasting but beneficial effects on cellular activity. It delays cellular senescence and rejuvenates cultured senescent mammalian cells. However, it also inhibits the growth of cultured tumour cells. Based on studies in several organisms, we speculate that carnosine exerts these apparently opposing actions by affecting energy metabolism and/or protein homeostasis (proteostasis). Specific effects on energy metabolism include the dipeptide's influence on cellular ATP concentrations. Carnosine's ability to reduce the formation of altered proteins (typically adducts of methylglyoxal) and enhance proteolysis of aberrant polypeptides is indicative of its influence on proteostasis. Furthermore these dual actions might provide a rationale for the use of carnosine in the treatment or prevention of diverse age-related conditions where energy metabolism or proteostasis are compromised. These include cancer, Alzheimer's disease, Parkinson's disease and the complications of type-2 diabetes (nephropathy, cataracts, stroke and pain), which might all benefit from knowledge of carnosine's mode of action on human cells. © 2013 Hipkiss et al.; licensee Chemistry Central Ltd.

Toward targeted treatments in tuberous sclerosis

Introduction. Tuberous Sclerosis Complex (TSC) is an autosomal-dominant disease caused by the loss of function of the heterodimeric complex hamartin/tuberin due to TSC1/TSC2 gene mutation. The consequent abnormal activation of mammalian target of rapamycin (mTOR), a serine threonine kinase regulating cellular growth, metabolism and proliferation, is responsible for the structural and functional abnormalities observed in TSC. mTOR inhibitors are a class of drugs specifically targeting the mTOR pathway with promising benefits as a specific targeted treatment of the disease. Areas covered. We have reviewed the literature focusing on the role of mTOR inhibitors in treating TSC-related conditions. They are currently approved for subependymal giant cell astrocytomas, renal angiomyolipomas and more recently for lymphangioleiomyomatosis, but a promising role has been shown also in the other clinical manifestation characteristics of TSC, such as cardiac rhabdomyomas, facial angiofibromas and epilepsy. Expert opinion. mTOR inhibition is considered a disease-modifying therapy and the best approach to prevent the progress of the natural history of the disease. For the first time we have the possibility not only to use a biologically targeted treatment, but also to address different manifestations at the same time, thus significantly improving the therapeutic outlook in this complex disease.

Extra-nuclear telomerase reverse transcriptase (TERT) regulates glucose transport in skeletal muscle cells

Telomerase reverse transcriptase (TERT) is a key component of the telomerase complex. By lengthening telomeres in DNA strands, TERT increases senescent cell lifespan. Mice that lack TERT age much faster and exhibit age-related conditions such as osteoporosis, diabetes and neurodegeneration. Accelerated telomere shortening in both human and animal models has been documented in conditions associated with insulin resistance, including T2DM. We investigated the role of TERT, in regulating cellular glucose utilisation by using the myoblastoma cell line C2C12, as well as primary mouse and human skeletal muscle cells. Inhibition of TERT expression or activity by using siRNA (100. nM) or specific inhibitors (100. nM) reduced basal 2-deoxyglucose uptake by ~. 50%, in all cell types, without altering insulin responsiveness. In contrast, TERT over-expression increased glucose uptake by 3.25-fold. In C2C12 cells TERT protein was mostly localised intracellularly and stimulation of cells with insulin induced translocation to the plasma membrane. Furthermore, co-immunoprecipitation experiments in C2C12 cells showed that TERT was constitutively associated with glucose transporters (GLUTs) 1, 4 and 12 via an insulin insensitive interaction that also did not require intact PI3-K and mTOR pathways. Collectively, these findings identified a novel extra-nuclear function of TERT that regulates an insulin-insensitive pathway involved in glucose uptake in human and mouse skeletal muscle cells. © 2014 Elsevier B.V.

Toward a scalable and consistent manufacturing process for the production of human MSCs

The development of novel, affordable and efficacious therapeutics will be necessary to ensure the continued progression in the standard of global healthcare. With the potential to address previously unmet patient needs as well as tackling the social and economic effects of chronic and age-related conditions, cell therapies will lead the new generation of healthcare products set to improve health and wealth across the globe. However, if many of the small to medium enterprises (SMEs) engaged in much of the commercialization efforts are to successfully traverse the ‘Valley of Death’ as they progress through clinical trials, there are a number of challenges that must be overcome. No longer do the challenges remain biological but rather a series of engineering and manufacturing issues must also be considered and addressed.

Market-oriented new product development of health promoting foods for the ageing population

Major factors influencing food development and food marketing strategies in global market places at present can be attributable to the changing age structure of the population. The significant shifts in global age structure will inevitably lead to the number of people aged 60 reaching an all-time high of one billion by the year 2020. The rapidly growing population of ageing people globally represents a large, neglected and very much under-developed category within the Food Industry. The primary focus of this study was the integration of knowledge creation techniques at early NPD stages, for the development of market-oriented new health promoting foods for the ageing population. The methodology of this study was centered on an exploratory sequential mixed methods strategy. Stage one of the study involved in-depth semi-structured interviews with 16 Stakeholders to facilitate the need identification stage of the NPD process. The main outputs identified were the need for: the fortification of foods for a preventative nutrition approach, the development of foods that targeted age-related conditions such as cognitive, heart, gut and bone health, the integration of ageing compensatory packaging adaptations and the creation of marketing messages with an active lifestyle message. Stage two consisted of a market-oriented computer assisted NPD technique, a user centered design interaction (UCD) to integrate consumers as co-creators throughout the idea generation stage of the NPD process. The most important product attributes identified in this stage included: products targeted at brain and cognitive health, liquid based beverages, easy to use packaging with environmentally friendly elements, simplistic marketing with a clear focus on health not age and realistic health claims constructed with consumer friendly terminology. Finally, Stage three used an abbreviated means-end chain (MEC) analysis to complete the concept development stage of the NPD process. This stage identified commercial information that could be used by food firms for the development of positioning and communication strategies. Equally, the information generated could be of high strategic importance to governments, policy makers, health professionals and medical professionals. The values and goals listed in this stage included: better overall health, active lifestyle, optimum nutrition and wellbeing feelings. Overall, this research illustrated that knowledge creation techniques can assist firms in the development of market-oriented health promoting foods for the ageing population.

Identifying health inequalities in individuals with major mental illness (MMI) using routine data

Abstract and Summary of Thesis: Background: Individuals with Major Mental Illness (such as schizophrenia and bipolar disorder) experience increased rates of physical health comorbidity compared to the general population. They also experience inequalities in access to certain aspects of healthcare. This ultimately leads to premature mortality. Studies detailing patterns of physical health comorbidity are limited by their definitions of comorbidity, single disease approach to comorbidity and by the study of heterogeneous groups. To date the investigation of possible sources of healthcare inequalities experienced by individuals with Major Mental Illness (MMI) is relatively limited. Moreover studies detailing the extent of premature mortality experienced by individuals with MMI vary both in terms of the measure of premature mortality reported and age of the cohort investigated, limiting their generalisability to the wider population. Therefore local and national data can be used to describe patterns of physical health comorbidity, investigate possible reasons for health inequalities and describe mortality rates. These findings will extend existing work in this area. Aims and Objectives: To review the relevant literature regarding: patterns of physical health comorbidity, evidence for inequalities in physical healthcare and evidence for premature mortality for individuals with MMI. To examine the rates of physical health comorbidity in a large primary care database and to assess for evidence for inequalities in access to healthcare using both routine primary care prescribing data and incentivised national Quality and Outcome Framework (QOF) data. Finally to examine the rates of premature mortality in a local context with a particular focus on cause of death across the lifespan and effect of International Classification of Disease Version 10 (ICD 10) diagnosis and socioeconomic status on rates and cause of death. Methods: A narrative review of the literature surrounding patterns of physical health comorbidity, the evidence for inequalities in physical healthcare and premature mortality in MMI was undertaken. Rates of physical health comorbidity and multimorbidity in schizophrenia and bipolar disorder were examined using a large primary care dataset (Scottish Programme for Improving Clinical Effectiveness in Primary Care (SPICE)). Possible inequalities in access to healthcare were investigated by comparing patterns of prescribing in individuals with MMI and comorbid physical health conditions with prescribing rates in individuals with physical health conditions without MMI using SPICE data. Potential inequalities in access to health promotion advice (in the form of smoking cessation) and prescribing of Nicotine Replacement Therapy (NRT) were also investigated using SPICE data. Possible inequalities in access to incentivised primary healthcare were investigated using National Quality and Outcome Framework (QOF) data. Finally a pre-existing case register (Glasgow Psychosis Clinical Information System (PsyCIS)) was linked to Scottish Mortality data (available from the Scottish Government Website) to investigate rates and primary cause of death in individuals with MMI. Rate and primary cause of death were compared to the local population and impact of age, socioeconomic status and ICD 10 diagnosis (schizophrenia vs. bipolar disorder) were investigated. Results: Analysis of the SPICE data found that sixteen out of the thirty two common physical comorbidities assessed, occurred significantly more frequently in individuals with schizophrenia. In individuals with bipolar disorder fourteen occurred more frequently. The most prevalent chronic physical health conditions in individuals with schizophrenia and bipolar disorder were: viral hepatitis (Odds Ratios (OR) 3.99 95% Confidence Interval (CI) 2.82-5.64 and OR 5.90 95% CI 3.16-11.03 respectively), constipation (OR 3.24 95% CI 3.01-3.49 and OR 2.84 95% CI 2.47-3.26 respectively) and Parkinson’s disease (OR 3.07 95% CI 2.43-3.89 and OR 2.52 95% CI 1.60-3.97 respectively). Both groups had significantly increased rates of multimorbidity compared to controls: in the schizophrenia group OR for two comorbidities was 1.37 95% CI 1.29-1.45 and in the bipolar disorder group OR was 1.34 95% CI 1.20-1.49. In the studies investigating inequalities in access to healthcare there was evidence of: under-recording of cardiovascular-related conditions for example in individuals with schizophrenia: OR for Atrial Fibrillation (AF) was 0.62 95% CI 0.52 - 0.73, for hypertension 0.71 95% CI 0.67 - 0.76, for Coronary Heart Disease (CHD) 0.76 95% CI 0.69 - 0.83 and for peripheral vascular disease (PVD) 0.83 95% CI 0.72 - 0.97. Similarly in individuals with bipolar disorder OR for AF was 0.56 95% CI 0.41-0.78, for hypertension 0.69 95% CI 0.62 - 0.77 and for CHD 0.77 95% CI 0.66 - 0.91. There was also evidence of less intensive prescribing for individuals with schizophrenia and bipolar disorder who had comorbid hypertension and CHD compared to individuals with hypertension and CHD who did not have schizophrenia or bipolar disorder. Rate of prescribing of statins for individuals with schizophrenia and CHD occurred significantly less frequently than in individuals with CHD without MMI (OR 0.67 95% CI 0.56-0.80). Rates of prescribing of 2 or more anti-hypertensives were lower in individuals with CHD and schizophrenia and CHD and bipolar disorder compared to individuals with CHD without MMI (OR 0.66 95% CI 0.56-0.78 and OR 0.55 95% CI 0.46-0.67, respectively). Smoking was more common in individuals with MMI compared to individuals without MMI (OR 2.53 95% CI 2.44-2.63) and was particularly increased in men (OR 2.83 95% CI 2.68-2.98). Rates of ex-smoking and non-smoking were lower in individuals with MMI (OR 0.79 95% CI 0.75-0.83 and OR 0.50 95% CI 0.48-0.52 respectively). However recorded rates of smoking cessation advice in smokers with MMI were significantly lower than the recorded rates of smoking cessation advice in smokers with diabetes (88.7% vs. 98.0%, p<0.001), smokers with CHD (88.9% vs. 98.7%, p<0.001) and smokers with hypertension (88.3% vs. 98.5%, p<0.001) without MMI. The odds ratio of NRT prescription was also significantly lower in smokers with MMI without diabetes compared to smokers with diabetes without MMI (OR 0.75 95% CI 0.69-0.81). Similar findings were found for smokers with MMI without CHD compared to smokers with CHD without MMI (OR 0.34 95% CI 0.31-0.38) and smokers with MMI without hypertension compared to smokers with hypertension without MMI (OR 0.71 95% CI 0.66-0.76). At a national level, payment and population achievement rates for the recording of body mass index (BMI) in MMI was significantly lower than the payment and population achievement rates for BMI recording in diabetes throughout the whole of the UK combined: payment rate 92.7% (Inter Quartile Range (IQR) 89.3-95.8 vs. 95.5% IQR 93.3-97.2, p<0.001 and population achievement rate 84.0% IQR 76.3-90.0 vs. 92.5% IQR 89.7-94.9, p<0.001 and for each country individually: for example in Scotland payment rate was 94.0% IQR 91.4-97.2 vs. 96.3% IQR 94.3-97.8, p<0.001. Exception rate was significantly higher for the recording of BMI in MMI than the exception rate for BMI recording in diabetes for the UK combined: 7.4% IQR 3.3-15.9 vs. 2.3% IQR 0.9-4.7, p<0.001 and for each country individually. For example in Scotland exception rate in MMI was 11.8% IQR 5.4-19.3 compared to 3.5% IQR 1.9-6.1 in diabetes. Similar findings were found for Blood Pressure (BP) recording: across the whole of the UK payment and population achievement rates for BP recording in MMI were also significantly reduced compared to payment and population achievement rates for the recording of BP in chronic kidney disease (CKD): payment rate: 94.1% IQR 90.9-97.1 vs.97.8% IQR 96.3-98.9 and p<0.001 and population achievement rate 87.0% IQR 81.3-91.7 vs. 97.1% IQR 95.5-98.4, p<0.001. Exception rates again were significantly higher for the recording of BP in MMI compared to CKD (6.4% IQR 3.0-13.1 vs. 0.3% IQR 0.0-1.0, p<0.001). There was also evidence of differences in rates of recording of BMI and BP in MMI across the UK. BMI and BP recording in MMI were significantly lower in Scotland compared to England (BMI:-1.5% 99% CI -2.7 to -0.3%, p<0.001 and BP: -1.8% 99% CI -2.7 to -0.9%, p<0.001). While rates of BMI and BP recording in diabetes and CKD were similar in Scotland compared to England (BMI: -0.5 99% CI -1.0 to 0.05, p=0.004 and BP: 0.02 99% CI -0.2 to 0.3, p=0.797). Data from the PsyCIS cohort showed an increase in Standardised Mortality Ratios (SMR) across the lifespan for individuals with MMI compared to the local Glasgow and wider Scottish populations (Glasgow SMR 1.8 95% CI 1.6-2.0 and Scotland SMR 2.7 95% CI 2.4-3.1). Increasing socioeconomic deprivation was associated with an increased overall rate of death in MMI (350.3 deaths/10,000 population/5 years in the least deprived quintile compared to 794.6 deaths/10,000 population/5 years in the most deprived quintile). No significant difference in rate of death for individuals with schizophrenia compared with bipolar disorder was reported (6.3% vs. 4.9%, p=0.086), but primary cause of death varied: with higher rates of suicide in individuals with bipolar disorder (22.4% vs. 11.7%, p=0.04). Discussion: Local and national datasets can be used for epidemiological study to inform local practice and complement existing national and international studies. While the strengths of this thesis include the large data sets used and therefore their likely representativeness to the wider population, some limitations largely associated with using secondary data sources are acknowledged. While this thesis has confirmed evidence of increased physical health comorbidity and multimorbidity in individuals with MMI, it is likely that these findings represent a significant under reporting and likely under recognition of physical health comorbidity in this population. This is likely due to a combination of patient, health professional and healthcare system factors and requires further investigation. Moreover, evidence of inequality in access to healthcare in terms of: physical health promotion (namely smoking cessation advice), recording of physical health indices (BMI and BP), prescribing of medications for the treatment of physical illness and prescribing of NRT has been found at a national level. While significant premature mortality in individuals with MMI within a Scottish setting has been confirmed, more work is required to further detail and investigate the impact of socioeconomic deprivation on cause and rate of death in this population. It is clear that further education and training is required for all healthcare staff to improve the recognition, diagnosis and treatment of physical health problems in this population with the aim of addressing the significant premature mortality that is seen. Conclusions: Future work lies in the challenge of designing strategies to reduce health inequalities and narrow the gap in premature mortality reported in individuals with MMI. Models of care that allow a much more integrated approach to diagnosing, monitoring and treating both the physical and mental health of individuals with MMI, particularly in areas of social and economic deprivation may be helpful. Strategies to engage this “hard to reach” population also need to be developed. While greater integration of psychiatric services with primary care and with specialist medical services is clearly vital the evidence on how best to achieve this is limited. While the National Health Service (NHS) is currently undergoing major reform, attention needs to be paid to designing better ways to improve the current disconnect between primary and secondary care. This should then help to improve physical, psychological and social outcomes for individuals with MMI.

Application of the UK Foresight Obesity Model in Ireland: The Health and Economic Consequences of Projected Obesity Trends in Ireland

Given the scale of the current obesity epidemic and associated health consequences there has been increasing concern about the economic burden placed on society in terms of direct healthcare costs and indirect societal costs. In the Republic of Ireland these costs were estimated at €1.13 billion for 2009. The total direct healthcare costs for six major obesity related conditions (coronary heart disease & stroke, cancer, hypertension, type 2 diabetes and knee osteoarthritis) in the same year were estimated at €2.55 billion. The aim of this research is to project disease burden and direct healthcare costs for these conditions in Ireland to 2030 using the established model developed by the Health Forum (UK) for the Foresight: Tackling Obesities project.

Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers

The emerging concept of psychobiotics—live microorganisms with a potential mental health benefit—represents a novel approach for the management of stress-related conditions. The majority of studies have focused on animal models. Recent preclinical studies have identified the B. longum 1714 strain as a putative psychobiotic with an impact on stress-related behaviors, physiology and cognitive performance. Whether such preclinical effects could be translated to healthy human volunteers remains unknown. We tested whether psychobiotic consumption could affect the stress response, cognition and brain activity patterns. In a within-participants design, healthy volunteers (N=22) completed cognitive assessments, resting electroencephalography and were exposed to a socially evaluated cold pressor test at baseline, post-placebo and post-psychobiotic. Increases in cortisol output and subjective anxiety in response to the socially evaluated cold pressor test were attenuated. Furthermore, daily reported stress was reduced by psychobiotic consumption. We also observed subtle improvements in hippocampus-dependent visuospatial memory performance, as well as enhanced frontal midline electroencephalographic mobility following psychobiotic consumption. These subtle but clear benefits are in line with the predicted impact from preclinical screening platforms. Our results indicate that consumption of B. longum 1714 is associated with reduced stress and improved memory. Further studies are warranted to evaluate the benefits of this putative psychobiotic in relevant stress-related conditions and to unravel the mechanisms underlying such effects.