Emergent Run-and-Tumble Behavior in a Simple Model of Chlamydomonas with Intrinsic Noise

Recent experiments on the green alga Chlamydomonas that swims using synchronized beating of a pair of flagella have revealed that it exhibits a run-and-tumble behavior similar to that of bacteria such as E. Coli. Using a simple purely hydrodynamic model that incorporates a stroke cycle and an intrinsic Gaussian white noise, we show that a stochastic run-and-tumble behavior could emerge, due to the nonlinearity of the combined synchronization-rotation-translation dynamics. This suggests the intriguing possibility that the alga might exploit nonlinear mechanics---as opposed to sophisticated biochemical circuitry as used by bacteria---to control its behavior.Comment: 5 pages, 2 composite figures (made of 12 separate EPS files

Brain energy metabolism: development and application of novel live methodologies

This thesis investigates methods of studying brain energy metabolism with a specific focus on the substrates oxygen and glucose. It details the in vitro development and in vivo characterisation of microelectrochemical sensors for the detection of brain tissue oxygen, and the in vivo characterisation of oxygen and glucose electrodes in the hippocampus utilising the technique of long-term in vivo electrochemistry (LIVE). Chapter 1 introduces the brain, energy metabolism and neurochemical analysis focusing on oxygen and glucose monitoring in the brain. Chapter 2 discusses the theory relevant to the studies performed in this work, whilst Chapter 3 is a detailed description of sensor construction and techniques used for the in vivo and in vitro characterisation of the sensors utilised in this thesis. The results are divided into five sections. The first of these, Chapter 4, details the in vitro characterisation of carbon paste electrodes (CPEs) and a Pt-based electrode modified with a membrane, methyl methacrylate (Pt-MMA) and makes comparisons between these two types of electrodes for use in vivo. Following on from the in vitro characterisation chapter, Pt-MMA electrodes were fully characterised in vivo and comparisons were made with previously published CPE data detailed in Chapter 5. The development and standardisation of a metal-free electrode for use in conjunction with fMRI studies for the detection of brain tissue oxygen is presented in Chapter 6. The complete in vivo characterisation of the fully characterised fMRI compatible O2 electrode developed in the previous chapter is detailed in Chapter 7. Chapter 8 demonstrates and characterises the simultaneous recording of oxygen and glucose using CPEs and a Pt-based glucose biosensor (Pt/PPD/GOx) in the hippocampus of freely-moving animals, and utilises these sensors to monitor brain energy metabolism in conjunction with a behavioural task. Finally, overall conclusions in relation to the work presented in this thesis are discussed in Chapter 9

Axonal Damage in Repetitive Concussive Traumatic Brain Injury: Characterization and Contributing Factors

There are an estimated 1.6-3.8 million concussions in the United States annually. Individuals who experience a single concussion are at low risk for long-term consequences. However, there is mounting evidence that experiencing multiple concussions can lead to persistent symptoms, cognitive impairment, and increased risk for neurodegenerative disease. The underlying pathophysiology of concussions is not well understood. To study the mechanisms that lead to these long-term consequences, a mouse model of repetitive concussive traumatic brain injury (rcTBI) was developed. Initial studies sought to characterize the histological and functional changes that occur after two closed-skull impacts in mouse. Similar to human traumatic brain injury, rcTBI produced axonal injury evident by amyloid precursor protein, neurofilament, and silver staining abnormalities in the absence of gross structural changes or cell loss. Microglia and astrocytes both became activated and were prominent in injured white matter by 7 days. Behaviorally, injury resulted in acute Morris Water Maze deficits that were not completely recovered by 7 weeks post-injury. Functionally, the velocity of axonal compound action potentials was slowed in both myelinated and unmyelinated axons. These alterations were accompanied by changes in white matter that were detectable by in vivo diffusion tensor magnetic resonance imaging (MRI). At 7 days post-injury, mean diffusivity and the diffusion of water parallel to axons in the corpus callosum and external capsule was reduced. However, these parameters did not correlate with increases in silver staining or microglial activation and indicate a need to develop better histological methods for assessing axonal injury after mild trauma. Future experiments will be conducted to quantify axonal injury by array tomography, a method outlined here briefly. The second goal of this work was to determine what factors might contribute to axonal injury in concussion. Specifically, the hypothesis that microglia may increase axonal injury acutely following rcTBI was tested. The CD11b-TK mouse line, a valganciclovir-inducible model of microglial depletion, was used to reduce microglia within the corpus callosum and external capsule by 35%. Quantification of silver staining determined that this had no effect on axonal injury at 7 or 21 days after rcTBI. Further reduction by 56% also did not alter axonal injury detectable by silver staining, APP or neurofilament labeling, or by electron microscopy. We additionally tested several pharmacological compounds to determine whether they could reduce the microglial response. None of the compounds tested--including minocycline, (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG), brilliant blue g (BBG), and microRNA-124 (miRNA-124)--were able to reduce the number of iba-1-positive microglia present in the corpus callosum after injury, which were quantified by stereology. Silver staining was unaffected. Use of the targeted toxin, Mac-1-Saporin, was found to dramatically reduce microglial number but also result in non-specific neuronal loss days 7 after rcTBI. Collectively, these experiments indicate that microglia appear to play a neutral role in regards to axonal injury acutely after repeat concussion. To test the role of microglia in the long-term, additional tools to manipulate the microglial response will need to be developed. Last, the contribution of Apolipoprotein E to axonal injury after moderate-severe traumatic brain injury was assessed in a transgenic mouse model carrying three human familial AD mutations (PS1M146V, tauP301L, and APPSWE). The Apolipoprotein E4 (APOE4) genotype is a risk factor for poor outcome following traumatic brain injury, especially in young patients. By analogy to APOE4\u27s effects on the risk of Alzheimer\u27s disease, one hypothesis is that APOE genotype influences amyloid-beta (Aβ) and tau deposition following injury. Surprisingly, the amount of amyloid-beta and tau as measured by stereology was similar between mice possessing the APOE2, 3, or 4 allele. However, APOE4 mice had significantly greater numbers of APP-positive axons. These results suggest that the APOE4 genotype may have a primary effect on the severity of axonal injury in the setting of acute traumatic brain injury. Altogether, this work presents the characterization of a mouse model of repetitive concussive traumatic brain injury that can be utilized to determine what factors contribute to pathophysiological changes and to aid in the design of future therapeutics

Brain energy metabolism: development and application of novel live methodologies

This thesis investigates methods of studying brain energy metabolism with a specific focus on the substrates oxygen and glucose. It details the in vitro development and in vivo characterisation of microelectrochemical sensors for the detection of brain tissue oxygen, and the in vivo characterisation of oxygen and glucose electrodes in the hippocampus utilising the technique of long-term in vivo electrochemistry (LIVE). Chapter 1 introduces the brain, energy metabolism and neurochemical analysis focusing on oxygen and glucose monitoring in the brain. Chapter 2 discusses the theory relevant to the studies performed in this work, whilst Chapter 3 is a detailed description of sensor construction and techniques used for the in vivo and in vitro characterisation of the sensors utilised in this thesis. The results are divided into five sections. The first of these, Chapter 4, details the in vitro characterisation of carbon paste electrodes (CPEs) and a Pt-based electrode modified with a membrane, methyl methacrylate (Pt-MMA) and makes comparisons between these two types of electrodes for use in vivo. Following on from the in vitro characterisation chapter, Pt-MMA electrodes were fully characterised in vivo and comparisons were made with previously published CPE data detailed in Chapter 5. The development and standardisation of a metal-free electrode for use in conjunction with fMRI studies for the detection of brain tissue oxygen is presented in Chapter 6. The complete in vivo characterisation of the fully characterised fMRI compatible O2 electrode developed in the previous chapter is detailed in Chapter 7. Chapter 8 demonstrates and characterises the simultaneous recording of oxygen and glucose using CPEs and a Pt-based glucose biosensor (Pt/PPD/GOx) in the hippocampus of freely-moving animals, and utilises these sensors to monitor brain energy metabolism in conjunction with a behavioural task. Finally, overall conclusions in relation to the work presented in this thesis are discussed in Chapter 9

Alcohol and drug related offences: Determining predictive factors for reducing re-offending

The association between dependent drug use and criminal behaviour is well known. This coupled with evidence about the efficacy of treatment in addressing drug use has led many jurisdictions to incorporate treatment interventions into their criminal justice systems. The aim of these interventions that use the law as a therapeutic agent (known as ‘therapeutic jurisprudence\u27) is to reduce by mandating drug dependent offenders into treatment, future offending. However, within the treatment effectiveness literature there is also evidence of individuals resolving their drug use problems without engagement in treatment. The term ‘natural recovery’ has been used to describe this phenomenon. Research into the processes involved in natural recovery has led to the development of the concept of Recovery Capital. Recovery Capital refers to an individual\u27s pre-existing access to social, community, physical and interpersonal, resources that facilitate and sustain change. In this research the notion of recovery capital was operationalized into a ! 00 item questionnaire that tapped the domains known to constitute recovery capital, namely Physical, Human, Social and Cultural Capitals. The key innovation of this research was to test out the predictive value of Recovery Capital for re-offending in a cohort of 150 drug related offenders. The impact on outcome of Recovery Capital was compared to other known criminogenic, demographic and drug use factors on the recidivism rates over an 18 month follow up period. The research was driven by four hypotheses. The first of these was that there would be a positive association between levels of Recovery Capital and outcome. This hypothesis was upheld. Not only were the levels of recovery significantly associated with outcome. but it was found that for every one point increment in global recovery capital score the risk of re-offending dropped by 5%. The second hypothesis was that the component parts of recovery capital would not be individually influential in determining outcome. This hypothesis was rejected. Each of the constituent components of recovery capital, namely Social, Physical, Cultural and Human, was significantly associated with outcome. The two strongest predictors were found to be Human and Cultural capitals with a one score increment respectively resulting in a 5.4% and a 9.2% decrease in risk of re-offending. The third hypothesis was that the disposition (sentence) handed down by the court would not influence outcome. This hypothesis was upheld. The court dispositions of court mandated treatment, probation, incarceration, Community service order or a fine had no impact on re-offending. The final hypothesis was that recovery capital, when compared to other potential predictive variables would be the strongest predictor. This hypothesis was upheld in that recovery capital. W\hen analysed using multivariate regression, was found, along with age to be the best predictor of outcome. Persons with high, as opposed to low, levels of recovery capital were 80%, less likely to re-offend. The implications of these findings arc that the social embeddedness of an individual, rather than any clinical or judicial intervention, is critical in determining the risk of re-offending. As such recovery capital merits greater investigation and acknowledgement, as a criminogenic variable

Bad for the health of the body, worse for the health of the mind:Female responses to imprisonment of in England 1853-1869

Upon committal to one of the newly established female convict prisons in the mid-nineteenth century, women entered a system intended to regulate them in body and in mind for the ends of reform. This article interrogates how women’s health needs were identified and contested by the prison officials and doctors tasked with their custody and care. It highlights the importance of broader temporal gender beliefs in dictating their treatment in this carceral space and explores how the women themselves exercised agency over the terms of their imprisonment. In addition, it reveals the previously underexplored transference of women between the institutions that made up the female convict estate that was prompted by concerns about the impact of a rigorous prison system on their physical and mental health

Why Theatre? A Study of Robert Wilson

Wilson’s unusual background influenced both the avantgarde nature of Wilson’s theatre and the humanity present in his work. Wilson accepts the people in his life as they are without trying to change them or ignore those differences. Wilson gives these people and their perspective, which society so often rejects, a voice. He sees art where others see a problem. Wilson’s theatre looks like nothing else, but his respect and acceptance of others, even those who are different and almost invisible to most of society, are just as innovative and refreshing to see in theatre

Editorial: Three challenges in realising the MIPAA

The year 2017 marked fifteen years since the adoption of the Madrid International Plan of Action on Ageing (MIPAA), deemed to be a major breakthrough in the way the world seeks to support older people. The MIPAA focuses on three priority areas: older persons and development, advancing health and wellbeing into old age and ensuring enabling and supportive environments, and sets out 239 recommendations in relation to its 35 objectives. The Madrid Plan is the successor to the Plan adopted during world’s first international policy framework on ageing, the Vienna International Plan of Action on Ageing (VIPAA) introduced some thirty years earlier in 1982. Although a landmark agreement in its own right, the implementation of the VIPAA was perceived to be of most relevance to advanced economies which already had aged populations, and little progress was made in implementing its’ recommendations in developing countries with younger age profiles (Sidorenkno & Zaidi,2018). The MIPAA reaffirmed commitments made in the VIPAA, but also sought to be of increased relevance in developing as well as developed countries. Further, the MIPAA took an explicitly rights based approach and encouraged the mainstreaming of ageing issues into general policy and development discourses (Sidorenko & Walker, 2004; Marin & Zaidi 2007), with a key commitment being to ‘build a society for all ages’ (United Nations, 2002). Fifteen years since the MIPAA’s adoption, there are 962 million people aged 60 years or over globally, over twice as many as in 1980 when preparations for the VIPAA were underway (UNPD, 2017). This figure is projected to rise to 2.1 billion by 2050 with the biggest growth to be seen in developing countries. Indeed, almost eight in every ten older people globally will live in a developing region by the middle of the century (ibid.). Whilst the MIPAA is not legally binding and responsibility for its implementation lies primarily with national governments, information and best practice sharing at the international level is strongly encouraged. Indeed, the United Nations has been collating evidence for its’ third five-year review on the implementation of the Plan (ECOSOC 2017). Thus, it is a timely opportunity to reflect on progress made in developing countries, as well as to analyse the challenges that lie ahead in regions set to grow old before they grow rich. This special issue of the International Journal on Ageing in Developing Countries brings together regional level perspectives on progress towards the MIPAA from Africa, Asia and Latin America and the Caribbean

Ageing and development: Putting gender back on the agenda

We live in a world where women over fifty account for almost one quarter of the total population. This article highlights the potential of global population ageing as a vehicle for socio-economic development and demonstrates the value of taking a gendered approach to ageing and development. With the use of country level data on gender equality, education, health and life expectancy in later life, the analysis shows that older women in low-income countries face disproportionate disadvantages relative to both their male counterparts in low-income countries and female counterparts in high-income countries. For instance, an older woman in a low-income country is over 24 times less likely to have completed secondary education than an older woman in a high-income country. Despite the widely documented female survival advantage, an older woman in a low-income country spend a smaller percentage of her remaining life expectancy at age sixty in good health than her male counterparts. Our analysis show there are strong correlations between gender inequality and diminished life expectancy and healthy life expectancy at age 60 amongst both genders, indicating that both older women and older men fare better when they live in societies which realise the contributions of women to the development process. The correlation is particularly strong in low-income countries,suggesting countries with the lowest levels of economic development have the most to gain from promoting gender equality. The United Nations Millennium Development Goals (2000-2015) had given an exclusive place to women in the standalone goal on maternal mortality and a goal on gender equality and female empowerment with explicit indicators on school enrollment amongst girls and literacy amongst young women. These goals are linked to the achievements such as the near doubling of the number of women in parliament and a near halving of the maternal mortality ratio over the last twenty years. However the development discourse has given minimal attention to women beyond reproductive age. The new, broader post-2015 Sustainable Development Goals provide unparalleled opportunities to place gender back on the emerging ageing and development agenda, support both older men and women to realise their potential and in the process maximize opportunities for prosperity and wellbeing for all