Infraslow (<0.1 Hz) oscillations in thalamic relay nuclei basic mechanisms and significance to health and disease states

In the absence of external stimuli, the mammalian brain continues to display a rich variety of spontaneous activity. Such activity is often highly stereotypical, is invariably rhythmic, and can occur with periodicities ranging from a few milliseconds to several minutes. Recently, there has been a particular resurgence of interest in fluctuations in brain activity occurring at <0.1 Hz, commonly referred to as very slow or infraslow oscillations (ISOs). Whilst this is primarily due to the emergence of functional magnetic resonance imaging (fMRI) as a technique which has revolutionized the study of human brain dynamics, it is also a consequence of the application of full band electroencephalography (fbEEG). Despite these technical advances, the precise mechanisms which lead to ISOs in the brain remain unclear. In a host of animal studies, one brain region that consistently shows oscillations at <0.1 Hz is the thalamus. Importantly, similar oscillations can also be observed in slices of isolated thalamic relay nuclei maintained in vitro. Here, we discuss the nature and mechanisms of these oscillations, paying particular attention to a potential role for astrocytes in their genesis. We also highlight the relationship between this activity and ongoing local network oscillations in the alpha (a; ~8-13 Hz) band, drawing clear parallels with observations made in vivo. Last, we consider the relevance of these thalamic ISOs to the pathological activity that occurs in certain types of epilepsy.

Impact of senescence and disease on the structural and functional performance of the visual pathway

The diagnosis and monitoring of ocular disease presents considerable clinical difficulties for two main reasons i) the substantial physiological variation of anatomical structure of the visual pathway and ii) constraints due to technical limitations of diagnostic hardware. These are further confounded by difficulties in detecting early loss or change in visual function due to the masking of disease effects, for example, due to a high degree of redundancy in terms of nerve fibre number along the visual pathway. This thesis addresses these issues across three areas of study: 1. Factors influencing retinal thickness measures and their clinical interpretation As the retina is the principal anatomical site for damage associated with visual loss, objective measures of retinal thickness and retinal nerve fibre layer thickness are key to the detection of pathology. In this thesis the ability of optical coherence tomography (OCT) to provide repeatable and reproducible measures of retinal structure at the macula and optic nerve head is investigated. In addition, the normal physiological variations in retinal thickness and retinal nerve fibre layer thickness are explored. Principal findings were: • Macular retinal thickness and optic nerve head measurements are repeatable and reproducible for normal subjects and diseased eyes • Macular and retinal nerve fibre layer thickness around the optic nerve correlate negatively with axial length, suggesting that larger eyes have thinner retinae, potentially making them more susceptible to damage or disease • Foveola retinal thickness increases with age while retinal nerve fibre layer thickness around the optic nerve head decreases with age. Such findings should be considered during examination of the eye with suspect pathology or in long-term disease monitoring 2. Impact of glucose control on retinal anatomy and function in diabetes Diabetes is a major health concern in the UK and worldwide and diabetic retinopathy is a major cause of blindness in the working population. Objective, quantitative measurements of retinal thickness. particularly at the macula provide essential information regarding disease progression and the efficacy of treatment. Functional vision loss in diabetic patients is commonly observed in clinical and experimental studies and is thought to be affected by blood glucose levels. In the first study of its kind, the short term impact of fluctuations in blood glucose levels on retinal structure and function over a 12 hour period in patients with diabetes are investigated. Principal findings were: • Acute fluctuations in blood glucose levels are greater in diabetic patients than normal subjects • The fluctuations in blood glucose levels impact contrast sensitivity scores. SWAP visual fields, intraocular pressure and diastolic pressure. This effect is similar for type 1 and type 2 diabetic patients despite the differences in their physiological status. • Long-term metabolic control in the diabetic patient is a useful predictor in the fluctuation of contrast sensitivity scores. • Large fluctuations in blood glucose levels and/or visual function and structure may be indicative of an increased risk of development or progression of retinopathy 3. Structural and functional damage of the visual pathway in glaucomatous optic neuropathy The glaucomatous eye undergoes a number of well documented pathological changes including retinal nerve fibre loss and optic nerve head damage which is correlated with loss of functional vision. In experimental glaucoma there is evidence that glaucomatous damage extends from retinal ganglion cells in the eye, along the visual pathway, to vision centres in the brain. This thesis explores the effects of glaucoma on retinal nerve fibre layer thickness, ocular anterior anatomy and cortical structure, and its correlates with visual function in humans. Principal findings were: • In the retina, glaucomatous retinal nerve fibre layer loss is less marked with increasing distance from the optic nerve head, suggesting that RNFL examination at a greater distance than traditionally employed may provide invaluable early indicators of glaucomatous damage • Neuroretinal rim area and retrobulbar optic nerve diameter are strong indicators of visual field loss • Grey matter density decreases at a rate of 3.85% per decade. There was no clear evidence of a disease effect • Cortical activation as measured by fMRI was a strong indicator of functional damage in patients with significant neuroretinal rim loss despite relatively modest visual field defects These investigations have shown that the effects of senescence are evident in both the anterior and posterior visual pathway. A variety of anatomical and functional diagnostic protocols for the investigation of damage to the visual pathway in ocular disease are required to maximise understanding of the disease processes and thereby optimising patient care.

A systems approach to cardiovascular health and disease with a focus on aortic wave dynamics

Cardiovascular diseases (CVDs) have reached an epidemic proportion in the US and worldwide with serious consequences in terms of human suffering and economic impact. More than one third of American adults are suffering from CVDs. The total direct and indirect costs of CVDs are more than $500 billion per year. Therefore, there is an urgent need to develop noninvasive diagnostics methods, to design minimally invasive assist devices, and to develop economical and easy-to-use monitoring systems for cardiovascular diseases. In order to achieve these goals, it is necessary to gain a better understanding of the subsystems that constitute the cardiovascular system. The aorta is one of these subsystems whose role in cardiovascular functioning has been underestimated. Traditionally, the aorta and its branches have been viewed as resistive conduits connected to an active pump (left ventricle of the heart). However, this perception fails to explain many observed physiological results. My goal in this thesis is to demonstrate the subtle but important role of the aorta as a system, with focus on the wave dynamics in the aorta.

The operation of a healthy heart is based on an optimized balance between its pumping characteristics and the hemodynamics of the aorta and vascular branches. The delicate balance between the aorta and heart can be impaired due to aging, smoking, or disease. The heart generates pulsatile flow that produces pressure and flow waves as it enters into the compliant aorta. These aortic waves propagate and reflect from reflection sites (bifurcations and tapering). They can act constructively and assist the blood circulation. However, they may act destructively, promoting diseases or initiating sudden cardiac death. These waves also carry information about the diseases of the heart, vascular disease, and coupling of heart and aorta. In order to elucidate the role of the aorta as a dynamic system, the interplay between the dominant wave dynamic parameters is investigated in this study. These parameters are heart rate, aortic compliance (wave speed), and locations of reflection sites. Both computational and experimental approaches have been used in this research. In some cases, the results are further explained using theoretical models.

The main findings of this study are as follows: (i) developing a physiologically realistic outflow boundary condition for blood flow modeling in a compliant vasculature; (ii) demonstrating that pulse pressure as a single index cannot predict the true level of pulsatile workload on the left ventricle; (iii) proving that there is an optimum heart rate in which the pulsatile workload of the heart is minimized and that the optimum heart rate shifts to a higher value as aortic rigidity increases; (iv) introducing a simple bio-inspired device for correction and optimization of aortic wave reflection that reduces the workload on the heart; (v) deriving a non-dimensional number that can predict the optimum wave dynamic state in a mammalian cardiovascular system; (vi) demonstrating that waves can create a pumping effect in the aorta; (vii) introducing a system parameter and a new medical index, Intrinsic Frequency, that can be used for noninvasive diagnosis of heart and vascular diseases; and (viii) proposing a new medical hypothesis for sudden cardiac death in young athletes.

Retinal Macroglial Responses in Health and Disease

Due to their permanent and close proximity to neurons, glial cells perform essential tasks for the normal physiology of the retina. Astrocytes andM¨uller cells (retinal macroglia) provide physical support to neurons and supplement them with several metabolites and growth factors.Macroglia are involved in maintaining the homeostasis of extracellular ions and neurotransmitters, are essential for information processing in neural circuits, participate in retinal glucose metabolism and in removing metabolic waste products, regulate local blood flow, induce the blood-retinal barrier (BRB), play fundamental roles in local immune response, and protect neurons from oxidative damage. In response to polyetiological insults, glia cells react with a process called reactive gliosis, seeking to maintain retinal homeostasis. When malfunctioning, macroglial cells can become primary pathogenic elements. A reactive gliosis has been described in different retinal pathologies, including age-related macular degeneration (AMD), diabetes, glaucoma, retinal detachment, or retinitis pigmentosa. A better understanding of the dual, neuroprotective, or cytotoxic effect of macroglial involvement in retinal pathologies would help in treating the physiopathology of these diseases.The extensive participation of the macroglia in retinal diseases points to these cells as innovative targets for new drug therapies.

Assessing the concordance of health and child protection data for 'maltreated' and 'unintentionally injured' children

Objectives: To quantify the concordance of hospital child maltreatment data with child protection service (CPS) records and identify factors associated with linkage. Methods: Multivariable logistic regression analysis was conducted following retrospective medical record review and database linkage of 884 child records from 20 hospitals and the CPS in Queensland, Australia. Results: Nearly all children with hospital assigned maltreatment codes (93.1%) had a CPS record. Of these, 85.1% had a recent notification. 29% of the linked maltreatment group (n=113) were not known to CPS prior to the hospital presentation. Almost 1/3 of children with unintentional injury hospital codes were known to CPS. Just over 24% of the linked unintentional injury group (n=34) were not known to CPS prior to the hospital presentation but became known during or after discharge from hospital. These estimates are higher than the 2006/07 annual rate of 2.39% of children being notified to CPS. Rural children were more likely to link to CPS, and children were over 3 times more likely to link if the index injury documentation included additional diagnoses or factors affecting their health. Conclusions: The system for referring maltreatment cases to CPS is generally efficient, although up to 1 in 15 children had codes for maltreatment but could not be linked to CPS data. The high proportion of children with unintentional injury codes who linked to CPS suggests clinicians and hospital-based child protection staff should be supported by further education and training to ensure children at risk are being detected by the child protection system.

Meaning or measurement? Researching the social contexts of health and settlement among newly-arrived refugee youth in Melbourne, Australia

What are the most appropriate methodological approaches for researching the psychosocial determinants of health and wellbeing among young people from refugee backgrounds over the resettlement period? What kinds of research models can involve young people in meaningful reflections on their lives and futures while simultaneously yielding valid data to inform services and policy? This paper reports on the methods developed for a longitudinal study of health and wellbeing among young people from refugee backgrounds in Melbourne, Australia. The study involves 100 newly-arrived young people 12 to 18 years of age, and employs a combination of qualitative and quantitative methods implemented as a series of activities carried out by participants in personalized settlement journals. This paper highlights the need to think outside the box of traditional qualitative and/or quantitative approaches for social research into refugee youth health and illustrates how integrated approaches can produce information that is meaningful to policy makers, service providers and to the young people themselves.

The value of health and wellbeing : an empirical model of value creation in social marketing

Purpose The purpose of this paper is to investigate the role of multiple actors in the value creation process for a preventative health service, and observe the subsequent impact on key service outcomes of satisfaction and customer behaviour intentions to use a preventative health service again in the future. Design/methodology/approach An online self-completion survey of Australian women (n=797) was conducted to test the proposed framework in the context of a free, government-provided breastscreening service. Data were analysed using Structural Equation Modelling (SEM). Findings The findings indicate that functional and emotional value are created from organisational and customer resources. These findings indicate that health service providers and customers are jointly responsible for the successful creation of value, leading to desirable outcomes for all stakeholders. Practical implications The results highlight to health professionals the aspects of service that can be managed in order to create value with target audiences. The findings also indicate the importance of the resources provided by users in the creation of value, signifying the importance of customer education and management. Originality/value This study provides a significant contribution to social marketing through the provision of an empirically validated model of value creation in a preventative health service. The model demonstrates how the creation and provision of value can lead to the achievement of desirable social behaviours - a key aim of social marketing.

Decriminalization of Health and Safety at Work in Australia

ABOUT THE BOOK As the title Safety or Profit? suggests, health and safety at work needs to be understood in the context of the wider political economy. This book brings together contributions informed by this view from internationally recognized scholars. It reviews the governance of health and safety at work, with special reference to Australia, Canada, Sweden, and the United Kingdom. Three main aspects are discussed. The restructuring of the labor market: this is considered with respect to precarious work and to gender issues and their implications for the health and safety of workers. The neoliberal agenda: this is examined with respect to the diminished power of organized labor, decriminalization, and new governance theory, including an examination of how well the health-and-safety-at-work regimes put in place in many industrial societies about forty years ago have fared and how distinctive the recent emphasis on self-regulation in several countries really is. The role of evidence: there is a dearth of evidence-based policy. The book examines how policy on health and safety at work is formulated at both company and state levels. Cases considered include the scant regard paid to evidence by an official inquiry into future strategy in Canada; the lack of evidence-based policy and the reluctance to observe the precautionary principle with respect to work-related cancer in the United Kingdom; and the failure to learn from past mistakes in the Deepwater Horizon disaster in the Gulf of Mexico. Intended Audience: Researchers; policymakers, trade union representatives, and officials interested in OHS; postgraduate students of OHS; OHS professionals; regulatory and socio-legal scholars.

Submission to: Strategic Review of Health and Medical Research (Australia) otherwise known as the McKeon Review

Public submission # 247 to the McKeon Review. The submission addresses the terms of reference on: How can we optimise translation of health and medical research into better health and wellbeing? (Terms of Reference 4, 8, 9, 10 and 11)

Social processes of health and physical education teachers’ identity formation: Reproducing and changing culture

This paper examines Initial Teacher Education students’ experiences of participation in health and physical education (HPE) subject department offices and the impact on their understandings and identity formation. Pierre Bourdieu’s concepts of habitus, field, and practice along with Wenger’s communities of practice form the theoretical frame used in the paper. Data were collected using surveys and interviews with student‐teachers following their teaching practicum and analysed using coding and constant comparison. Emergent themes revealed students’ participation in masculine‐dominated sports, gendered body constructions, and repertoires of masculine domination. Findings are discussed in relation to their impact on student‐teachers’ learning, identity formation, and marginalizing practices in the department offices. Implications for teacher education and HPE are explored.

A submission to the Tasmanian Department of Health and Human Services consultation “Healthy Tasmania Five Year Strategic Plan”

This submission will address a number of questions raised in section 5.2, “Potential Future Initiatives to target smoking”, of the Healthy Tasmania Five Year Strategic Plan – Community Consultation Draft. Each question has been answered within this submission. This submission will also address the possibility of legal challenges to these proposed changes, a pivotal consideration when implementing any tobacco control laws. This is due to the aggressive nature of the tobacco industry, as illustrated by their attempts to challenge plain packaging laws in the country and through international treaties. The evidence provided in my submission illustrates that prevention of initiation of smoking during adolescence has various benefits in terms of reduction of negative smoking behaviors in later life. I argue that increasing the minimum legal age of purchasing for tobacco to 21 will benefit both the levels of underage smoking as well as the age of onset of initiation of smoking, due to the greater difficulties that those who are underage would experience in accessing tobacco products. I will also address the question of whether the minimum smoking age should be increased to 25.

Y chromosome evidence of earliest modern human settlement in East Asia and multiple origins of Tibetan and Japanese populations

Background: The phylogeography of the Y chromosome in Asia previously suggested that modern humans of African origin initially settled in mainland southern East Asia, and about 25,000 30,000 years ago, migrated northward, spreading throughout East Asia. H

Tracing the Origins of Hakka and Chaoshanese by Mitochondrial DNA Analysis

Hakka and Chaoshanese are two unique Han populations residing in southern China but with northern Han (NH) cultural traditions and linguistic influences. Although most of historical records indicate that both populations migrated from northern China in the last two thousand years, no consensus on their origins has been reached so far. To shed more light on the origins of Hakka and Chaoshanese, mitochondrial DNAs (mtDNAs) of 170 Hakka from Meizhou and 102 Chaoshanese from Chaoshan area, Guangdong Province, were analyzed. Our results show that some southern Chinese predominant haplogroups, e.g. B, F, and M7, have relatively high frequencies in both populations. Although median network analyses show that Hakka/Chaoshanese share some haplotypes with NH, interpopulation comparison reveals that both populations show closer affinity with southern Han (SH) populations than with NH. In consideration of previous results from nuclear gene (including Y chromosome) research, it is likely that matrilineal landscapes of both Hakka and Chaoshanese have largely been shaped by the local people during their migration southward and/or later colonization in southern China, and factors such as cultural assimilation, patrilocality, and even sex-bias in the immigrants might have played important roles during the process. Am J Phys Anthropol 141:124-130, 2010. (C) 2009 Wiley-Liss, Inc.

Effects of atrazine herbicide on physiological, biochemical and histological biomarkers of developmental stages of larvae and fry in Caspian kutum, Rutilus frisii kutum

To investigation of the toxic effects of atrazine on newly hatched larvae and releasing age fry of the Caspian Kutum, Rutilus frisii kutum, the 96h LC50 was determined as 18.53 ppm and 24.95 ppm, respectively. Newly hatched larvae were exposed to three sublethal concentrations of atrazine (1/2LC50, 1/4LC50 and 1/8LC50) for 7 days. Different histopathological alterations were observed in fins and integument, gills, Kidney, digestive system, liver and the brain of the exposed larvae. Fry’s were exposed to one sublethal concentration of atrazine (1/2LC50) for four days, and like the larvae’s, many histopathological alterations were observed in fins and integument, gills, Kidney, digestive system, liver and the brain of the exposed fry’s, too. Also, measurements of the body ions: Na+, K+, Ca2+, Mg2+ and Cl- in atrazine exposed larvae and fry’s compare to control groups showed that atrazine is changed the body ions composition. No significant differences were found in length growth rate, weight growth rate and the condition factor of the atrazine exposed larvae and fry. Immunohistochemical localization of the Na+, K+-ATPase in integumentary and gill ionocytes, showed no differences in dispersion pattern of the ionocytes in atrazine exposed larvae and fry, compare to control group. Measuring the dimensions of the ionocytes and counting the ionocytes showed that atrazine is affecting on ionocytes by mild increasing in size and mild decreasing in number. Ultrastructural studies, using SEM and TEM, showed that atrazine have significant effects on cellular and subcellular properties. It caused necrosis in surface of the pavement cells in branchial epithelium, necrosis in endoplasmic reticulum of the ionocytes and changed the shape of the mitochondria in these cells. Results showed that sublethal concentrations of atrazine were very toxic to larvae and fry of the Rutilus frisii kutum, and at these levels can made some serious histopathological alterations in their tissues. Related to the severe histopathological alterations in osmoregulatory organs, like gill, kidney and digestive system, and the alterations in the body ion composition, it could be concluded that atrazine could interfere with the osmoregulation process of the Rutilus frisii kutum at the early stages of the life history.